Idoc - Pub - Audit Checklist For Store Department

Audit Checklist for Store Department
Sr. Check points Observation Recommendatio Action

No. n taken by
01 Is the control copy of store
department SOPs available?
02 Is the personnel having knowledge
of current GMP requirements?
03 Is the incoming raw materials entry
register available?
04 Is the housekeeping maintained?
05 Is the sampling booth area
cleaned?
06 Is the weighting balance having
proper tag of calibration status?
07 Is the balance calibration record
available?
08 Are the calibrated standard weights
available?
09 Is the calibration certificate
available?
10 Is the standard weights are
properly stored?
11 Is the quarantine, approved and
rejected area designated?
12 Are the UNDER TEST label pasted
on all the incoming raw materials?
13 Are the SAMPLE label pasted on
all the sampled raw materials?
14 Are the APPROVED labels pasted
on all the approved raw materials?
15 Are the raw materials stored at
their respective place?
16 Check the cleaning and
housekeeping condition record of
quarantine, approved and rejected
area.
17 Are the packing materials stored
separately?
18 Is the cleaning and housekeeping
maintained at packing material
store area?
19 Is the temperature and relative
humidity record maintained for all
respective area?
20 Is the approved vendor list
available?
21 Is the FIFO system follow?
22 Check the production requisition
slip record?
23 Check the issuance record.
24 Check the dispatch record.
25 Check the general cleaning and
housekeeping of store.
26 Check the personnel hygiene.
27 Check the safety equipments.
28 Check the drum storage yard for
cleaning, housekeeping and status.
29 Check the proper segregation at
drum storage yard?
30 Check the other records.
31 Is line clearance activity
performed?
You might also like:
 Self Audit Checklist for Maintenance Department
 Self Audit Checklist for Quality Control Department
 Self Audit Checklist for Production Department
 Internal Audit Plan as per GMP
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Self Audit Checklist for Quality Control Department
Sr. Check points Observation Recommendation Action

No. taken by
01 Is the control copy of QC department SOPs
available?
02 Are the personnel having knowledge of
current GMP requirements?
03 Is the housekeeping maintained?
04 Is the weighting balance having proper tag of
calibration status?
05 Is the balance calibration record available?
06 Are the calibrated standard weights
available?
07 Is the calibration certificates available?
08 Is the standard weights are properly stored?
09 Are the status labels available on each
instrument?
10 Is the instrument calibration record
available?
11 Check the temperature and humidity record.
12 Check the cleaning record.
13 Check the cleaning of sampling devices.
14 Are all the sampling devices properly stored?
15 Check the general cleaning and
housekeeping of QC.
16 Are the specifications available for raw
material, packing material, in-process
samples, intermediates and finished
products?
17 Check the in-process testing record.
18 Check the raw material testing record.
19 Check the final product testing record.
20 Check the stability record.
21 Check the stability chamber record.

22 Check the solution preparation and
standardize record.
23 Check the control sample record.
24 Check all instrument log book.
25 Check the primary standards and its storage.
26 Check the mobile phase status of GC and
HPLC.
27 Check the HPLC column record.
28 Check the test request slip record.
29 Check the personnel hygiene.
30 Check the safety equipments.
31 Check the other records.
32 Check the environment where control

sample store?.
33 Is log book of destruction of control sample is
maintained?
34 Is the out of calibrated instrument well
labeled?
35 Is QC Chemist validated?
36 Is the sample in QC lab well labeled?

37 Are the personnel following GLP?
38 Are training given to new personnel?
39 Are all QC personnel in proper dress code?
40 Is glassware breakage log book maintained?

41 Check DM water analysis record.
42 Check reference standard records?
43 Is proper sampling plan available?
Internal Audit Plan as per GMP
:This document describes the conduct of the Management review of the quality system for G
Conformance Certification, including the conduct of an internal audit to assure the system meets
requirements of ISO Guidelines and is effectively implemented..
2.0 Objective: To Provide Documented Procedure for review of the quality system for GMP Conformance Certificat
including the conduct of an internal audit to assure the system meets the requirements.
Scope : To define role/responsibility of various functions responsible for Internal audit
4.0 Responsibility :
o Board of Internal Audit and Management Review Committee: Arranges for the internal audit
gathers all information for the Management Review.
o QA Management Committee: Provides all information as required by the Board of Internal Audit
Management Review Committee and is responsible for follow-up corrective and preventive actions
o QA Internal Auditor(s): Conduct the internal audit according to GMP.
5.0 Procedure :
 The QA Management Committee, by consensus, selects three qualified individuals for the Board
Internal Audit and Management Review Committee. Members to the Committee serve until they
replaced.
 The Board of Internal Audit and Management Review Committee arranges for the half yearly inte
audit to be conducted.
 The date for the audit is established by mutual agreement between the Board of Internal Audit a
Management Review Committee and the General Manager Production and Asst. Manager Produc
(AMP).
 The audit is conducted by any member of the board or Internal auditor qualified to participate on
Certification Board so long as the auditor is not a member of the QA Management Committee
qualified and knowledgeable in certification, auditing.
 The audit must be conducted at least every 06 months.
 During the audit, personnel responsible for the area audited are immediately notified of the outco
of the audit of their area.
 During an audit, it is possible that a difference of opinion can arise as to the severity of
observation. It is important not to spend too much time debating the merits of the observation.
does not appear that the difference of opinion can be resolved, then the auditee should be inform
that the audit report is subject to review by the Board of Internal Audit and Management Rev
Committee and the QA Management
 The draft report is issued to the Board of Internal Audit and Management Review Committee wi
14 calendar days. The Committee members review and comment on the report and a final repo
issued.
 The final internal audit report is submitted to the QA Management Committee.
 The QA Management committee drafts a response to the audit report that is finalized after review:
 Findings, nonconformities, trends, and other opportunities for improvement are identif
investigated to determine the causes; and corrective/preventive actions are developed. These acti
are implemented as soon as possible and recorded.
 The response to the internal audit report is submitted to the Board of Internal Audit and Managem
Review Committee for their concurrence.
 Upon agreement on the response to the internal audit, the Board of Internal Audit and Managem
Review Committee prepares a complete Certification Program Management Review Report
includes, as appropriate,:
 Results of internal and external audits
 Feedback from clients and interested parties related to the fulfillment of the Certification Process
 Feedback concerning impartiality
 Follow-up actions from previous Certification Program Management Review Reports
 The status of corrective or preventive actions
 The fulfillment of objectives
 Changes that could effect the management system
 Appeals and complaints
 The Board of Internal Audit and Management Review Committee submit their Certification Progr
Management Review Report to the QA Management Committee.
 The Certification Program Management Review Report with the response to the internal aud
discussed at the next meeting of the full Board. The expected outputs of the review includes decisi
and actions related to:
 Improvement of the effectiveness of the management system and its processes.
 Resource needs.
 Decisions and actions of the Board are documented in the Board Minutes and all o
Corrective/Preventive Actions are reviewed and their status documented at all subsequent quart
Board Meetings.
 Effectiveness of completed actions is reviewed at the next Program Management Review.
6.0 Abbreviations :
 GMP: Good Manufacturing Practice
 QA : Quality Assurance
Self Audit Checklist for Production Department
Sr. Check points Observation Recommendation Acti

No tak
. by
1. Is the control copy of production department SOPs
available?
2. Are the personnel having knowledge of current GMP
requirements?
3. Are the lots of raw material properly stored?
4. Are the lots of raw material having proper labels of
status?
5. Is the housekeeping maintained?
6. Is the weighting balance having proper tag of calibration
status?
7. Is the balance calibration record available?
8. Are the calibrated standard weights available?
9. Is the calibration certificate available?
10. Is the standard weights are properly stored?
11. Is the reactor area cleaned?
12. Is the status label of reactor available?
13. Is the BMR requisition slip record available?
14. Check the calibration status of temperature gauges.
15. Check the calibration status of pressure gauges.
16. Check the status of centrifuge.
17. Check the cleaning of centrifuge and centrifuging area.
18. Check the condition of centrifuge bags.
19. Check the status of dryer.
20. Check the cleaning of dryer and drying area.

21. Check the calibration status of temp, Gauge of dryer.
22. Check the trays and trolley condition.
23. Check the status of sifter.
24. Check the cleaning of sifting area.

25. Check the status of multi mill.
26. Check the cleaning of milling area.
27. Check the finished product packing area.
28. Check the availability and stock of packing materials.
29. Check the temperature and humidity record.
30. Check the cleaning of sampling devices.
31. Are all the sampling devices properly stored?
32. Check the general cleaning and housekeeping of plant.
33. Check the test request slip record.
34. Check the personnel hygiene.
35. Check the safety equipments.
36. Check the other records.
37. Is ECR available?
38. Check the ECR.
39. Check the condition of fluid bed dryer.

40. Check the condition of reactors.
41. Are there work instruction labeled on all equipments.
42. Are records maintained for Solvent Receipt, Usage &
Recovery In Plant?
43. Check the records of Solvent Receipt, Usage &
Recovery In Plant.
44. Is there any training record for new employee?
45. Check the training record and training schedule.
46. Is the pipeline properly marked with directional arrows?
47. Is logbook of all Equipment properly maintained?
Vendor Audit for Validation

1. GENERAL:
1.1 Building Maintenance
1.2 Reception
1.3 Administrative Block/O
1.4 Utility Block
1.5 Maintenance
1.6 Surroundings
2. PERSONNEL:
2.1 : Or
2.2 : Qu
2.3 : Pro
Me
Fo
Fo
2.4 : Pe
Fo
Fo
2.5 : Fa
Fo
Fo
Wa
2.6 : Pe
Sh
WC
Lo
Ca
2.7 : Jo
Re
2.8 : Tra
2.9 : En
2.10 : Dr
2.11 : Sy
2.12 : Pe
3 PLANT & BUILDING :

.
3.1 : Well equipped and sufficient area for Storages
a) : Raw Material ____________
b) : Packing Material ____________
c) : Intermediate ____________
d) : Finished Goods ____________
e) : Cleaning / Schedule ____________
f) : Cleaning of used equipment

and accessories ____________
g) : Separate area for storage of incoming material
 Quarantine area
 Approved materials Storage
 Rejected material Storage
 Sampling area
 Dispensing area
3.2 Adequate cleaning , washing and toilet area
3.3 Separate canteen area

3.4 Utilities like compressed air, steam, nitrogen gas
area qualified and lines are identified with arrow
mark for flow direction.
3.5 HVAC are providing for critical operation.
3.6 Drain is properly sanitized for critical area.
3.7 Water purification system

3.8 Water distribution system and quality of water
used
3.9 Men and materials movement system
3.10 Area is product dedicated or group of products

are manufactured then se the list of the product.
3.11 Cross contamination possibilities
3.12 Area cleaning procedure
3.13 Procedure of handling of rejected material.
3.14 Lighting level
3.15 Handling of sewage and waste
3.16 Sanitization of process equipments
3.17 Pest control system
3.18 : EQUIPMENT
a) Design MOC of contact parts

b) Qualification of equipment
c) Cleaning operation and preventive maintenance
procedures
d) Cleaning frequency
e) Measuring device calibration procedure
f) Cleaning validation approach
g) Computerized system are qualified as per CCF
part 11
h) Access to the computerized system is limited
k) Identification
l) Cleaning requirement for same product
for Product Change Over
m) Housekeeping & Sanitation
n) Special Procedure / Precaution
4 MANUFACTURING CONTROL:
.
4.1 : Identification level for material under processing
4.2 : Written Manufacturing Procedure
4.3 : Deviation Control Procedure
4.4 : Means of Communication
4.5 : Status label for rejected / released material
4.6 : Used container control
5. TSE QUESTIONNAIRE:
5.1 : Have you obtained the COS Certificate from EDQM for the
Material you are supplying to us? If yes please attach the copy.
5.2 : Is any of the starting material used in the manufacturing from
Animal Origin. If yes, Please ensure to obtain the TSE free Certificate
from your supplier.
5.3 : Is the Production Line dedicated?
5.4 : If NO Please Specify:-

a) Are the equipments shared with any other product, which uses the animal
original starting material?
b) Do you have sufficient Cleaning Procedure?
b) Is cleaning procedure validated?
5.5 : Is your batch COA contains the TSE / BSE free Declaration. If no submit an
undertaking to send the batch wise TSE / BSE free Declaration for all
supplies to us?
6. RECORD KEEPING :
6.1 : Material issue control ________________
6.2 : Equipment Log ________________
6.3 : Process Record ________________
6.4 : In-Process Results ________________
7. RAW MATERIAL CONTROL:

7.1 : Raw Material Receipt Control __________________
7.2 : Approved Material Segregation __________________
7.3 : Rejected Material Control __________________
8. QUALITY CONROL:
8.1: Raw Material Specification / Test Procedure & its control_______
8.2: Calibration Record ______
8.3: Finished Product Analysis & Release control _______
8.4: Testing facilities _______
9. INFORMATION RELATED TO OTHER PRODUCT MANUFACTURED:
9.1: List of product manufactured (Attach Sheet)
9.2: Product change over control (Cleaning Validation) _______
10. FILING SYSTEM:
10.1 Retrievable ______________
11. NON CONFORMANCES IF ANY:
CRITICAL
MAJOR
OTHER
12. CORRECTIVE ACTIONS:
13. PREVENTIVE ACTIONS:
14. CLOSURE OF AUDIT:
CONCLUSION
SIGN
DATE
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Monday, December 6, 2010

Self Audit Checklist for Maintenance Department
Sr. Check points Observatio Recommendatio Action

No. n n taken by
01 Is the control copy of Maintenance

department SOPs available?
02 Is the personnel having knowledge of

current GMP requirements?
03 Is the preventive maintenance schedule

available?
04 Check the preventive maintenance
records.
05 Are equipments labeled with last

maintenance date and next due
maintenance date?
06 Are the equipment qualifications

available?
07 Check the equipment qualification

record.
08 Is the temperature gauges calibration

record available.
09 Check the temperature gauges

calibration record.
10 Are the pressure / vacuum gauge

calibration record available?
11 Check the calibration record.
12 Check the break down maintenance

record.
13 Check the DM water generation record.
14 Check the AHU maintenance record.
15 Check the AHU’s filter cleaning record.
16 Check the AHU’s differential pressure

record.
17 Is there any training schedule for new

entrant in maintenance department?
18 Are new entrant trained after join

maintenance department?
19 Are there any documents for

postponement of the schedule
maintenance?
20 Is the department follow the

postponement of the schedule
maintenance and send it to review by
QA department?
21 Is there check list for each equipment

for preventive maintenance?
22 Check the equipment check list.
23 Are all electrical motor labeled and well

maintained?
24 Check the status of the electrical motor.
25 Check the maintenance status of DG

Set.
26 Is the maintenance store area clean?
27 Check the housekeeping of

maintenance store area.
28 Are all storage tanks properly labeled?
Out of specification (OOS) result in Microbiological Analysis
1.0 OBJECTIVE: To lay down a procedure for handling of out of specification (OOS) result in
Microbiological analysis and monitoring.
2.0 RESPONSIBILITY
Quality Control Executive/ Microbiologist
3.0 ACCOUNTABILITY
Quality Control Manager
4.0 PROCEDURE
In all the reports the identified reason shall be written on a continuation sheet to the annexure
provided. A copy of the above investigation report shall be maintained with the batch
manufacturing records concerned to increase awareness and for any future reference
4.1 STERILITY TEST

4.1.1 If evidence of microbial growth is found, the product to be examined does not comply with
thetest for sterility, unless it can be clearly demonstrated that the test was invalid for causes
unrelated to the product to be examined .The test may be considered invalid only when one or
more of the following conditions are fulfilled:
4.1.1.1The data of the microbiological monitoring of the sterility testing facility shows fault;
4.1.1.2 A review of the testing procedure used during the test in question reveals a fault;
4.1.1.3 Microbial growth is found in the negative controls;
4.1.1.4 After determination of the identity of the microorganisms isolated from the test, the
growth of this species or these species may be ascribed unequivocally to faults with respect to
the material and / or the technique used in conducting the sterility test procedure.
4.1.2 If the test is declared to be invalid it is repeated with the same number of units as in the original
test.
4.1.3 If no evidence of microbial growth is found in the repeat test the product examined complies with
the test for sterility. If microbial growth is found in the repeat test the product examined does not
comply with the test for sterility.
4.2 ENVIRONMENTAL MONITORING
4.2.1 If the microbial counts are found to be more than or equal to the alert limit then
open a deviation report (annexure I) through Q.C. Head to the concerned Production head.
Production personnel shall check the working discipline, supply of air, safety measures etc.
4.2.2 If the count exceeds or reaches the action limit then the urgent notification to the Production
head and Engineering Head through Q.C. Head shall be followed by an investigation for the
same. –
- Supply of air
- Working discipline
- Review of data from the same place and others from the incubated plates
- If any of the plates does not indicate the same then no action is necessary.
- If any of the plates indicates more count then perform additional cleaning, disinfection or
fumigation and retraining to the operator shall be given.
- All activities shall be recorded as per the annexure attached with this SOP.
- More number of samplings (i.e. double the original) shall be preformed at the same location
where the counts observed were beyond or equivalent to the action limit but an additional
relevant parameter of monitoring shall also be performed which shall be incorporated with the
same annexure.
- All the batches manufactured during the said period shall be subjected to the microbial
analysis for MLT / Sterility &BET in order to ensure that the batches manufactured are in
accordance with the relevant finished product specifications. The investigation report shall be
submitted to the Q.C. - Head
4.2.3 If the bio-burden is found out of specified limit in the core areas the identification of the
organism shall be performed.
4.2.4 Stop the production immediately and check all the possible parameters, which can affect bio-
burden of the area.
4.2.5 Check the pressure differential of the area, which must be within the specified limit.
4.2.6 Check the air velocity of LAF /HEPA filters, which must be within the specified limit.
4.3 If the investigation / review of manufacturing activities (e.g. sterilization process, aseptic
filtration, environmental conditions, personnel practices) indicates failure of manufacturing
activities, then the batch shall be considered as failed to comply sterility.
4.4 MICROBIOLOGICAL AND BET EXAMINATION OF WATER
If only the alert is exceeded without finding an undesirable microorganism the release of the
preparation for which this water has been used, has to be taken under hold till the result comes.
In case of the counts touching the action limit then all the batches manufactured shall be re
analyzed by taking 25 grams and making the allowance for the larger size specimen for the
analysis.
In the case of counts crossing or touching the alert limit or action limit in any type of water the
same will be intimated to the production department and maintenance department. If the result
cannot be attributed to the analytical error, sampling error, contamination in the container
sampled then the microorganism detected must be identified / differentiated by taking sample
from all other points.
4.4.1 Adequate sanitization of the system shall be ensured to eliminate the source of contamination
with a rigorous check for the same.
4.4.2 All the investigations made shall be recorded in the annexure III provided with this SOP.
4.5 MICROBIOLOGICAL EXAMINATION OF RAW MATERIAL / FINISHED PRODUCT
4.5.1 The first action is to intimate the Q.C. Head.
4.5.2 Retest the same material/product but with a sample size of 25 grams by making allowance for
the larger size specimen.
4.5.3 Results for the same shall be intimated to the Q.A. Head for final decision.
5.0 REASON FOR REVISION
Harmonization of format
6.0 TRAINING:
Trainer -- Head – Quality Control
Trainees-- Quality Control Chemists & Assistants
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 1 : Head of Department – Quality Control
Original Copy : Head – QUALITY ASSURANCE.
ANNEXURE –I
FORMAT FORDEVIATION REPORT TO PRODUCTION DEPARTMENT

(Deviation Report About the environmental monitoring)
Revision No. : 00
REF. SOP NO.: Page No.: 1 of 1
Effective Date:
Sampling point where deviation occurred: Date:
Name of the Product Batch no.:
Deviation : Parameter:
Requirement :
Results : Signature :
Corrective action in Production Department:
Cleaning, Disinfection, Change of disinfectant, Checking of LAF unit parameters
Checking of HVAC system, Education to Operators, Repair/Maintenance Work (Cross
whichever is not applicable and specify actions taken).
Maintenance Repair / Comments :

………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
……………………………………………………………..
Name : Signature :
Date:
Repeated Sampling :
Parameter:
Result:
Comments by Q.C. Head for Approval of Production :

………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………
Signature :
ANNEXURE - II
Format for Corrective Report After Sampling of Environmental Parameters in Production
Revision No. : 00
Effective Date:
Date : Deviation :
Date of repeated deviation :
Corrective Measures in Microbiological Lab
Checking of condition s of LAF unit during working , Checking of equipment
Growth promotion test for the media used.
Done By : Checked
By :
Results of Microbiological Impurity of Finished Product :
Name : Date : Signature :

Comments of Quality of Quality of Control - Head :
Comments of Quality Assurance - Head :
ANNEXURE –III
INVESTIGATION REPORT FOR FAILURE IN TEST FOR BACTERIAL ENDOTOXIN & M.L.T
Revision No. : 00
Effective Date:
Sample
Analyzed on Analysed By Checked By
Preparation parameters for
Sampling container Procedure of sampling GP test of media
Any testing error
BET
Micro tips Test tubes Pipette
LAL reagent
Batch No. Mfg. Expiry Reconstituted

on
.LAL Reagent water
Batch No. Expiry Blank
Parameters of depyrogenation/sterilization apparatus:

Validation Status Calibration Status
Results of other samples with same conditions tested on the same day.
Details of Raw material used in finished product
Result
Test repeated
Date Result
Microbiologist
ACTION TAKEN :
Production Head Engineering Head Quality

Control Head
CONCLUSION
(Results of MLT for Other Samples to be enclosed)
Microbiologist QC
Manager
Date: Date:
Remarks from Q.C. Head

Name: Sign Date :
 Disposing of microbiological culture media

 Out of Specification Procedure
 Reprocessing of Out of Specification Batch
 OUT OF SPECIFICATION INVESTIGATION FORM
Contract Laboratory Approval Questionnaire
S. No. Questions
1.0 GENERAL INFORMATION
1.1 Name and Address of Laboratory:
1.2 Contact Person:

Name:
Phone No.: Mobile No.: E-mail ID:

2.0 FACILITIES:
 Please specify what type of analysis you are performing?
3.0 PERSONNEL:
3.1 Number of Staff: No.
 Director(s)/ responsible person of the organization:
 Head/ Responsible person for Analysis:
 Q A:
 Q C:
 R & D Lab:
 Microbiology:
 Others:
3.2 No. of Approved persons:
S. Questions Yes No Comment

No. s
3.3 Do you have a written training program for analyst?
3.4 Does your training program include the following:
 GLP
 GMP
 Job training
 Safety and Environmental issues
 ISO principals
3.5 Is efficiency of training regularly checked?
 By examination
 By any other relevant process
3.6 Are there written job descriptions for all

employees?
4.0 INSTRUMENTS AND CALIBRATION:
4.1 Is there an approved preventive maintenance
program for all equipment used in laboratory?
(Attach a list of Instruments)
4.2 Is SOP of all instruments present?
4.3 Is SOP of calibration of all instruments present?
4.4 Are all instruments properly calibrated and labeled?
4.5 Is there a calibration calendar maintained?
5.0 QUALITY MANAGEMENT:
5.1 What is your QA System based on?
 GMP
 cGMP
 USFDA
 ISO 9001:2000
5.2 Are you regularly inspected?
 By clients
 By National authority
 By Foreign authority
 By FDA

No. s
5.3 Does your Laboratory have GMP/ USFDA
/cGMP/ ISO approval? If Yes specify
Name of authority Date of Certificate
1.
2.
3.
(Attach copy of certificate)

6.0 QUALITY ASSURANCE
6.1 Is there system for rejection of sample?
6.2 Do you have specification approved by QA for
working/reference standards of the product?
For Physical, Chemical requirements
For Microbiological requirements
6.3 Is there procedure for sample handling and its
inspection regarding:
 Name of customer
 Sample quantity
 Batch No.
 Date
 Product related to Pharmacopoeia
6.4 Do you use statistical method for evaluation?
 Total sample received
 No. of sample passed
 No. of sample failed
6.5 Do you have all documented procedures for each

and every step?
6.6 Are there validated:
 Analytical procedure?
 Cleaning procedure?
7.0 ENVIROMENT MANAGEMENT SYSTEM:

7.1 Do you have any environmental policy?

No. s
7.2 Do you have ISO 140001 certificate?
(Attach copy)
7.3 Do you check the environmental conditions of
laboratory regarding:
 Temperature
 Relative Humidity
8.0 WATER:
8.1 Which type of water used for analysis?
8.2 How will you check the quality of water and it is
free of contamination?
Questionnaire filled by:

Name
Signature and stamp of company
Designation
Date:
 Vendor Approval Questionnaire
 Sending sample to contract lab
 CLEANING OF QUALITY CONTROL LABORATORY
 APPROVAL AND REJECTION OF PACKAGING MATERIALS
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First Aid
Purpose: To provide a documented guideline for the first aid treatment n case of any accident.
2.0 Objective: To provide a first aid treatment.
3.0 Scope: Employees / Visitors / workmen.
 Follow up : Officer Personnel & Administration
 Over all responsibility : General Manager (Adm).
5.0 Procedure :
 Training
 First aid training shall be given to selected employees of each department.
 Detail training of the first aid shall be given to some employees of the company.
 The list is as follows and shall be available in each department for easy reach out
during emergency.
List of trained employees
Serial No. Department Name of Trained employees
 The first aid box shall be numbered and located at identified and marked
positions as following –
Locations of first aid box
Serial No. First aid box number Location of First aid Box
 Each first aid box shall contain following -
Contents of first aid box

Serial No. First Aid box Contents Quantity
 Every Monday from Personnel department personnel or General Manager (Adm) shall
Review the contents of first aid box and shall replenish the required item. The
Record of review shall be kept.
Review of first aid box

Date/day Contents Replenishment Reason for Reviewed Discarded
checked details replenishment by Items
OK/not OK submitted
to QA.
Accident Prevention Guidelines
urpose : To provide a documented procedure for preventing accident & Recording accident.
2.0 Objective : To maintain safety aspects
3.0 Scope : Preventing accident & Recording accident
 Follow up : Concern department head
 Over all responsibility: Personnel & Administration Manager.
5.0 Procedure :
 Accident Prevention
 Workman shall engage themselves in the duties which have been assigned to them.
The execution of their duties must be in the safe manner laid down in S.O.P. for the
operation, of the machine or duty concerned.
 Removal of guards or safety devices, cleaning of machines which they are
Running, etc., are expressly forbidden.
 Workmen working beyond the height of 10 feet shall wear the safety belt.
 If any employee / work man working beyond the height of 10 feet on ladder shall work
with one additional work man / employee to hold ladder.
 Safety instructions given or posted on Notice Boards are to be followed.
 Workman shall not keep sharp edge tools into their pocket.
 Any employee / workman working with electricity shall wear safety shoes &
Sock proof gloves.
 Any workman working with hazardous chemicals / acid shall wear the safety
Wears like goggles, gloves etc.
 Speed of vehicle inside the factory premises shall not exceed 20 km / hr.
 When welding work is to be carried out in closed area, extra fire extinguisher
Shall be provided.
 After working with oil, floor shall be cleaned thoroughly to wipe out the oil.
Solvents shall be stored in tight closed container.
 Used drums of solvent / chemicals shall be discarded by skilled workman.
 Sufficient emergency light shall be provided.
 Entry into transformer yard / explosive storage yard shall be restricted to selected
Personnel.
 Machine which is under maintenance shall be labeled as “Under Maintenance”.
 Workman shall enter into water tank, drainage, septic tank only after permission Of
Personal & Administration department.
 Workman shall carry out repairing work of high pressure line / high temperature Line /
or any explosive line only after permission of Engineering In charge.
 Wear earplugs near high noise area.
ecording of Accident
 Accident shall be recorded into Accident Register.
 The accidents are categorized as critical major and minor depending on the
 Seriousness of the incident.
 Action taken upon Accidents:
 The First aid, if required, after the accident shall be provided at the earlier marked
Locations and trained persons are available.
 The telephone no. of fire station, doctor, ambulance shall be displayed in all the
Departments to call upon in an emergency.
 The affected employee shall be immediately rushed to the hospital, if needed and is
provided the required medical help.
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Tuesday, December 14, 2010

Guidelines for production activities as per safety & cGMP requirement
Purpose : To provide guideline to ensure that different production activities are carried out in compliance with
safety & cGMP requirement, at pre-determined frequency.
Objective : To provide a documented guideline to ensure that different production activities are carried out in
compliance with safety & cGMP requirement, at pre-determined frequency.
Scope : Scope of this SOP covers all the production disciplines.
 Primary : Officer Production
 Secondary : Executive Production
5.0 Procedure :
 ORGANISATION & FUNCTION:

 The department must have a team that would perform all the function meeting cGMP
requirements. It must also address to documentation, audits and training aspects pertaining to
production jobs.
 The production department organization must be structured to ensure that production

functions are carried out safely, in accordance with cGMP requirements, efficiently and promptly
to support other service areas. It must be resourced with adequate numbers of appropriately
qualified and trained staff.
 PREVENTION OF CONTAMINATION AND CROSS CONTAMINATION:
 Before starting any process in equipment make sure equipment should be cleaned and line
clearance has been given by QA.
 The production area should be clean and free from dust and dirt so the intermediate and final
product could not be contaminated.
 The cleaning of production area should be looked after by PA department.
 TRAINING:
 All the staff shall be covered for cGMP, Safety and Job-related training as per the training
procedure.
 STANDARD OPERATING PROCEDURES:
 SOP must be prepared for all activities that are quality critical or safety critical or relate to key
business areas. These SOPs must be prepared, reviewed & authorized and controlled in
accordance with Site SOP.
 The SOPs must include specific maintenance instructions, lubrication details, Spares
requirements, frequency of maintenance, responsibilities for carrying out the job &
documentation, etc. as appropriate. The department activities must be reviewed to identify
operations which need preparation of SOP and the current SOPs must be updated / reviewed
as scheduled.
 AUDITS:
 Department audits must be carried out to monitor the production aspects of departmental
activities in regard to its impact on SHE, Energy Conservation and Quality matters.
 VALIDATION:
 According to cGMP requirement process validation should be done.
 CHANGE CONTROL:
 All changes must be fully documented, assessed and authorized prior to the work being carried
out.
 In line with good documentation practice, change in process must be controlled as per the
good manufacturing practices. If any Change occurs it should be reported to QA department
with reason.
n documents.
 The documents will include following:
 Batch Manufacturing Record : Documentation pertaining BMR is to give information about

progress in production of intermediate as well as final finished product include every information
regarding to the product like analytical report, condition of reaction given for reactor etc.
 Equipment Cleaning Record: Before conducting next step in process cleaning of equipment
should be required. To follow cGMP ECR should be filled by production department before
starting every process. By checking ECR, QA department give line clearance to production
department.
 Validation Documents: Documentation pertaining to validation would include protocol and

reports for DQ, IQ and OQ activities and would be in line with the guidelines given. Protocols
and reports must also include supplier’s documentation (e.g. pressure test, calibration
certificate, etc.) besides the reports generated at site.
 ICH Guidelines for Pharmaceuticals

 GUIDELINES FOR EMERGENCY MANAGEMENT PLAN
 SAFETY MANUAL AS PER ICH GUIDELINES
 Instructions for Engineering department as per safety and cGMP
requirements
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Monday, November 29, 2010

GUIDELINES FOR EMERGENCY MANAGEMENT PLAN
ON-SITE EMERGENCY MANAGEMENT

Emergency Leader / Main Controller (Senior Plant Manager).
Co-ordinate all activities from Emergency Control Center.
Duties:
 Assess extent and nature of emergency.
 Sequential stoppage of operation as per requirement.
 In case of fire, necessary arrangement and provision of fire squad and systems to the
emergency spot and its neighbouring sections.
 Organise necessary ambulance and medical treatment for affected persons if required.
 Arrangement of necessary hospitalization of victims.
 Evacuation of site (partially or full) if required.
 Preserve evidence.
 Organise investigation.
 Before allowing re-entry to the site check if the conditions are safe (Toxicity, fire hazard,
structural stability etc.).
 Re-starting of plant operations only after ensuring steps for prevention of re-occurrence.
 Arranging for evacuation of neighbouring population if need be
 Deal with media.
ADVISORY TEAM
Responsibility of Advisory Team.
 On hearing the emergency alarm will proceed emergency control center.
 Remain with Emergency Leader at the emergency control center and advice him as needed.
 In case Emergency Leader has to leave his post for some reasons any of the member of the
Advisory Team will take over as the Emergency Leader.
 If needed Factory Manager can deputy Emergency Leader to the site to be of help to the
incident controller.
 Deal with media.
ACTION TEAM – A
 Shift in-charge of affected plant.
 Dy Manager / Asst. Manager of affected plant.
 P.E. of affected plant.
 Inform emergency control center / security about location and nature of emergency.
 Inform his department head.
 Minimise the consequence by
 Eliminating source of ignition.
 Shutting down the operation as per requirement and other areas as guided by the incident
controller.
 Arranging to activate fire hydrant system.

 Ensuring the appropriate use of fire fighting material by fire fighting squad.
 Stopping loading / charging operations.
 Evacuating the plant if required in consultation with incident controller.
Department Head
Take over the responsibilities of the shift in-charge upon arrival and proceed as
listed above.
Security and Fire Fighting squad
 Proceed the scene of emergency
 Consult the shift –in-charge and decide the line of action.
 Ensure the stock of fire fighting material.

ACTION TEAM – A
DUTIES OF SENIOR CHEMISTS:
1. As shift in charge will be involved in fire fighting operations senior chemist will ensure
that
 Operations of affected area will be stopped and reactions will be stopped in safer mode
with consulting shift-in-charge.
 Evacuation of affected area.
 Shifting of raw material intermediates from affected area.
 Duties of chemists and junior chemists.
2. Chemists and junior chemists will form fire fighting team with guidance of incident
controller start fire fighting with fire extinguishers and then with fire hydrant system if
required.
ACTION TEAM – B
 Shift-in-charge of neighbouring plant / departments.
 Dy. Managers, Ams, neighbouring plant / departments.

 Manager Maintenance
 Manager Electricals.
On hearing Alarm
When instructed by the Emergency Leader
 Ensure that Fire hydrant pumps are in operation.
 Inform people about the emergency.
 Prepare for the evacuation with short notice.
 Arrange head count, repeat this at Assembly point.
AMs, Dy. Ams of other Department.
 Proceed to own areas.
 Take over responsibilities from shift-in-charges and ready to shut down plant if needed.
Manager – Maintenance
 Provide Engineering assistance to Emergency Leader.

 By ready with rescue equipments to extricate trapped personnel.
Manager – Electricals.
 Ensure that adequate power supply is made available for sensitive plant operation and
emergency lighting.
 Make available an electrician near incident controller.

ACTION TEAM – C
Security Officer / Safety Officer
On hearing Alarm
Security Officer
 Proceed towards emergency.
 Control traffic.
 Arrange guard at gate to inform essential personnel.
 Prevent unauthorized entry at gate.
 Get additional help if needed.
 Communicate with city Fire Brigade.
 Arrange Fire Fighting squad to fight fire.
Safety Officer
 Proceed to scene of Emergency
 Ensure adequate supply of safety appliances.
 Inform with consultation with advisory team to Factory Inspector and other Authorities.
 Offer any help expected, advice with First Aid render First Aid to injured person.
 Keep in touch with doctors and medical team.
 Ensure availability of vehicle for moving injured to hospital.

ACTION TEAM – D
 Doctors.
 First Aiders
 Stores-incharge
For Doctors / Nurse
 Keep Ambulance ready to proceed to scene of Emergency at short notice.
 Priorities causalities for treatment call First Aiders.
 Consider sending causalities for specialist treatment.
 Arrange hospitalization, additional ambulances.
For First Aiders
Proceed to the site and hospital as per decided by Emergency Leader to render assistance.
Stores-in-charge.
Arrange additional supplies of Fire Fighting or Safety equipments as required.
ACTION TEAM – E
All staff members not listed in emergency action team.
Contact workmen and supervisors.
On hearing Alarm
 Get back to work places (if safe) and await instructions from supervisors.
 Avoid panic
 Do not go to the scene of Emergency unless specifically instructed by Emergency Leader.
 Contract persons should stop work and assemble at security gate.
WORKS TO BE DONE FOR MOCKDRILL
1. Location of emergency control center
2. Location of assembly polls.
3. Emergency alarm system.
4. Formation of observer’s team.
5. Formation of fire fighting team from each shift.

6. First aid training (specially to QC chemists as availability is round the clock).
7. Facilities in First Aid / Ambulance room.
8. Prior training of fire fighting to all teams.
9. Training programs for all teams as per their functions.

 ICH Guidelines for Pharmaceuticals
 Guidelines for production activities as per safety & cGMP requirement
 Guidelines for Engineering & Maintenance
 Internal Audit Plan as per GMP
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Saturday, November 27, 2010

ICH Guidelines for Pharmaceuticals
What is the purpose of ICH ?
The objective of ICH is to increase international harmonisation of technical requirements

to ensure that, safe, effective and high quality medicines are developed and registered in
the most efficient and cost effective manner.
Goal of ICH
The goal of ICH is to promote international harmonisation by bringing together

representatives from
the three ICH regions (Europe, Japan & USA) to discuss and establish common
guidelines
Stability
Q1A(R2) Stability Testing of New Drug Substances and Products
Q1B Stability Testing : Photostability Testing of New Drug Substances and

Products
Q1C Stability Testing for New Dosage Forms
Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug
Substances and Products
Q1E Evaluation of Stability Data
Q1F Stability Data Package for Registration Applications in Climatic Zones

III and IV
Analytical Validation
Q2(R1) Validation of Analytical Procedures: Text and Methodology
Q2A Validation of Analytical Procedures: Methodology (in Q2(R1)
Impurities
Q3A(R2) Impurities in New Drug Substances
Q3B(R2) Impurities in New Drug Products
Q3C(R4) Impurities: Guideline for Residual Solvents
Pharmacopoeias
Q4 Pharmacopoeias
Q4A Pharmacopoeial Harmonisation
Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in

the ICH Regions
Q4B Annex 1Evaluation and Recommendation of Pharmacopoeial Texts for

Use in the ICH Regions on Residue on Ignition/Sulphated Ash General
Chapter
Q4B Annex 2 Evaluation and Recommendation of Pharmacopoeial Texts for

Use in the ICH Regions on Test for Extractable Volume of Parenteral
Preparations General Chapter

Use in the ICH Regions on Test for Particulate Contamination: Sub-Visible
Particles General Chapter
Q4B Annex 4A Evaluation and Recommendation of Pharmacopoeial Texts

for Use in the ICH Regions on Microbiological Examination of Non-Sterile
Products: Microbial Enumeration Tests General Chapter
Q4B Annex 4B Evaluation and Recommendation of Pharmacopoeial Texts
Products: Tests for Specified Micro-organisms General Chapter
Q4B Annex 4CEvaluation and Recommendation of Pharmacopoeial Texts

Products: Acceptance Criteria for Pharmaceutical Preparations and
Substances for Pharmaceutical Use General Chapter

Use in the ICH Regions on Disintegration Test General Chapter

Use in the ICH Regions on Uniformity of Dosage Units General Chapter

Use in the ICH Regions on Dissolution Test General Chapter

Use in the ICH Regions on Test for Sterility General Chapter
Quality of Biotechnological Products
Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from

Cell Lines of Human or Animal Origin
Q5B Quality of Biotechnological Products : Analysis of the Expression

Construct in Cells Used for Production of r-DNA Derived Protein Products
Q5C Quality of Biotechnological Products : Stability Testing of

Biotechnological/Biological Products
Q5D Derivation and Characterisation of Cell Substrates Used for
Production of Biotechnological/Biological Products
Q5E Comparability of Biotechnological/Biological Products Subject to

Changes in their Manufacturing Process
Specifications
Q6A Specifications : Test Procedures and Acceptance Criteria for New Drug
Substances and New Drug Products: Chemical Substances (including
Decision Trees)
Q6B Specifications : Test Procedures and Acceptance Criteria for

Biotechnological/Biological Products
Good Manufacturing Practice
Q7 Good Manufacturing Practice Guide for Active Pharmaceutical

Ingredients
Pharmaceutical Development
Q8(R1) Pharmaceutical Development
Quality Risk Management
Q9 Quality Risk Management
Pharmaceutical Quality System

Q10 Pharmaceutical Quality System
Q8/9/10 Q&As Questions & Answers

document
 GUIDELINES FOR EMERGENCY MANAGEMENT PLAN

 Quality Manual as per ICH Guidelines
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SAFETY MANUAL AS PER ICH GUIDELINES
Chemical industries are more prone to safety hazards, in terms of fire, explosion
etc., resulting in huge loses of resources and precious lives.
Hence, it is of utmost importance that each one, irrespective of his position in the
organization should exhibit a high sense of responsibility to safeguard the safety of
his area of operation, in his own as well as in the interest of the organization.
The hazards could be of various types, arising from chemical, mechanical, electrical
or civil in nature.
1. Chemical Hazards:
Most of the accidents occurring in chemical industries are of this nature. The
causes for the hazards can be attributed to:
i) Process deficiencies.
ii) Faulty equipment design
iii) Equipment failures.
iv) Lack of training for the operating personnel.
v) Improper storage and handling of incompatible chemicals.
vi) Poor taste for GMP.
vii) Human error, etc, etc.
i) Chemical processes :
The processes involving many of the chemicals with different chemical

characteristics should be well established and validated in lab/ pilot plant scale
before being implemented for commercial production. HAZOP study should be
conducted for each stage of the process and possible hazards in the process should
be eliminated.
ii) Equipment design:
Adequate attention should be paid while designing of an equipment for a process,

taking into consideration of moc of the equipment, process parameters like
temperature, pressure, safe operational capacity, safety gadgets like flame-arrester,
vent line valve, control valves etc.
iii) Process equipments:
All process equipments which have bearing on the process control, such as
temperature indicators, pressure / vacuum gauges, safety / control valves etc.
should be of reliable quality and tested for performance before being installed.
There should also be a system for periodic inspection and maintenance of these
equipments.
iv) Training:
Training plays an important role in the skill development process. All the
operational persons should be adequately trained for the job.
v) I. Storage and Handling of chemicals:
1. All chemicals based on their chemical properties and incompatible nature with
other chemicals must be stored as stipulated in their MSDS.
2. Chemically incompatible materials should not be allowed to come into direct

contact with each other under any circumstances.
3. Proper personnel safety equipments, such as apron, goggles, face shield, nose
mask, safety shoes should be worn while handling corrosive and hazardous
chemicals.
4. Adequate fire-fighting equipments such as fire-extinguishers, sand filled buckets,

access to fire hydrant system should be provided near the storage place.
5. No loose electrical cables or cables with broken joints should be permitted in the
storage premises. Proper earthing has to be done wherever flammable solvents are
loaded or unloaded.
6. Right type of material handling equipments such as fork-lifter, drum trolley,

cylinder trolley, etc should be available.
7. All electrical fittings, such as lighting, switches etc. in the storage area should be of
flame proof category.
8. it must be ensured that MSDS (Material Safety Data Sheet) for all the hazardous
chemicals being stored must be made available to the stores incharge and it is the
responsibility of the stores incharge to make sure that the storage and handling is
done in compliance to the procedures stipulated in the MSDS.
9. Persons operating in the material handling functions should be adequately trained

to handle safety and fire-fighting equipments.
10. As a safety need, every storage room should be provided with an exit door, which
is to be properly identified and kept un-locked.
11. Good house keeping is an important requirement in storage godowns. There must
be clear passage area for free material movements.
v.2. In compatible chemicals:
1. There are chemicals, which remain harmless if stored in isolation, but upon
allowing coming into direct contact, could pose severe fire, explosion hazards.
Some of this type of chemicals are

i) Con H2SO4 vs KMnO4
ii) Glycerol vs KMnO4
iii) Acetone
Methanol vs CrO3
Glycerine
iv) Co. HNO3 vs alcohols, ketones, ethers etc.
v) Sodium metal vs H 2O
vi) Sodium hydride vs H2O
vii) Hydrogen peroxide vs flammable organic solvents
In all the above cases instant fire will take place, due to the high amount of heat
produced as a result of the vigorous reaction between these compounds.
2. Certain type of chemicals is sensitive towards stress, shock and adverse

thermal/pressure conditions. Subjected to any of such environmental conditions,
they decompose at such a fast rate that it would lead to Explosions e.g.
1. Nitrates (ammonium nitrate)
2. Persulphates (ammonium persulphate)
3. Peroxides (hydrogen peroxide)
4. Permanganates (potassium permanganate)
5. Perchlorates (ammonium / sodium / potassium)
6. Dichromates (ammonium)
7. Hydroxylamines and their salts.
8. Azides (sodium azide) etc, etc.

3. There are many chemicals which are highly reactive with water / moisture. Upon
contact with water, they react violently resulting in Fire / Chemical splash. These
are to be stored in leak proof water tight containers in a dry place, e.g.
1. Acetyl chloride 2. Aluminium chloride
3. Acetic anhydride 4. Thionyl chloride
5. Calcium hydride 6. Sodium metal
7. Sodium hydride 8. Con. Sulphuric acid etc, etc.
4. Few of the chemicals are very corrosive in nature and can cause severe blisters /
deformity / loss of vision etc, if they come into contact with human body. All
personal protective equipments such as hand gloves, apron, goggles, nose mask,
safety shoes should be worn by those handling these chemicals e.g.
1. All mineral acids (HF, HCl, HNO3, H2SO4)
2. Certain organic acids (formic and acetic acids)
3. Alkalies (ammonium, sodium and potassium hydroxides)
4. Chloro compounds (acetyl chloride, Thionyl chloride, mono and tri-chloro acetic
acid, aluminium chloride etc.)
v.3. Storage of flammable solvents:
Based upon the degree of flammability (Flash points), flammable solvents are
classified under the following 3 categories:
i) Class A-solvents having flash point 0 to 23oC.

ii) Class B-solvents having flash point >23 to 65 oC
iii) Class C-solvents having flash point >65 to 93 oC
v.3.1 Precautions to be observed in storage:
1. All solvents of category A and B should be stored only in metallic containers, well
closed, in a cool place at the designated area.
2. No hot jobs such as welding, cutting or bracing is permitted inside the storage
place or in the vicinity.
3. All electrical fittings and fixtures should be of flameproof in nature.
4. Adequate safety and fire-fighting equipments should be available for emergency.
5. Permission for entry should be through authorization only.
6. All relevant MSDS should be available with the incharge of stores.
7. No electric / battery operated equipment for material movement should be

permitted in solvent storage areas.
8. Basic training for fire-fighting systems should be imparted to all the operating
staff.
9. No fire generating materials, such as match box, cigarette lighter is permitted in

the premises.
10. No solvent dozing operations is permitted in the storage area.
11. Flammable solvent storage warehouse should meet the statutory requirements of
Indian Explosive Act.
vi. Static Electric Discharge and Fire Hazards:
One of the most hidden hazard, causing fire and explosion in chemical industry is
associated with the unique property of several solvents and organic compounds to
acquire electric charges termed as “static electricity”, which subsequently get
discharged in the form of electric spark, causing the disaster.
Most of flammable solvents, particularly non-polar solvents, finely divided metallic

and organic particulates, acquire static electric charges on their surface by virtue of
constant motion, separation, abrasion or on prolonged stagnation.
vi) I. Causes for Static Electric Discharges:
1. By virtue of the chemical configuration of the material.
2. High velocity flow of a solvent through any non-metallic pipe.
3. Flow of a solvent down from a height in the form of a spray.
4. Storage in non-conductive containers like plastic / poly propylene / PVC or HDPE

containers.
5. Inadequate earthing system.

6. Prolonged storage.
7. Spinning of a powdered material in a high speed centrifuge without being earthed

properly. (The hazard will be more severe if the particulate contain even traces of
flammable solvents).
8. Accumulation of too much dust particles in a confined area.
9. Low level of Rh in the vicinity.
10. Operations involving mixing, blending or spinning.
2. Preventive Measures
11. Allow flammable solvents to flow through metallic pipes only. These pipes should
be earthed to the ground with proper conduits.
12. While charging a solvent into a reactor/container, ensure that the liquid is not
dropped from the top to fall to the bottom. Always ensure that the liquid reaches
the bottom of the vessel, through metal pipes.
13. Avoid storage in non-conductive containers, such as those with moc PVC/PP/HDPE.
Always store only in metal containers.
14. Loading and unloading of bulk flammable solvents should be permitted only in
authorized premises (refer Petroleum Act of India). Proper earthing connections
should be provided to both the storage container and the receiver.
15. Before operating any centrifuge, ensure that it is being properly earthed to the
ground. Also, before scooping out any material from the centrifuge, ensure that the
metallic scoop is also earthed (plastic or nonconductive equipments are not
advisable for scooping material from centrifuges).
16. To avoid dust explosion, which is likely in large powder handling units, provide
adeauzte ventilation so as to prevent dust accumulation which is the cause for this
kind of hfazards.
17. Wherever possible spray water in the surroundings of large solvent storages, as
higher humidity helps to dissipate static charges (water particles are good electric
conductors).
Caution:
Never ever let any live electric cable come in contact with earthing cables, as the
consequences could be disastrous.
vii) Handling and Storage of Gas Cylinders
Handling of compressed and liquefied gases, contained in cylinders calls for special
attention, as these are of potentially high hazards, in case of any leakage or
bursting up of the container.
There are about 101 permanent, as well as liquefied gases, which are being
conveyed in specially designed cylinders and these gases are contained under high
pressures (18 kg/cm2 to 250 kg/cm2) and are identified with unique colour codes.
Some of the commonly used gases and the corresponding colour codes of the
cylinders are:
vii.1. Precautions to be observed in storage and handling.
1. Always store filled gas cylinders in a cool and ventilated and sheltered area, away
from heat and direct sunlight.
2. No hot jobs, such as welding, bracing, cutting or grinding, is permitted in the gas
storage area.
3. Always keep the cylinder properly capped. The cylinder valve is the most delicate
and vulnerable part of the cylinder. Never allow the Needle valve of the cylinder to
get damaged, while loading/unloading and shifting operations.
4. Store the cylinders in vertical position, near a solid support, properly fastened with
a metal chain to avoid their falling.
5. In case of any leakage of the cylinder, never attempt to repair the valve. Isolate
the cylinder from the main stream and keep it in an open and cool area and seek
help from the cylinder supplier.
6. The cylinder storage area should be located always, away from the main/process
building and under no circumstances should any gas cylinder be used inside the
processing areas. Gas cylinders should be kept away from corrosive acid fumes,
which could corrode the cylinder body and damage the cylinder valve.
7. Never try to apply grease on the cylinder valve/nozzle, as certain highly reactive
gases like hydrogen can ignite the organic mass, causing fire.
8. For shifting gas filled cylinders, always use cylinder trolleys and never let them roll
on their body.
9. Never try to open any cylinder without having the appropriate type of regulators.
10. As a safe practice, always store the cylinders outside the building in the proper
designated area, and draw the gases into the operational area through metal pipes
with suitable safety valve.
11. Adequate training is to be imparted to those handling gaseous chemicals regarding

safety equipments, first-aid measures and the antidotes to be applied in case of
emergency.
12. It is always preferable to keep minimum possible inventory for better handling,
especially for toxic and flammable gases.
13. Do not store incompatible gases together, as this could lead to explosion in case of
simultaneous leakage from both the cylinders.
e.g. Hydrogen vs Chlorine
Ammonia vs Chlorine
viii) Mechanical type of Hazards
Though hazards associated with mechanical type occur mostly in engineering

industries, foundries, automobile sector, etc., they are also not uncommon in
chemical industries.
Some of the safety precautions recommended are:
1. All the process equipments such as reaction kettles, pressure vessel etc. should be
properly maintained and periodically pressure tested to ascertain their capability to
withstand the optimum pressure for which they are designed.
2. Never ever subject the equipment to more pressure than the designed capacity.
All equipments where pressure reactions are carried out, should be provided with
safety pressure releasing valves.
3. The vent line of process reactors (except pressure reactors, designed for specific
services) should be vented outside the process block, preferably through a
scrubber, depending upon the nature of the effluent gases generated in the
chemical processes.
4. All temperature indicators, pressure gauges, control valves, pressure releasing

valves attached to the process equipments must be periodically tested and their
proper functioning should be ensured (most of the accidents are attributed to
equipment malfunctioning and breakdowns).
5. Ensure that all the moving parts of an equipment, such as the shaft of a drying
oven, blades of a fan, coupling of a mechanical pump, the belt of a motor fan are
provided with proper metal guards so that they do not come into contact with
human body.
6. High speed hydro extractors should be periodically inspected through regular

maintenance system to ensure that al moving portions such as the central shaft,
mechanical pulleys, etc., do perform to the desired level.
7. All utility lines, conveying steam, chilled water, brine, vacuum, nitrogen etc,
should bear clear identification tags and preferably they are to be identified with
distinct colour code system.
8. As a safety measure it is highly advisable to purge nitrogen gas into the reaction
vessels before start of the process, thereby reducing the oxygen concentration
inside the reactor and thus reducing the fire risk.
ix) Electrical Hazards:

Safety precautions to be observed:
1. All electric fixtures such as cables, wires, switches, electronics fittings should be of
standard quality and free from any manufacturing deficiency.
2. Overloading of any supply point by drawing more power than the recommended
norm should be totally avoided:
3. It must be ensured that all the electric fittings, fixtures, lightings, induction
motors etc, should be of flame proof quality.
4. All electric equipments and fittings should be safe guarded against moisture,
chemical fumes etc, and periodically inspected by regular maintenance systems.
5. Electric panel boxes, main control switches etc. should be properly housed in a
proper ventilated block, away from the plant and must be tagged for easy
identification.
6. All equipments, receivers, storage tanks, barrels etc., should be adequately

earthed to the ground through metal conduits and should be periodically inspected
for their continuity of electricity.
7. Cables and electric wires used should be of single piece and should not have any
joint.
8. Never let the electric and earthing cables come in touch with each other at any
point.
9. Portable inspection lamps/lights should be strictly prohibited in the process blocks.

10. Keep the electrical panel box surroundings dry and provide rubber mats in front of
the panel door to avoid any electric shock to the operating personnel.
11. Whenever any equipment is under maintenance / repairs, ensure that the power to
the equipment is switched off from the main panel and proper tagging is done at
the panel switch, as well as on to the equipment.
12. Only qualified and authorized personnel should be permitted to perform electrical
jobs.
INDUSTRIAL FIRE AND PREVENTIVE METHODS
1. DEFINITION FOR FIRE:
Fire, combustion or burning of any substance needs basically 4 things to occur.
a) A fuel [this can be: any organic matter; such as a solvent, oil, wood, paper, etc.].
b) Oxygen [usually air].
c) A certain amount of energy in the form of heat.
d) Free radical reaction. The chemistry of combustion indicates that the union of
Oxygen and the fuel is not direct, but through a series of steps wherein the actual
reaction taken place between Oxygen and the free radicals liberated by the heated
fuel at the point of ignition.
2. CLASSIFICATION OF FIRES:
Basically all the type of fires can be classified into the following major categories.
a) Class A Fires:
These are fires on ordinary combustible materials, such as paper wood, rags etc.
which can be put off by the quenching and cooling effect of water. For
extinguishments of such type of fires, use of water, form or dry chemical fire
extinguishers would be effective.
b) Class B Fires:
These are fires occurring in flammable liquids such as oils, organic solvents, petro
chemicals etc., where a blanketing or smothering effect is essential to put the fire
out. Fire extinguishers like Foam, CO2, and Dry chemical are recommended for this
type of fires, which provide a blanketing effect around the fire, thus, preventing air
from coming into contact with the burning substance.
Water is effective for oil fires, only when it is used in the form of a spray or mist, but
as such is not advisable to use in fires involving solvents and oils, which are
immiscible with water.
c) Class C Fires :
These fires are associated with Electrical fittings, fixtures, such as electrical panel
boxes, electric cables, electric ad electronic equipments etc. Non conductive
extinguishing agent such as CO2 gas is the most ideal and recommended fire
extinguisher for Electric Fires.
d) Class D Fires:
These are fires in metals, such as Li, Na, K, Zn, Mg etc. and mishandling of this type
of fires can cause explosion and spread to other areas. Special attention and
training is needed to handle metal fires.
Normal fire fighting agents used for extinguishing are dry sand, dry powder,
graphite etc.
It is important to understand the meaning of some of the fire control terms and
definitions of certain critical physical characteristics of solvents which will help to
understand the degree of flammability of a particular Product.
1. Flash point (flash p):
This is the lowest temperature at which the liquid will give off enough flammable
vapours at or near its surface, such that in an intimate mixture with air and a spark
or flame, it ignites.
The flash point of a flammable liquid is usually determined by the standard method
of test for flash point with the Tag Closed Cup Tester (TCC) or with the Tag Open Cup
Tester (TOC). The results recorded with Tag Open Cup Tester (TOC) is always found
to be 5-10oF higher (less flammable) than that being recorded with Closed Cup
Tester.
The closed cup flash point value is usually several degree lower (more flammable)
than the open cup, as the test in the former case is made on a saturated vapour-air
mixture, whereas in the letter case, the vapour has free access to air and thus is
slightly this reason open cup values more nearly simulate actual condition.
2. Fire point (fire p):
This is the lowest temperature at which a mixture of air and vapour continues to
burn in an open container when ignited. It is usually above the flash point.
Wherever the flash point data is not available, fire point figures can be considered
as significant as flash point to understand the degree of flammability of the
material.
3. Auto ignition temperature:
This is the temperature at which a material (solid, liquid or gas) will self-ignite and
sustain combustion in the absence of a spark or flame. This value is influenced by
factors such as the size, shape, the material of the hot surface, rate of heating etc.
etc.
4. Vapour Density:
This value expresses the ratio of the density of the vapours to the density of air.
The vapours of most of the flammable solvents are heavier tan air, with the result
that they tend to travel at ground level making them more dangerous, as the risk
will be more in case of a fire, since the vapours do not get diluted with air. Hence,
in operational areas, where such higher V.D. solvents are used, the ventilating
outlets should be at the lower level. Similarly, wherever, the liquids of low V.D. is
handled, the ventilator should be at the higher level.
5. Melting point (mp):

This is the temperature at which the solid and liquid forms of a substance exist in
equilibrium. This value also gives the indication at what minimum temperature a
flammable solid substance can become flammable solvent.
6. Boiling point (bp):
This is the temperature at which the vapour pressure on the liquid surface becomes
equivalent to the atmospheric pressure and at this temperature a continuous flow of
vapour bubbles occur from throughout the liquid body and it is an indication as to
how much volatile the liquid could be.
As the boiling point is proportionate to the pressure to which it is subjected to, it is

apparent that lower the pressure (higher vacuum), lower would be the boiling point
and lesser will be the vapour pressure and vis-à-vis.
This physical characteristic of liquids can be made use of, in preventing many
hazards like Fire, Thermal decomposition of the product etc by subjecting the
distillation process to take place under reduced pressure.
7. Chemical Formula:
In the event of lack of data regarding the flammable nature of a product, the
chemical formulation of the product can give a clue regarding its flammable nature
to a certain extent. For instance, if a product consists only of Carbon and Hydrogen
(Hydro carbon), it can be assumed to be flammable and if it is in liquid form and
having a low boiling point, it can be considered to be more flammable.
8. Flammable liquids:
Based on the degree of flammability, liquids of flammable nature are classified

broadly into 3 categories as per the Petroleum Act of India.
v. Class-A solvents having the flash point 0 to 23 oC
vi. Class-B solvents having the flash point >23 to 65oC
vii. Class-A solvents having the flash point >65 to 93 oC
FIRE PROTECTION
The two major aspects of Fire Protection are 1. Prevention and 2. Loss
minimization.
1. Prevention:
The most undisputed aspect of Fire protection is it’s prevention. Since, for a fire to
occur, all the 3 basic requirements, Fuel, Oxygen and source of Heat are needed to
combine, by avoiding any of the 3 basic requirements, Fire can be prevented. For
instance let us take an example of an industry which uses large volumes of Acetone
in an open atmosphere. Now, for a fire to happen, among the 3 requirements, two
of them i.e. Fuel and Oxygen (from air) are already available in the vicinity. The
third requirement for Fire is heat.
From the flash point data, Acetone has a Flash point of 0oF, which means that at all
temperatures above 0oF Acetone would give out enough vapours which on
combining with Oxygen of air, can form a flammable mixture in case if it comes into
contact with a spark, flame or a hot surface or any other source of ignition. Thus, in
an installation using Acetone, following avenues are available from Fire Protection
point of view:
1. The working temperature (ambient) should be kept less than the Flash point,
0oF of Acetone, so that the vapour pressure of acetone at that temperature is
lowered to considerable extent and consequently it does to give out enough
vapours for the Fire to take place.
2. The supply of atmospheric oxygen must be cut off. This is possible in two
ways.
i) By applying vacuum in the processes which taken away the air from the liquid
surface.
ii) By providing a continuous stream of Nitrogen gas flow over the surface of the
liquid (also termed Nitrogen blanketing).
3. Eliminating all source of ignition in the operational as well as in the

surroundings and enforcing following steps:
i) smoking and carrying of materials of ignition, such as match box, unprotected

electric lamps etc should be strictly prohibited.
ii) Hot operations, such as welding, gas cutting, bracing should not be carried out in
and around the operational area.
iii) All the electrical fittings and fixtures and electric motors used in the process area
should be Flame proof in nature.
4. The area must be ventilated so that even though acetone gives off enough
vapour to form a flammable mixture with air, the vapour will be drawn out of
the area by means of the fume exhaust as rapidly as it is formed, thus
preventing the accumulation of vapour concentration.
Below is a brief account of the 3 essential supporters of fire and the means to
reduce their influence for Fire Protection.
A) OXYGEN:
Although under certain specific conditions, chemicals can initiate fire even in the
absence of oxygen for short duration (e.g. Fires associated with sulphur /
phosphorous chlorine, hydrogen etc.), for sustained propagation of Fire, oxygen is
very essential. Also the higher the concentration of oxygen in the atmosphere,
more would be the intensity of fire. In industrial atmosphere it is difficult to
manipulate the oxygen concentration in the working area, particularly since a
concentration of oxygen, far below normal to keep fires from starting, would also be
too low to support human life.
When it becomes necessary to work with such products, which by mere contact with
air of atmosphere, can initiate a Fire, following steps are recommended for their
safe handling.
i) Isolate such products, such as sodium azide, sodium hydride etc. which are
highly reactive with atmospheric oxygen from the main stream of materials and
store them in containers under vacuum, or follow the guidelines for storage as
mentioned in their respective MSDS.
ii) Keep such products under a blanket of inert gas such as nitrogen, helium or
argon.
B) HEAT:
In industrial fires the most easily overlooked fact is that all the major Fires that had
occurred, had a modest beginning in the initial stages, which might have gone
unnoticed and hence uncontrolled. Then, since fires are by definition exothermic,
the very small fire started by a tiny heat source, supplies to its surroundings more
heat than it absorbs, thus enabling it to ignite more fuel and oxygen mixture, and so
on until very quickly there is more heat available than is needed to propagate a
large Fire.
The heat for the initial Fire to start might have been provided by various sources of
ignition such as high environmental (ambient) temperatures, hot surfaces,
mechanical friction, spark from a switch, static electric discharge, an open flame or
from a jot job, like welding, gas cutting etc.
It is worthwhile here to look into the various aspects of the “ignition source” and
find ways to effectively curtail them.
a) Open flames:
It is of utmost importance that near the operating areas, wherein flammable

solvents are being handled, strict vigilance be exercised to check heat sources like
burners, lamps, matches, welding torches, lighting etc. If there are both type of
operations, viz. operations involving flammable solvents and hot type of jobs, in the
same premises, they should be isolated properly by thick wall of cement and bricks.
Never should any flammable material such as wood / plywood / thermacoal be used
for the construction of the partition.
b) Electrical sources:
Some of the common source of electric heating are from non certified lightings,
cables, switches, starters, electric motors, digital electronic indicators, overloading
of supply point, poor earthing systems etc. As a matter of safety, it is advisable to
have all electrical switches and electric panel board properly housed in a separate
block, away from the main plant / operating premises.
c) Over heating:
Processes which need high pressure steam and involve high temperature reactions,
runaway reactions, special processes, etc. should be identified and these are to be
segregated from the relatively safer processes. HAZOP study should be undertaken
before the implementation of such processes and special attention has to be paid in
training the persons operating such plants.
i. Hot surfaces:
The most common hot surfaces in a chemical industry are equipment like, drying
oven, boiler, steam line, hot oil system etc. These equipments must be housed in a
quarantined location preferably away from the operating area (boiler / thermo pack
and electrically) heated drying oven in any case should be way from the process
block). All the supply lines conveying steam, hot oil, hot water, hot air etc. should
be properly insulated and maintained. It must be remembered that Flammable
solvents, having the auto ignition temperature, lower than any of these hot
surfaces, can get ignited themselves in case of their contact.
ii. Spontaneous ignition:
Many fires are caused by the heat of reaction produced when chemicals,
incompatible in their chemical characteristics come into contact with each other,
which are further accelerated by external source of heat and air. Few of such
commonly used chemicals, having incompatibility with each other are:
i) Chromic acid with flammable solvents, such as acetone, alcohols, hydrocarbons

etc.
ii) Potassium permanganate with con. Sulphuric acid.

iii) Con. Nitric acid with organic solvents and any organic mass.
iv) Con. Hydrogen peroxide solution with flammable solvents.
v) Sodium hydride, elements like sodium, potassium lithium etc. with water.
Many of fire investigations have proved beyond doubt that the cause of fire in most
of the cases was due to neglect, poor house keeping practices, accumulation of
flammable wastes such as cotton rags, residual oil and grease etc.
iii) Sparks:
Sparks may be produced from various sources, such as from electric motors,
switches, loose electric connections or by static electric discharges. Sparks are also
generated from friction between mechanical parts, by hammering and chiseling
etc. to avoid electric sparking, some of the recommended precautions are:
i) All the electrical fittings, such as switches, lighting, induction motors etc. should
be flameproof in nature.
ii) Electric panels, main control switches etc must be away from the process block.
iii) Electric cables/wires connected to equipments should be of the right quality and
should be in one piece (there should not be any joints on the cable).
iv) Proper earthing should be provided to all equipments, storage vessels etc.
v) No flammable solvents must be stored or collected in non-conducting containers

(such as plastic buckets, PVC/HDPE containers etc.).
Similarly, sparks produced by mechanical operations can be contained to a great

extent by adopting following precautions:
i) All moving parts of the mechanical equipment, such as the shaft of the gear box,
shaft of the fan in a drying oven, clutches of a centrifuge etc must be greased and
maintained in good condition.
ii) Hammering and chiseling should be avoided as far as possible inside the
process plant.
If at all they have to be done, use hammers / chisles made of brass or gun metal,
which does not produce sparks on hammering.
a) Static Electric Discharge:
This is a phenomena in which certain products, mostly of organic liquids and non-
polar solvents get electrically charged on their surface, by virtue of factors, such as
high speed discharge, fall from heights, separation at a higher speed, prolonged
storage etc. Causes for fire in many industries especially chemical and paper, are
attributed to this unique phenomena. Most of these occur during the months when
the atmospheric humidity is low and artificial heating is don(droplets of water in a
humid atmosphere acts as a suitable conduit to carry away the acquired electric
charges from the liquid surfaces, thus preventing a spark to generate by static
discharge). Maintaining a humidity of 40 to 50% in rooms where flammable
solvents are being handled, will greatly help to reduce the risk of a spark due to
static discharge. Electrical grounding of storage tanks, process equipments,
discharge pipings etc. are mandatory as per Indian Petroleum Act and it must be
strictly enforced.
In all the equipments as far as possible the use of belts should be avoided and the
use of metallic chains or direct shaft driven systems should be encouraged.
Storage of flammable solvents in non-conducting containers allowing a solvent to

fall from a height in the form of a spray, pumping of a flammable solvents through a
non-conducting pipe etc. are potential causes for static sparks and must be totally
avoided.
i. Friction:
One of the major causes for industrial Fire can be attributed to the heat / spark
generated by friction from the moving parts of mechanical equipments, e.g. fan
blades rubbing the sides of outer casting, poorly lubricated bearings of a rotating
body like hydro extractor, uncooled mechanical seal of a reactor etc.
ii. Fuel
Combustion takes place most easily between oxygen of air and a fuel in its vapour
or finely divided particle state. As solid chemicals need preheating for their
transformation from solid stage to liquid stage they are relatively safe, particularly if
their melting points are high. But in case of liquids, most of them give out sufficient
amount of vapours even at lower temperatures which can form a flammable mixture
with air and ignite themselves.
This particular temperature which is an indicator to measure the hazard potential of

a solvent is termed as the Flash point, as already discussed. As it is evident from
above explanations, lower the flash point, higher would be fire risk. Indian
Petroleum Act of 1934 and 1976, has classified all the petroleum and flammable
liquids into three categories on the basis of their flash points; and also has
stipulated conditions for their receipt, storage and movement.
As a matter of safety and fire prevention, all solvent storage tanks above ground
level should have dikes constructed out of bricks and cement so that in the event of
any leakage or fire, it can be contained within a limited area, thus preventing it from
spreading.
An important factor to be considered for safety with respect to flammable liquids, is

to prevent accumulations of high vapour concentration of flammable liquids in a
closed environment. Adequate ventilation should be provided in the solvet handling
area. While designing the ventilation / exhaust systems it should be ensured that
for vapours of high vapour density, the exhaust system should be on the lower side
of the building and for light density solvents it should be on the upper side and also
it must be ensured that the motor and the switch of the system should be of flame
proof.
It is of utmost importance that a totally comprehensive standard operating

procedure (SOP) should be framed and implemented, with respect to receipt,
storage and handling of Flammable solvents and all the operating persons should
be adequately trained to handle these solvents safely. There is no substitute to
Educating and Training the people.
It is also worth probing when a new process is developed that, whether or not it is
possible to substitute Flammable and Hazardous chemicals with non-flammable/less
flammable and non-hazardous chemicals. If cost is the prime factor in favour of a
flammable solvent other indirect benefits, such as savings in installation of high cost
safety devices, training cost, high insurance premium etc. should be assessed by
substituting with a non-flammable solvent. However in any event, usage of
flammable solvents in a chemical process cannot be avoided irrespective of the
quantum.
Besides flammable solvents, other possible disasters in industry, which can be

prevented well and only by preventive means are:
Dust Explosion:
Like static electric discharge, another lurking industrial hazard is dust explosion.
Practically any flammable material in the form of the particles or dust, mixed with
air at the right proportion, when comes into contact with a spark (mostly generated
by static discharges), flame or heat will burn so rapidly as to cause a severe
explosion which is termed as Dust Explosion. This kind of hazard commonly occurs
in industries handling, plastic, grain, flour, coal dust, metal powders, fertilizers,
wood dust, powdered milk, detergent powder, paper dust and industries handling
sulphur and phosphorous powders. Some of recommended precautions to minimize
dust explosion are:
b) Housekeeping: Good house keeping practices like proper storage, stacking,

handling, maintaining of proper temperature conditions in the warehousing and
manufacturing blocks, usage of proper equipments for material handling etc. are
very important.
c) Do not allow the dust to accumulate to alarming proportions. This can be achieved
by providing effective exhaust system.
d) All the dust particles generated in the process, should be taken out through metal
ducts, and the vent of such ducts must be outside the block, preferably, taken to a
distant location.
e) Proper earthing should be provided to the pulverizing / dust generating
equipments / ductings etc.
f) Use of belt driven equipments, conveyors etc. should be minimized as far as

possible. Instead metallic chain driven / shaft driven equipments must be
encouraged.
g) Cleaning of floors, equipments etc should be done by vacuum methods and

cleaning by sweeping, dusting with brooms, dust rags etc should be totally avoided.
h) The use of compressed air to blow the dust off the equipments/floors etc, thus
helping the formation of dangerous dust clouds is totally FORBIDDEN.
i) Exposed piping / beams etc. in a powder processing area should be cleaned

frequently to prevent the dust from accumulating on them.
j) It is a wrong notion that by providing a false ceiling in a powder processing unit,

accumulation of dust on the piping and other projections can be eliminated. But
incidents have proved the other way. Unless the ceiling is extremely well designed
and installed, there is a great possibility for the dust particles to escape through the
crevices and joints of the ceiling and get settled on the upper side of the ceiling. As
this will not be visible to human eyes operating on the ground level, there is a great
risk of dust accumulation over a period of time, depending on the nature and
volume of operations, and it could lead to a serious dust explosion, when a spark is
generated in that area.
k) As in the case of Flammable solvents, any kind of source of ignition, such as open
flame, smoking, welding/cutting, grinding, electric sparks from loose contacts or
from static discharges, should be avoided.
l) Use of inert gas like nitrogen, in closed vessel operations has been found very
effective and rewarding in preventing Fire and Explosions.
LOSS (CONTROL)
One of the equally important aspects of Fire protection is also to devise various
alternates/methods to minimize the loss, in case of a major fire. There have been
major Fires all around, and loss of precious human lives and properties. Although
investigations help to identify to some extent the cause of Fire, in most events they
are inconclusive or doubtful, as most the live evidences of fire gets destroyed or
distorted in the fire itself and the findings of the investigations normally are based
on assumptions and hypothesizes.
What is more important is how to prevent a Fire totally from happening and how
best maximum salvage could be done in case of any such unfortunate incident.
Some of the safety steps recommended include the following:
1. Before any new chemical process is to be introduced on commercial scale in

the plant, the process, equipments and their basic designs the polluting
discharges, by-products, toxicity of the chemical ingredients, the hazardous
properties of both the process and chemicals used etc should be critically
evaluated (Hazop study) and appropriate hazard preventive methods should
be evolved.
2. Segregate processes involving large usage of flammable solvents and

hazardous chemicals from relatively safer processes and safer chemicals and
as far as possible make separate modules for both the types. Wherever it is
not viable or feasible to have separated by constructing approved fire proof
walls (with bricks and concrete):
Caution:
It must be ensured that there should not be any holes or cracks on the fire wall.
Every hole made on the wall to permit utility pipes / electric cable trays etc. to pass
through must be properly sealed with cement, so that no flammable vapour could
pass through such holes.
3. In many Fire incidents, it has been observed that the Fire Exit Doors provided
in the process blocks, to enable the persons trapped to escape safely, in the
event of fire, had caused more damage than any use, because of the reason
that either they were not maintained regularly for proper functioning, or the
path to the Exit Door were blocked with materials, storage drums etc. as a
result of which access to the door became difficult and the very purpose of
the door was defeated.
It is of utmost importance that the Fire Doors should be greased regularly and must
be tried for smooth functioning atleast once in a day and a record should be
maintained. No materials whatsoever should be stored on the pathway to the Exit
Door, and the approach way should be clearly highlighted with painting.
There should also be proper indicators to locate the Exit Doors and the most
importance caution to be observed is that these doors should never ever be bolted
tightly or locked.
4. Ensure that in the process blocks, the inventory of flammable solvents is kept
to the minimum possible level and the bunks, lids etc of all the storage drums
/ tanks are tightly closed. There should be clear space for movement
between the storage drums and in the event of Fire, these are to be moved
out of the building depending upon the situation. In case if it is not
accessible to reach the drums, they should be kept cool, by spraying a jet of
water from the Fire Hydrant system.
5. In each process module, there must be a smoke detector, connected

electronically to the Fire alarm system so that in the event of a fire, the alarm
system gets activated and Fire siren is blown automatically.
In case there are more than one plant/module, it is suggested that the Fire alarm
system from each of the module may be connected to one main Fire Alarm Display
board located at a central location preferably at the “Time Office / Security Office”.
Similarly, the fire display board should be provided with suitable indicator system to
identify the exact location of fire.
6. Needless to mention, there must be adequate Fire fighting equipments, easily
accessible in the case of emergency. Location of the Fire fighting equipments
is also equally important, so that they must be easily accessible.
7. In some of the safety conscious organizations, a separate group of persons,

from various functional areas, such as production, engineering, electrical etc
form a core group who are imparted special training on safety and Fire
fighting operations and are available round the clock to ensure that all safety
norms are being complied., This group also conducts safety audits of each
operational area on regular basis and recommends corrective and preventive
measures.
8. One of the most important aspects in Fire Protection is to prevent the Fire
from spreading from floor to floor in a multistoreyed building. Mostly the fire
spreads through open staircases, elevators, cutouts for future installations
etc. not only that the fire spreads through these `ventilators’, these also get
choked with fumes, hot air, noxious gases etc. and the stair cases often
become real death traps. One way to prevent this kind of hazard, is to
provide proper enclosures to stair cases and elevators at each floor with self
closing doors. It is important to remember that these doors should have self
closing arrangement, as there is always a tendency among people to keep
the door open. Similarly, all open cut-out on the floors, must be closed with
brick and cement.
9. It is also worth considering that in a process block, utilizing highly explosive

chemicals such as peroxides, nitrates, persulphates, azides etc. part of the
building on the less important side, may be constructed with less strong
materials like hollow ceramic tiles, gypsum boards etc, so that in the event of
an explosion these may act as a vent to the expanded gases and thus save
the main building from collapse.
10.However, the most effective way to prevent fire damages can be achieved
only through educating and training the operating staff n regular basis and to
inculcate a sense of ownership and alertness.
FIRE FIGHTING
As already discussed earlier, to extinguish a fire it is essential that at least one of
the three components of fire viz., Fuel, Air (oxygen) or Heat is cut off from the
system or its concentration is drastically reduced.
Although cutting the fuel supply is the best option to contain the Fire, in many cases
either it is difficult or not practicable, but in case the Fire is on a large storage tank
or a big reactor, and it has a pumping system connected to a far off storage vessel,
then the solvent can be pumped out from these containers to the safe storage
vessel as the Fire blazes only on the surface of the liquid. It is also important to
keep the burning tank cool with a jet of high pressure water so that the temperature
is brought down below the ignition temperature of the liquid.
Simultaneously, the oxygen supply to the Fire also should be restricted as

effectively as possible by using appropriate fire extinguishers like Foam,
carbondioxide, dry powder, sand etc. selection of the right type of the fire
extinguisher is very very important. Incidentally, dry sand is an universal fire
extinguisher and can be used in all type of fires.
Some of the common type of fire extinguishing agents are:
1. Water:
The most commonly used fire extinguishing agent is water. It is the cheapest and
most effective media, especially when applied in the form of a fine spray. It has a
blanketing effect on the fire if sprayed, as the fine droplets of water act as a barrier
to prevent the air ingression to the fire point. More importantly it cools down the
fire surroundings below the autoignition temperature of the liquid, which results in
the extinguishing of the fire.
However, water has certain limitations too. It is good, as describedc earlier, for fires
with materials like wood, paper, cellulose, liquids miscribe with it, etc. but not
suitable for items like Oil, Petrol, Organic solvents having lower density than water,
Liquids immiscible with it, fires in metals etc. etc.
Water is not recommended for oil fires, and fires involving immiscible organic
solvents etc as these being lighter than water will float on the water surface and
also due to the impact of the water jet, will scatter all around carrying the fire along
with it. In such cases blanketing will also be difficult as the fire will be floating
around with water. The consequence could be disastrous, if this floating fire goes
down to the Gutter and Sewerage, as this could result in more spread of the fire,
affecting other plants as well.
Explosions have also been reported inside open gutters resulting in massive loss to
property and human lives.
2. Soda-acid Fire Extinguisher:
This kind of extinguishers are operated by inverting them and directing the nozzle
of the hose towards the base of the flame. Int his type, a small bottle of con. H 2SO4
is kept around a saturated solution of sodium bicarbonate inside a metal cylinder,
having an outlet connected to a small rubber-hose. When it is overturned, the acid
comes into direct contact with sodium bicarbonate present in the water, generating
CO2 gas, which in turn pressurizes the water to come out of the extinguishers under
pressure. Such extinguishers need to be recharged once in a year, irrespective of
the fact whether they have been used or not. This type of extinguishers are useful
for ordinary type of fires on paper, wood, cotton, waste rags etc.
3. Dry chemical powder (DCP) Fire Extinguishers:
In this type, there will be a small high pressure CO2 cylinder inside the body of the
extinguisher, surrounded with fine sodium carbonate powder. When the
extinguisher is put into operation, the CO2 cylinder gets punctured and due to the
high gas pressure generated, the soda powder is driven out through the nozzle of
the cylinder. These are equally effective as the soda-acid extinguishers has a good
blanketing effect on the Dire. These also need annual replacement of the sodium
carbonate powder, as it has a great tendency for cake formation on prolonged
storage.
4. Foam Type Fire Extinguishers:

Another important type of Fire Extinguishing agent is Foam, which is very effective
controlling Fires on oil, paints, organic solvents, liquids immiscible with water etc.
Chemically this Form is produced by bubbling CO 2 or an inert gas through a form
forming liquid. While an operation the entrapped CO 2 gas inside the bubbles formed
by emulsification, gets coated on the burning surface, thus creating an effective
barrier between fire and oxygen of the air.
5. Fire hydrant and fire hoses:
Despite the limitations, for fighting uncontrollable fire, water is the most effective
fire extinguishing agent and in fact there is no substitute for water. One of the most
effective ways of fire protection is to install a suitable fire hydrant system, having
access for high pressure water at all the crucial locations. In this system sufficient
quantity of water is stored in an underground tank exclusively built for Fire fighting
purpose and from this tank water is circulated through 4” to 6” dia metal pipes laid
underground by a powerful mechanical pump. At all the crucial locations tapping is
provided from the main line and these are connected to the Fire hoses. It is
important to ensure that the pump is maintained regularly by a systematic
maintenance schedule and the hose reel is free from defects. As a good safety
practice, it is suggested that the fire hydrant system should be activated at least
once in a week and checked for the performance.
Other Type of Fires:
Some other type of Fires which though not common, are equally disastrous and all
preventive steps must be taken to avert their occurrence.
a) Gas Fires:
This type of fires can be put out with the use of fire extinguishers of CO 2 dry
chemicals and in certain cases with water also, but the most important step should
be to turn off the gas valve from the source. If source of supply is far away, ad
likely to take time to reach there, the best way to fire fight is to keep the
surrounding area cool by spraying water continuously, till the gas valve is closed
and in the meantime utilizing the Fire extinguishers at the fire.
Caution: On some occasions though the fire is extinguished successfully, people
forget to close the supply valve for long periods, with the result the gas
concentration can increase to explosive limit leading to explosion.
b) Metal:
Fires on metals is very dangerous and often difficult to extinguish. Ordinary Fire
fighting agents may not be suitable, depending upon the type of the metal and the
volume. Normal metal Fires are associated with metals, such as sodium, potassium,
Lithium, Magensium, Zinc etc. Fire fighting agents such as sodium chloride, sodium
bicarbonate, graphite, magnesium carbonate, magnesium oxide are found effective
for controlling the Fire.
Caution: Water should never be used to extinguish metal fires, as this can result in
explosion which would further spatter burning metal particles to great distances,
thus helping the fire spread.
STORAGE AND HANDLING
OF
HAZARDOUS MATERIALS.
As a large number of materials of different nature are to be stored in process

industries, warehouses, laboratories etc. it is highly essential that these are stored
safely and properly and a high sense of good house keeping practice is to be
maintained. For the purpose of safe storage, these chemicals can be classified into
different groups, based on their chemical characteristics.
a) Explosive chemicals:
These are chemicals which under certain conditions of heat, pressure, shock etc.
undergo rapid decomposition, evolving large volumes of gas and heat, which in
turn further heats up the surrounding air to expand so rapidly that the entire
process ends up in what is called explosion.
The magnitude of such explosions is always proportional to the nature of the

explosive and the quantum involved. It also depends upon the chemicals and other
objects in the near surroundings.
Storage and handling of this type of materials should be done with extreme caution.
Some of the recommendations for their storage are:
1. all type of chemicals falling under this category, such as nitrates, chlorates, per
sulphates, per iodates, azides, perioxides etc should be stored in a separate block,
away from the main buildings and human habitation.
2. before storing these materials, it should be ensured that the manufacturer’s

guidelines for storage, handling and disposal is strictly followed. No material should
be accepted for storage, if the relevant material safety data sheet (MSDS), is not
available. Remember the old and deteriorated explosives may prove more
dangerous than fresh materials.
(Instances have been reported of massive explosion, resulting in extensive disaster

and loss of human lives, when an attempt was made to shift an old stock of
Ammonium nitrate packed in gunny bags from a warehouse).
3. Ensure that the environment conditions, such as temperature, RH etc. is

compatible to the stability of the product.
4. Avoid storage for prolonged periods. FIFO system should be followed in the
warehouse.
5. Proper material handling equipments should be used during transportation from

one location to another.
6. Rough handling, dragging of the containers, stacking at higher levels thus creating
more strain on the bottom containers, etc should be totally avoided.
7. No attempt should be made to scrap out the material with any metal object nor
should it be pulverized or powdered.
8. Disposal of explosive chemicals should be done only as per the procedure laid
down in the MSDS or as per the maufacturer’s instructions.
a) Flammable chemicals:
Combustible materials can be of all the 3 types viz; solids, liquids, or gases,
although the rate of Fire propagation is different for each type. The propagation is
least in the case of solids, as the vapour pressure being very low at ambient
temperatures, it takes much longer time for the solids to get heated up to produce
sufficient vapours to get ignited. However, the rate of propagation is much faster in
the case of liquids and still faster in case of gases. As a matter of fact in case of
vapour Fires, the rate of propagation is so fast that they normally end up in
explosions aggravating the situations.
Some of the recommendations for storage are:
1. All flammable solvents must be stored in a cool place, under shelter with proper
ventilations. The storage store should be away from the main building.
2. The containers should be properly closed and should not be in leaking/damaged

condition.
3. No hot jobs, such as welding, gas cutting, grinding or any other source of ignition
such as naked flame, smoking etc should be allowed in and around the storage
area.
4. As far as possible electrical equipments and fixtures, such as lighting fans, water
coolers, air conditioners etc must be avoided in the storage block and if at all they
are to be installed, it must be ensured that they should be flameproof in nature.
5. No electrically operated equipments or automobiles is permitted inside the solvent

storage area for any type of operation such as material movement etc.
6. Proper earthing should be provided to all the storage vessels.
7. It must be ensured that no operation such as transfer of a solvent from one

container to another, dozing from a bulk container etc is undertaken inside the
storage block.
8. Adequate fire fighting equipments should be available at strategic locations to
handle emergency.
9. Movement in solvent farm area and in flammable solvent storage blocks, should
be restricted and only authorised personnel should be allowed to operate in these
areas.
10. Proper colour coding should be implemented for correct identification of the
solvents and also all the pipe lines conveying these solvents shold have proper
identification tags.
11. Regular training should be imparted to the staff by competent personnel on fire
fighting and salvage techniques.
a) Oxidising agents:
Since oxidizing agents are capable of generating oxygen, by way of heat, chemical
decomposition or by interaction with other incompatible materials, they help fire to
ravage, even in the absence of atmospheric air or oxygen. Following categories of
chemicals are considered to be most powerful oxidizers and these are to be handled
very cautiously.
e.g. Peroxides, Persulphates, Perchlorates, Periodates, Permanganates, Bromates,

Nitrates, Chromates, Dichromates, perborates, ozone etc.
As a general rule, all flammable solvents must be stored away from oxidising
chemicals and these should never be allowed to come into contact with each other.
e.g. Instant Fire will take place if Chromic acid comes into contact with organic
solvents such as acetone, alcohols, hydrocarbons etc. Equally dangerous is the
interaction between potassium permanganate and con. Sulphuric acid which would
also result instantaneous fire.
Similarly potassium permanganate or chromic acid can set ablaze poly hydric
alcohols such as glycerol, if they come into contact with each other.
Also it is advisable to store the oxidizing chemicals in a separate store, away from
the operational areas, having adequate ventilation and cooling arrangement, since
most of these chemicals are susceptible to thermal decomposition.
b) Water sensitive chemicals:
There are many chemicals which undergo decomposition upon contact with water
and the rate of some of the decomposition processes is so fast that it results in
explosion and Fire.
i) metallic elements, such as sodium, potassium, rubidium, magnesium, lithium

etc.
ii) metal salts such as hydrides, nitrides, sulphides, carbides, borides, acid
anhydrides, concentrated mineral acids.
iii) Organic chloro compounds such as acetyl chloride, Thionyl chloride etc.
These compounds are to be stored in water proof storage rooms, in air tight
containers preferably on dry sand beds, which normally acts as good adsorbant, in
case of any leakage.
As these are very reactive with water, steam etc., a caution board in bold letters
should be displayed outside the storage room, strictly prohibiting the use of water in
that area, in case of any fire.
Only recommended fire fighting agents, such as Drypowder, CO2 should be used in
the affected area.
c) Toxic chemicals:
These chemicals can be both Organic or Inorganic, as well as in all the 3 forms viz.
solids, liquids or gases.
1. Store these chemicals, especially if they are in the liquid form, in well closed
containers in a cool place with adequate ventilation. This is more relevant, if the
material is low in its boiling point.
2. Ensure that as far as possible they are not allowed to come into contact with
atmospheric oxygen, moisture etc. as many of the otherwise harmless chemicals
become toxic due to chemical degradation, with air and moisture. (Chemicals such
as chloroform, carbon tetrachloride etc., can produce the highly toxic gas phosgene,
by their interaction with atmospheric oxygen and moisture, particularly when stored
in mild steel containers).
3. Ensure that toxic chemicals are not stored along with other chemicals, particularly
with those meant for human consumption such as IP/BP grade products.
4. There must be proper identification tags on toxic chemicals, clearly indicating the
route through which they enter human body and severity of toxicity.
5. All safety aids, such as hand gloves, nose masks, fresh air masks, goggles etc
should be available handy and use of these equipments should be strictly enforced,
through proper education and training.
6. Appropriate antidotes against each of the toxic chemicals should be made

available at the site and people handling the toxic substances must be trained to
handle them in case of emergency.
7. Material safety data sheet should be consulted before going to handle toxic
products.
d) Corrosive chemicals:
Some of the common corrosive chemicals, being used in chemical industries are:
1. concentrated mineral acids
2. anhydrides of organic acids.
3. some of the organic chloro compounds (acetyl and Thionyl chlorides).
4. liquid bromine, iodine, chlorine and some of their compounds
5. alkalis, such as hydroxidces of ammonia, sodium potassium, calcium, barium
6. oxides and pentoxides of certain non metals, such as phosphorous (P 2O5),

sulphur (SO2, SO3), some of metal halides (AlCl3) etc. etc.
As corrosive chemicals can cause severe injuries to human body, including loss of
vision or damage to limbs, causing permanent deformity, it is very important that of
safety aids, such as goggles, face shields, nose and fresh air masks, aprons, hand
gloves, safety shoes etc. should be utilized while handling such hazardous products.
e.g. strong alkalis like sodium hydroxide, potassium hydroxide, liquor ammonia
solution can damage the eye permanently, if there is a splash and they come into
contact with eye. No alkaline material should be handled without goggles and
handgloves.
Contact any part of the body by concentrated mineral acids such as Sulphuric and
nitric acids, can cause severe burns and blisters. Always wear protective aids such
as gloves, goggles, aprons and safety shoes while handling these chemicals.
Hydrofluoric acid:
It is extremely irritating and corrosive to skin, eyes and mucous membrane.

Inhalation of vapours may cause ulcers of upper respiratory tract. Prolonged
contact with skin can lead to destruction of the blood vessels and tissues and
gangrene may follow on the affected areas. Never allow the liquid or its vapours to
come into contact with the skin and eyes. Also safety equipments like gloves,
goggles, aprons, fresh air masks and safety shoes should be worn before handling
it.
Dimethyl sulphate:
It is colourless and odourless liquid and contact of this chemical on the skin will not
cause any feeling of discomfort or irritation for hours together, but later on there
would be intense pain and irritation on the affected part of the body causing painful
blisters. Make sure that safety aids like goggles, gloves, aprons and safety shoes
are used while handling this product.
e) Compressed gases:
There are several liquefied and natural gases used in chemical industry for
manufacturing purposes. These are conveyed in specially designed cylinders with
unique colour codes for easy identification.
Some of the most commonly used gases in chemical industries are:

1. ammonia
2. carbon dioxide
3. air compressed
4. chlorine
5. Fluorine
6. Helium
7. Hydrogen
8. Mono methylamine
9. Nitrous oxide
10.Nitrogen
11.Oxygen
12.Sulphur dioxide etc.
These gases can be flammable, toxic or corrosive in nature and extreme care should
be taken in their storage and handling.
Some of the precautions to be observed are:
a) keep the full cylinders always in a vertical position, near a solid support like the
wall of the building, duly fastened to the wall with metal chains, to prevent them
from falling down.
b) The storage place should be located away from the main building and should be
provided with suitable cover, so as to avoid direct sun rays falling on to these
cylinders.
c) The storage block should be adequately ventilated so that the vapour
accumulation is minimum in case of leakage.
d) Keep the cylinders capped and take all precaution to ensure that the needle valve
of the cylinder is not damaged during transportation from one place to another.
e) Avoid storage of incompatible gases together and also it is advisable to keep

minimum possible inventory at any time.
f) Use the recommended gas regulators while using the cylinder and never try to
repair the valve of a leaking cylinder. In case of leakage remove the leaking
cylinder to an isolated area in a cool place and let the gas bleed off slowly and in
case it is toxic or corrosive, inform the authorized dealer immediately,
g) Always use cylinder trolleys for shifting the cylinders from one place to another
and never drag or roll the cylinders on hard surface.
h) Do not apply any grease or lubricants on the cylinder nozzles, as gases like
hydrogen oxygen etc. can ignite the organic matter.
HEALTH & SAFETY INFORMATION
Risk Phrases
R1 Explosive when dry.
R2 Risk of explosion by shock, friction, fire or other sources of ignition.
R3 Extreme risk of explosion by shock, friction, fire or other sources of ignition.
R4 Forms very sensitive explosive metallic compounds.
R5 Heating may cause an explosion.
R6 Explosive with or without contact with air.
R7 May cause fire.
R8 Contact with combustible material may cause fire.
R9 Explosive when mixed with combustible material
R10 Flammable
R11 Highly flammable.

R12 Extremely flammable
R14 Reacts violently with water
R15 Contact with water liberates extremely flammable gases.
R16 Explosive when mixed with oxidizing substances.
R17 Spontaneously flammable in air.
R18 In use, may form flammable / explosive vapour-air mixture.
R19 May form explosive peroxides.
R20 Harmful by inhalation
R21 Harmful in contact with skin.
R22 Harmful if swallowed
R23 Toxic by inhalation
R24 Toxic in contact with skin.
R25 Toxic if swallowed.

R26 Very toxic by inhalation.
R27 Very toxic in contact with skin.
R28 Very toxic if swallowed.
R29 Contact with water liberates toxic gas.
R30 Can become highly flammable in use.
R31 Contact with acids liberates toxic gas.
R32 Contact with acids liberates very toxic gas.
R33 Danger of cumulative effects.
R34 Causes burns
R35 Causes severe burns.
R36 Irritating to eyes.
R37 Irritating to respiratory system.
R38 Irritating to skin.

R39 Danger of very serious irreversible effects.
R40 Possible risks of irreversible effects.
R41 Risk of serious damage to eyes.
R42 May cause sensitization by inhalation.
R43 May cause sensitization by skin contact.
R44 Risk of explosion if heated under confinement.
R45 May cause cancer
R46 May cause heritable genetic damage.
R48 Danger of serious damage to health by prolonged explosure.
R49 May cause cancer by inhalation.
R50 Very toxic to aquatic organisms.
R51 Toxic to aquatic organisms.
R52 Harmful to aquatic organisms.

R53 May cause long-term adverse effects in the aquatic environment.
R54 Toxic to flora
R55 Toxic to fauna
R56 Toxic to soil organisms
R57 Toxic to bees
R58 May cause long-term adverse effects in the environment
R59 Dangerous for the ozone layer.
R60 May impair fertility
R61 May cause harm to the unborn child.
R62 Possible risk of impaired fertility.
R63 Possible risk of harm to the unborn child.
R64 May cause harm to breastfed babies
R65 Harmful may cause lung damage if swallowed.

Combination of R-phrases
R14/15 Reacts violently with water liberating extremely flammable gases.
R15/29 Contact with water liberates toxic, extremely flammable gas.
R20/21 Harmful by inhalation and in contact with skin.
R20/22 Harmful by inhalation and if swallowed
R20/21/22 Harmful by inhalation and in contact with skin and if swallowed.
R21/22 Harmful in contact with skin and if swallowed.
R23/24 Toxic by inhalation and in contact with skin
R23/25 Toxic by inhalation and if swallowed.
R23/24/25 Toxic by inhalation, in contact with skin and if swallowed.
R24/25 Toxic in contact with skin and if swallowed.
R26/27 Very toxic by inhalation and in contact with skin.
R26/28 Very toxic by inhalation and if swallowed.

R26/27/28 Very toxic by inhalation, in contact with skin and if swallowed.
R27/28 Very toxic in contact with skin and if swallowed.
R36/37 Irritating to eyes and respiratory system.
R36/38 Irritating to eyes and skin
R36/37/38 Irritating to eyes, respiratory system and skin.
R37/38 Irritating to respiratory system and skin.
R39/23 Toxic: danger of very serious irreversible effects through inhalation.
R39/25 Toxic: danger of very serious irreversible effects if swallowed.
R39/23/24 Toxic: danger of very serious irreversible effects through inhalation
and in contact with skin.

R39/23/25 Toxic: danger of very serious irreversible effects through inhalation
and if swallowed.
R39/24/25 Toxic: danger of very serious irreversible effects in contact with
skin and if swallowed.
R39/23/24/25 Toxic: danger of very serious irreversible effects through
inhalation, in contact with skin and if swallowed.
R39/26 Very toxic: danger of very serious irreversible effects through
inhalation.
R39/27 Very toxic: danger of very serious irreversible effects in contact
with skin.
R39/28 Very toxic: danger of very serious irreversible effects if swallowed.
R39/27/28 Very toxic: danger of very serious irreversible effects in contact
with skin and if swallowed.
R39/26/27/28 Very toxic: danger of very serious irreversible effects through
Inhalation, in contact with skin and if swallowed.
R40/20 Harmful: possible risk of irreversible effects through inhalation.
R40/21 Harmful: possible risk of irreversible effects in contact with skin.

R40/22 Harmful: possible risk of irreversible effects if swallowed.
LIST OF INCOMPATIBLE CHEMICALS
CHEMICAL TO BE KEPT OUT OF CONTACT WITH
Acetic acid Chromic acid, Nitric acid, Hydroxyl compounds, ethylene,

Glycol, Perchloric acid, Peroxides, Permanganates.
Acetylene Chlorine, Bromine, Copper, Fluorine, Silver, Mercury
Metals (powdered Carbon Tetrachloride or other chlorinated

aluminium,
Magnesium, Hydrocarbons, carbon dioxide and Halogens.
Sodium or
Potassium)
Ammonia Mercury (in Manometers for instance) Chlorine, Iodine,

Bromine, Hydrofluoric acid (G)
Ammonium Acids, Metal Powders, Flammable Liquids, Chlorates,

Nitrate Nitrates, Finely divided organic or combustible materials.
Aniline Nitric acid, hydrogen peroxide
Bromine Ammonia, Acetylene, Benzene, Finely divided metals
Chromic Acid Acetic acid, Glycerine, Alcohol, Methanol, Flammable

Liquids in general.
Hydrogen Copper, Chromium, Iron, Most metals and their Salts,

peroxide Alcohol’s, Acetone, Organic materials, Aniline,
Flammable liquids, Combustile materials.
Iodine Acetylene, Ammonia (Aqueous and Gas) Hydrogen
Mercury Acetylene, Ammonia
Cons. Nitric acid Acetic acid, Aniline, Chromic acid, flammable liquids and
gases
Oxalic acid Mercury
Perchloric acid Acetic anhydride, alcohol, paper, wood.

Potassium Glycerine, Ethylene Glycol, Benzaldehyde, Sulphuric acid
permanganate
Sodium Water, carbon tetrachloride, carbon dioxide
Sulphuric acid Potassium permanganate and compounds of similar light

metals such as sodium
Oxidising
Substances which give rise to highly exothermic reactions in contact with other
substances, particularly flammable substances.
Flammable
Extremely flammable liquids have a flash point less than 0C and a boiling point less
than or equal to 35C.
Harmful and irritant
Substances which present moderate risks to health by inhalation, ingestion or skin

absorption, inhalation, ingestion or skin absorption. Substances which are non-
corrosive but are liable to cause inflammation through immediate prolonged or
repeated contact with the skin or mucous membranes.
Explosive
Substances which may explode under the effect of flame or heat or which are more
sensitive to shock of friction than dinitrobenzene.
Toxic
Substances which present a serious risk of acute or chronic poisoning by inhalation

ingestion or skin absorption.
Corrosive
Substances which destroy living tissue
Dangerous to the environment
Substance which, were they to enter into a environment, would present or might
present an immediate or delayed danger for one or more components of the
environment.

 TRAINING MANUAL AS PER ICH GUIDELINES
 EMS PROCEDURE MANUAL
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 Procedure Of Corrective And Preventive Action
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o ► 12/26 - 01/02 (19)
 Procedure for conducting Stability Studies
 Out of Calibration of instruments
 Analytical report numbering
 Validation of QC Chemist
 Record maintained by Quality control department

 Labeling by Quality control department
 Functions of Quality control department
 Cleaning of HPLC columns
 Re-testing of raw materials and intermediates
 Acceptance of raw materials on supplier certificat...
 Sending sample to contract lab
 Sampling, testing and release of raw materials
 Calculation in QC department
 Opening and closing of QC department
 Cleaning of sampling tools
 Standardization and storage of Reference and Worki...
 Preparation, Standardization and Shelf-life of Vol...
 Sampling of Raw Material
 Internal Audit Plan as per GMP
o ► 12/19 - 12/26 (1)
 Quality Control of Capsules
o ► 12/12 - 12/19 (59)
 Calibration of Disintegration test apparatus
 Calibration of Friability test apparatus
 Calibration of serological water bath
 Bar Coding System for packaging materials
 Code numbering system of packaging material
 Cleaning & Sanitisation of Sampling room
 Operating Leak test Apparatus

 Sampling and Testing of packing materials
 Operation of colony counter
 Operation of compound microscope
 Out of specification (OOS) result in Microbiologic...
 Media Fill operation in the sterile dry powder fil...
 Disposing of microbiological culture media
 Preparation of Microbial Plates
 Operation and Cleaning of Laminar bench
 Maintaining of Bacterial Cultures
 Limulas Amoebocyte lysate test (LAL)
 Monitoring Personnel of sterile area in Aseptic ar...
 Operation and Calibration of Heating-Blocks
 Environmental monitoring of the microbiology labor...
 Fumigation and de-fumigation of Aseptic area
 Swab sampling and testing for clean rooms
 Monitoring of Aseptic area by Passive air sampling...
 Air sampling in Sterile area
 Cleaning and disinfections of Aseptic area
 Validating Corporate Computer Systems: Good IT Pra...
 Guidelines for production activities as per safety...
 Requisition and issuance of Raw materials
o ► 12/05 - 12/12 (89)
o ▼ 11/28 - 12/05 (43)
 EMS PROCEDURE MANUAL

 STERILITY TESTING
 VALIDATION OF INCUBATORS
 OPERATION AND CLEANING OF MOIST HEAT STERILIZER
 FERTILITY ( GROWTH PROMOTION ) TEST FOR MEDIA.
 DEPYROGENATION OF LAB APPARATUS
 OPERATION AND CALIBRATION OF MICROPIPETTE
 CULTURE MEDIA PREPARATION FOR MICROBIAL TEST
 MONITORING OF ENVIRONMENTAL CONDITIONS OFCONTROL S...
 OPERATION AND CALIBRATION OF HPLC SYSTEM (SIMADZU...
 DESTRUCTION OF ANALYTICAL SAMPLES AFTER TESTING
 OPERATION OF CENTRIFUGE
 PROCEDURE FOR OPERATING OF SONICATOR
 OPERATION AND CALIBRATION OF REFRACTOMETR
 OPERATION AND CALIBRATION OF KARL FISCHER APPAR...
 OPERATION AND CALIBRATION OF POLARIMETER
 OPERATION AND CALIBRATION OF BULK DENSITY APPARATU...
 OPERATION AND CALIBRATION OF pH METER
 OPERATION AND CALIBRATION OF SHORE HARDNESS TESTER...
 OPERATION AND CALIBRATION OF BURSTING STRENGTH TES...
 Monitor the Quality of Water for Injection
 MONITORING OF WATER FOR INJECTION QUALITY
 MONITORING OF PURIFIED De-Minerlised WATER
 MONITORING OF RAW, POTABLE AND REVERSE OMOSIS WA...
 CLEANING OF QUALITY CONTROL LABORATORY

 WORKSHEET FOR STABILITY STUDY
 STABILITY STUDY PROTOCOL FOR ANALYTICAL METHOD VAL...
 TRAINING MANUAL AS PER ICH GUIDELINES
 SAFETY MANUAL AS PER ICH GUIDELINES
 GUIDELINES FOR EMERGENCY MANAGEMENT PLAN
 Quality Manual as per ICH Guidelines
 PROCEDURE FOR CHECKING THE CORRECTNESS OF ...
 SWAB SAMPLING FOR CLEANING VALIDATION
 OPERATION, CLEANING, STORAGE, CALIBRATION AND REGE...
 STORAGE OF HAZARDOUS CHEMICALS & DESTRUCTION AFTE...
 OPERATION AND CALIBRATION OF DISSOLUTION TEST ...
 OPERATION AND CALIBRATION OF ULTRAVIOLET SPECTROPH...
 RETESTING OF PACKAGING MATERIALS
 RETESTING AND RE SAMPLING OF RAW MATERIALS
 HANDLING OF REFERENCE STANDARDS, PREPARATION AND ...
 LABORATORY DISCIPLINE IN QC LAB
 OPERATION AND CALIBRATION OF ANALYTICAL BALANCE
 REVIEW AND APPROVAL OF ANALYTICAL RAW DATA
o ► 11/21 - 11/28 (13)
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EMS PROCEDURE MANUAL

INDEX
Sr . Ref Procedure Issue

no
1 EP1 Identification of environmental aspects & impacts 01
2 EP2 Evaluation of significant environmental aspects & impacts 01
3 EP3 Regulatory and legal requirements 01
4 EP4 Setting and reviewing objectives and targets 01
5 EP5 Communication 01
6 EP6 Waste management 01
7 EP7 Effluent monitoring 01
8 EP8 Storage, handling and disposal of cloths waste & prevention of 01

pollutions.
PROCEDURE FOR IDENTIFICATION OF ENVIRONMENTAL ASPECTS
PURPOSE
THIS PROCEDURE DEALS WITH IDENTIFICATION, EVALUATION, AND REVIEW
OF ENVIRONMENTAL ASPECTS AND THEIR IMPACTS.
SCOPE
THIS PROCEDURE COVERS ALL ACTIVITIES, SERVICES AND PRODUCTS OF THE MPPL.
PROCEDURE
THE MANAGEMENT REPRESENTATIVE (MR) FORMS A CROSS FUNCTIONAL TEAM AND

IN COORDINATION WITH EXTERNAL CONSULTANT WILL CONDUCT AN ENVIRONMENTAL
REVIEW ONCE IN 12 MONTHS ( YEARLY ) AND PROVIDE THE RESULTS FOR
ASSESSMENT TO THE MANAGING DIRECTOR.
THE RESULTS OF FINDING ARE DOCUMENTED IN THE INITIAL ENVIRONMENTAL

REVIEW REPORT. IF THE ENVIRONMENTAL REVIEW TEAM DETERMINES THAT
ADDITIONAL INFORMATION’S NEEDED TO EVALUATE PRODUCT OR ACTIVITY. MR WILL
ASSIGN THE RESPONSIBILITY FOR COLLECTING THE INFORMATION’S TO
APPROPRIATE TEAM MEMBER. LIST OF ENVIRONMENTAL ASPECTS IS DETERMINED.
THE RESULTS OF THE MOST RECENT ENVIRONMENTAL REVIEW ARE REVIEWED AS

PART OF THE MANAGEMENT REVIEW PROCESS, BASED ON THE REVIEW; IT
DETERMINES THE NEED TO UPDATE THE ENVIRONMENTAL IMPACT EVALUATION.
ASSESSMENT AND EVALUATION OF ASPECTS SHALL BE DONE BY DEEPT. HEADS FOR

DETERMINING THE SIGNIFICANCE OF IMPACT AS PER ENVIRONMENTAL ASPECT
CREATION EVALUATION TABLE. THE DIRECTOR UNDERTAKES THE DETAILED
EVALUATION OF IDENTIFIED ENVIRONMENTAL ASPECTS. THE SIGNIFICANT ASPECTS
ARE PRIORITIZED AFTER DISCUSSION TO TAKE UP FOR SETTING OF OBJECTIVES.
AN ASPECT SHALL BE CONSIDERED HIGHLY SIGNIFICANT IF IT RATES ABOVE 250

POINTS AS PER THE TABLE , IF IT RATES BETWEEN 100 AND 200 POINTS IT SHALL BE
CONSIDERED AS MEDIUM SIGNIFICANT AND LESS THAN 100 POINTS SHALL BE
CONSIDERED LOW SIGNIFICANT.
ENVIRONMENTAL ASPECTS THAT ARE COVERED UNDER LEGISLATIVE REQUIREMENTS

SHALL BE CONSIDERED HIGHLY SIGNIFICANT IF ANY SUCH FAILS TO MEET THE
REQUIREMENTS IRRESPECTIVE OF THE LOW RATING IN THE TABLE.
THE LIST OF ASPECTS AND CRITERIA FOR SIGNIFICANCE EVALUATION IS KEPT UP TO

DATE. NEW ENVIRONMENTAL ISSUES ( ASPECTS ) AS DECIDED IN MANAGEMENT
REVIEW MEETING MAY BE CONSIDERED IN EMS.
RESPONSIBILITY AND AUTHORITY
SECTION IN CHARGE IS RESPONSIBLE FOR IDENTIFYING ENVIRONMENTAL ASPECTS

IN HIS AREA.
MR IS RESPONSIBLE FOR CONDUCTING THE ENVIRONMENTAL REVIEW.
DIRECTOR IS RESPONSIBLE FOR THE SIGNIFICANCE OF IMPACTS.
EP2: Evaluation of significant Environmental Aspects & Impacts
0.0 Scope
This procedure describes the responsibilities and methods for determining aspects,
impacts and their significance of MPPL operations.
1.0 Purpose
This procedure exists to ensure that MPPL significant environmental aspects and impacts are
identified in order that the EMS may address them.
2.0 Responsibilities
- the Director must ensuring that this document is updated as often as is
- necessary to ensure that it is relevant to MPPL working practices.
- The Director is responsible for ensuring that all managers & supervisors are aware of those
aspects & impacts, which are generated by their work.
3.0 Procedure:
3.1 Aspects Evaluation
The environmental aspects of MPPL operations include:
- energy consumption
- resource consumption
The Director determines the aspect and impacts using an input – output process model ,
recording the resources used and products developed .
Having determined these, the Director then determines the impacts of these aspects and
impacts under normal conditions.
3.2 Significance criteria test
Having determined an impact, the Director then uses the criteria test to determine whether or
not an aspect of MPPL operations is environmentally significant. The questions are listed in
order of priority.
1. Is the issue controlled by environmental legislation?
2. Is an effluent’s / emission’s / waste’s quantity or concentration at units controlled by an

environmental regulatory permit ?
3. Has anyone complained about the effluent/emissions/waste?
4. Can the emissions be the cause of an upset on pollution control equipment ?
5. Does the process consume more than 5% of the company’s energy requirements ?
6. In an emergency, is there potential for an unintentional spillage of liquid or atmospheric

emission migrating outside the boundaries of the site and causing environmental
damage ?
The significant aspects are rated on from 4.3.1 F1(appendix-1), in order of significance. The
greater the number of yes answers, the more significant the aspect.
The list of significant , ranked impacts is then used as a trigger for setting the objectives and
targets.
Cross reference: Aspect and impact analysis
EP 2: Regulatory and legal requirements

1.0 Scope:
This procedure applies to all regulated process conducted by MPPL
2.0 Purpose:
This procedure outlines the responsibilities for supervising the implementation of legislation
relating to the environment .
3.0 Responsibility:
The MR is responsible for maintaining the register of legislation and other requirements, and for
implements any changes triggered by new regulations.
4.0 Procedure:
MPPL operates under a number of different consents imposed by the environment authorities.
The Director holds copies of the COMPANY (ies ) are
1. The Environment (Protection) Act, 1986
These are supported by other acts, statutory regulations. This must be adhered to the
requirements.
The MR keeps up to date with legislation by subscribing to environments management. A copy

of this publication is held in the office. The company also keeps up to date with legislation and
other requirements through communications from the Manufacture’s Associations guidelines on
the environments.
All relevant legislation is maintained in a register of legislation and other requirements which is
held in Appendix 2, on Form EPF -R1 (appendix 2) Legal register of key processes ,
legislations, Releases and environmental impacts.
Cross reference:
Legal Register (Form EPF -R1)
EP : 3 Setting and Reviewing Objectives and Target

1.0 Scope:
This procedure is applicable for setting and reviewing the objectives & targets for MPPL
2.0 Purpose:
The aim of this procedure is to define new objectives and targets, and to review and update
objectives and targets . Targets should be quantifiable where possible and relate to the
objectives contains in the environmental policy.
3.0 Responsibility:
The MR has overall responsibility for the implementations of this procedure.
4.0 Procedure:
4.1 On an annual basis the operations Director is responsible for co-coordinating the objectives
and targets within the context of:
ü Findings resulting from the audit programme
ü Evaluation of the impacts register
ü Emerging legislation
ü Evaluation emerging environmental issues , such as phase out of specific hazardous

materials
ü New (environmental) technology
ü Reviewing process against current objectives and targets
1.1 The MR is responsible for ensuring that objectives and quantified targets are set for reducing
waste, and energy use in all production departments.
1.2 The MR is responsible for ensuring that any relevant technical objectives and target are set e.g.
development of new procedures, improved management of environmental impacts.
1.3 The maintenance Supervisor is responsible for ensuring that relevant objectives and targets
are set for maintenance activities.
1.4 The Director is responsible for setting relevant objectives and targets, e.g. looking for
environmentally friendly alternatives for hazardous materials, and establishing a phase – out
schedule.
4.2 In addition to the annual objectives and target setting, objectives and targets may also be
set by managers when necessary , e.g. in case of new legislation or incidents . These must be
communicated to the Director.
4.3 The Director is responsible for consolidating environmental objectives and target provided
by the managers and for ensuring that targets are consistent with the environmental policy and
objectives
1. Include environmental high risk issues
2. Are quantified where possible
3. Include a cost benefit analysis where possible
4. Are demanding but achievable.
4.4 The Director is responsible for presenting the consolidated objectives and targets for
Management review and for communicating approved targets to relevant personnel.
4.5 Director is responsible for rotating an up to date list of objectives and targets together with
any superseded list and corrective actions.
Cross reference:
Environmental Objectives Chart (EPF- F1)
EP : 4 Communication
1.0 Scope :
This procedure applies to internal as well as external communication between employees of

MPPL suppliers, customers, and various applicable regulatory authorities.
2.0 Purpose:
Purpose of this procedure is to establish effective communication between internal & external
customer so that effective Environmental Management System can be established in MPPL.
3.0 Responsibility: &
4.0 Procedure:
Refer appendix of this procedure –EMS Communication Matrix.
EP 5: Waste management
5.0 Scope :
This procedure applies to all waste management conducted by MPPL.
6.0 Purpose:
The purpose of this procedure is to make sure that:
All waste management activities are conducted in accordance with the requirements of relevant
legislation , regulations and other statutory codes .
Consistently high standards of waste management are observed at all times and in all places
The management realizes every opportunity for waste minimization.

7.1 PRODUCTION MANAGER:
ü Contract waste carriers.
ü Retain copy waste carrier licenses (if applicable).
ü Monitor the performance of waste Disposal.
7.2 SUPERVISOR:
ü Keep an inventory of all waste products
ü Advise the MR on suitable waste contractors.
ü Sign and retain waste transfer documentation.
ü Describe each waste.
ü Develop and implement a waste minimization strategy.
8.0 Procedure
Any waste that is produced at MPPL is appropriately stored treated and disposed off some waste ,
such as scrap & other cloths waste( such as copper’ iron gun cloths powder etc.) several key
steps must be incorporated from waste production through to final disposal viz.
Identification and description of waste,
Appropriate storage of waste materials,
Transfer of waste materials to known persons only,
Completing and retaining waste transfer documentation,
Checking the performance of waste contractors.

Identification and description of waste:
All controlled wastes should be identified and recorded in a waste inventory. the inventory
should as a minimum contain details of :
A description of each waste, which should include :
The disposal method employed , i.e. waste carrier and skip type
where possible the inventory should the approximate quantities of each waste produced , per week
cans per month etc.
An example of a waste inventory and a blank pro-forma are included in the appendices of this
procedure .
Appropriate waste storage:
All waste produced must be stored appropriate storage shall
consider security from vandals ,children , trespassers and wildlife ,
clearly label waste storage compound
clearly label special wastage. , e.g. asbestos or minerals greases ,
investigate if the waste requires segregation due to the potential effects of any mixing of wastes.
Include an inspection program of storage areas commensurate with the risk ..
Transfer of waste material:
All waste contractors employed to remove waste materials must be in the list of approved
supplier.
COMPLETING AND RETAINING WASTE TRANSFER DOCUMENTATION

Each waste transfer to a waste carrier shall be recorded with the appropriate waste transfer note
Where waste transfers a repetitive and consists of general waste only an annual transfer note shall
be acceptable.
Waste transfer notes shall be retained for month of 2years.
EP 6 Effluent Monitoring
1. Scope
This procedure defines the responsibilities and actions to ensure that the company complies
with all the requirements of all trade effluent discharge consent.
2. Responsibilities
The Director is responsible for ensuring compliance with trade effluent discharge consents, and
communicating with Waste control ( AMC ) & control of pollution) authority.
Production Manager is responsible for informing the Director of any planned change in process ,
which may result in change to the nature , and composition of a trade effluent.
3. Procedure
3.1 The company must comply with the relevant consent limits at all times .
3.2 Trade effluent must only be discharged from the specified points as detailed on individual
consents.
3.3 Monitoring points at all times without prior notification for the purpose of inspecting ,testing or
sampling effluent.
3.4 Trade effluent must not contain any oily substances .

A process change that may affect any effluent consent held necessitates a review of this
procedure . The Production manager must be notified of any such change.
Cross reference:
Effluent quality monitoring register.( EPF -R4)

EP 7 : Storage , handling and disposal of cloth waste and prevention of pollution
1.0 Scope
This procedure describes the responsibilities for, and the action to be taken , for the disposal ,
storage and handling of cloths waste and prevention of pollution.
2.0 Purpose
This procedure exists to ensure the safe and effective handling and storage of cloths waste, in
order to prevent pollution
All personnel involved in the disposal , handling and storage of cloths waste, have a responsibility
for following this procedure .
Relevant seniors are responsible for ensuring all personnel under their jurisdiction are fully aware of
this procedure .
The Production Manager is responsible for regular checks and monitoring.
4.0 Procedure
4.1. CLOTHS WASTE
cloths waste must be stored in the designated areas prior to use these are :-
processing in the designated area
raw material in desired area
4.2.waste - cloths waste
4.2.1 all waste cloths waste should be stored in designated storage area having three ( 3’ ) feet
boundary.
4.2..2 Related person should wear long shoes & equipped with long fork for handling the
scrape.
5.0 GENERAL:
5.1 When transporting or cloths scrape be taken to precaution.
5.2 It is offence to cause waste pollution, either deliberately or accidentally.
5.3 waste shall not be carried out in the store premises.

 TRAINING MANUAL AS PER ICH GUIDELINES
 Effluent Treatment Plant
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TRAINING MANUAL AS PER ICH GUIDELINES
1.0 INTRODUCTION
Pharmaceutical Ltd. recognizes the importance of formalized training programs to
impart training to all employees of various levels.
This “Training Manual” is prepared at the beginning of calendar year to enhance the
effectiveness of training procedure existing in the company.
Training Manual includes the various Types of training and cGMP training schedules
for each department, which identifies the name of the topic, targeted audience &
trainer to conduct the training in all organized manner.
Departmental training schedules are prepared by concerned departmental head in

coordination with the head – QA, keeping in mind the background of training needs.
“SOP” training is not included in the Manual, since it will be covered in the change
management system, via a separate SOP. Whenever a new SOP is made (or)
existing SOPs is revised, the respective dept. personnel are trained to make them
familiar with the activities mentioned in the SOPs to make them effective.
2.0 OBJECTIVE
To ensure that all the employees working in Pharmaceutical Ltd., are capable to
perform the duties as per the cGMP, SOPs and procedures and each employee of
Pharmaceutical Ltd., shall improve the relevant knowledge, expertise and to
consolidate the same to discharge their duties effectively. cGMP advises that
appropriate training is required to perform the jobs effectively, which in turn helps in
maintaining the quality system.
3.0 SCOPE
This procedure applies for training of all levels of employees and permanent
workers, working in
Pharmaceutical Ltd.
4.0 RESPONSIBILITIES
Departmental heads are responsible to ensure that the training programs are
conducted as per the schedule in respective departments.
Personnel & administration department is responsible to coordinate with the trainer,
trainee and departmental heads and to monitor the schedules, to organize the
trainings and to keep the training records, department wise and individually.
Trainer should prepare / refer the (training) course material and a questionnaire will
be prepared for each topic in consultation with the departmental heads / seniors.
After completion of each session, trainer should evaluate feedback. If some body
needs retraining it should be organized in coordination with the personnel and
administrative department.
Each trainee should sign in their departmental training log after attending the
training program.
Each employee is responsible to attend the training / retraining as per the schedule
communicated to him.
QA shall verify whether the Training program is carried out as per the schedule
during their audits.
5.0 PROCEDURE
TYPES OF TRAINING:
5.1 Induction training
5.2 On job training
5.3 GMP training (Interim),
5.4 External training

MANUAL PREPARATION:
 Individual Departmental Schedules of training topics are prepared by the respective

departmental heads, reviewed by Executive – P & A, which is Approved by D.G.M –
Q.A/Q.C and Authorized by Sr. G.M – Manufacturing and then included in the training
Manual.
 The schedules are prepared by departmental head in consultation with Executive –

P & A, D.G.M – Q.A/Q.C, identifying the training needs of personnel in respective
departments in connection with cGMP system. By including individual departmental
schedules besides the coverage of other kind of topics a training Manual shall be
compiled by Q.A.
 A training Manual for the next calendar year may be prepared in the month of
March or in advance as appropriate.
 Training Manual should be approved by D.G.M – Q.A/Q.C and Authorized by Sr. G.M–
Mfg. prior to issuance and implementation.
 A copy of the training Manual shall be issued to personnel dept and Personnel
Department will circulate a copy of the departmental training schedules to the
respective head of departments.
 A master copy of training Manual shall be retained at Q.A and controlled copy
circulated to Executive – P & A.
5.1 Induction training
(Chemists, Officer, Executives & Above)
Each new employee from supervisory and above will be given induction training in the
following aspects:
 Introduction about the company’s code of conduct and job responsibilities.
 Personal hygiene, dos & don’ts.
 Importance of GMP and its compliance, key elements of GMP and GLP (Good
laboratory practices) as appropriate.
 An induction program will be arranged by Executive – P & A, where the new person
will be made familiar with the contact people in each dept. and the activities that are
being carried out in those departments.
Induction training (workman / Workmen)
Each new employee will be given induction training in the following aspects by
Executive – P&A.
 Introduction about the company.
 Definition of GMP, its importance and basic rules of GMP.
 Personal hygiene, personal up keepment at the work place and gowning

procedures.
 Briefing about their job responsibilities.
Evaluation of Induction training
 Evaluation of induction training will be done by oral questioning and interactive

sessions; hence no specific evaluation will be done. Mainly this training is to make
the employees familiar with the organization and their job roles / requirements in
brief and to know the preliminary information about the organization and the
contact personnel.
5.2 “On the job” training:

 The topics will be selected on the basis of training needs related to the job by
department Heads periodically. The training will be conducted “on the job” at the work
places like manufacturing floor and in the Q.C lab etc (In brief at the work place.)
 If required, classroom sessions will be also conducted to impart the knowledge

about the theory as decided by the department Head (trainer).
 Training on relevant process equipment/analytical instruments, manufacturing

process steps and detailed procedure to operate the same equipment/ instruments
to be practically demonstrated / explained. Other procedures shall also be
practically explained on the job as applicable.
 Trainer shall write the remark that participants were “trained”, head of department
review shall be carried out and review comments shall be recorded in the same
format.
 On job training shall be documented only in the format “Department Training Log”.
 Schedules are prepared by head of department for on job training and the same will
be complied to make the employees pertinent to their relevant jobs that they carried
out.
5.3 GMP Training:
 GMP training schedules are prepared as part of training Manual by each dept. Head,
reviewed by Manager – personnel, Approved by D.G.M - Q.A / Q.C, and Authorized by
Sr. G.M - Manufacturing.
 Training sessions shall be conducted by the respective department Heads as per

the schedules and necessary evaluation shall be done at the end of the training
session, which shall be documented in the training logs and training cards and brief
summary is recorded in the on the job training format.
Evaluation of GMP training:
 The effectiveness of the training will be evaluated for GMP training.
 Trainees will be assessed by written test (objective questionnaire) / oral as

appropriate depending on the training topic.
 The understanding about the topic on which participant was trained will be
assessed by the percentage of marks obtained. The trainee should obtain more
than 80% Marks. The trainee who scores less than 80% will be retrained. Suitable
method of departments can adopted for oral assessments.
5.4 External training:
External training will be imparted to chemists, Officers / Executives and other

personnel based on the needs. Normally following training topics are covered under
this training.
 cGMP (current Good Manufacturing Practice).
 GLP (Good Laboratory Practice).
 Validations.
 Regulatory aspects.
 Other topics as appropriate.
External training shall be recorded in the individual training cards, no specific

formats /Logs are maintained for this kind of training. Training evaluation record
shall be maintained.
6.0 TRAINING RECORD:
6.1 All the employees training details are recorded in Training Card
maintained at Personnel dept. and in the respective “Log Book” for
Training. .
6.2 Training needs shall be identified by the respective department heads, before
preparation of schedules to be included in subsequent calendar year training
Manual.
6.3 All the training related formats are specified in the Annexure. Each training
shall be recorded as in the Annexure as Indicated below.
7.0 MODEL DOCUMENTS / FORMATS:
7.1 Annexure – I: Induction Training Format.
7.2 Annexure – II: GMP / On job Department Training Log.
7.3 Annexure – III: GMP/ On Job Training Report Format.
7.4 Annexure – IV: Employee Training Card.
ANNEXURE-I
INDUCTION TRAINING FORMAT
Issued By: Topic: INDUCTION TRAINING
(Executive – P & A)
Name of the Employee: Designation:
Dept: Date of joining:

Remarks After training by Executive – P & A
Remarks After training by Head - Q.A
Conducted By Sign Date
1.
2.
Note:-One form shall be filled for each employee
After Induction training program, Details shall be recorded in the

following form.
ANNEXURE-II
GMP / ON JOB DEPARTMENT TRAINING LOG
Name Of Trainer: Date:
Designation
Location: Duration of Training:
Title Of Training
Topics Covered
Name Of Designatio Departme Employee Trainer Sign

S. No.
Employee n nt Signature
ANNEXURE-III
GMP/ ON JOB TRAINING REPORT FORMAT
Issued By: Sign : Date : Dept :
Head - Q.A
Topic: Date :
Demonstration / Explaining / Counselling / Class room training
( which ever it appropriate)

Brief description/ Review:
Type of Evaluation Written / Oral
Trainer Name: Sign

ANNEXURE – IV
EMPLOYEE TRAINING CARD
NAME
: DATE OF
JOINING:
DEPARTMENT
:
DESIGNATION:
SR Date Topic Mode Mode of Sign of Remark Name Sign

of of Evaluati Employ s by & Sign of
No Traini training on ee Trainer of Dept
. ng Trainer .
Head
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
Writte
Writte
n/
n / Oral
Oral
All kinds of training programs attended by the participant shall be

recorded in the following format. These formats are maintained one
individually for the each employee.
8.0 Training Course Material
Training course material should be prepared / referred for each training class or
relevant SOP Procedures, Quality Manuals, Quality Policy and instructions ICH
guidelines.
9.0 Training Feed back and evaluation
Training feedback should be obtained after conducting classroom training &

Questionnaire evaluation shall be done as appropriate.
Evaluation should be done as per the respective SOP.

10.0 Individual department training: Individual Department Training
Schedule is as per the list.
10.1 Production
10.2 Stores
10.3 Engineering
10.4 Quality Control
10.5 Personnel
10.6 Quality Assurance
Quality Manual as per ICH Guidelines
Title: Table of Contents Section: QM 0.1
Sr. No. Description ISO 9001 Clause Ref. Section No.

01 Table of Contents -- QM-0.1
02 Revision History -- QM-0.2
03 List of Controlled Manual Holders -- QM-0.3
04 Introduction -- QM-1.0
05 Scope of the Quality Management System -- QM-2.0
06 Exclusions & Justifications -- QM-3.0
07 Quality Management System 4.0 QM-4.0
08 Management Responsibility 5.0 QM-5.0
09 Resource Management 6.0 QM-6.0
10 Product Realization 7.0 QM-7.0
11 Measurement Analysis and Improvement 8.0 QM-8.0
12 Organogram -- QM-9.0
Title: Revision History Section: QM 0.2

Page No.
Sr. No. Brief Description of Change Rev. No.
Title: List of Controlled Manual Holders Section: QM 0.3
Sr. No. Manual Holders Copy No.
01 TM / MR 01 (Master Copy)
02 Production / Stores / Quality Control /Purchase / Marketing 02
03 Certification Agency 03
Title: Introduction Section: QM 1.0
Our Company is one of the leading company in its class.
We at our company are dedicated to supply quality products with above mentioned
High Quality Testing Equipment, Highly qualified technical staff, in-house tool room,
checking & packing we are confident of handling your requirements.
Title: Scope of the Quality Section: QM 2.0
Management System
Scope of the Quality Management System for ISO 9001: 2000 Standard Implementation is as
Under :
Manufacturer and Exporter of Bulk Drugs and Pharma

Intermediates
Title: Exclusions & Justifications Section: QM 3.0
The Following Clauses of ISO 9001:2000 Standard are not applicable in purview with the Scope
of the Organization:
Clause 7.3 : Design & Development :-
The organization is manufacturing as per the IP (31431-39-7), USP and B.P. and doesn’t have its
own design hence this clause is not applicable.
Title: Quality Management System Section: QM 4.0
4.1 GENERAL REQUIREMENTS
The company has established, documented, implemented and maintained a quality management
system to continually improve its effectiveness in accordance with ISO 9001:2000 QMS
standards
The process needed for quality management system and their applications throughout the
organization are identified.
The sequences and interaction of these processes are determined and documented in respective
sections of this manual and in respective documents. Also a Flow chart of interaction of these
processes is prepared.
The criteria and methods needed to ensure that both operation and control of these processes are
effective are determined.
Availability of resources and information necessary to support the operation and monitoring of
these processes are ensured.
These processes are monitored, measured and analyzed.
Action necessary to achieve planned results and continual improvement of these processes are
implemented.
These processes are managed by company in accordance with the requirements of ISO
9001:2000
Nitration process is outsourced and the same is controlled through outgoing and incoming
quality checks and the reports for the same are being maintained.
4.2 DOCUMENTATION
4.2.1 General
The Quality Management System Documentation includes:-
 Quality Policy and Quality Objectives

 Quality Manual
 Quality System Activities required by ISO 9001:2000 standards, which is identified by

the organization for its operations to be effective.
 Work instructions, SOPs, product specifications, inspection and testing procedures,

supplier provided standards, etc.
 Quality records
4.2.2 Quality Manual

This manual is in full conformity with requirements of ISO 9001 : 2000 Standards and is
supported by further levels of documentation as detailed in 4.2.1
The scope of quality management system covers activities relating to “scope” The documented
procedures established for the quality management activities under the scope are defined in level
‘B’ documentation.
This manual and cross-reference procedures in Process Interactions Chart describe the
interaction between various processes under the scope of Quality Management System.
4.2.3 Control of Documents
Documents as described in 4.2.1 are controlled, implemented, circulated, reviewed and approved
as activity flow charts, referred as under:
4.2.4 Control of Records

It is essential that Quality Records are maintained, since the records are the objective evidence
that the system is operating effectively at all stages. The activities for Control of Records are
referred as under:
ACTIVITY REFERENCE:
PROCEDURE MANUAL- MANAGEMENT REPRESENTATIVE
Title: Management Responsibility Section: QM 5.0
5.1 MANAGEMENT COMMITMENT
The company commits itself to the development and implementation of quality management
system and continually improves its effectiveness. Regular meetings wherein the importance of
meeting customer requirements and feedback are communicated to employees whenever
necessity arises will achieve this. The administrative personnel are briefed regularly about the
statutory and regulatory requirements in meeting.
The quality policy is established and the text of the Quality Policy is given in 5.3
The Quality Policy is supported by tangible Quality Objectives as given in 5.3
Management Reviews are conducted regularly to ascertain effectiveness of QMS (refer 5.6)
The company ensures that adequate resources are made available to meet customer requirement,
Quality System requirements as well as statutory and regulatory requirements.
5.2 CUSTOMER FOCUS
The Company has belief in the philosophy that, CUSTOMER is the purpose of its business.
Employees are regularly trained on customer focus. The feedback from customer in terms of
quality, delivery, quality complaints etc. are accorded top priority and their cause and preventive
measures are immediately implemented.
Customer Satisfaction is enhanced through regular meeting with customer/representatives and
fulfilling their targets in terms of quality, delivery lead-time and price expectations. Periodically
customer feedback form is sent to ascertain their needs and expectations.
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MANAGEMENT REPRESENTATIVE AND MARKETING
5.3 QUALITY POLICY
Considering the needs and expectations of customers and our company’s business strategy, Top
Management has formulated the quality policy:
The quality policy of the company is defined, documented and made known to all the employees
by way of display at prominent places and emphasizing its intents in regular training at all level.
The policy is regularly reviewed in management review meeting for its continuing suitability and
revised as and when necessary.
ACTIVITY REFERENCE:
QUALITY POLICY
5.4.1 QUALITY OBJECTIVES
The quality objective is segmented department wise and the measures to evaluate its
achievements are defined. These objectives are periodically reviewed, updated and MR identifies
actions for implementation.
ACTIVITY REFERENCE:
QUANTIFICATION OF QUALITY OBJECTIVES
5.4.2 QUALITY MANAGEMENT SYSTEM PLANNING
The Management Representative ensures that the quality management system is planned with
defined responsibility and authorities, which is documented in Quality Activities. The system is
planned to meet the requirements of clause 4.1 and quality objectives as defined in clause 5.4.1
of the manual.
The integrity of the QMS is ensured by way of review of the system, when the scope of the
system is enhanced or when new product lines are introduced. Quality Manual and Quality
Activities are reviewed for changes as and when required.
Internal audit results are reviewed and the corrective actions are standardized in the quality
system Documents.
Product configuration changes are reviewed and product related documents are updated as
applicable.
Corrective and preventive actions are reviewed and the changes are standardized in appropriate
documents.
The result of internal and external audit is reviewed and appropriate corrective and preventive
actions are initiated.
5.5.1 Responsibility, Authority and Communication
The organogram chart included in Section 09.0 of this manual shows the relationships between
the respective functions.
All employees are responsible for the quality of their own work and for advising their
responsible Manager or supervisor of any conditions that are adverse to the quality of the work
being produced or adverse to the satisfactory operations of the quality system.
Managers and supervisors are responsible, and have the authority within their defined areas of
control for:
 the quality of work carried out
 initiating action to prevent the occurrence of nonconformance
 identifying and recording quality problems

 initiating, recommending and providing solutions to quality problems.
The responsibilities and authorities of the organization chart are described as below:
TOP MANAGEMENT
Responsibility:
a) Overall business development of the organization
b) Financial Management of the organization
c) Recruit executives in Managerial Cadre
d) Formulate quality policy with objectives for the organization
e) Overall responsible for implemented quality management system
Authority:
a) Make key decisions and can supercede decisions taken by others
b) Approve purchase of capital goods
c) Approve the formulated quality management system
d) Final authority in all policies of the company
HOD– OPERATIONS
Responsibility:
a) Maintain Harmonic cultures in the company
b) Liaison and handling prospective customers
c) Recruitment of personnel at works
d) Handling and resolving customer complaints
e) Execution of work orders in time
f) Procurement of all material and services required for the organization
g) Manage supplier development
h) Overall responsible for processes of the organization
i) To implement on-line inspection stage wise
j) To plan production and manpower
k) Impart regular training at shop floor
l) To maintain plant and machinery and general house keeping
m) Co-ordinate with Materials, QC&I and Design department
Authority:
a) Approve all purchases of material and services
b) Approve recruitment personnel at works
c) Sanction commercial transactions at work
d) Approve the formulated quality management system
SUPERVISOR
Responsibility:
a) To Inspect, approve, reject all incoming material
b) To Inspect, approve, reject process activity
c) For final inspection of the product
d) Co-ordination with third party for inspection
e) Co-ordination with production dept. for product quality improvement
f) Co-ordination with MR for QMS implementation
Authority:
a) Approve deviation in production processes
b) To prepare dispatch documents
c) Control of material at shop floor
d) Recruit workers required for production activity
5.5.2 MANAGEMENT REPRESENTATIVE
Management Representative’s Responsibilities and authorities include:-
 Preparation, Updating and maintenance of Quality Manual
 Issue of Quality Manual. Quality Activities
 Implementation of Quality Systems.
 Review of document & data control, making current version available, precludes use of
obsolete documents, identifying nature of change.
 Control of quality records is means of identification, collection, indexing, disposition and

retention time.
 Liaison with external agency for ISO 9001 certification
 Conducting the internal quality audit as per schedule, recording non-conformities, and
verification of effectiveness of corrective action against non-conformities.
 Conducting the Management Review Meeting and reporting the finding of IQA to Top
Management.
 Promoting the awareness of customer requirements throughout the organization.

5.5.3 INTERNAL COMMUNICATION
Internal communication channels are ensured as follows:-
 Quality Policy: Display, Induction Program & Training
 Quality Objectives: Distribution of documents
 Customer Feed Back: Meetings, Letters, Emails, Feedback form & proactive actions
 Internal Audit, C & P Actions: Management Review Meetings
 MR is overall responsible to maintain internal communication channels.
5.6 MANAGEMENT REVIEW
5.6.1 General
Top Management with all HODs will conduct Management Review Meeting once in every six
months or as when required. The purpose of the meeting is to ensure that Quality System meets
or exceeds the requirement of ISO 9001 : 2000 standard. In addition it will assess the Quality
System’s continued suitability with respect to achieving company’s Quality Policy and
Objectives and opportunity for improvement in quality management system, quality policy and
quality objectives.
The MR records review inputs in agenda for management review. Review outputs are recorded
in minutes of MRM and communicated to all concerned.
5.6.2 Review Input

The input to management review shall include:
a) Results of internal audit and external audit
b) Customer feedback and complaints
c) Routine Operational performance of the organization
d) Status of corrective and preventive actions taken
e) Pending actions from previous management reviews
f) Changes that are required/effected in documentation of QMS
g) Other general points
5.6.3 Review Output

The review output is recorded by MR and shall include decisions and actions, target date and
responsibility related to:
a) Improvement of effectiveness of quality management system
b) Improvement in processes to meet customer requirements
c) Requirement of resources necessary for effective overall functioning
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MANAGEMENT REPRESENTATIVE
Title: Resource Management Section: QM 6.0
6.1 PROVISION OF RESOURCES
The Company ensures provision of resources that are needed:-
 To implement and maintain the quality management system and continually improve its
effectiveness.
 To enhance customer satisfaction by meeting customer requirements.
 The resource needs are identified through activities such as product planning, internal
audit, management reviews and review of quality objectives.
6.2 HUMAN RESOURCES
6.2.1 General
The Company ensures that personnel performing work affecting product quality are competent
on the basis of appropriate education, training, skills and experience.
6.2.2 Competence, Awareness & Training

Necessary competence needed for performing work affecting product quality are determined by
the MR and HODs and documented.
The personnel are assessed on the basis of determined competence requirements. Gaps, if any,
are assessed and training is provided to personnel to meet the competence need. The training
may be in-house or external classroom training.
The effectiveness of the actions taken in terms of enhancing the competence levels is evaluated.
Employees are made known the requirement of skills and knowledge required relating to the jobs
they handle and how they contribute for attaining quality objectives.
Appropriate records are maintained regarding, education, training, skills & experience
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MANAGEMENT REPRESENTATIVE
6.3 INFRASTRUCTURE
Infrastructure needs are assessed on the basis of the resource requirement and business plan.
The infrastructure such as building and amenities for the operators are provided.
Tools & Tackles, Testing Instruments, Testing facilities are provided on the basis of quality plan.
Need for supporting services such as logistics, computer support, etc. are provided.
6.4 WORK ENVIRONMENT

The Company ensures that proper layout, adequate ventilation, lighting, house keeping systems
and safety devices maintain the work environment neatly where appropriate.
Title: Product Realization Section: QM 7.0
7.1 PLANNING OF PRODUCT REALIZATION
The Company plans the requirement of quality and identifies the controls of the process,
inspection and test methods, measurement needs and standards of acceptability, acquisition of
any controls, equipment, etc.
The quality planning also includes the compatibility of product/process, establishment inspection
and test activities, development of newer measurement methods, identification of inspection and
testing requirement, identification and preparation of quality records.
For each product line, such controls are defined in quality plan and are used as a means of
controlling quality. Quality Plan is prepared for final approval of equipment
7.2 CUSTOMER RELATED PROCESS
7.2.1 Development of requirements related to products
The Company identifies the requirements specified by customer though work order inputs and
application details provided by customer, delivery schedules desired b customers and feedback
on products supplied.
Requirements not specified by customer, who is required for intended use are identified by
Departmental Head.
Statutory and regulatory requirements related to the products are identified through customer
communication
Any additional requirements related to the products are identified based on the organization’s
experience in supplying products to similar application
7.2.2 Review of requirements related to the product
The Company ensures to review the requirements related to the product as follows:-
Product specification/application is reviewed during the order processing and any mismatch or
incompatibility is reported to the customer. Order requirements are reviewed and recorded.
Delivery requirements are reviewed and recorded.
During this review, if any product or order requirements are deviating from those previously
expressed, they are resolved
After review it is ensured that confirmation to customer is established to prove ability to meet
customer requirements.
Where the customer requirements are communicated verbally, the customer requirements are
confirmed in review documents as above, prior to acceptance.
When the product requirements are changed, the amendments are reviewed and the changes are
incorporated on all relevant internal documents.
The document changes are made known and communicated to relevant functions.
7.2.2 Customer Communication
The various communication systems to customers are as follows

Product information: sales executives communicate product configuration and price information.
Order handling, queries and amendment handling are carried out by Marketing Personnel and
communicated to customers.
Customer feed back and complaints are analyzed and communicated to them.
ACTIVITY REFERENCE:
PROCEDURE MANUAL - MARKETING
7.3 DESIGN AND DEVELOPMENT
EXCLUDED
7.4 PURCHASING
7.4.1 Purchasing Process
The Quality System Activities ensure that products, Raw material & Packaging Material are
purchased form approved sources only
Any new source of product / make shall approve based of evaluation and/or trial production,
which shall access the ability of the source to meet the company’s quality and delivery
requirements.
The extent of control on the source of supply is based on the product criticality. This is defined in
product quality plan.
The results of supplier performance in terms of adherence to quality and delivery requirements
are monitored. The data is reviewed by HOD Purchase and Top Management and the supplier are
evaluated once in a year.
Records of evaluation, re-evaluation and ratings are maintained.
7.4.2 Purchasing information
Purchasing specification describes the following data.

Product configuration, code, makes, size and other unique information.
Requirements of approval of product such as test certificates, need for Quality system
Certificates and as per Raw Material Testing Plan
The Company ensures that adequacy of Purchase requirements are reviewed prior to release.
7.4.3 Verification of purchased products
The purchased products are verified by one of the following methods.
 Verification of Test Certificates
 Product evaluation through a plan of evaluation
 Receiving inspection as per receiving inspection plan
 Where specified by customer or when required by the company, the verification may be
done at supplier’s premises by company or by Customer.
 The verification method may include product evaluation, Supplier Quality System Audit.
In such case, purchasing information shall specify the method of verification and sub-sequent
product release.
ACTIVITY REFERENCE:
PROCEDURE MANUAL – PURCHASE
7.5 PRODUCTION AND SERVICE PROVISION
7.5.1 Control of Production and Service Provision
The production activity is carried out under controlled condition.

The information about the product configuration is provided to the Technicians and Engineers
Operations are carried out as per work instruction/ purchase order.
The equipment used for Production and testing is ensured have the requisite capability through
preventive maintenance of equipments.
Technicians and Engineers are provided with necessary Equipments and Instruments.
The monitoring of process and testing is as per Quality Plan.
The products are released to the next stage and delivery after due verification and recording.
7.5.2 Validation of process for production

Production process is validated by way of Inspection and control as per Quality plan.
No Special Process is presently carried out in the company and if any such process is carried out
in future, the records for the same will be maintained.
7.5.3 Identification and Traceability

The constituent parts, products in-process, finished products and packed products ready for
dispatch are identified by means of status boards, displayed besides the product.
The status of products after each verification stage is clearly identified as passed or failed by way
of recording on the Inspection Reports.
Traceability of constituent parts is accomplished by means of unique Batch numbers.
7.5.4 Customer Property

The organization receives drawings and samples from the customer and the same are controlled.
7.5.5 Preservation of Products
The products and constituent parts of the products are preserved appropriately to avoid any
damage or deterioration during storage, handling, packaging and delivery.
Suitable work instructions are issued to the personnel carrying-out these activities.
7.6 CONTROL OF MONITORING AND MEASURING DEVICES
The selection of the Instruments and test equipments is done in such a way that measurement
uncertainty is known and is consistent with accuracy required.
To control, calibrate and maintain inspection, measuring and test equipment to provide evidence
of conformity of product to specified requirements the procedure for calibration and
Maintenance of Instrument is followed.
It is also ensured that monitoring and measurements are carried out and in a manner that is
consistent with the monitoring and measurement requirements.
For this purpose, list of measuring and test equipment is prepared.
To ensure valid results, measuring equipment is Calibrated at specified intervals, or prior to use,
against measurement standards traceable to international or national measurement standards;
where no such standard exists, the basis used for calibration or verification is recorded.
ACTIVITY REFERENCE:
PROCEDURE MANUAL – PRODUCTION & QUALITY CONTROL
Title: Measurement Analysis and Section: QM 8.0

Improvement
8.1 GENERAL
The Company plans and implements the monitoring, measurement, analysis and improvement
process as follows:-
 To demonstrate that products produced conform to specification
 To ensure that quality management system requirements are conformed
 To continually improve the effectiveness of quality management system
 In order to measure, analyze and continually improve, methods including statistical

methods are used. The extent of use of statistical method are explained in 8.2.3
8.2 MEASUREMENT AND MONITORING

8.2.1 Customer Satisfaction
In addition to other method, performance of the Quality Management system is also measured by
monitoring the information related to customer perception provided by customers.
8.2.2 Internal Quality Audit

Internal audits are conducted at regular intervals based on a plan. The purpose of such audits is to
ascertain:-
Whether the planned system as outlined in this manual, Activities and other quality system
Documents as defined in 4.2.1 are complied with and whether the documented system is in
accordance with the requirements of ISO 9001:2000 standards.
Whether the implemented system is effective and maintained
An audit program is planned as follows:-
 The frequency and duration of an audit is determined based on the volume of activity,
importance of the activity.
 The area or department to be audited and
 Results of previous audits
8.2.3 Monitoring and Measurement Of Processes

Methods such as graphs, charts, are used to demonstrate that the processes achieve or deviate
from the targets.
When planned results are not achieved, appropriate plans are identified and implemented to
effect correction and corrective actions to ensure conformity of the product.
8.2.4 Monitoring and Measurement of Products

The Company ensures that the products are verified at appropriate stages viz., on receipt, various
production process stages and pre delivery stage. The requirements are verified against the
receiving inspection plan, in-process quality plans and customer purchase order.
Evidence of conformity of the products as defined above is maintained in the form of inspection
reports, test log/test report. These records indicate the persons authorizing product release for the
next stage or delivery to customer.
The deliveries of products are affected only after all quality requirements are completed
satisfactorily.
8.3 CONTROL OF NON-CONFORMING PRODUCT
The Company ensures that products, which do not conform to product requirements, are
Identified and controlled to avoid inadvertent use or delivery. Activity for non-conforming
products describes the controls involved in segregating non-conforming products, quarantine
areas for non-conforming products, the responsibilities and authorities for evaluation,
notification and disposal of non-conforming products.
The methods of dealing with non-conforming products are :-
 Required actions such as rework, to eliminate the detected non-conformity
 By authorizing use non-conforming products, or release for dispatch or accept under

authorized concessions by the authority as defined 5.5.1, or where applicable, by
customer.
 By taking action to scrap after due care that the scrapped products do not find its way to
the original intended use.
8.4 ANALYSIS OF DATA
The Company determines the data to be collected, analyzed to demonstrate suitability and
effectiveness of quality management system and to effect continual improvement.
The various data collected are:
 Measurement data
 Defect data
 Customer feedback data
 Analysis of these data shall provide information on :
 Level of customer satisfaction
 Level of conformity to specification
 Trends of product specification compliance, opportunity for improvement
 Supplier performance
 Tools and techniques such as graphs, charts, brainstorming etc. are used in the analysis of
data
8.5 IMPROVEMENT
8.5.1 Continual Improvement
Continuous improvement in the effectiveness of quality management system is achieved through

the use of :
 Well defined Quality policy

 Measurable quality Objectives
 Audits that identify opportunities for improvement
 Analysis of data of product conformance and operational performance, customer

satisfaction and supplier performance
 Corrective and preventive actions
 Management review
 Improvement opportunities are tracked for effective implementation and achievement of

desired results
8.5.2 Corrective Action

The Company takes appropriate action to eliminate the cause of non-conformities in order to
prevent recurrence. The corrective actions will be appropriate to the effects of non-conformities.
Activity for corrective action ensures the following requirements are defined :-
 The methods followed to review non-conformities and customer complaints
 The determination of cause of non-conformities
 Develop solutions that are needed to eliminate the recurrence of non-conformity
8.5.3 Preventive Action
The Company takes appropriate action to eliminate the potential cause of non-conformities in
order to prevent occurrence. The preventive actions will be appropriate to the effects of non-
conformities.
Activities for preventive action ensures the following requirements are defined :-
 The determination of potential cause of non-conformities
 Recommend actions that are needed to prevent occurrence of non-conformity
 Implement the actions identified to prevent occurrence of nonconformity
 Records of the results of action taken
 Reviewing the preventive actions taken

ACTIVITY REFERENCE:
PROCEDURE MANUAL – QUALITY CONTROL & INSPECTION
PROCEDURE MANUAL – MANAGEMENT REPRESENTATIVE
Sampling and Testing of packing materials
1.0 OBJECTIVE : To lay down a procedure for sampling and testing of packing materials.
2.0 RESPONSIBILTY
Microbiologist / Q.C Executive
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 Collect the intact packs of Bottles / ROPP caps / Inner caps or any other primary packing
materials (Annexure-1) from the consignment and transfer to Microbiology laboratory. Carry out
sampling under laminar air flow in MLT area. Seal the containers properly and send it back to
warehouse.
4.2 Prepare 3x100ml of 0.9% of NaCl solution and sterilize by autoclaving ,for sample of each
consignment of packaging material (for small items like caps ,rubber stoppers used for oral
packaging material etc) .
4.3 Open the sample under LAF and submerge 20units in the prepared solution and swirl it for 10
min.
4.4 Transfer the solution in sterile filtration unit & filter the solution with 0.45mm filter membrane of
100ml each.
4.5 Then transfer the filter membrane in sterile SCD agar plate and incubate at 35°C for 72 hrs
,for bacteria,
SDA agar plate, for fungi, and incubate at 20-25°C for 120 hrs and note the observations, for
pathogens submerge the filter membrane in 100ml of sterile SCD Medium and proceed for the
testing of pathogens as per SOP
Formula : No. of cfu in each unit=Number of cfu observed on filter membrane / 6 (unit)
Limit: Bacteria NMT 5 cfu / unit, Fungi NMT 1 cfu / unit and pathogens nil / unit.
4.6 For vials and bottles used for oral packaging material pour 5 ml of sterile solution into
each of the 15 containers with the help of sterile pipette and thoroughly wet the inner walls and
filter the solution in sterile 0.45mm filter membrane.
4.7 Then pour rinsed solution from 5 vials in each three sterile 0.45mm membrane filter assembly
and filter the solution.
4.8 Then transfer the filter membrane in sterile SCD agar plate and incubate at 35°C for 72 hrs ,
(for total bacterial count), SDA agar plate, (for total fungal count) , and incubate at 20-25°C for
72 hrs and note the observations ,for pathogens submerge the filter membrane in 100ml of
sterile SCD Medium and proceed for the testing of pathogens as per G.P No.-
Formula : No. of cfu in each unit =Number of cfu observed on filter membrane / 5 (unit)
4.9 For pathogen testing test for S aureus , Pseudomonas , E. coli and Salmonella as per SOP
No. K/QC/059.
4.10 Limit (for oral packing materials: for bottles or vials): For bacteria: 100 cfu / unit , For
fungi: 10 cfu / unit., pathogens: Nil / unit
4.11 Limit (for injectable packing materials, Like vials, rubber-stoppers etc ): For
bacteria.
NMT 10 cfu / unit , For fungi. <1 cfu / unit , pathogens: Nil / unit
4.11 Foils( Aluminum, PVC / PVDC Films)- Cut (three replicates) inner 20 x 20 cm with sterile
tools and use contact plate (RODAC plate) for sampling
Formula :No. of cfu in 100cm2 =Sum of the number of cfu observed on three RODAC
plates/ 3x 19
Limit: 50 cfu / 100cm2 (for bacteria).
5 cfu / 100cm2 (for fungi). And nil pathogen.
4.12 Note the observations in the format given in annexure-II.
5.0 ABBREVIATIONS :
cfu – Colony forming unit
°C – Degree centigrade
6.0 ANNEXURES : Annexure – Iand II
ANNEXURE – 1
Rubber plugs, Caps – 20 Nos.
Up to 20ml Bottle- 15 Nos.
30 , 50 , 60 & 100 ml Bottle – 12 Nos.
125 ml Bottle – 9 Nos.
170 , 250 , 375 ml Bottle – 6 Nos.
Vials – 20 Nos.
Frequency of testing – For every export batches OR as per requirement.
ANNEXURE –II
FORMAT FOR TESTING OF PACKAGING MATERIALS

SAMPLE CONSIGNMENT No./DATE
SAMPLE TY./AREA SAMPLED BY
MEDIA PREPERATIONS:
MEDIA NAME MEDIA BATCH NO. STERILI. CYCLE MEDIA LOT PREPAR
NO.
0.1%Buffered NaCl- soln.
Soyabean Casein Digest Agar
Sabouraud Dextrose Agar
Medium used for submerging the sample: 0.9%Buffered NaCl- solution.
TOTAL AEROBIC MICROBIAL COUNT:
LIMIT : Bacteria: Cfu per Bottle Fung Cfu per Bottle

TEST MEDIUM PLATES: For Bacteria For Fungi
No. of plates used : 1 1
Medium used : SCDA SDA
Observation Of Microbial Count
Days ¯ SCDA( for bacteria at 30-35°C) SDA( for fungi at 20-25°C)
Dil. ® +ve -ve Cfu / plate +ve -ve control Cfu / plate
control control control
Ist day
2nd day
3rd day
4th day
5th day
Calculation:
(B) TEST FOR PATHOGEN
MEDIA PREPERATIONS:
MEDIA NAME MEDIA BATCH STERILIZATION CYCLE MEDIA PREPARED ON

NO. LOT NO.
Cetrimide broth Media
Mac koncy broth
Tetrathionate broth Preparation of media by boiling
MEDIA NAME MEDIA B. NO. STERILIZATION CYCLE MEDIA PREPARED ON

LOT NO.
Cetrimide agar
Brilliant Green Agar
Xylose Lysine Deoxy. agar
Mac koncy Agar
LIMIT – Must be absent
Organism to be Primary test Secondary test Inference

tested
S.aureus
Pseudomonas
E. coli
Salmonella
TBC= cfu/unit , TFC= cfu/unit , Pathogens =
INFERENCE: The above sample complies / does not complies the test.
 Sampling, testing and release of raw materials

 Dispensing of packing materials
 Re-testing of raw materials and intermediates
 SAMPLING OF PACKAGING MATERIALS
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Operation of colony counter
1.0 OBJECTIVE : To lay down a procedure for operation of colony counter.

2.0 RESPONSIBILTY
Microbiologist / Executive
3.0 ACCOUNTABILITY
Head - Quality Control
4.0 PROCEDURE
4.1 Ensure that the instrument is clean & free from dust.
4.2 Ensure that the magnifying lens is fixed on its stand.
4.3 Ensure that the marker is connected to either right or left side of the instrument.
4.4 Switch on the mains.
4.5 Switch on the power button. The internal light will be flashed ‘ON’ and the digital screen will
show ‘0000’ figure in red. Again pressing this button will turn the power.’ OFF’.
4.6 Now press the plate containing colonies to be counted.
4.7 Now, mark each and every colony one after the other by pressing the tip of the marker.
4.8 The number of colonies will automatically get displayed on the screen can be reset to 0000 by
pressing the RESET button.
4.9 The counting can be done manually by pressing the MANUAL button.
4.10 Switch ‘OFF’ the instrument and put under cover when not required.
Harmonization of format.
6.0 TRAINING:
Period - One day

7.0 DISTRIBUTION:
Certified Copy No. 2 : For Display Near The Colony Counter
 Operation of compound microscope

 Sampling and Testing of packing materials
 Preparation of Microbial Plates
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Operation of compound microscope
1.0 OBJECTIVE : To lay down a procedure for operation of compound microscope.
2.0 RESPONSIBILTY
Microbiologist / Executive
3.0 ACCOUNTABILITY
Head – Quality Control
4.0 PROCEDURE
4.1 Keep the microscope on the clean and stable platform.
4.2 Switch on the main switch of microscope so that bulb will glow.
4.3 Adjust the low power objective, by rotating the revolving nose piece in position.
4.4 Adjust the focus of light with the help of condenser.

4.5 Now place the objective ( high power / oil immersion whichever is required) in position by
moving the resolving nose piece.
4.6 Place the slides on the stage, set the objective at the closest position w.r.t slide then slowly lift
the objective with coarse adjusting screw, while observing through the eye piece, till the field
appears clearly ( if the oil immersion objective is in use, place on drop of immersion oil on the
slide before placing it on the stage and then lower the objective just to touch the oil drop.
4.7 Make the field clearer with the help of fine adjustment and then observe the slide.
4.8 Slide can be moved in left, upper and lower direction to observe the complete smear area with
help of slide stage screw and coarse adjustment.
4.9 After completion of observation, remove the slide, clean the objective lens and condenser with
cotton soaked in xylene. Bring the 10x objective in the active position. Lower down the
condenser and place low power objective in position.
4.10 Do not allow the oil to harden on the lens.

6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : For Display Near The Microscope
 Operation of colony counter

 Sampling and Testing of packing materials
Out of specification (OOS) result in Microbiological Analysis
1.0 OBJECTIVE: To lay down a procedure for handling of out of specification (OOS) result in
Microbiological analysis and monitoring.
2.0 RESPONSIBILITY
Quality Control Executive/ Microbiologist
3.0 ACCOUNTABILITY
4.0 PROCEDURE
In all the reports the identified reason shall be written on a continuation sheet to the annexure
provided. A copy of the above investigation report shall be maintained with the batch
manufacturing records concerned to increase awareness and for any future reference
4.1 STERILITY TEST
4.1.1 If evidence of microbial growth is found, the product to be examined does not comply with
thetest for sterility, unless it can be clearly demonstrated that the test was invalid for causes
unrelated to the product to be examined .The test may be considered invalid only when one or
more of the following conditions are fulfilled:
4.1.1.1The data of the microbiological monitoring of the sterility testing facility shows fault;
4.1.1.2 A review of the testing procedure used during the test in question reveals a fault;
4.1.1.3 Microbial growth is found in the negative controls;
4.1.1.4 After determination of the identity of the microorganisms isolated from the test, the
growth of this species or these species may be ascribed unequivocally to faults with respect to
the material and / or the technique used in conducting the sterility test procedure.
4.1.2 If the test is declared to be invalid it is repeated with the same number of units as in the original
test.
4.1.3 If no evidence of microbial growth is found in the repeat test the product examined complies with
the test for sterility. If microbial growth is found in the repeat test the product examined does not
comply with the test for sterility.
4.2 ENVIRONMENTAL MONITORING
4.2.1 If the microbial counts are found to be more than or equal to the alert limit then
open a deviation report (annexure I) through Q.C. Head to the concerned Production head.
Production personnel shall check the working discipline, supply of air, safety measures etc.
4.2.2 If the count exceeds or reaches the action limit then the urgent notification to the Production
head and Engineering Head through Q.C. Head shall be followed by an investigation for the
same. –
- Supply of air
- Working discipline
- Review of data from the same place and others from the incubated plates
- If any of the plates does not indicate the same then no action is necessary.
- If any of the plates indicates more count then perform additional cleaning, disinfection or
fumigation and retraining to the operator shall be given.
- All activities shall be recorded as per the annexure attached with this SOP.
- More number of samplings (i.e. double the original) shall be preformed at the same location
where the counts observed were beyond or equivalent to the action limit but an additional
relevant parameter of monitoring shall also be performed which shall be incorporated with the
same annexure.
- All the batches manufactured during the said period shall be subjected to the microbial
analysis for MLT / Sterility &BET in order to ensure that the batches manufactured are in
accordance with the relevant finished product specifications. The investigation report shall be
submitted to the Q.C. - Head
4.2.3 If the bio-burden is found out of specified limit in the core areas the identification of the
organism shall be performed.
4.2.4 Stop the production immediately and check all the possible parameters, which can affect bio-
burden of the area.
4.2.5 Check the pressure differential of the area, which must be within the specified limit.
4.2.6 Check the air velocity of LAF /HEPA filters, which must be within the specified limit.
4.3 If the investigation / review of manufacturing activities (e.g. sterilization process, aseptic
filtration, environmental conditions, personnel practices) indicates failure of manufacturing
activities, then the batch shall be considered as failed to comply sterility.
4.4 MICROBIOLOGICAL AND BET EXAMINATION OF WATER
If only the alert is exceeded without finding an undesirable microorganism the release of the
preparation for which this water has been used, has to be taken under hold till the result comes.
In case of the counts touching the action limit then all the batches manufactured shall be re
analyzed by taking 25 grams and making the allowance for the larger size specimen for the
analysis.
In the case of counts crossing or touching the alert limit or action limit in any type of water the
same will be intimated to the production department and maintenance department. If the result
cannot be attributed to the analytical error, sampling error, contamination in the container
sampled then the microorganism detected must be identified / differentiated by taking sample
from all other points.
4.4.1 Adequate sanitization of the system shall be ensured to eliminate the source of contamination
with a rigorous check for the same.
4.4.2 All the investigations made shall be recorded in the annexure III provided with this SOP.
4.5 MICROBIOLOGICAL EXAMINATION OF RAW MATERIAL / FINISHED PRODUCT
4.5.1 The first action is to intimate the Q.C. Head.
4.5.2 Retest the same material/product but with a sample size of 25 grams by making allowance for
the larger size specimen.
4.5.3 Results for the same shall be intimated to the Q.A. Head for final decision.

6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
ANNEXURE –I
FORMAT FORDEVIATION REPORT TO PRODUCTION DEPARTMENT
(Deviation Report About the environmental monitoring)

Revision No. : 00
Effective Date:
Sampling point where deviation occurred: Date:
Name of the Product Batch no.:
Deviation : Parameter:
Requirement :
Results : Signature :
Corrective action in Production Department:
Cleaning, Disinfection, Change of disinfectant, Checking of LAF unit parameters
Checking of HVAC system, Education to Operators, Repair/Maintenance Work (Cross
whichever is not applicable and specify actions taken).
Maintenance Repair / Comments :

………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
……………………………………………………………..
Name : Signature :
Date:
Repeated Sampling :
Parameter:
Result:
Comments by Q.C. Head for Approval of Production :

………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………………………………………………………
………………………………………………………………
Signature :
ANNEXURE - II
Format for Corrective Report After Sampling of Environmental Parameters in Production

Revision No. : 00
Effective Date:
Date : Deviation :
Date of repeated deviation :
Corrective Measures in Microbiological Lab
Checking of condition s of LAF unit during working , Checking of equipment
Growth promotion test for the media used.
Done By : Checked
By :
Results of Microbiological Impurity of Finished Product :
Comments of Quality of Quality of Control - Head :
Comments of Quality Assurance - Head :
ANNEXURE –III
INVESTIGATION REPORT FOR FAILURE IN TEST FOR BACTERIAL ENDOTOXIN & M.L.T
Revision No. : 00
Effective Date:
Sample
Analyzed on Analysed By Checked By

Preparation parameters for
Sampling container Procedure of sampling GP test of media
Any testing error
BET
Micro tips Test tubes Pipette
LAL reagent
Batch No. Mfg. Expiry Reconstituted

on
.LAL Reagent water
Batch No. Expiry Blank
Parameters of depyrogenation/sterilization apparatus:
Validation Status Calibration Status
Results of other samples with same conditions tested on the same day.
Details of Raw material used in finished product
Result
Test repeated
Date Result
Microbiologist
ACTION TAKEN :
Production Head Engineering Head Quality

Control Head
CONCLUSION
(Results of MLT for Other Samples to be enclosed)

Microbiologist QC
Manager
Date: Date:
Remarks from Q.C. Head

Name: Sign Date :

 Out of Specification Procedure
 Reprocessing of Out of Specification Batch
 OUT OF SPECIFICATION INVESTIGATION FORM
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Media Fill operation in the sterile dry powder filling
1.0 OBJECTIVE: To lay down a procedure for Media Fill operation in the sterile dry powder Filling
facility..
2.0 RESPONSIBILTY
Microbiologist, Operator concerned/Production officer/QA Officer
3.0 ACCOUNTABILITY
Quality Control Manager/ Production Manager
4.0 PROCEDURE
PRE-START UP:
4.0 Ensure that all the equipments, HVAC system, water system and other utility services of the
facility are validated.
4.1 Ensure that the Gamma irradiation certification report of the lactose + SCDM (Soyabean
Casein Digest) mixture (3:1) from BARC and sterility test report (done in-house) is available.
4.2 Ensure that solubility test report and growth promotion/inhibition test report of sterile
lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.3 Ensure that solubility test report and growth promotion/inhibition test report of sterile
lactose+SCDM mixture is available. [Solubility should be NLT 1gm/10 ml of WFI].
4.4 Ensure that freshly distilled WFI to be used for filling, is autoclaved and the sample given for
sterility test.
4.5 Ensure that all the contact parts of Dry Powder Filling machine are duly cleaned and
sterilized or sanitized.
4.6 Ensure that the last Environmental Control Reports of the area are conforming to the
acceptance standard.
4.7 Ensure that the Liquid Filling machine is done inside the sterile filling area on the previous day
after autoclaving /sanitization.
4.8 Ensure by manometer readings, that the pressure balancing of the sterile area is as per
requirement.
4.9 Ensure that the cleaning, sanitization and fumigation of the area is done on the previous day.
START UP
4.9 Enter the sterile area as per SOP using gowns sterilized 4days back.
4.10 Check the cleanliness of the sterile area.
4.11 Check the cleanliness of the Liquid Filling machine.
4.12 Check and confirm the temperature and RH of liquid filling room is as per the requirement.
4.13 Assemble the Liquid Filling machine.Ensure that that filling of liquid and liquid can be done
simultaneously.
4.14 Measure the nonviable particulate count of filling cabinet and filling room.
OPERATION
4.15 Bring the autoclaved WFI container near the liquid filling assembly.
4.16 Transfer sterile SCDM liquid from the container in to liquid hopper.
4.17 Transfer sterile dried rubber stoppers (sterilized 4 days back) in to the hopper of stoppering unit.
Send sample for sterility testing simultaneously.
4.18 Put the inlet suction tube of Liquid Filling Assembly into the WFI container.
4.19 Set the Liquid Filling machine for the respective dose.
4.20 Remove the Liquid Filling Assembly and all the contact parts. Disinfect it, clean it and get it
sterilized/sanitised.
4.21 Ensure that all the left over rubber stoppers are given outside the sterile area for destruction.
4.22 Shut down the vial liquid-filling machine as per SOP
CLEANING:
4.23 Ensure that all the tools and accessories containers etc. used during media fill are given for
cleaning/sanitization/sterilization.
4.24 Follow the cleaning and sanitization SOP for cleaning of sterile area.
4.25 Do the extra cleaning and sanitization of the floor/walls/machine after media fillrun with 10%
Bacillocide and Lysol solution
ACCEPTANCE CRITERIA:
4.26 Initial validation: During initial validation, it should qualify all three consecutive media fill run i.e.
during each run there should not be growth in more than two vials.
4.27 Revalidation: Only one media fill run in which there should not be any growth in more than two
vials.
ELIGIBILITY CRITERIA FOR PERSONNEL PERFORMING MEDIA FILL RUN :
4.28 Persons involved in media fill should be medically examined and declared fit within last one year.
4.29 Persons should be trained on general hygiene and current gowning procedure, and the present
health condition should be O.K.
4.30 The personnel should be microbiologically monitored during run.
NOTES
In case of any positive growth in any vial during the incubation period.\
4.31 It should be isolated and identified to the genus level.
4.32 If the isolated organism is other than the house flora, thorough investigation shall be carried out
by Quality Assurance and Production.
4.33 The source of the contamination must be established.
In case of any failure in media fill run:
4.34 When there is no assignable cause, media fill shall be repeated three times and production
should commence only after all the three runs meet the acceptance criteria.
4.35 When there is assignable cause, after rectification of the cause, repeat the media fill run
once.
4.36 Before and during media fill run no special cleaning shall be carried out.
4.37 Normal production can resume only after minimum one day of environmental monitoring
compliance report.
4.38 Batches filled before the final result of the media fill run shall not be released to the market till the
media fill run passes in case of initial validation.
4.39 The routine environmental monitoring plates shall be kept for 14 days (in case of any growth) to
help in investigation of any positive growth in the media filled vials.
4.40 If for any reason the media fill run is considered invalid vials shall not be incubated.
4.41 Media fill runs can be aborted for the same reason that a product lot would be aborted. All
media filled units filled before an incident that would cause an aborted fill must be incubated.
4.42 During media fill all the Operators, Officers& Maintenance staff who are authorized to do the
sterile filling, supervision and maintenance must be involved in media fill trial.
4.43 The volume of liquid filled must be sufficient to wet all surfaces including the closure and
to facilitate inspection.
4.44 The line must be run at a slower speed than normal production run to give greater
exposure time.
4.45 Total duration of the routine media fill must be the same or more as the longest process
conducted on that line.
4.45 The incubation temperature of the filled containers must be sufficient to promote
microbial growth at 30-35oC. for 336hrs(stored upright) followed by 20-25oC. for 336 hrs.
(stored upside down).
4.47 Personnel that conduct the inspection of incubated media fills must have training on
basic microbiological concepts ,concepts of media fill and examples of contaminated container
showing various stages of growth.
POST MEDIA FILL RUN :
4.48 Filled incubated vials should be optically checked by microbiologist and certified.
4.49 Incubate the vial samples with no growth approximate 5 vials for 14 days with normal house flora
and 5 vials with organisms used for the sterility test growth promotion for 14 days.
4.5 Temp. range for incubation 1st two week at30 to 35o C. (vials stored upright).
4.51 Next two week at 20 to 25o C. (vials stored upside down).
4.52 These vials should show promotion of growth.
ANNEXURE - I
LIST OF PERMITTED INTERVENTIONS DURING FILLING
These are the activities which are performed during normal working in the sterile filling area:
1) Adjustment of weight in the dosing wheel.
2) Adjustment of Stopper holding spring.
3) Transfer of liquid from container to hopper.

4) Transfer of stoppers from bag to hopper.
5) Picking unstoppered vials from the outfeed back to conveyor for stoppering.
6) Adjustment of separator.
7) Picking up of fallen vials from turn table.
8) Cleaning of machine with vacuum cleaner.
9) Adjustment of stoppering channel height.
10) Adjustment of stoppering pressure rollers.
11) Replacing of a piston from the wheel.
12) Adjustment of turn table over load sensor.
13) Lifting and closing of the LAF cabinet door.
14) Checking the weight in balance.
15) Adjustment of dosing air.
16) Cleaning of vacuum pot.
17) Pushing stopper in the channel by forceps.
18) Power interruption (samples should be marked)
19) Number of personnel in sterile filling area (8 persons).
20) Multiple dosing of the liquid.
21) Running the machine at a slower speed than actual production run.
22) Covering the working shift usually 12 hours and shift Change over
23) Entry of maintenance person for repairing of M/C
ANNEXURE - III
ACCEPTANCE CRITERIA FOR MEDIA FILL SIMULATION
MAXIMUM
NO.OF
PERCENTAGE BATCH SIZES
REJECTED
OF FAILURE
VIALS
ACCEPTABLE
AT 95%
CONFIDENCE
LEVEL
5000 10000 20000 50000 100000 INFINITY
2469 2668 2808 2912 2951 2995
3676 4047 4339 4575 4670 4747
4684 5207 5670 6044 6207 6294*
24698 26686 29944
46093 47047 47047
62911 62911
* Normal media fill run size

 Operation of colony counter
 Operation of compound microscope
 Out of specification (OOS) result in Microbiological Analysis
Disposing of microbiological culture media
1.0 OBJECTIVE : To lay down a procedure for disposing of microbiological culture media.
2.0 RESPONSIBILTY
Microbiologist /Q. C Executive
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 INTRODUCTION:
4.1.1 Bacteriological culture media contains all the nutritive sources which favors rapid growth of
different types of Micro-organisms. Some selective media’s are used for cultivating specific type
of Pathogenic organisms. The micro-organisms grown either on enriched or selective
media’s if not disposed or destroyed in proper way can cause contamination of the
environment which in turns is very hazardous.
4.2 METHOD:
4.2.1 Collect all the used semi solid media’s in plastic bag containing about 50 ml of 2.5% Savlon
solution and close the opening tightly with a tag or rubber-band and transfer the it to the
incinerator.
4.2.2 For liquid media add 2.5% disinfectant (savlon), to the liquid media ,mix it well ,hold for half an
hour and then discard them in a stream of running tap water.
4.2.3 The plates & test tubes are then thoroughly washed with soap water and sterilized by
autoclaving.
4.3 PROCEDURE FOR CLEANING OF GLASS-WARES
4.3.1 INTRODUCTION
Proper cleaning of glassware’s used in microbiology laboratory is very important in

microbiological work. If the equipments used in microbiology are not cleaned properly, due to
contamination, the microbiological results may get affected; also it can cause danger to the
persons handling the equipment and risk of infection due to potential hazards of pathogenic
cultures.
GMP require the standard procedure for glassware cleaning used in microbiological
work. This procedure provides Guidelines for proper cleaning of glassware in micro
section.
4.3.2 METHOD FOR CLEANING
4.3.2.1Keep all the glassware’s used in microbiology in the cupboard of the tables used by the
Microbiologists to work.
4.3.2.2Do not use these glass wares in chemical
testing.
4.3.2.3Rinse all the glass wares with tap water two to three times.
4.3.2.4Dip all the glass wares in 2% v/v solution (prepared in D.M water)of teepol or liquid soap for at
least 4 hours, for depyrogenation dip it into 2.5% NaOH solution.
4.3.2.5Remove the glass wares from the solution.
4.3.2.6Rinse twice with D.M water followed by rinsing once with W.F.I
4.4 ABBREVIATIONS
W.F.I= Water For Injection, NaOH= Sodium hydroxide, %=Percentage, v/v =Volume by volume
D.M water= De mineralized water
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
 CULTURE MEDIA PREPARATION FOR MICROBIAL TEST

 Out of specification (OOS) result in Microbiological Analysis
 Media Fill operation in the sterile dry powder filling
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Wednesday, December 15, 2010

Preparation of Microbial Plates
1.0 OBJECTIVE: The objective of this SOP is: to lay down a procedure for preparation of plates
that can be used as settling plates and in various microbiological analysis.
2.0 RESPONSIBILITY
The Microbiologist shall be responsible for preparation of settle plates, their pre-incubation and
related documentation.
3.0 ACCOUNTABILITY:
Executive - Quality Control
4.0 PROCEDURE:
4.1 Media with the content of agar can be used for the preparation of settle plates like.
i) Soyabean Casein Digest Agar (SCDA) - For enumerating Bacteria and Fungi (required for
Environmental monitoring and Microbial limit tests.)
ii) Sabarauds Dextrose Agar (SDA) – For estimation of fungi.( Required for Microbial limit
tests. )
4.2 Prepare media as per SOP.
4.3 Follow the gowning procedure and enter the M.L.T Room by following SOP.
4.4 Clean the LAF with 70% I.P.A and wait till drying.
4.5 Switch on LAF and UV lamp 15 min. before pouring the plates.
4.6 Open the containers containing sterile petri-dishes (That are previously sterilized by
Autoclaving) and place on the working surface table of L.A.F.
4.7 Open the containers containing sterile petri-dishes and place them on the working table of
LAF.
4.8 Take out the cotton plug of conical flask containing agar medium.
4.9 Sterilize the mouth of the conical flask by flaming it and start pouring about 20-25 ml of
medium to each petri-dish quickly .
4.10 Cover the plates and keep under LAF, till they are solidified.
4.11 After getting solidified, preincubate the plates to the incubator at 30-35°C for 48 hrs to check
any accidental contamination.
4.12 Check each and every plate under colony counter before exposure to the environment for
monitoring.
4.13 Record the activity in Media preparation record.
5.0 TRAINING :
Trainer -- Executive – Quality Assurance
Trainees -- Microbiologists
Period -- One day
6.0 DISTRIBUTION:
Certified Copy No. 2 : Microbiology Department
Available Guidance and Best Practices for Conducting Forced Degradation

Studies
Forced degradation or stress testing is undertaken to demonstrate specificity when
developing stability-indicating methods, particularly when little information is available
about potential degradation products. These studies also provide information about the
degradation pathways and degradation products that could form during storage. Forced
degradation studies may help facilitate pharmaceutical development as well in areas
such as formulation development, manufacturing, and packaging, in which knowledge of
chemical behavior can be used to improve a drug product.
The available regulatory guidance provides useful definitions and general comments
about degradation studies. However, guidance concerning the scope, timing, and best
practices for degradation studies is very general. Various issues related to stress testing
are addressed in numerous guidance documents but not always in the context of stress
testing. For example, the available guidance discusses issues such as stereo chemical
stability, degradation product identification thresholds, polymorphism and crystal forms,
stability of (parenteral) combination products, and mass balance but does not address
these issues in the context of degradation studies.
The FDA and International Conference on Harmonization (ICH) guidance provides very
little information about strategies and principles for conducting forced degradation
studies, including problems of poorly soluble drugs and exceptionally stable
compounds. In particular, the issue of how much stress is adequate in stress testing is
not addressed specifically. Overstressing a molecule can lead to degradation profiles
that are not representative of real storage conditions and perhaps not relevant to
method development. Therefore, stress-testing conditions should be realistic and not
excessive. In this regard, it is the amount of stress that is important and not necessarily
the extent of degradation. Indeed, some compounds may not degrade significantly after
considerable exposure to stress conditions. Also somewhat unclear is what should be
done at each development phase from both a regulatory and a scientific perspective.
Although FDA does not require degradation studies for an investigational new drug
(IND) application, prelimi-nary degradation studies are useful for the development of the
stability-indicating methods that will be used during the clinical trials.
This article provides a practical interpretation and summary of the available guidance
and some suggestions for best practices for conducting forced degradation studies.
Overview of regulatory guidance

According to the available guidance, forced degradation studies are carried out for the
following reasons:
● Development and validation of stability-indicating methodology
● Determination of degradation pathways of drug substances and drug products
● Discernment of degradation products in formulations that are related to drug
substances versus those that are related to non–drug substances (e.g., excipients)
● Structure elucidation of degradation products
● Determination of the intrinsic stability of a drug substance molecule Degradation
studies have several defining characteristics. They are carried out in solution and/or the
solid state
● Involve conditions more severe than accelerated testing (e.g., _40 0C; 75% relative
humidity; in excess of ICH light conditions; high and low pH, oxidation, etc.)
● Are typically carried out on one batch of material
● Include conditions that analyze thermolytic, hydrolytic, oxidative, and photolytic
degradation mechanisms in the drug substance and drug product (as appropriate)
● are not part of the formal stability program.
Summary of requirements at the IND phase

Although the reporting of degradation studies is not required in IND applications,
preliminary studies may be carried out to facilitate the development of stability-indicating
methodology. Studies can be conducted on the drug substance and developmental
formulations to test for degradation by thermolysis, hydrolysis, oxidation, and photolysis
or to evaluate the potential chemical behavior of the active ingredient.
A draft guidance document suggests that results of one-time stress studies should be
included in Phase 3 applications for INDs.
Summary of requirements for marketing application

Completed studies of the degradation of the drug substance and drug product are
required at the new drug application (NDA) stage, including isolation and/or
characterization of significant degradation products and a full written account of the
degradation studies performed.
Drug substance-For degradation studies of a drug substance, FDA requests the

following at the time of registration:
● stressing the drug substance in solution or suspension at acidic and alkaline pH and
under oxidation conditions
● stressing the solid bulk drug substance at temperature and temperature–humidity
conditions in excess of accelerated conditions
● stressing the drug substance photolytically in the solid state and/or in solution in
excess of ICH conditions
● demonstration of the specificity of stability-indicating methods with forced-degraded
samples or with the drug substance spiked with appropriate markers
● isolation and/or full characterization (by means of NMR, mass spectrometry [MS], UV
analysis, etc.) of all significant degradation products if possible. Procedures for the
preparation and/or isolation (where applicable) and structure determination of the
degradation products should be reported. Unsuccessful attempts to identify significant
degradation products should also be documented
● the chemical and physical properties of degradation products, if available
● The mechanism and kinetics of formation of each degradation product, if available.
The guidance says to determine reaction kinetics “if practicable,” thereby
acknowledging the difficulty in cases in which the mechanism may be complex (e.g.,
autoxidation).
Other issues that may be investigated but are not explicitly requested for degradation
studies are the physical and chemical stability of important crystal forms, mass balance,
and the formation of stereoisomers.
Drug product-The guidance specifies the following for degradation studies of the drug
product at the time of registration:
● challenge methods intended for monitoring the stability of the drug product with the
degraded samples or with the drug substance spiked with a mixture of known
degradation products
● isolation and characterization of significant degradation products, if possible. The
identity and chemical structure, procedure for isolation and purification, mechanism of
formation (including order of reaction), and chemical and physical
properties should be reported, if available. These degradation products include any drug
substance–related compounds such as drug substance degradation products, drug
substance–excipient degradation products, drug substance– extractive degradation
products, and so forth.
● distinction between degradation products that are related to drug substances and
those related to non–drug substances
● photolysis of the drug product in excess of ICH light conditions
Information requested in the submission. The available guidance explicitly requests

the following in the NDA documentation:
● for degradation products: identity and structure; procedure for isolation (where
applicable) and characterization; mechanism of formation, including order of reaction;
and physical and chemical properties
● information about stress testing of the drug substance and drug product (the guidance
does not state specifically what information is required).
At the time of this writing (May 2001), more-specific guidance for the reporting of stress
testing was found in FDA draft guidance documents dealing with stability and method
validation. According to these documents, the applicant should provide
● degradation pathways of the drug substance, alone and in the drug product
● a discussion of the possible formation of polymorphic and enantiomeric substances;
the possible formation of any stereoisomer’s is implied
● data showing that neither the freshly prepared nor the degraded placebo interferes
with the quantitation of the active ingredient
● data from stress studies of the drug substance and drug product demonstrating the
specificity of the assay and analytical procedures for degradation products. These data
may take the form of representative instrument output (e.g., chromatograms) and/or
degradation information obtained from stress studies (e.g., results of peak purity
experiments performed on degraded samples).
Experimental approach
The experimental protocol for degradation studies of new drug substances and drug
products ideally will result in samples that either have been degraded 10% or have been
exposed to an amount of energy that slightly exceeds that supplied under accelerated
storage conditions (e.g., 400C for 6 months).
Forced degradation studies should be conducted whenever a stability-indicating method
is required. Studies may need to be repeated as methods, processes, or formulations
change. Alternatively, methods can be developed with a mixture of the known
degradation products, if available. Forced degradation studies should be performed on
each unique formulation before formal stability studies begin.
Table I shows a general outline for degradation studies of new drug substances and
drug products that was endorsed at the workshop. Sufficient exposure of a drug
substance or drug product is achieved when the drug substance has degraded 10%
from its initial amount or after an exposure in excess of the energy provided by
accelerated storage (e.g., 400C for 6 months), whichever comes first. Application of this
rule of thumb may result in no degradation in some cases. The goal is to generate
degradation in profile that mimics what would be observed in formal stability studies
under ICH conditions.
The duration of storage required at a given temperature can be estimated by making
conservative kinetic assumptions. The energy of activation, Ea, represents the
quantitative relationship between reaction rate and temperature. The range of activation
energies for most drug substances is 12–24 kcal/mole with an average of about 19–20
kcal/mole.
Assuming activation energy of 12 kcal/ mole affords nearly a doubling of the reaction
rate for every 100C increase in temperature. (Recognize that this is a conservative
estimate and that activation energy of 20 kcal/mole affords about a 2.5- to 3-fold
increase in reaction rate for every 10 0C increase in temperature.) With this relationship,
one can calculate the amount of time a sample should be stored at a specified
temperature to achieve the energy equivalent of exposure at accelerated stability
conditions (e.g., 400C for 6 months). A sample of bulk drug substance stored at 80 0C
would be stored for 12 days. Thus, for a compound that degrades with Ea -12
kcal/mole, storage at 800C for 12 days is kinetically equivalent to storage at 40 _C for 6
months.
Suggested equipment and exposure levels for photo stability stress testing are
described in ICH and FDA guidance. Light storage should be in sufficient excess of ICH
light conditions. The guidance states that solution-phase degradation studies of a drug
substance can be carried out in solution or in suspension. The use of inert organic
cosolvents may be indicated in cases in which drug substances are extremely insoluble
but recognize the potential of any organic co solvent to react with the drug substance
under a given set of stress conditions.
For drug products, non–drug substance related peaks should be distinguished from
drug substance related compounds. This process can be accomplished through
comparative analysis of stressed samples of drug substance alone, of drug substance
plus excipients, and of excipients alone. Stressing drug substance and/or excipient
blends instead of final dosage forms may be adequate for the determination of
degradation pathways of a drug product. However, there may be significant differences
in degradation profiles observed between blends and actual drug products.
Consideration also should be given to the possibility of a reaction between the drug
substance and components of a film-coating or capsule shell. For combination
parenteral or aerosol products, the guidance recommends an investigation of the
chemical compatibility or stability of multiple actives that will be combined before
administration. By extension, any combination product should be stressed to examine
for drug–drug interactions potentially manifested by accelerated degradation and/or new
degradation pathways and products. Early investigation can facilitate development of an
optimum formulation as well as stability-indicating methodology. Consideration may be
given to stereochemical stability, mass balance, and crystal-form stability.
Stereoisomers should be treated like any other potential degradation product. Failure to
observe an increase in stereoisomers during forced degradation studies may be
sufficient justification to eliminate testing for stereoisomers during stability studies.
Investigation of the mass balance in degraded samples can reveal the adequacy of the
analytical methods to examine for degradation products. Assessing mass balance is the
process of adding the assay value and levels of degradation products to see how
closely these add to 100% of the initial value, with due consideration of the margin of
analytical error. In cases in which substantial mass loss is observed, efforts to account
for the missing mass should be made such as consideration of response factors or the
formation of highly retained or volatile degradation products. FDA recognizes that mass
balance may not be obtained in all cases and instead emphasizes the thoroughness of
the investigation to determine the specificity of the assay and the pathways of
degradation. The chemical and physical stability of crystal forms, if relevant, should be
investigated. This analysis could include evaluation of stressed solid-state samples for
changes in crystallinity or crystal form.
Method specificity for the active ingredient can be established by peak purity
experiments using hyphenated techniques such as liquid chromatography (LC)–MS,
LC–UV (photodiode array detection), and LC–NMR or orthogonal methods. If needed,
degradation product structure elucidation can be accomplished with hyphenated
techniques (e.g., LC–MS, LC–UV, and LC–NMR) or by synthesis and/or isolation.
Structure elucidation may be postponed until the drug demonstrates safety and efficacy.
A decision to isolate and/or characterize a degradation product should be based
primarily on results obtained from formal stability studies of the drug substance and
drug product whenever possible. The guidance provides the identification thresholds for
degradation products in drug substances and drug products found in formal stability
studies.
Summary
Forced degradation studies of new drug substances and drug products are essential to
help develop and demonstrate specificity of stability-indicating methods and to
determine the degradation pathways and degradation products of the active ingredients.
They also can be useful in the investigation of the chemical and physical stability of
crystal forms, the stereochemical stability of the drug substance alone and in the drug
product and mass-balance issues, and for differentiating drug substance–related
degradation products in formulations. Procedures for the preparation of specific
degradation products needed for method validation often emerge from these studies.
Knowledge gained from these studies can be used to guide formulation development
and improve manufacturing and packaging processes.
For marketing applications, current FDA and ICH guidance recommends inclusion of the
results, including chromatograms of stressed samples, demonstration of the stability-
indicating nature of the analytical procedures, and the degradation pathways of the drug
substance in solution, solid state, and drug product. The structures of significant
degradation products and the associated procedures for their isolation and/or
characterization also are expected to be included in the filing. The experimental protocol
for degradation studies will depend on the active ingredients and formulation involved
because the chemistry of each compound is different. A target of the lesser of 10%
degradation of the active ingredient or exposure to energy in slight excess of
accelerated storage is recommended. A compound may not necessarily degrade under
a given stress condition. No further stressing is advised in these cases.
References
1. FDA, “International Conference on Harmonization: Stability Testing of New Drug
Substances and Products,” Federal Register 59 (183), 48753–48759 (22 September
1994) (ICH Q1A).
2. FDA, “International Conference on Harmonization: Draft Revised Guidance on Q1A(R)
Stability Testing of New Drug Substances and Products,” Federal Register 65 (78),
21446–21453 (21 April 2000) [ICH Q1A(R)]. This revised guideline reached Step 4 of
the ICH process on 8 November 2000. Implementation as of this writing — EU: adopted
by CPMP, November 2000, issued as CPMP/ICH/2736/99.MHW: to be notified. FDA: to
be notified.
3. FDA,“Draft Guidance for Industry, Stability Testing of Drug Substances and Drug
Products,” Federal Register (Notices) 63 (109), 31224–31225 (8 June 1998)
(combination of ICH Q1A-Q1C and Q5C, draft).
4. FDA, “INDs for Phase II and III Studies of Drugs, Including Specified Therapeutic
Biotechnology Derived Products,” Federal Register (Notices) 64 (76), 19543–19544 (21
April 1999).
5. FDA, Center for Drug Evaluation and Research, “Submitting Documentation for the
Stability of Human Drugs and Biologics” (Rockville, MD, February 1987).
6. FDA, “International Conference on Harmonization: Guideline for the Photostability
Testing of New Drug Substances and New Drug Products,” Federal Register 62 (95),
27115–27122 (16 May 1997) (ICH Q1B) and References 1 and 2.
7. FDA, “International Conference on Harmonization: Guideline on Impurities in New Drug
Substances,” Federal Register (Notices) 61 (3), 371–376 (4 January 1996) (ICH Q3A)
and FDA, “International Conference on Harmonization: Draft Revised Guidance on
Impurities in New Drug Substances,” Federal Register (Notices) 65 (140), 45085–
45090 (20 July 2000) [ICH Q3A(R)]. ICH Q3A(R) currently is at Step 3.
8. FDA, “International Conference on Harmonization: Guideline on Impurities in New Drug
Products,” Federal Register (Notices) 62 (96), 27453–274561 (19 May 1997) (ICH Q3B)
and FDA, “International Conference on Harmonization: Draft Revised Guidance on
Impurities in New Drug Products,” Federal Register (Notices) 65 (139), 44791–44797
(19 July 2000) [ICH Q3B(R)]. ICH Q3B(R) currently is at Step 3.
9. A,“Draft Guidance for Industry on Analytical Procedures and Methods Vaidation
Chemistry, Manufacturing, and Controls Documentation,” Federal Register (Notices) 65
(169), 52776–52777 (30 August 2000).
10.FDA, “International Conference on Harmonization: Guideline on the Validation of
Analytical Procedures: Methodology, Availability, Notice,” Federal Register 62 (96),
27463–27467 (19 May 1997).
11.A. Conners, G.L.Amidon, and V.L. Stella, Chemical Stability of Pharmaceuticals (Wiley
and Sons, New York, New York, 2d Ed., 1986), p. 19 and Reference 3.
12 FDA,“International Conference on Harmonization: Guidance on Q6A Specifications: Test
Procedures and Acceptance Criteria for New Drug Substances and New Drug Products:
Chemical Substances,” Federal Register (Notices) 65 (251), 83041–83063 (29
December 2000) (ICH Q6A) and FDA, “International Conference on Harmonization:
Draft Guidance on Q6A Specifications: Test Procedures and Acceptance Criteria for
New Drug Substances and New Drug Products: Chemical Substances,” Federal
Register (Notices) 62 (227), 62889–62910 (25 November 1997) (ICH Q6A). PT
VALIDATION OF ANALYST
1.0 OBJECTIVE
To lay down a procedure to establish capability of analyst to perform analysis accurately.
2.0 RESPONSIBILITY
Quality Control Officer / Quality Control Executive
3.0 ACCOUNABILITY :
4.0 PROCEDURE
4.1.1 Samples of known analytical values shall be identified by the Quality Control Manager.
4.1.2 The analytical value(s) of sampler(s) along with acceptable limit(s), AR no., and code no.
shall
be recorded by Quality Control Manager in a register maintained for this purpose.
4.1.3 All the coded samples shall be kept in sealed vials in the refrigerator and shall be
used within
the period specified on the label.
4.1.3 The necessary information required for analysis of coded samples shall be disclosed to the
analyst.
4.2 The analyst shall be undergone validation for either one or more of following areas of
analysis.
4.2.1 Assay (by HPLC, UV or Chemical )

4.2.2 Moisture content
4.2.3 Melting point
4.2.4 Identification (by IR Spectrophotometer or Chemical ) .
4.2 The Analyst validation shall involve use of one or more of the following instruments.
4.2.1 HPLC
4.2.2 UV Spectrophotometer
4.2.3 Auto-apparatus ( Titrator , KF Titrator )
4.2.4 Melting point apparatus
4.2.5 IR Spectrophotometer
4.2.6 The results of analyst shall be checked for cGlp compliance and compared with expected
values.
4.2.7 The capability to perform tests by Analyst shall be considered satisfactory if the results reported
by the Analyst are within the acceptable limits , and documentation as per the
requirement.
4.2.8 The analyst shall be revalidated once in two years.
4.2.9 The details like calculations, chromatograms, strip charts alongwith comments of Quality
Control Manager shall be filed in training file of analysts.
TEST ACCEPTANCE LIMIT

Assay (HPLC) (on as is basis) + 0.5% of the initial reported value
2.
Assay (by titration) (on as is basis) +.5 % of the initial reported value
Assay (by UV) on as is basis) +.5% of the initial reported value.
Water (by KF) +.5% of the initial reported value
IR should be compared with initial IR
Spectra.
Melting range should be within the range
4.3 ABBREVIATIONS
AR No. = Analytical Reference Number.,cGLP = Current Good Laboratories Practices.

HPLC = High performance liquid chromatography.,UV = Ultra violet.
IR = Infra red,KF = Karl fisher.

6.0 TRAINING:
Trainer -- Manager – Quality Control

Trainees -- Chemist / Assistants
Period -- One day
7.0 DISTRIBUTION:

8.0 ANNEXURES:
Nil
Validation of QC Chemist
1.0 Purpose : To provide an instruction for the validation of QC Chemist.

2.0 Objective : To provide a documented procedure for the validation of QC Chemist.
Scope : This procedure is applicable for QC Chemist .
 Primary : QC Chemist / QC-Officer
 Secondary : Overall: QC – In charge
5.0 Procedure :
 Following method used for the validation of QC Chemist to confirmed his / her
analytical skills.
 QC In-charge identifies a previously analyzed and approved batch sample.
 Identified batch sample shall be coded and hand over to QC Chemist with all
the details of test procedure.
 QC Chemist qualified on the criterion as follows:
 QC Chemist performs the analysis and documents the result as per Good
Laboratory Practices.
 QC Chemist performs the analysis and meets the acceptance criteria as per below
mentioned table.
 The QC Chemist working in laboratory shall be qualified on one or more tests as
required by the QC In-charge.
 The QC Chemist shall be qualified once a year.
 A record shall be maintained.
 Incase of QC Chemist fails to meet the criteria, the QC Chemist shall be trained and
re-qualified. The training record shall be recorded
Acceptance Criteria for Chemist Validation

Sr. Test Acceptance Criteria
No.
01 Assay test by HPLC % RSD of Retention Time and Area of six replicate
injection should not more than 2 %
02 Impurity test by HPLC % RSD of two replicate injection for highest impurity
should not more than 10 %
03 IR test Three separate analysis, which shall be concordant
with each other.
04 Water / LOD test % RSD of triplicate analysis should not more than 2
%
10 % moisture / LOD range 0 to 0.5 %
5 % moisture / LOD range 0.5 to 2.0 %
2 % moisture / LOD range 2 % above
05 UV test % RSD of three replicated absorption of solution of
particular concentration at specified wavelength
should not be more than 2 %
06 GC test % RSD of Retention Time and Area of six replicate
injection should not more than 2 %
07 Sp. Gravity test % RSD of six replicates reading should not more
than 2 %
08 Specific Optical % RSD of six replicates reading should not more
Rotation test than 2 %
09 Assay by chemically % RSD of six replicate analysis should not be more
test than 2 %
Cleaning Validation Procedures
 General concept
 Three consecutive validations will be performed to prove that the method is validated.
 Whenever a new product is introduced, equipment usage and nature of potential contaminant
will be studied to assess whether it poses a challenging study for cleaning validation.
 If the new product represents worst case, study/ identify/develop method of cleaning to be
employed. Simultaneously develop Analytical method for cleaning and validate the same.
 Revalidation Policy.
 Level of cleaning:
 Levels of cleaning during processing depends on:
o Equipment usage (e.g. dedicated or not)
o Stages of manufacturing
o Nature of contaminant (e.g. solubility, toxicity, color etc.)
 Our policy is to carry out cleaning after the end of each process, so that the equipment is clean
and ready for the next use.
 Elements of cleaning validation:
 Cleaning validation study includes:
 Cleaning Procedure
o Identification of equipment
o Characterization of products
o Determination of cleaning agents
 Analytical method and its validation
 Sampling procedure
 Establishment of acceptance criteria
 Validation protocol
 Validation Reports
 Cleaning Procedure:
 Prior to developing cleaning validation study, evaluate the following:
o Identification of Equipments:
 Identify equipments to be cleaned.
 Identify difficult to clean areas
 Check for ease of dismantling
o Characterization of products:
 Study activity/toxicity, solubility of the active substance of current batch and dosage and batch
size of next product to be taken on the equipment.
o Determination of Cleaning Agents:
 Identify cleaning agents to be used
 Identify number of cleaning cycles
 Identify equipments / materials to be used for cleaning.
o Based on above, prepare detailed written cleaning procedures for each equipment.
 Analytical Methods and its validation:
 In order for the analytical testing of the cleaning validation samples to yield meaningful results,
the analytical methods used should be validated.
 Analytical method validation for cleaning should include limit of detection, limit of
quantification, acceptance criteria and rationale for setting the specified limits.
 Sampling Procedure:
 Sampling plan for validation study should be drawn which includes:
 Sampling technique: Type of Sampling methods to be used are,
o Direct surface sampling by swab.
o Rinse water sampling (for equipment cleaning).
o Plate exposure (for area cleaning).
 Sampling Locations:
o Two easy to clean and two hard to clean areas should be clearly defined in Protocol.
 Sampling Procedure:
o Should mention how many samples are to be taken
 Swab samples should be taken separately for chemical and microbiological studies
 For each of chemical and microbiological analysis take 2 swabs from easy to clean hard to clean
locations
 How the samples are to be taken
 Sample Numbering:
o Swab samples should be numbered numerically and sequentially like 01, 02 etc for
identification.
 Establishment of Acceptance Criteria:
o Based on the data available calculate acceptance criteria for both Pharmacological dose method
and limiting the level of product to 10 ppm which appear in the following product.
o Of these two, choose the criterion with stringent limits and detectable by analytical
method.
o Microbiological limit is 50 CFU/100 cm2. Per swab
 Validation Protocol
 Validation protocol defines protocol number.
 Protocol defines a validation team that will be responsible for carrying out validation studies.
Validation team comprises of at least one responsible person from production, QC & QA
department.
 Responsibilities of team member are:-
o Production – Carrying out cleaning methods & implementing validation protocol.
o Quality Control – Developing analytical method for cleaning, sampling, testing & recording the
results.
o Quality Assurance – Issuing & reviewing of protocol, supervision of validation activities.
 Validation protocol given details location, product manufactured, profile of active ingredient,
cleaning agents used, testing equipment to be used, sampling points, sampling procedures, limit
of detection acceptance calculation, surface area, validation report etc.
 Responsible persons from Production, QC and QA should formally approve the cleaning
validation protocol.
 After approval Validation protocol is issued to QC Department.
 QC will perform validation studies in accordance with protocol and record results in validation
report.
 Validation Procedure:
 After completion of the manufacturing process, workman will clean the equipment.
 If the cleaned equipment is listed in the protocol, production person will inform QC Department
to collect samples for testing and QA department for supervision.
 QA/QC chemist will first check visually for cleanliness of equipment.
 If it observed not clean, instruct for re-cleaning.
 If it observed visually cleaned, collect samples separately for both chemical and microbial
analysis (if required) from locations given in the protocol as per sampling procedure.
 Samples are carried to QC, where testing of the samples will be done using validated Analytical
method.
 Validation Report:
 QC will record the results of testing in the protocol.
 QC will return the protocol with documented results and attachments like work sheet, graphs,
chromatograms etc. to QA for review.
 After completion of documented studies, QA will write conclusions regarding acceptability of
the results and status of procedures considered for validation.
 Any recommendations based on the documented results will be mentioned.
 References to the procedures used for cleaning, sampling and testing should be mentioned in the
validation report.
 All the members of validation team should approve conclusion
 In cases where it is unlikely that further batches of the product will be manufactured for a period
of time, it is advisable to generate interim reports on batch-to-batch basis till such time the
cleaning validation study is complete.
 If the results of validation of any of the three studies are non-conforming to set limits of
acceptance criteria, QC should inform immediately to QA.
 Further manufacturing process on the equipment/in the area should be suspended.
 Re-validation should be performed.
 Prior to re-validation, cleaning methods/procedures, sampling methods/ procedures and
analytical procedures employed should be re-checked and reviewed.
 Re-validation Policy:
 Revalidation of validated cleaning procedures will be considered –
o Once in a year, three replicate studies will be performed.
o In case of changes in equipment/process of product
 If the new product represents worst-case challenge
1.0 The result of inadequate cleaning procedures is that any of a number of contaminants may be
present in the next batch manufactured on the equipment such as:
o Precursors to the Active Pharmaceutical Ingredient
o By-products and/or degradation products of the Active Pharmaceutical
Ingredient
o The previous product
o Solvents and other materials employed during the manufacturing process.
o Micro-organisms
This is particularly the case where microbial growth may be sustained by the product.
o Cleaning agents themselves and lubricants
2.0 Cleaning techniques to be evaluated
o Manual cleaning
o CIP (Clean-in place)
o COP (clean-out-of-place)
o Semi automatic
o Automatic
o Time considerations
o Number of cleaning cycles.
SWAB SAMPLING FOR CLEANING VALIDATION
1.0 OBJECTIVE :
To establish a procedure for swab sampling for validation of test surface to evaluate cleaning efficacy.
2.0 RESPONSIBILITY:
Quality Control Chemist / Quality Assurance Chemist.
3.0 ACCOUNTABILITY:
Quality Control Manager / Quality Assurance Manager
4.0 PROCEDURE
FOR CHEMICAL EVALUATION:
4.1 SWAB : A clean room laundered polyurethane foam swab molded into a
polypropylene stick.
TRANSPORT : Capped test tubes made of glass.
CONTAINER
SAMPLING : As mentioned in the validation protocol of analytical method used

for SOLVENT analysis of swab samples of respective active ingredients.
4.2 Swab sampling procedure :
4.2.1 Pipette out 10ml of sampling solvent in transport container.
4.2.2 Remove a swab from its protective bag using a clean latex hand glove.
4.2.3 Avoid touching the swab head to prevent its contamination.
4.2.4 Transfer the swab in transport container (test tube)containing 10ml of sampling solvent and allow the
swab to soak completely.
4.2.5 Take out the swab from sampling solvent and squeeze the tip against inner surface of test tube to
remove excess solvent in such a manner that excess sampling solvent drips inside the test tube.
4.2.6 Hold the stem of swab without touching the head of the swab.
4.2.7 Using one side of moistened swab wipe the test surface of 2” x 2” with 10 firm horizontal strokes as
illustrated in Fig. 1.
4.2.8 At the end of each stroke, lift the swab carefully.
4.2.9 Turn the swab over to its other side, wipe the test surface of 2” x 2” with 10 firm vertical strokes as
illustrated in figure no.2.
4.2.10 At the end of each stroke, lift the swab carefully.
4.2.11 Hold the steam of the swab without touching the head of the swab and let the swab drop into the
transport container. Cap the transport container and send for analysis after labeling the same.
4.3 PROCEDURE FOR MICROBIOLOGICAL EVALUATION :
4.3.1. Take a sterile swab to sampling point.
4.3.2. Make the swab with (1) sampling point and (2) Date on outer cover.
4.3.3 Put on the clean latex hand gloves and disinfect the same with 70% IPA.
4.3.4 Take out the sterile swab carefully from the outer cover and swab the complete selected area (10
x 10cm).
4.3.5. Replace the swab immediately inside the cover, close if and send for analysis.
4.4. ABBREVIATIONS:
IPA = Iso- Propyl Alcohol
5.0 REASON FOR REVISION:

6.0. TRAINING:
Trainees-- Quality Control Chemists
Period -- One day
7.0. DISTRIBUTION:

8.0. ANNEXURES:
Nil.
9.0. REFERENCES
In-house.
Type Of Validation Procedures
1) PROCESS VALIDATION
 prospective validation
 concurrent validation
2) cleaning validation
3) change control
4) Re- validation
Cleaning validation
Documented evidence to establish that cleaning procedures are removing residues to
predetermined levels of acceptability, taking into consideration factors such as batch size, dosing,
and toxicology and equipment size.
Validation
Action of proving and documenting that any process, procedure or method actually and
consistently leads to the expected results.
Process validation
Documented evidence which provides a high degree of assurance that a specific process will
consistently result in a product that meets its predetermined specifications and quality
characteristics
Concurrent validation
Validation carried out during routine production of products intended for sale.
Prospective validation
Validation carried out during the development stage on the basis of a risk analysis of the
production process, which is broken down into individual steps; these are then evaluated on the
basis of past experience to determine whether they may lead to critical situations.
Retrospective validation
Involves the evaluation of past experience of production on the condition that composition,
procedures, and equipment remain unchanged.
- The sources of data for this validation may include batch documents, process control chart,
maintaince logbook, records of personnel change process capability studies, fp data and stability
results.
Validation report (VR)
A document in which the records, results and evaluation of a completed validation programme
are assembled and summarized. It may also contain proposals for the improvement of processes
and/or equipment.
Process Validation Program

The number of process runs for validation should depend on the complexity of the process or the
magnitude of the process change being considered. For prospective and concurrent validation,
three consecutive successful production batches should be used as a guide, but there may be
situations where additional process runs are warranted to prove consistency of the process
For retrospective validation, generally data from 10 to 30 consecutive batches should be
examined to assess process consistency, but fewer batches can be examined if justified.
Critical process parameters should be controlled and monitored during process validation studies.
Process parameters unrelated to quality, such as variables controlled to minimize energy
consumption or equipment use, need not be included in the process validation.
Process validation should confirm that the impurity profile for each API is within the limits
specified. The impurity profile should be comparable to, or better than, historical data and, where
applicable, the profile determined during process development or for batches used for pivotal
clinical and toxicological studies.
Approaches to validation
5.1.1 There are two basic approaches to validation—one based on evidence obtained through
testing (prospective and concurrent validation), and one based on the analysis of accumulated
(historical) data (retrospective validation). Whenever possible, prospective validation is
preferred. Retrospective validation is no longer encouraged and is, in any case, not applicable to
the manufacturing of sterile products.
5.1.2 Both prospective and concurrent validation, may include:
• extensive product testing, which may involve extensive sample testing (with the estimation of
confidence limits for individual results) and the demonstration of intra- and inter-batch
homogeneity;
• simulation process trials;
• challenge/worst case tests, which determine the robustness of the process; and
• control of process parameters being monitored during normal production runs to obtain
additional information on the reliability of the process.
5.2 Scope of validation
5.2.1 There should be an appropriate and sufficient system including organizational structure and
documentation infrastructure, sufficient personnel and financial resources to perform validation
tasks in a timely manner. Management and persons responsible for quality assurance should be
involved.
5.2.2 Personnel with appropriate qualifications and experience should be responsible for
performing validation. They should represent different departments depending on the validation
work to be performed.
5.2.3 There should be proper preparation and planning before validation is performed. There
should be a specific programmed for validation activities.
5.2.4 Validation should be performed in a structured way according to the documented
procedures and protocols.
5.2.5 Validation should be performed:
— for new premises, equipment, utilities and systems, and processes and procedures;
— at periodic intervals; and
— when major changes have been made. (Periodic revalidation or periodic requalification may
be substituted, where appropriate, with periodic evaluation of data and information to establish
whether requalification or revalidation is required.)
5.2.6 Validation should be performed in accordance with written protocols. A written report on
the outcome of the validation should be produced.
5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full
production scale) should be validated, to demonstrate consistency. Worst case situations should
be considered.
5.2.8 There should be a clear distinction between in-process controls and validation. In-process
tests are performed during the manufacture of each batch according to specifications and
methods devised during the development phase. Their objective is to monitor the process
continuously.
5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to
demonstrate its suitability for routine processing. The defined process, using the materials and
equipment specified, should be shown to result in the consistent yield of a product of the
required quality.
5.2.10 Manufacturers should identify what validation work is needed to prove that critical
aspects of their operations are appropriately controlled. Significant changes to the facilities or the
equipment, and processes that may affect the quality of the product should be validated. A risk
assessment approach should be used to determine the scope and extent of validation required.
Analytical Method Validation
WHY VALIDATE ANALYTICAL PROCEDURES ?

There are many reasons for the need to validate analytical procedures. Among them
are regulatory requirements, good science, and quality control requirements. The
Code of Federal Regulations (CFR) 311.165c explicitly states that “ the accuracy,
sensitivity, specifi city, and reproducibility of test methods employed by the fi rm shall
be established and documented. ” Of course, as scientists, we would want to apply
good science to demonstrate that the analytical method used had demonstrated
accuracy, sensitivity, specifi city, and reproducibility. Finally management of the
quality control unit would defi nitely want to ensure that the analytical methods that
the department uses to release its products are properly validated for its intended
use so the product will be safe for human use.
CYCLE OF ANALYTICAL METHODS

The analytical method validation activity is not a one - time study. This is illustrated
and summarized in the life cycle of an analytical procedure in Figure 1 . An analytical
method will be developed and validated for use to analyze samples during the early
development of an active pharmaceutical ingredient (API) or drug product. As drug
development progresses from phase 1 to commercialization, the analytical method
will follow a similar progression. The fi nal method will be validated for its intended
use for the market image drug product and transferred to the quality control laboratory
for the launch of the drug product. However, if there are any changes in the
manufacturing process that have the potential to change the analytical profi le of the
drug substance and drug product, this validated method may need to be revalidated
to ensure that it is still suitable to analyze the API or drug product for its intended
purpose.
General Concepts
 Validation is the act of demonstrating and documenting a procedure that operates

effectively.
 The discussion of the validation of analytical procedures is directed to the four most
common types of analytical procedure:
 Identification tests
 Quantitative tests for impurities content
 Limit tests for the control of impurities
 Quantitative tests of the active moiety in samples of drug substance or drug product or
other selected components in the drug product.
 Typical validation characteristics which should be considered are:
 Accuracy
 Precision
 Specificity
 Quantitation Limit
 Linearity and Range
 Robustness
 Method Validation Parameter for the assay of Mebendazole:
 Linearity: Mebendazole to be analyzed as per proposed method. The results obtain is used to
statistically evaluate for coefficient of determination (r 2), standard error of estimate and y
intercept.
 Precision: Precision of the chemical method is ascertained by carrying out the analysis as per the
procedure and as per normal weight taken for analysis. Repeat the analysis five times.
Calculate the % assay, mean assay, % Deviation and % relative standard deviation and
%RSD.
 Accuracy: Accuracy of the method is ascertained by standard addition method at 3 levels.
Standard quantity equivalent to 80%, 100% and 120% is to be added in sample.
 Method Validation Parameter for residual solvent by GC for Mebendazole:
 Specificity: Resolution of the analyte peak from the nearest peak: Solution of each of the analyte
was injected separately and their retention time is noted. The standard working solution
containing a mixture of the component being analyze is also injected and each of
analyte peaks is check for its resolution from the nearest.
 Precision:
 Repeatability: Six replicate injections of standard solution for system precision should
analyze as per the proposed method and from the chromatograms obtained the
percentage % RSD is calculated.
 Intermediate precision: The purpose of this test is to demonstrate the intermediate
precision of the method when method is executed by a different analyst and on different
day. Results obtained will be compared.
 Linearity and Range: Solution of analyte solvent, having different concentration
should make separate from L.O.Q. concentration, which is 50% to 150%. The result
obtained is statistically evaluated for coefficient of determination (r 2), standard error of
estimate and y intercept.
 LOD & LOQ:
 The limit of Detection (L.O.D.) was calculated as per below equation:
LOD = 3.3 X SD
Slope
 The limit of Quantification (L.O.Q.) was calculated as per below equation:

LOQ = 10 X SD
Slope
 Accuracy / % Recovery (By Standard Addition Method): Accuracy of the method
was ascertained by standard addition method at 3 levels.
 Standard solution quantity equivalent to 50%, 100% and 150% are added in sample.
 The solutions amount is analyzed by the proposed method and chromatogram
obtained.
 The amount recover by the method is compared to the amount added. Percent
deviation is calculated at each levels and a grand average across all the levels are also
calculated.
Methanol standard concentration –– 3000 ppm
Acetic acid standard concentration –– 5000 ppm
DMF standard concentration –– 880 ppm
Robustness:
 The evaluation of robustness should be considered during the development phase and
depends on the type of procedure under study. It should show the reliability of an
analysis with respect to deliberate variations in method parameters.
 If measurements are susceptible to variation in analytical conditions, the analytical
condition should be suitably controlled or a precautionary statement should be included
in the procedure.
 One consequence of the robustness should be that a series of system suitability
parameters (e.g. resolution test) is established to ensure that the validity of the
analytical procedure is maintained whenever used.
PROCESS OF ANALYTICAL METHOD VALIDATION

The typical process that is followed in an analytical method validation is
chronologically listed below:
1. Planning and deciding on the method validation experiments
2. Writing and approval of method validation protocol
3. Execution of the method validation protocol
4. Analysis of the method validation data
5. Reporting the analytical method validation
6. Finalizing the analytical method procedure
The method validation experiments should be well planned and laid out to ensure
effi cient use of time and resources during execution of the method validation. The best
way to ensure a well - planned validation study is to write a method validation protocol
that will be reviewed and signed by the appropriate person (e.g.,
laboratory management and quality assurance).
The validation parameters that will be evaluated will depend on the type of
method to be validated. Analytical methods that are commonly validated can be
classifi ed into three main categories: identifi cation, testing for impurities, and
assay. Table 3 lists the ICH recommendations for each of these methods.
Execution of the method validation protocol should be carefully planned
to optimize the resources and time required to complete the full validation
study. For example, in the validation of an assay method, linearity and accuracy may be
validated at the same time as both experiments can use the same standard solutions.
A normal validation protocol should contain the following contents at a
minimum:
(a) Objective of the protocol
(b) Validation parameters that will be evaluated
(c) Acceptance criteria for all the validation parameters evaluated
(d) Details of the experiments to be performed
(e) Draft analytical procedure
The data from the method validation data should be analyzed as the data are
obtained and processed to ensure a smooth fl ow of information. If an
experimental error is detected, it should be resolved as soon as possible to reduce any
impact it may have on later experiments. Analysis of the data includes visual
examination of the numerical values of the data and chromatograms followed by
statistical treatment of the data if required.
Upon completion of all the experiments, all the data will be compiled into a
detailed validation report that will conclude the success or failure of the validation
exercise. Depending on the company ’ s strategy a summary of the validation data may
also be generated. Successful execution of the validation will lead to a final analytical
procedure that can be used by the laboratory to support future analytical work for the
drug substance or drug product.
METHOD REVALIDATION
There are various circumstances under which a method needs to be revalidated.
Some of the common situations are described below:
1. During the optimization of the drug substance synthetic process, signifi cant
changes were introduced into the process. To ensure that the analytical method
will still be able to analyze the potentially different profi le of the API, revalidation
may be necessary.
2. If a new impurity is found that makes the method defi cient in its specifi city,
this method will need to be modifi ed or redeveloped and revalidated to ensure
that it will be able to perform its intended function.
3. A change in the excipient composition may change the product impurity
profi le. This change may make the method defi cient in its specifi city for the
assay or impurity tests and may require redevelopment and revalidation.
4. Changes in equipment or suppliers of critical supplies of the API or fi nal drug
product will have the potential to change their degradation profi le and may
require the method to be redeveloped and revalidated.
STABILITY STUDY PROTOCOL FOR ANALYTICAL METHOD VALIDATION
TABLE OF CONTENTS
Item No. Item Page No.
-- Table of content 1
1.0 Objective 2
2.0 Scope 2
3.0 Responsibility 2
4.0 Stability tests on Finished Product 2
Quality specifications for the proposed shelf-

4.1 2
life
4.1.1 Batches details 3
4.1.2 Specifications of test methods 4

4.1.3 Study design and study conditions 4
4.1.4 Analytical test procedures 6
4.1.5 Results of tests 7
Results format – Annexure-II 8-9
Conclusion 11
1.0 OBJECTIVE:
 To perform long term stability study on production batches to evaluate and justify
the recommended shelf life. Storage conditions and desired packing.
2.0 SCOPE:
 Scope of the study is to perform:
 Long term stability studies: A minimum of one batch per year for long term
stability study and any batch where a process change is made which will affect the
stability and quality of the product.
3.0 RESPONSIBILITY:
Sr. Team Designati

Department Responsibility
No. Member on
1. Quality Manager Issue and review of Stability
Assurance protocol
(QA)
2. Quality Manager Implementation and supervision

Control of Stability protocol
(QC)
3. Quality QC Officer To carry out QC test procedures

Control
4.0 STABILITY TESTS ON FINISHED PRODUCT
 Quality specifications for the proposed shelf life
 The recommended shelf life, storage conditions, and desired packaging should be
accompanied by the results of the testing.
 Product Mebendazole USP packaged in a double laminated aluminum sachet.
 Batches details:
Batch No. Mfg. Date Exp. Date Batch Size

Specifications and Test Methods
pecifications for long-term stability study.
Sr. No. Test Limits
1 DESCRIPTION:
2 IDENTIFICATION (IR)
3 ASSAY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
7 RESIDUE ON IGNITION
 All of the analytical methods used for carrying out the above mentioned tests are
the same as those described in European Pharmacopoeia – Annexure-I.
udy Design and Study conditions

o Long term stability studies: One batch per year.
ong-Term Storage Conditions and Testing Frequency
o Samples of Mebendazole USP. were packaged in a double laminated

aluminium sachet. Total 10 samples should be packed as per stability program. (9
samples as per stability program and one additional sample). Sample quantity is
about 3 gm in each pack.
o The samples were then stored in an environmental chamber at temperature

25°C  2° C & Relative Humidity 60%  5%
Temperature: 25°C  2° C
Relative 60%  5%
humidity:
Time interval: 0 Month (initial

month)
3 Months
6 Months
9 Months
12 Months
18 Months
24 Months
36 Months
48 Months
60 Months
ANALYTICAL TEST PROCEDURES
The following Test methods were applied to verify product integrity during the
time period tested as per Specification.
 DESCRIPTION
DENTIFICATION (IR)
 RELATED SUBSTANCES (BY THIN LAYER CHROMATOGRAPHY)
 LOSS ON DRYING
 MELTING POINT :
 CLARITY :
 RESIDUE ON IGNITION:
 ASSAY :
o Results of tests
All test results shall be recorded in attached Annexure-II:
o Conclusion:
 Conclusion shall be marked after completion of stability sample testing at each

time interval.
 And completion of total stability study, overall conclusion shall be marked.
Annexure-II
Results of Long term testing at Temperature 25°C  2° C & Relative

Humidity 60%  5%
Product name :
Batch No :
Manufacturing date :
Pack : Double laminated aluminum sachet
Batch size :
Sr. Test Limit Analysis (after months)
No. s
0 3 6 9 12
Mont Mont Mont Mont Mont

h h h h h
1 DESCRIPTION:
CHROMATOGRA-PHIC .
3
PURITY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
Sr. No. Test Limits Analysis (after months)
0 3 6 9 12
Month Month Month Month Month
8. ASSAY
Humidity 60%  5%
Product name :
Batch No :
Batch size :
Sr. Test Limi Analysis (after months)

No. ts
0 18 24 36 48 60
Mont Mont Mont Mont Mont Mont

h h h h h h
1 DESCRIPTION:
CHROMATOGRA-PHIC
3
PURITY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
Test Limits Analysis (after months)

Sr. 0 3 6 9 12
No.
8. ASSAY
 Conclusion:
 Analytical Method Validation

 Cleaning Validation Procedures
 VALIDATION OF ANALYST
 Validation of QC Chemist
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 VALIDATION OF INCUBATORS
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Analytical Method Validation
WHY VALIDATE ANALYTICAL PROCEDURES ?
There are many reasons for the need to validate analytical procedures. Among them
are regulatory requirements, good science, and quality control requirements. The
Code of Federal Regulations (CFR) 311.165c explicitly states that “ the accuracy,
sensitivity, specifi city, and reproducibility of test methods employed by the fi rm shall
be established and documented. ” Of course, as scientists, we would want to apply
good science to demonstrate that the analytical method used had demonstrated
accuracy, sensitivity, specifi city, and reproducibility. Finally management of the
quality control unit would defi nitely want to ensure that the analytical methods that
the department uses to release its products are properly validated for its intended
use so the product will be safe for human use.
CYCLE OF ANALYTICAL METHODS

The analytical method validation activity is not a one - time study. This is illustrated
and summarized in the life cycle of an analytical procedure in Figure 1 . An analytical
method will be developed and validated for use to analyze samples during the early
development of an active pharmaceutical ingredient (API) or drug product. As drug
development progresses from phase 1 to commercialization, the analytical method
will follow a similar progression. The fi nal method will be validated for its intended
use for the market image drug product and transferred to the quality control laboratory
for the launch of the drug product. However, if there are any changes in the
manufacturing process that have the potential to change the analytical profi le of the
drug substance and drug product, this validated method may need to be revalidated
to ensure that it is still suitable to analyze the API or drug product for its intended
purpose.
General Concepts
 Validation is the act of demonstrating and documenting a procedure that operates effectively.
 The discussion of the validation of analytical procedures is directed to the four most common
types of analytical procedure:
 Identification tests
 Quantitative tests for impurities content
 Limit tests for the control of impurities
 Quantitative tests of the active moiety in samples of drug substance or drug product or other
selected components in the drug product.
 Typical validation characteristics which should be considered are:

 Accuracy
 Precision
 Specificity
 Quantitation Limit
 Linearity and Range
 Robustness
 Method Validation Parameter for the assay of Mebendazole:
 Linearity: Mebendazole to be analyzed as per proposed method. The results obtain is used to statistically
evaluate for coefficient of determination (r2), standard error of estimate and y intercept.
 Precision: Precision of the chemical method is ascertained by carrying out the analysis as per the
procedure and as per normal weight taken for analysis. Repeat the analysis five times.
Calculate the % assay, mean assay, % Deviation and % relative standard deviation and %RSD.
 Accuracy: Accuracy of the method is ascertained by standard addition method at 3 levels. Standard
quantity equivalent to 80%, 100% and 120% is to be added in sample.
 Method Validation Parameter for residual solvent by GC for Mebendazole:
 Specificity: Resolution of the analyte peak from the nearest peak: Solution of each of the analyte was
injected separately and their retention time is noted. The standard working solution containing a
mixture of the component being analyze is also injected and each of analyte peaks is check for
its resolution from the nearest.
 Precision:
 Repeatability: Six replicate injections of standard solution for system precision should analyze
as per the proposed method and from the chromatograms obtained the percentage % RSD is
calculated.
 Intermediate precision: The purpose of this test is to demonstrate the intermediate precision
of the method when method is executed by a different analyst and on different day. Results
obtained will be compared.
 Linearity and Range: Solution of analyte solvent, having different concentration should make
separate from L.O.Q. concentration, which is 50% to 150%. The result obtained is statistically
evaluated for coefficient of determination (r2), standard error of estimate and y intercept.
 LOD & LOQ:
 The limit of Detection (L.O.D.) was calculated as per below equation:
LOD = 3.3 X SD
Slope
 The limit of Quantification (L.O.Q.) was calculated as per below equation:
LOQ = 10 X SD
Slope
 Accuracy / % Recovery (By Standard Addition Method): Accuracy of the method was
ascertained by standard addition method at 3 levels.
 Standard solution quantity equivalent to 50%, 100% and 150% are added in sample.
 The solutions amount is analyzed by the proposed method and chromatogram obtained.
 The amount recover by the method is compared to the amount added. Percent deviation is
calculated at each levels and a grand average across all the levels are also calculated.
Methanol standard concentration –– 3000 ppm
Acetic acid standard concentration –– 5000 ppm
DMF standard concentration –– 880 ppm
Robustness:
 The evaluation of robustness should be considered during the development phase and
depends on the type of procedure under study. It should show the reliability of an analysis with
respect to deliberate variations in method parameters.
 If measurements are susceptible to variation in analytical conditions, the analytical condition
should be suitably controlled or a precautionary statement should be included in the procedure.
 One consequence of the robustness should be that a series of system suitability parameters
(e.g. resolution test) is established to ensure that the validity of the analytical procedure is
maintained whenever used.
PROCESS OF ANALYTICAL METHOD VALIDATION

The typical process that is followed in an analytical method validation is chronologically listed
below:
1. Planning and deciding on the method validation experiments
2. Writing and approval of method validation protocol
3. Execution of the method validation protocol
4. Analysis of the method validation data
5. Reporting the analytical method validation
6. Finalizing the analytical method procedure
The method validation experiments should be well planned and laid out to ensure
effi cient use of time and resources during execution of the method validation. The best way to
ensure a well - planned validation study is to write a method validation protocol that will be
reviewed and signed by the appropriate person (e.g., laboratory management and quality
assurance).
The validation parameters that will be evaluated will depend on the type of
method to be validated. Analytical methods that are commonly validated can be
classifi ed into three main categories: identifi cation, testing for impurities, and assay. Table 3
lists the ICH recommendations for each of these methods.
Execution of the method validation protocol should be carefully planned
to optimize the resources and time required to complete the full validation
study. For example, in the validation of an assay method, linearity and accuracy may be
validated at the same time as both experiments can use the same standard solutions.
A normal validation protocol should contain the following contents at a
minimum:
(a) Objective of the protocol
(b) Validation parameters that will be evaluated
(c) Acceptance criteria for all the validation parameters evaluated
(d) Details of the experiments to be performed
(e) Draft analytical procedure
The data from the method validation data should be analyzed as the data are
obtained and processed to ensure a smooth fl ow of information. If an experimental error is
detected, it should be resolved as soon as possible to reduce any impact it may have on later
experiments. Analysis of the data includes visual examination of the numerical values of the
data and chromatograms followed by statistical treatment of the data if required.
Upon completion of all the experiments, all the data will be compiled into a
detailed validation report that will conclude the success or failure of the validation
exercise. Depending on the company ’ s strategy a summary of the validation data may also be
generated. Successful execution of the validation will lead to a final analytical procedure that
can be used by the laboratory to support future analytical work for the drug substance or drug
product.
METHOD REVALIDATION
There are various circumstances under which a method needs to be revalidated.
Some of the common situations are described below:
1. During the optimization of the drug substance synthetic process, signifi cant
changes were introduced into the process. To ensure that the analytical method
will still be able to analyze the potentially different profi le of the API, revalidation
may be necessary.
2. If a new impurity is found that makes the method defi cient in its specifi city,
this method will need to be modifi ed or redeveloped and revalidated to ensure

that it will be able to perform its intended function.
3. A change in the excipient composition may change the product impurity
profi le. This change may make the method defi cient in its specifi city for the
assay or impurity tests and may require redevelopment and revalidation.
4. Changes in equipment or suppliers of critical supplies of the API or fi nal drug
product will have the potential to change their degradation profi le and may
require the method to be redeveloped and revalidated.
Type Of Validation Procedures
1) PROCESS VALIDATION
 concurrent validation
2) cleaning validation
3) change control
4) Re- validation
Cleaning validation
Documented evidence to establish that cleaning procedures are removing residues to
predetermined levels of acceptability, taking into consideration factors such as batch size, dosing,
and toxicology and equipment size.
Validation
Action of proving and documenting that any process, procedure or method actually and
consistently leads to the expected results.
Process validation
Documented evidence which provides a high degree of assurance that a specific process will
consistently result in a product that meets its predetermined specifications and quality
characteristics
Concurrent validation
Validation carried out during routine production of products intended for sale.
Prospective validation
Validation carried out during the development stage on the basis of a risk analysis of the
production process, which is broken down into individual steps; these are then evaluated on the
basis of past experience to determine whether they may lead to critical situations.
Retrospective validation
Involves the evaluation of past experience of production on the condition that composition,
procedures, and equipment remain unchanged.
- The sources of data for this validation may include batch documents, process control chart,
maintaince logbook, records of personnel change process capability studies, fp data and stability
results.
Validation report (VR)
A document in which the records, results and evaluation of a completed validation programme
are assembled and summarized. It may also contain proposals for the improvement of processes
and/or equipment.
Process Validation Program

The number of process runs for validation should depend on the complexity of the process or the
magnitude of the process change being considered. For prospective and concurrent validation,
three consecutive successful production batches should be used as a guide, but there may be
situations where additional process runs are warranted to prove consistency of the process
For retrospective validation, generally data from 10 to 30 consecutive batches should be
examined to assess process consistency, but fewer batches can be examined if justified.
Critical process parameters should be controlled and monitored during process validation studies.
Process parameters unrelated to quality, such as variables controlled to minimize energy
consumption or equipment use, need not be included in the process validation.
Process validation should confirm that the impurity profile for each API is within the limits
specified. The impurity profile should be comparable to, or better than, historical data and, where
applicable, the profile determined during process development or for batches used for pivotal
clinical and toxicological studies.
Approaches to validation
5.1.1 There are two basic approaches to validation—one based on evidence obtained through
testing (prospective and concurrent validation), and one based on the analysis of accumulated
(historical) data (retrospective validation). Whenever possible, prospective validation is
preferred. Retrospective validation is no longer encouraged and is, in any case, not applicable to
the manufacturing of sterile products.
5.1.2 Both prospective and concurrent validation, may include:
• extensive product testing, which may involve extensive sample testing (with the estimation of
confidence limits for individual results) and the demonstration of intra- and inter-batch
homogeneity;
• simulation process trials;
• challenge/worst case tests, which determine the robustness of the process; and
• control of process parameters being monitored during normal production runs to obtain
additional information on the reliability of the process.
5.2 Scope of validation
5.2.1 There should be an appropriate and sufficient system including organizational structure and
documentation infrastructure, sufficient personnel and financial resources to perform validation
tasks in a timely manner. Management and persons responsible for quality assurance should be
involved.
5.2.2 Personnel with appropriate qualifications and experience should be responsible for
performing validation. They should represent different departments depending on the validation
work to be performed.
5.2.3 There should be proper preparation and planning before validation is performed. There
should be a specific programmed for validation activities.
5.2.4 Validation should be performed in a structured way according to the documented
procedures and protocols.
5.2.5 Validation should be performed:
— for new premises, equipment, utilities and systems, and processes and procedures;
— at periodic intervals; and
— when major changes have been made. (Periodic revalidation or periodic requalification may
be substituted, where appropriate, with periodic evaluation of data and information to establish
whether requalification or revalidation is required.)
5.2.6 Validation should be performed in accordance with written protocols. A written report on
the outcome of the validation should be produced.
5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full
production scale) should be validated, to demonstrate consistency. Worst case situations should
be considered.
5.2.8 There should be a clear distinction between in-process controls and validation. In-process
tests are performed during the manufacture of each batch according to specifications and
methods devised during the development phase. Their objective is to monitor the process
continuously.
5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to
demonstrate its suitability for routine processing. The defined process, using the materials and
equipment specified, should be shown to result in the consistent yield of a product of the
required quality.
5.2.10 Manufacturers should identify what validation work is needed to prove that critical
aspects of their operations are appropriately controlled. Significant changes to the facilities or the
equipment, and processes that may affect the quality of the product should be validated. A risk
assessment approach should be used to determine the scope and extent of validation required.
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Cleaning Validation Procedures
 General concept
 Three consecutive validations will be performed to prove that the method is validated.
 Whenever a new product is introduced, equipment usage and nature of potential contaminant
will be studied to assess whether it poses a challenging study for cleaning validation.
 If the new product represents worst case, study/ identify/develop method of cleaning to be
employed. Simultaneously develop Analytical method for cleaning and validate the same.
 Revalidation Policy.
 Level of cleaning:
 Levels of cleaning during processing depends on:
o Equipment usage (e.g. dedicated or not)
o Stages of manufacturing
o Nature of contaminant (e.g. solubility, toxicity, color etc.)
 Our policy is to carry out cleaning after the end of each process, so that the equipment is clean
and ready for the next use.
 Elements of cleaning validation:
 Cleaning validation study includes:
 Cleaning Procedure
o Identification of equipment
o Characterization of products
o Determination of cleaning agents
 Analytical method and its validation
 Sampling procedure
 Establishment of acceptance criteria
 Validation protocol
 Validation Reports
 Cleaning Procedure:
 Prior to developing cleaning validation study, evaluate the following:
o Identification of Equipments:
 Identify equipments to be cleaned.
 Identify difficult to clean areas
 Check for ease of dismantling
o Characterization of products:
 Study activity/toxicity, solubility of the active substance of current batch and dosage and batch
size of next product to be taken on the equipment.
o Determination of Cleaning Agents:
 Identify cleaning agents to be used
 Identify number of cleaning cycles
 Identify equipments / materials to be used for cleaning.
o Based on above, prepare detailed written cleaning procedures for each equipment.
 Analytical Methods and its validation:
 In order for the analytical testing of the cleaning validation samples to yield meaningful results,
the analytical methods used should be validated.
 Analytical method validation for cleaning should include limit of detection, limit of
quantification, acceptance criteria and rationale for setting the specified limits.
 Sampling Procedure:
 Sampling plan for validation study should be drawn which includes:
 Sampling technique: Type of Sampling methods to be used are,
o Direct surface sampling by swab.
o Rinse water sampling (for equipment cleaning).
o Plate exposure (for area cleaning).
 Sampling Locations:
o Two easy to clean and two hard to clean areas should be clearly defined in Protocol.
 Sampling Procedure:
o Should mention how many samples are to be taken
 Swab samples should be taken separately for chemical and microbiological studies
 For each of chemical and microbiological analysis take 2 swabs from easy to clean hard to clean
locations
 How the samples are to be taken
 Sample Numbering:
o Swab samples should be numbered numerically and sequentially like 01, 02 etc for
identification.
 Establishment of Acceptance Criteria:
o Based on the data available calculate acceptance criteria for both Pharmacological dose method
and limiting the level of product to 10 ppm which appear in the following product.
o Of these two, choose the criterion with stringent limits and detectable by analytical
method.
o Microbiological limit is 50 CFU/100 cm2. Per swab
 Validation Protocol
 Validation protocol defines protocol number.
 Protocol defines a validation team that will be responsible for carrying out validation studies.
Validation team comprises of at least one responsible person from production, QC & QA
department.
 Responsibilities of team member are:-
o Production – Carrying out cleaning methods & implementing validation protocol.
o Quality Control – Developing analytical method for cleaning, sampling, testing & recording the
results.
o Quality Assurance – Issuing & reviewing of protocol, supervision of validation activities.
 Validation protocol given details location, product manufactured, profile of active ingredient,
cleaning agents used, testing equipment to be used, sampling points, sampling procedures, limit
of detection acceptance calculation, surface area, validation report etc.
 Responsible persons from Production, QC and QA should formally approve the cleaning
validation protocol.
 After approval Validation protocol is issued to QC Department.
 QC will perform validation studies in accordance with protocol and record results in validation
report.
 Validation Procedure:
 After completion of the manufacturing process, workman will clean the equipment.
 If the cleaned equipment is listed in the protocol, production person will inform QC Department
to collect samples for testing and QA department for supervision.
 QA/QC chemist will first check visually for cleanliness of equipment.
 If it observed not clean, instruct for re-cleaning.
 If it observed visually cleaned, collect samples separately for both chemical and microbial
analysis (if required) from locations given in the protocol as per sampling procedure.
 Samples are carried to QC, where testing of the samples will be done using validated Analytical
method.
 Validation Report:
 QC will record the results of testing in the protocol.
 QC will return the protocol with documented results and attachments like work sheet, graphs,
chromatograms etc. to QA for review.
 After completion of documented studies, QA will write conclusions regarding acceptability of
the results and status of procedures considered for validation.
 Any recommendations based on the documented results will be mentioned.
 References to the procedures used for cleaning, sampling and testing should be mentioned in the
validation report.
 All the members of validation team should approve conclusion
 In cases where it is unlikely that further batches of the product will be manufactured for a period
of time, it is advisable to generate interim reports on batch-to-batch basis till such time the
cleaning validation study is complete.
 If the results of validation of any of the three studies are non-conforming to set limits of
acceptance criteria, QC should inform immediately to QA.
 Further manufacturing process on the equipment/in the area should be suspended.
 Re-validation should be performed.
 Prior to re-validation, cleaning methods/procedures, sampling methods/ procedures and
analytical procedures employed should be re-checked and reviewed.
 Re-validation Policy:
 Revalidation of validated cleaning procedures will be considered –
o Once in a year, three replicate studies will be performed.
o In case of changes in equipment/process of product
 If the new product represents worst-case challenge
1.0 The result of inadequate cleaning procedures is that any of a number of contaminants may be
present in the next batch manufactured on the equipment such as:
o Precursors to the Active Pharmaceutical Ingredient
o By-products and/or degradation products of the Active Pharmaceutical
Ingredient
o The previous product
o Solvents and other materials employed during the manufacturing process.
o Micro-organisms
This is particularly the case where microbial growth may be sustained by the product.
o Cleaning agents themselves and lubricants
2.0 Cleaning techniques to be evaluated
o Manual cleaning
o CIP (Clean-in place)
o COP (clean-out-of-place)
o Semi automatic
o Automatic
o Time considerations
o Number of cleaning cycles.
 SWAB SAMPLING FOR CLEANING VALIDATION
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Vendor Audit for Validation
1. GENERAL:
1.1 Building Maintenance

1.2 Reception
1.3 Administrative Block/O
1.4 Utility Block
1.5 Maintenance
1.6 Surroundings
2. PERSONNEL:
2.1 : Or
2.2 : Qu
2.3 : Pro
Me
Fo
Fo
2.4 : Pe
Fo
Fo
2.5 : Fa
Fo
Fo
Wa
2.6 : Pe
Sh
WC
Lo
Ca
2.7 : Jo
Re
2.8 : Tra
2.9 : En
2.10 : Dr
2.11 : Sy
2.12 : Pe
3 PLANT & BUILDING :

.
3.1 : Well equipped and sufficient area for Storages
a) : Raw Material ____________
b) : Packing Material ____________
c) : Intermediate ____________
d) : Finished Goods ____________
e) : Cleaning / Schedule ____________
f) : Cleaning of used equipment

and accessories ____________
g) : Separate area for storage of incoming material
 Quarantine area
 Approved materials Storage
 Rejected material Storage
 Sampling area
 Dispensing area
3.2 Adequate cleaning , washing and toilet area
3.3 Separate canteen area
3.4 Utilities like compressed air, steam, nitrogen gas

area qualified and lines are identified with arrow
mark for flow direction.
3.5 HVAC are providing for critical operation.
3.6 Drain is properly sanitized for critical area.
3.7 Water purification system

3.8 Water distribution system and quality of water
used
3.9 Men and materials movement system
3.10 Area is product dedicated or group of products

are manufactured then se the list of the product.
3.11 Cross contamination possibilities
3.12 Area cleaning procedure
3.13 Procedure of handling of rejected material.
3.14 Lighting level
3.15 Handling of sewage and waste
3.16 Sanitization of process equipments
3.17 Pest control system
3.18 : EQUIPMENT
a) Design MOC of contact parts

b) Qualification of equipment
c) Cleaning operation and preventive maintenance
procedures
d) Cleaning frequency
e) Measuring device calibration procedure
f) Cleaning validation approach
g) Computerized system are qualified as per CCF
part 11
h) Access to the computerized system is limited
k) Identification
l) Cleaning requirement for same product
for Product Change Over
m) Housekeeping & Sanitation
n) Special Procedure / Precaution
4 MANUFACTURING CONTROL:
.
4.1 : Identification level for material under processing
4.2 : Written Manufacturing Procedure
4.3 : Deviation Control Procedure
4.4 : Means of Communication
4.5 : Status label for rejected / released material
4.6 : Used container control
5. TSE QUESTIONNAIRE:
5.1 : Have you obtained the COS Certificate from EDQM for the
Material you are supplying to us? If yes please attach the copy.
5.2 : Is any of the starting material used in the manufacturing from
Animal Origin. If yes, Please ensure to obtain the TSE free Certificate
from your supplier.
5.3 : Is the Production Line dedicated?
5.4 : If NO Please Specify:-

a) Are the equipments shared with any other product, which uses the animal
original starting material?
b) Do you have sufficient Cleaning Procedure?
b) Is cleaning procedure validated?
5.5 : Is your batch COA contains the TSE / BSE free Declaration. If no submit an
undertaking to send the batch wise TSE / BSE free Declaration for all
supplies to us?
6. RECORD KEEPING :
6.1 : Material issue control ________________
6.2 : Equipment Log ________________
6.3 : Process Record ________________
6.4 : In-Process Results ________________
7. RAW MATERIAL CONTROL:
7.1 : Raw Material Receipt Control __________________
7.2 : Approved Material Segregation __________________

7.3 : Rejected Material Control __________________
8. QUALITY CONROL:
8.1: Raw Material Specification / Test Procedure & its control_______
8.2: Calibration Record ______
8.3: Finished Product Analysis & Release control _______
8.4: Testing facilities _______
9. INFORMATION RELATED TO OTHER PRODUCT MANUFACTURED:
9.1: List of product manufactured (Attach Sheet)
9.2: Product change over control (Cleaning Validation) _______
10. FILING SYSTEM:
10.1 Retrievable ______________
11. NON CONFORMANCES IF ANY:
CRITICAL
MAJOR
OTHER
12. CORRECTIVE ACTIONS:
13. PREVENTIVE ACTIONS:
14. CLOSURE OF AUDIT:
CONCLUSION
VALIDATION OF INCUBATORS
1.0 OBJECTIVE
To lay down a procedure for validation of incubator in microbiology

laboratory.
2.0 RESPONSIILTY
Microbiologist / Executive.
3.0 ACCOUNTABILITY
Quality Assurance Control
4.0 PROCEDURE
4.1 DETAILS OF THE STANDARD THERMOMETER USED FOR VALIDATION OF

LAB THERMOMETER.
4.1.1 Type : Liquid - Glass lab Thermometer.
4.1.2 Place the standard thermometer dipped in glycerin in incubator at various

locations as mentioned in annexure-II.
4.1.3 The incubator is set for desired temperature with the knob on control panel of
incubator
` e.g 32.5 0C, 35 0C & 22.5 0C.
4.1.4 Wait till the temperature reaches at set point & note down the temp. displayed on
the small screen of incubator and compare this temp. with standard thermometer
kept near the RTD probe.Likewise check the temperature after every 15 minutes up
to one hour and note down the readings on the format.
4.1.5 Record any difference between the displayed temp. & temp. showed by standard
thermometer and set the incubator accordingly
4.1.6 Frequency of validation : once in a year.
4.1.7 The observations are noted in the format of annexure-I
4.2 PROCEDURE FOR VALIDATION OF D.H.S (HOT AIR OVEN):
4.2.1 Keep all the apparatus wrapped thrice with aluminum foil inside DHS
as locations shown
in the diagram.
4.2.2 Keep the Spore loaded strips (having spore of B subilis) & Endotoxin
indicator indicators
having 10,000EU/vial in DHS(hot air oven) kept in 30ml vial wrapped thrice with
aluminum foil at locations shown in the diagram keep one vial unbaked as PPC.
Set the hot air oven at 250C ,wait till the temperature reaches upto the set
temperature.
4.2.3 After reaching the set temperature, note the time & temperature, hold for one hour
4.2.4 After completion of depyrogenation cycle ,switch off the power supply
and take out
Indicators for testing.
4.3 Procedure for testing reduction of endotoxin as under.
4.3.1 Take out the baked endotoxin loaded vial from the DHS.
4.3.2 Reconstitute 1ml of LRW in the baked vial and transfer 100l of
sample to the
depyrogenated reaction tube kept in heating block at 37 0 C and add 100l of

LAL in the
same tube in duplicate.
4.3.3 Prepare the dilutions for PPC for confirming 10,000EU/vial .
4.3.4 Note the gel clot after incubation of one hour
4.4. Procedure for testing of reduction of prepared spore loaded strip(B

subtilis):
4.4.1 Transfer (spore loaded) strip from backed vials and are inoculated in100ml
sterile SCD
media and incubate at 30 – 350C for 7 days to observe for any turbidity, if any,
report to Manager QC..
6.0 TRAINING:
Trainer - Head – Quality Control
Period -- One day
7.0 DISTRIBUTION:
8.0 ANNEXURES:
Annexure 1. Formats for Instrument validation.
9.0 REFERENCES:
USP 25 page no.-1890 & 2251
ANNEXURE-1
INSTRUMENT VALIDATION
. Microbiology NAME OF Incubat

LOCATION laboratory INSTRUMENT or
MANUFACTURED BY MODEL No.
IDENTIFICATION No. INSTALLED ON

SET TEMPERATURE = C
TIME TEMP. RECORDED DISPLAYED MINIMU MAXIMU DEVIATI
TEMP. M M ON
LOCATIONS INSIDE THE + -

CHAMBER
1 2 3 4 5 6
INITIAL C C
TEMP
C C C C C C C C C
AFTER 15 C C
MIN
C C C C C C C C C
AFTER 30 C C
MIN
C C C C C C C C C
AFTER 45 C C
MIN
C C C C C C C C C
AFTER 60 C C
MIN
C C C C C C C C C
LIMIT:-  2% of Set Temperature
CONCLUSION: The incubator is maintaining / does not maintaining set temperature

within
Specified limits.
VALIDATED BY: CHECKED BY:
DATE: DATE:
NEXT VALIDATION MANAGER /QC
DUE ON DATE

 Type Of Validation Procedures
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STABILITY STUDY PROTOCOL FOR ANALYTICAL METHOD VALIDATION
TABLE OF CONTENTS
Item No. Item Page No.
-- Table of content 1
1.0 Objective 2
2.0 Scope 2
3.0 Responsibility 2
4.0 Stability tests on Finished Product 2
Quality specifications for the proposed shelf-

4.1 2
life
4.1.1 Batches details 3
4.1.2 Specifications of test methods 4
4.1.3 Study design and study conditions 4
4.1.4 Analytical test procedures 6
4.1.5 Results of tests 7
Results format – Annexure-II 8-9

Conclusion 11
1.0 OBJECTIVE:
 To perform long term stability study on production batches to evaluate and justify
the recommended shelf life. Storage conditions and desired packing.
2.0 SCOPE:
 Scope of the study is to perform:
 Long term stability studies: A minimum of one batch per year for long term
stability study and any batch where a process change is made which will affect the
stability and quality of the product.
3.0 RESPONSIBILITY:
Sr. Team Designati

Department Responsibility
No. Member on
1. Quality Manager Issue and review of Stability

Assurance protocol
(QA)
2. Quality Manager Implementation and supervision

Control of Stability protocol
(QC)
3. Quality QC Officer To carry out QC test procedures
Control
4.0 STABILITY TESTS ON FINISHED PRODUCT
 Quality specifications for the proposed shelf life
 The recommended shelf life, storage conditions, and desired packaging should be
accompanied by the results of the testing.
 Product Mebendazole USP packaged in a double laminated aluminum sachet.
 Batches details:
Batch No. Mfg. Date Exp. Date Batch Size

Specifications and Test Methods
pecifications for long-term stability study.
Sr. No. Test Limits
1 DESCRIPTION:
3 ASSAY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
 All of the analytical methods used for carrying out the above mentioned tests are
the same as those described in European Pharmacopoeia – Annexure-I.
udy Design and Study conditions
o Long term stability studies: One batch per year.

ong-Term Storage Conditions and Testing Frequency
o Samples of Mebendazole USP. were packaged in a double laminated

aluminium sachet. Total 10 samples should be packed as per stability program. (9
samples as per stability program and one additional sample). Sample quantity is
about 3 gm in each pack.
o The samples were then stored in an environmental chamber at temperature

25°C  2° C & Relative Humidity 60%  5%
Temperature: 25°C  2° C
Relative 60%  5%
humidity:
Time interval: 0 Month (initial

month)
3 Months
6 Months
9 Months
12 Months
18 Months
24 Months
36 Months
48 Months
60 Months
ANALYTICAL TEST PROCEDURES
The following Test methods were applied to verify product integrity during the
time period tested as per Specification.
 DESCRIPTION
DENTIFICATION (IR)
 RELATED SUBSTANCES (BY THIN LAYER CHROMATOGRAPHY)
 LOSS ON DRYING
 MELTING POINT :
 CLARITY :
 RESIDUE ON IGNITION:
 ASSAY :
o Results of tests
All test results shall be recorded in attached Annexure-II:
o Conclusion:
 Conclusion shall be marked after completion of stability sample testing at each

time interval.
 And completion of total stability study, overall conclusion shall be marked.
Annexure-II

Humidity 60%  5%
Product name :
Batch No :
Batch size :
Sr. Test Limit Analysis (after months)

No. s
0 3 6 9 12
Mont Mont Mont Mont Mont

h h h h h
1 DESCRIPTION:
CHROMATOGRA-PHIC .
3
PURITY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
Sr. No. Test Limits Analysis (after months)
0 3 6 9 12
8. ASSAY
Humidity 60%  5%
Product name :
Batch No :
Batch size :
Sr. Test Limi Analysis (after months)

No. ts
0 18 24 36 48 60
Mont Mont Mont Mont Mont Mont

h h h h h h
1 DESCRIPTION:
CHROMATOGRA-PHIC
3
PURITY
4 MELTING POINT
5 LOSS ON DRYING
6 CLARITY
Test Limits Analysis (after months)

Sr. 0 3 6 9 12
No.
8. ASSAY
 Conclusion:

 Type Of Validation Procedures
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Opening and closing of QC department
1.0 Purpose : To provide an instruction for opening and closing of QC department.

bjective : To provide a documented procedure for opening and closing of QC department.
3.0 Scope : This procedure is applicable for opening and closing of QC
department.
 Primary : QC Chemist / QC Officer
 Secondary : Overall: QC – Incharge
5.0 Procedure :
 Opening Procedure.
 Check the lock of main door of the department. It should be locked, if the door is not
locked inform to Security department.
 Open the lock of Main door.
 Check for obnoxious smell or odour and ensure the absence of odour or smell.
 Switch ON the departmental lights.
 Before switching ON the precise testing equipment ensure that the voltage stabilizer
through which power supply is made to such equipment is under operation.
 Closing Procedure.
 All the instruments except automatic instrument on which program is going on are
switched “OFF”.
 Gas supply stations and cylinders are turned “OFF”.
 Water supply is put “OFF”.
 Fill the water supply tank of stability chambers with DM water.
 Containers of all volatile and fuming liquids are properly closed.
 Record room is locked.
 Switch “OFF” the lights and air conditioner.
 The department entrance door is locked.
 Hand over the key of main door to security department.
Cleaning of sampling tools
1.0 Purpose : To provide an instruction for cleaning of sampling tools.
2.0 Objective : To provide a documented procedure for cleaning of sampling tools.
Scope : This procedure is applicable for cleaning of sampling tools in QC Department.

 Primary : QC Chemist / QC Officer
 Secondary : Overall: QC – Incharge
5.0 Procedure :
 After sampling of raw materials / finished products, keep used tools in poly bag.
 Affix the label “TO BE CLEANED’ on poly bag.
 Bring the un-cleaned tools to QC department for cleaning.
 Remove tools from the bag and clean with water.
 Ensure that there is no adhered material on the tool.
 If required use suitable solvent for the cleaning of tools, then thoroughly wash with water.
 Dry the sampling tools.
 Place the tools in to new poly bag.
 Affix the label “CLEANED” on poly bag.
 Keep the cleaned sampling tools at its respective place.
 Cleaning & Sanitisation of Sampling room

 Washing of dispensing tools
 Cleaning of Sampling Area
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Standardization and storage of Reference and Working standards
Purpose : To provide instructions for selection, standardization and storage of reference and working
standards.
Objective: To provide documented procedures for selection, standardization and storage of reference and
working standard
cope : This procedure is applicable for selection, standardization and storage of reference and working
standards in QC Department.
 Primary : QC Chemist
 Secondary : Overall QC Officer
5.0 Procedure :
 Selection and Storage of Reference Standards.
 Reference standard/substance RS are issued by the respective Pharmacopoeia Commission.
 They are the official standards.
 Select current lots of the reference standards.
 Store them in suitable container (e.g. desiccators) moisture free atmosphere under
temperature-controlled condition.
 Maintain records for reference standard in respective logbook.
 Selection, Standardization and Storage of Working Standards.
 Working Standard shall be used for routine analysis.
 Working standards should be standardized at regular intervals against the reference

standards.
 Procedure for Raw Materials working standards.

 Working standards are selected from amongst the raw materials received and approved by the
QC.
 The selected raw material’s working standards having high purity or negligible impurities and
low moisture content.
 For solvent working standard shall be used from any reputed external manufacturer, pure
grade materials with certificate of analysis.
 Selected raw material working standard shall be re-tested and note down the observations in
respective worksheet.
 Procedure for Intermediates and Finished Products working standards.
 Selected intermediate and finished product working standards can be prepared by repeated
crystallization in suitable solvents.
 These working standard having high purity or negligible impurities and low moisture / loss on
drying content.
 R&D and QA should authorize procedures for the preparation of intermediate and finished
products working standard.
 Approved methods should be used for the preparation of working standard.
 Working standards should be standardized at regular intervals against the reference standards
or previous working standards.
 Frequency of standardization: Once in a Year.
 Standardization should be done in triplicate analysis.
 Loss On Drying / Moisture content and Assay tests parameters taken for standardization.
 The average value should be reported.
 Note down the observations in respective worksheet. And maintained relevant graphs in
respective working standard file.
 Re-standardization shall be done within + 15 days from the said date.

 Bottle of working standards should be stored in a desiccators having activated silica gel, and
kept at controlled temperature.
 Information on status label includes name of material, working standard batch number, purity,
LOD / moisture content, date of preparation, valid up to etc.
 Storage of working standards.
 After standardization the working standard is divided into equal quantities
 (Approx – 2 to 10 gm each) and filled appropriate vials / bottles (minimum 2 to 4). Vials should
be cleaned and dried.
 Each vial/bottle is to be used for three months from the date of opening and then discarded.
Open on date shall be mentioned on the label.
 The other information of the label includes name of material, open on date, purity, LOD/Water
value, and use before date and valid up to.
 The bottles are then sealed and kept in desiccators at the prescribed storage condition for the
future use.
 The temp of the area of storage is maintained and monitored daily.
 The last bottle is kept for use as a reference std. during next standardization. Reference
standard to be re-validated every year.
 HANDLING OF REFERENCE STANDARDS, PREPARATION AND HANDLING OF

WORKING STANDARDS
 ANALYTICAL REFERENCE NUMBERING SYSTEM
 Preparation, Standardization and Shelf-life of Volumetric solutions, Standard
reagent solution and Indicators
 OPERATION, CLEANING, STORAGE, CALIBRATION AND REGENERATION OF
HPLC COLUMN
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Preparation, Standardization and Shelf-life of Volumetric solutions, Standard reagent

solution and Indicators
Purpose : To provide instructions for the Preparation, Standardization and Shelf-life of Volumetric solutions,
Standard reagent solution and Indicators.
Objective : To provide documented procedures for Preparation, Standardization and Shelf life of Volumetric
solutions, Standard reagent solution and Indicators
cope : This procedure is applicable for preparation, standardization and shelf life of volumetric
solutions, standard reagent solution and indicators in QC Department.
 Primary : QC Chemist
 Secondary : Overall: QC Officer
5.0 Procedure :
 Volumetric Solutions
 Volumetric solution shall be prepared as mentioned in the respective procedure.
 Volumetric solutions shall be prepared by accurately weighing a specified quantity & dissolving
it to produce a specific volume.
 Records shall be maintained in respective logbook.
 Volumetric solutions shall be standardized by titration against a primary standard or by titration

with a standard solution that has been recently standardized against a primary standard.
 Record shall be maintained.
 Volumetric solutions shall be standardized before use; shelf life of this solution is one month
from the date of preparation. Discard the solution after one month or if observed hazy.
Note: Strength of the volumetric solutions should not deviate more than 10% of the prescribed
strength.
 All volumetric solutions should be standardized in triplicate set & % RSD should not be more
than 0.20 %. Average value shall be reported.
 All the bottles should be labeled indicating the name, strength of the solution, date of
preparation, signature of the person who prepared it, use before date, standardization due on,
date of standardization.
 Records shall be maintained for each solution starting with the value determined when the
solution was prepared & continuing with the values determined throughout the shelf life of the
solutions in respective register.
 This record shall be retained for at least 1 year after the solution has expired.
 Solutions of limited stability should be prepared on the day of use & discarded on completion
of analysis.
 Standard Reagent Solutions:
 Standard Reagent solutions shall be prepared as mentioned in the respective procedure.
 Standard Reagent solutions shall be prepared by accurately weighing a specified quantity &
dissolving to produce a specific volume.
 Records shall be maintained in respective register.
 All the bottles should be labeled indicating the name, strength of the standard reagent solution,
date of preparation, signature of the person who prepared it, use before date.
 Shelf life of these standard reagent solutions is Three months from the date of preparation.
Discard the solution after three months or if observed hazy.
 This record shall be retained for at least 1 year after the solution has expired.
 Indicators:
 Use readymade indicators of MERCK make.
 PREPARATION AND STANDARDISATION OF VOLUMETRIC SOLUTIONS AND

REAGENTS
 Preparation and Maintenance of Standard Operating Procedure
 Standardization and storage of Reference and Working standards
 Instructions for Self Life of Documents
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Sampling of Raw Material
1.0 Purpose : To provide instructions for sampling of Raw Material for Testing Purpose.
Objective: To provide a documented procedure for raw material sample quantity for testing.
3.0 Scope : This procedure for raw material sample method for testing in QC Department.
 Primary : QC Chemist
 Secondary : Overall: QC Officer
5.0 Procedure :
 On receiving the requisition of the raw material from the store. The QC Chemist will draw the
sample from store with proper safety. If sample is in tanker from outside factory gate.
 Sample will be done by the chemist with equipments such as.
 If the sample is in crystal form & powder form the sample will be taken by SS sample tube.
 If the sample is in liquid form then sample will be taken by glass sample tube.
 If the sample is in tanker the chemist will take the sample from the each compartment of the
tanker of the bottom. And top of the each compartment with the help of glass sample tube.
 Amount of the sample to be drawn.

 If the sample is in solid form (like crystal or powder) then 50.0 Gms of the sample to be
withdraw.
 If the sample is in liquid form then 250.0ml of the sample to be withdraw.
 Sample to be taken from each batch or lot as per the package label. If the package are less
than 10. The sample should be drawn from each & every package is more than 10. Then
sample should be taken as per this rule √n + 1.
 We after drawing the sample chemist will put the label of UNDER TESTING on the package or
drums from where sample has been taken.
 Chemist will bring the sample to QC lab and test the sample as per SOP of testing method.
 If the sample is approved as per SOP then sample will be approved QC Manager and test
report will be sent to store incharge and production incharge and chemist will put the approved
label on the package of the new material and remove the under test label.
 If the sample is not passed as per SOP testing method. The QC Manager will reject the raw
material and sent the report to the store incharge and plant incharge, after that QC Chemist
will put the REJECT label on the package or drum and remove the UNDERTESITNG label.
 here n = Number of package
 SAMPLING OF STERILE RAW MATERIAL

 RAW MATERIAL (RM) SAMPLING, ANALYSIS AND APPROVAL (NON-STERILE)
 RETESTING AND RE SAMPLING OF RAW MATERIALS
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Internal Audit Plan as per GMP
This document describes the conduct of the Management review of the quality system for GMP Conforma
Certification, including the conduct of an internal audit to assure the system meets the requirements of
Guidelines and is effectively implemented..
To Provide Documented Procedure for review of the quality system for GMP Conformance Certification, inclu
the conduct of an internal audit to assure the system meets the requirements.
To define role/responsibility of various functions responsible for Internal audit
o Board of Internal Audit and Management Review Committee: Arranges for the internal audit and gather
information for the Management Review.
o QA Management Committee: Provides all information as required by the Board of Internal Audit
Management Review Committee and is responsible for follow-up corrective and preventive actions.
o QA Internal Auditor(s): Conduct the internal audit according to GMP.
5.0 Procedure :
 The QA Management Committee, by consensus, selects three qualified individuals for the Board of Inte
Audit and Management Review Committee. Members to the Committee serve until they are replaced.
 The Board of Internal Audit and Management Review Committee arranges for the half yearly internal aud
be conducted.
 The date for the audit is established by mutual agreement between the Board of Internal Audit
Management Review Committee and the General Manager Production and Asst. Manager Production (AMP
 The audit is conducted by any member of the board or Internal auditor qualified to participate on
Certification Board so long as the auditor is not a member of the QA Management Committee, is qualified
knowledgeable in certification, auditing.
 The audit must be conducted at least every 06 months.

 During the audit, personnel responsible for the area audited are immediately notified of the outcome of
audit of their area.
 During an audit, it is possible that a difference of opinion can arise as to the severity of an observation.
important not to spend too much time debating the merits of the observation. If it does not appear that
difference of opinion can be resolved, then the auditee should be informed that the audit report is subjec
review by the Board of Internal Audit and Management Review Committee and the QA Management
 The draft report is issued to the Board of Internal Audit and Management Review Committee within
calendar days. The Committee members review and comment on the report and a final report is issued.
 The final internal audit report is submitted to the QA Management Committee.
 The QA Management committee drafts a response to the audit report that is finalized after review:
 Findings, nonconformities, trends, and other opportunities for improvement are identified; investigate
determine the causes; and corrective/preventive actions are developed. These actions are implemented
soon as possible and recorded.
 The response to the internal audit report is submitted to the Board of Internal Audit and Management Rev
Committee for their concurrence.
 Upon agreement on the response to the internal audit, the Board of Internal Audit and Management Rev
Committee prepares a complete Certification Program Management Review Report that includes,
appropriate,:
 Results of internal and external audits
 Feedback from clients and interested parties related to the fulfillment of the Certification Process
 Feedback concerning impartiality
 Follow-up actions from previous Certification Program Management Review Reports
 The status of corrective or preventive actions
 The fulfillment of objectives
 Changes that could effect the management system

 Appeals and complaints
 The Board of Internal Audit and Management Review Committee submit their Certification Prog
Management Review Report to the QA Management Committee.
 The Certification Program Management Review Report with the response to the internal audit is discusse
the next meeting of the full Board. The expected outputs of the review includes decisions and actions rela
to:
 Improvement of the effectiveness of the management system and its processes.
 Resource needs.
 Decisions and actions of the Board are documented in the Board Minutes and all open Corrective/Preven
Actions are reviewed and their status documented at all subsequent quarterly Board Meetings.
 Effectiveness of completed actions is reviewed at the next Program Management Review.
6.0 Abbreviations :
 GMP: Good Manufacturing Practice
 QA : Quality Assurance
 Self Audit Checklist for Maintenance Department

 Self Audit Checklist for Production Department
 Self Audit Checklist for Quality Control Department
 Self Audit Checklist for Store Department
Quality Control of Capsules
Quality control should be carried out during all stages of manufacturing operation which is the primary
requirement of good manufacturing practices.
Emptyhard capsules
According to Japanese Pharmacopoeia, the test called ‘purity’ uses five capsules which are tested
individually. Each is placed in a 100 ml conical flask and shaken vigorously after adding 50 ml of water
37C throughout the test. The capsule passes the test if it completely dissolves within 10 mins giving
odorless, neutral (or slightly acidic).
Weight variation
For hard capsules: Accurately weigh 10 capsules. By suitable means the contents of each capsule should
be removed. The weights of emptied shells should be recorded individually. The difference of both the
weights will yield the net weight of the contents. Then calculate acceptance value.
For soft capsules: pre weigh 10 capsules. Cut the capsules by suitable means (either scissors or any
open blade) remove the contents by washing with a suitable solvent and let the solvent evaporate by
placing them at room temperature for about 30 mins. Weigh the individual shells. Calculate the
acceptance value.
Content uniformity
Hard capsules containing 25 mg or more of the drug contents should meet content uniformity
requirements.
Assay 10 capsules individually and calculate the acceptance value.
The requirement is met if the acceptance value of 10 capsules is less than or equal to 15%. If acceptance
value is greater than 15% or is about 25 % then, test the next 20 units and calculate the acceptance
value. The 30 capsules if less than or equal to 15% and no individual unit is 1-25*0.01 nor more than
1+25*0.01.
Calculation of acceptance value:

(Reference value-mean of individual contents ) + acceptability constant * sample standard deviation
Disintegration:
The disintegration of capsules is different from those of tablets because the determination of end point is
difficult owing to the adhesive nature of shell. The shell pieces after disintegration may agglomerate
forming large mass of gelatin taking more time to dissolve and may adhere to the mesh thus, blocking the
holes.
According to USP, place one dosage unit in each of the tubes of the basket with water or any other
specified medium (depends on individual monograph) maintained at 37 + 2C. Attach a removable wire
cloth with a plain square weave of 1.8-2.2 mm of mesh aperture and a wire diameter of 0.60-0.655 mm to
the surface of upper rack of the basket assembly. Observe the capsules for a time limit (specified in
individual monograph), at the end of prescribed time, all of the capsules must have been disintegrated
excluding the fragments from the capsule shell. If 1 or 2 capsules fail, the test should be repeated on
additional of 12 capsules. Then, not fewer than 16 of the total 18 capsules tested should disintegrate
completely.
Dissolution
Place each of the capsules in the apparatus 1, excluding air bubbles from the surface of the capsule.
Operate immediately at specified rate within specified dissolution medium at 37 + 0.5C. Aliquots should
be withdrawn at specified time points mentioned in individual monograph.
The requirements are met if the quantity of active ingredients dissolved conforms the following:
1) At stage 1 (S1): When 6 capsules are tested, amount of each of the dissolved content should not be
less than +/- 5% of the mentioned in monograph.
2) At stage 2 (S2): when 6 capsules are tested, the average of 12 (both from step 1and 2) should be
equal to or greater than 15% and no capsule should be than 15%.
3) At stage 3 (S3): when 12 capsules are tested, the average of 24 capsules (all 1,2 and 3 steps) should
be equal to or greater than the amount mentioned in the monograph, not more than two units are less
than 15% and no unit s less than 25%.
NOTE: 15%, 25% represent Q1 and Q2 unless and otherwise mentioned in the monograph.
“Quality is not the step that can be incorporated at last, it is mandatory and should be inbuilt into the
products” to, make this happen, apart from all these mandatory tests certain other tests can be performed
like
Raw materials1
The gelatin of the capsule shells should be assayed for various physical properties like bloom strength 3,
viscosity and its loss (by atomic force microscopy).4 Chemical tests like purity, microbial properties, and
limits for heavy metals like arsenic, ash content should be determined.
The colorants should also be checked for purity, limits for heavy metals, color properties, dye content,
subsidiary dye content and color value.5
Machine output
The manufacturing machine’s output should be monitored continuously via the dimensional correctness
during each lot production.
The color of the capsules should be checked against a standard strip; in case of any changes the gelatin
solution should be adjusted by adding standardized dye solutions which can be ensured via thin layer
chromatography.
Moisture content
Moisture content can be monitored with the aid of data the drying kilns can be adjusted.
Loss on drying
Determination of loss on drying via the oven method consumes more time. To prevent this advanced
methods like infrared balances, humidity meter etc.
Sorting of defects
After electronic or manual inspection, they are sampled by quality control inspectors. The results should
meet the inspection plan, if not the capsules should be resorted or rejected depending upon frequency of
faults.
Printing inspection
Quality inspectors sample the lot and are inspected for quality of print. The results will again be compared
with the inspection plan and in case if it does not match then, either capsules should be resorted or
rejected depending upon number of faults present.
Final inspection
After the capsules are placed in final containers, samples are checked for various parameters like
dimensions, physical defects and color. These samples are also subjected to various microbial tests also.
 Functions of Quality control department

 CLEANING OF QUALITY CONTROL LABORATORY
 CONTROL OF ISSUANCE OF RECORD OF ANALYSIS
 Labeling by Quality control department
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Friday, December 17, 2010

Calibration of Disintegration test apparatus
1.0 OBJECTIVE : To lay down the procedure for operation and calibration of Disintegration test
apparatus
2.0 RESPONSIBILITY
Quality Control Chemist / Quality Assurance Officer.
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 FOR GENERAL CLEANING
4.1.1 Ensure that the power supply to the apparatus is switched OFF before cleaning.
Clean the equipment with a clean dry cloth per day. Occasionally wet cloth dipped in dilute
soap solution may be used. Precaution has to be taken to clean the equipment immediately
with dry cloth to remove the moisture.
4.1.2 Clean the beaker and basket at the end of every operation.
4.2 OPERATING INSTRUCTIONS
4.2.1 Ensure the apparatus is properly connected to the power supply.
4.2.2 When the power is switched ON the TIMER and TEMP. shows digital value.
4.2.3 Set the temperature 37°C by using SET, TEMP. , D , Ñ, DISP.SEL and ENTER
keys.
4.2.4 Set the timer 15.00 by using SET, TIME. , D , Ñ, DISP.SEL and ENTER keys.
4.2.5 Start the temperature by push the ENTER key.
4.2.6 Fill the beaker of DT apparatus with Purified water and adjust the temperature
between 37 ± 1 OC
4.2.7 Fix the beaker in its position and adjust the level of water so that when the basket
is in upper most position, wire mesh of the basket is 25 mm below the water level, and when it is
at lower most position the wire mesh is at least 25 mm above the bottom of the beaker.
4.2.8 Once the set temperature is attain 37 ± 1 OC.
4.2.9 In case of dispersible tablets, water temperature should be maintained within 15

to 25 OC.
4.2.10 Place on tablet / capsule in each of the tube and insert a disc in each of the tube.
4.2.11 Start the apparatus and Note the time taken by the last tablet / capsule for
complete disintegration.
4.2.12 Switch OFF the apparatus and power supply after the test is over, clean the
basket, discs and beaker.
4.3 CALIBRATION PROCEDURE
4.3.1 Follow steps 4.2.1 to 4.2.7
4.3.2 Start the basket – rack assembly and Timer simultaneously.
4.3.3 Place the standardized calibrated thermometer to record the actual temperature against the
temperature displayed.
4.3.4 Note the temperature of water in the beaker and Oscillation per minute of the basket-rack
assembly.
4.3.5 Switch OFF the apparatus and record the observations in the calibration record as per
annexure –1.
4.3.6 Report and discrepancy observed during calibration or operation of the instrument to Quality
Assurance Manager and notify the defect to Service Engineer to rectify the defect. Affix ‘Under
Maintenance’ label on the instrument.
4.4 ACCEPTANCE CRITERIA
4.4.1 The temperature shall be between 37 ± 1 OC.
4.4.2 The frequency of basket rack shall be between 29 to 32 per minute.
4.5 FREQUENCY OF CALIBRATION
Once in a month and after each maintenance job.
4.6 ABBREVIATIONS :
QA = Quality Assurance
DT = Disintegration test
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : For Calibration File
Certified Copy No. 3 : For Display Near The Disintegration
ANNEXURE –I
INSTRUMENT CALIBRATION RECORD
Revision No.: 00
REF. SOP NO.: Page No. : 1 of 1
Effective from:
Name of Instrument : Disintegration Test Apparatus
Instrument Ser. :
No.
Make & Model :
Calibration date :
Calibration due on :
Sr.No. PARAMETER OBSERVATIONS LIMIT
1 Strokes per min. Basket 1 29- 32 cycles /

min.
2 Strokes per min. Basket 2
3 Temperature by probe. Basket 1
4 Temperature by Standard thermometer .

Basket 1
37 ± 1 OC
5 Temperature by probe. Basket 2
6 Temperature by Standard thermometer.

Basket 2
7 Distance travel by Basket 1 53-57 mm
8 Distance travel by Basket 1
Standard Thermometer Identification No. : ________

REMARKS : Satisfactory / Not satisfactory.
 Calibration of Friability test apparatus

 OPERATION AND CALIBRATION OF DISSOLUTION TEST APPARATUS
 Operating Leak test Apparatus
 OPERATION AND CALIBRATION OF BULK DENSITY APPARATUS
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Calibration of Friability test apparatus
1.0 OBJECTIVE : To lay down the procedure for operation and calibration of friability test
apparatus
2.0 RESPONSIBILITY
Quality Control Chemist / QA Chemist
3.0 ACCOUNTABILITY
Quality Control Manager / QA Manager.
4.0 PROCEDURE
4.1 GENERAL CLEANING
4.1.1 Clean the apparatus free of dust with dry cloth from out side every day.
4.1.2 Clean the rotating disc and unloading pan from inside with dry cloth at the start and end of every
operation. Wet cloth may be used occasionally if cleaning is not proper with dry cloth but this
should follow drying of the inner surface by first wiping with dry cloth and exposure to
atmosphere air.
4.2 OPERATING INSTRUCTIONS

4.2.1 Ensure that apparatus is properly connected with power supply.
4.2.2 Weigh tablets to be tested and record the weight {WI}.
4.2.3 Switch on the main switch of power supply.
4.2.4 Press MODE key and select count mode.
4.2.5 Press SET button and set the RPM to 25 with the help of numerical key’s (0 to 9) & press
ENTER
4.2.6 Key located on the front side of the instrument.
4.2.7 Load the weighed tablets in the drum, close the lid and secure it by tightening he screw and
press ENTER and then press START to run test.
4.2.8 After the completion of set rotations, the apparatus will automatically unload the tablets into the
tray. Observe the tablets.
4.2.9 Dedust the tablets, weigh and record the weight {W2}.
Calculate the percentage Friability by the following formula;
Initial Wt. of Tablets (W1) – Wt. of tablets After 100 rotation (W2) X 100
Initial Wt. of Tablets (W1)
4.2.10 Dstroy the tested tablets as per SOP.
4.3 CALIBRATION PROCEDURE
4.3.1 Switch on the power supply.
4.3.2 Set the RPM to 25 and start the machine simultaneously with the stop watch. Count the actual
rotations and not the time required for the same.
4.3.3 Similarly set the RPM to 100 and note the time required and actual rotations.
4.3.4 Apparatus is in proper working condition if,
4.3.4.1 Time required for 25 rotations is 1 min ± 05 sec.
4.3.4.2 Time required for 100 rotations is 4 min ± 20 sec.

4.3.5 Record the observation in the calibration record as per Annexure – 1.
4.3.6 Affix a “Calibration Status” label on the instrument.
4.3.7 In case of any discrepancy, report the observations to QC manager / QA Manager and notify
the defect to Engg. Department. Affix an ‘UNDER MAINTENANCE” label on the instrument.
4.4. FREQUENCY
Once in a month and after each maintenance job.
.0 REASON FOR REVISION
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 3 : For Display Near The Friability Test Apparatus
ANNEXURE – 1
Revision No.: 00
Effective from:
Name of Instrument Friability Test Apparatus
Instrument Ser. No. :
Make & Model : Electrolab.
Calibration date :
SET ROTATION
ROTATION ROTATIONS OBSERVED
ACCEPTANCE
Sr. DISPLAYED TIM
MA CRITERIA
No. E
NUALLY
25 1 min ± 05
sec
1.
100 4 min ±
2 20 sec

 Calibration of Disintegration test apparatus
 Operating Leak test Apparatus
 OPERATION AND CALIBRATION OF KARL FISCHER APPARATUS
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Calibration of serological water bath
BJECTIVE: To lay down the procedure for operation and calibration of serological water bath.
2.0 RESPONSIBILITY:
Q.C. Chemist
3.0 ACCOUNTABILITY:
Head - Q.C.
4.0 PROCEDURE:
4.1. PRECAUTIONS
4.1.1 Ensure that the Water Bath is cleaned every week .
4.1.2 Ensure that water bath is never operated without DM water, otherwise heater will
be damaged.
4.1.3 Check that water does not fall on the thermostat knob ( bellow the tray ).
4.1.4 Ensure that the mercury bulb of the thermometer is always dipped in water.
4.2 WORKING PROCEDURE
4.2.1 Maintain the DM water level in the water bath & switch 'ON' the main switch of the
Water Bath.
4.2.2 Set the thermostat knob to the desired temperature setting on the knob ( 0 – 100
settings ).
4.2.3 If desired temperature is not achieved, then fine tune the thermostat knob as per
requirement.
4.2.4 Switch OFF the water bath when not in use.
4.3 CLEANING OPERATION Frequency: once in a week
4.3.1 Drain all the water from the Water Bath.

4.3.2 Scrap the side and bottom of Water Bath with help of Nylon gauze.
4.3.3. Wash with soap solution and rinse thoroughly it with DM water.
4.3.4 Wipe the surface of Water Bath with cloth.
4.3.5 Frequency for cleaning: Once in a week
4.4 CALIBRATION Frequency: Quarterly once
4.4.1 Set the temperature of serological water bath at 45C and switch on the
instrument.
4.4.2 Wait till temperature gets stabilized .
4.4.3 Note the temperature by calibrated thermometer and record it as initial

temperature.
4.4.4 After one hour again note the temperature.
4.4.5 Follow the similar procedure by setting the temperature to 100°C.
4.4.6 Record the observations in the calibration format as mentioned in annexure I
4.4.7 Acceptance Criteria: The temperature should be within  2 C of the set

temperature.
4.4.8 Affix calibration tag , if calibration is satisfactory & under maintenance if found
unsatisfactory.
4.5 ABBREVIATION
C - Degree centigrade
6.0 TRAINING:

Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 3 : For Display Near Water Wath
Original Copy : beginning – QUALITY ASSURANCE.
ANNEXURE I
INSTRUMENT CALIBRATION RECORD
Revision No.: 00
Effective from:
: Serological Water Bath/Water wath

Name Of Instrument
Manufactured By : Medica Instrument/
Identification No. :
Date Of Calibration :
Next Calibration Due On :

Set Initial Temperature Limits Remarks
Temperature Temperature after 1 Hr. ( °C )
( °C ) ( °C )
45 43 – 47 °C
100 98 – 102 °C
Frequency : Quarterly once.

 OPERATION AND CALIBRATION OF REFRACTOMETR

 1.0 OBJECTIVE:

 To lay down a procedure for sampling of packing materials so as to get the representative sample
of the whole lot.

 2.0 RESPONSIBILITY

 2.1 The Chemist / Assistant - Quality Control Packaging shall be:
 2.1.1. Responsible for receiving the GRN and entering the details in Packaging Material
register.
 2.1.2. Responsible for the ensuring appropriate cleanliness of sampling area and
integrity of consignment.
 2.1.3. Responsible for ensuring proper documentation for sampling and assembling of
adequate number of samples for analysis purpose.
 2.1.4. Responsible for proper sampling of PM as per Military Standard 105 D from the
pack (s) and its appropriate identification on each sampled container (s).
 2.1.5. Responsible for carrying out analysis of material (s) accurately & precisely.
 2.1.6. Responsible for maintaining the Reserve Sample and it’s Record.
 2.1.7. Responsible for ensuring proper labelling on packs.
 2.1.8. Responsible for recording the data in the sampler’s remarks and test data sheet.
 2.1.9. Responsible for intimating to Executive – QC, in case of any non-conformance.

 2.2 The Executive - Quality Control shall be:

 2.2.1 Responsible for verifying the recorded data of sampled consignment by Quality Control
– Officers and review of the same.
 2.2.2 Responsible for updating the document as per regulatory requirement
 2.2.3 Responsible for imparting training to sub-ordinates.
 2.2.4 Responsible for taking decisions on non-conformance in co-ordination with Head –
Quality Assurance / Quality Control

 3.0 ACCOUNTABILITY

 Manager – Quality Control


 4.0 PROCEDURE:

 4.1 Receive Goods Receipt Note (GRN) from Warehouse and record relevant
informations in packaging material register (Refer Annexure-1).
 4.2 Take out Photocopy of Sampler’s Check List - PM (Refer Annexure – 2).
 4.3 The separate sampler’s remark shall be used for each lot of Batches.
 4.4 Prepare the “UNDER TEST” label from the computer system to affix on the
consignment.
 4.5 Check the delivered items to ensure that the quantity received corresponds with
the GRN Quantity
 4.6 Fill the necessary details in Sampler’s Check List by taking the reference of
Goods Receipt Note (GRN). If discrepancy found in GRN inform to warehouse for
corrective action.
 4.7 Go to the Quarantine area and identify the material to be sampled from
Quarantined label which is affixed by Warehouse on the packs.
 4.8 In case of Aluminium and PVC foils carry out the sampling under Laminar Air
Flow (LAF).
 4.9 Cleaning of LAF shall be carried out on every alternate day or early if required.
The LAF shall be cleaned with wet mop followed by dry mop.
 4.10 The cleaning shall be recorded in the cleaning record for LAF as given in
Annexure - 3.
 4.11 Ensure that the surrounding area is clean, if not get it clean, prior to start of the
sampling.
 4.12 Check the packing condition of the material and details mentioned on the Under
Test labels.
 4.13 Verify that the Quarantine Labels are affixed by Warehouse Personnel.
 4.14 In case of any discrepancies intimate to Executive / Head - Quality Assurance or
Head - Quality Control for necessary action.
 4.15 Ensure that packs are cleaned externally and open the packages only after
ensuring the proper cleaning. Observe the material for any abnormalities and record it on
the Sampler’s Check List.
 4.16 Check the following points during sampling of the material: -
 4.16.1 Mode of packing,
 4.16.2 Indication of packing,
 4.16.3 Details available on pack (Containers),
 4.16.4 No. of packs (containers) received,
 4.16.5 Total quantity received,
 4.16.6 No. of packs (containers) sampled,
 4.16.7 Quantity to be sampled.
 4.16.8 Name of the person who sampled along with date of sampling.

 4.17 Withdraw the samples randomly by opening different containers /
Boxes as per n +1 and take out sampling quantity for visual inspection as per sampling
plan MIL – STD 105D Acceptable Quality Level (AQL) (Refer Annexure – 5).
 4.18 Note down the sampled quantity in Sampler’s checklist based on the number of
packages to be sampled.
 4.19 Examine the sampled material as per AQL against the approved standard for
general appearance, deviation from normal visual quality, colour, text etc. wherever
applicable.
 4.20 Record the results in approved Visual Inspection Report for Aluminium foil and
PVC Foil.
 4.21 After completion of sampling the material pack shall be resealed with BOPP
Tape or tied with the help of cable – tie.
 4.22 Affix the “UNDER TEST” refer Annexure – 4. to all the rolls of sticker labels,
foils and every container of rubber plugs. For all other packaging materials at least one
“UNDER TEST” Label shall be affixed on bottom container/ pack of each pallet.
 4.23 Affix the SAMPLED BY QC (Refer Annexure – 4) sticker label duly signed and
mentioning the container number according to sampling plan, on outer container of the
material from which sample is taken.
 4.24 Check that the number of packs is correct as mentioned in under test label.
 4.25 Take out composite sample for analysis as per respective Packing Material
Specifications. Put the sampled quantity in self-sealing polybag bearing the label of
“SAMPLE FOR ANALYSIS” Refer annexure – 4.
 4.26 Carry out testing of the packaging material as per the laid down specifications of
respective material.
 4.27 The sampling procedure described above will not be applicable for Tertiary
Packaging material like Shipper, pad, partition and corrugated trays. For these materials
only one unit shall be collected and carry out the analysis as per laid down specification.

 5.0 REASON FOR REVISION
 Harmonization of format

 6.0 TRAINING:

 Trainer -- Manager – QC
 Trainee -- Chemist / Associate – QC Packaging
 Period -- One day

 7.0 DISTRIBUTION:

 Certified Copy No. 1 : Head of Department – Quality Control
 Certified Copy No. 2 : File Copy for Packaging Department
 Certified Copy No. 3 : Head – PLANT OPERATIONS
 Certified Copy No. 4 : For Display in Packaging Laboratory
 Original Copy : Head – QUALITY ASSURANCE

 8.0 ANNEXURES:

 Annexure - 1 : Format for Packaging Material Register
 Annexure - 2 : Format for Sampler’s Remarks
 Annexure - 3 : Format for Cleaning Record of LAF.
 Annexure – 4 : Format for labels of UNDER TEST, SAMPLE FOR ANALYSIS and
SAMPLED
 Annexure – 5 : 105 D Military Standard Acceptable Quality Level Chart

 9.0 REFERENCE:
APPROVAL AND REJECTION OF PACKAGING MATERIALS
1.0. OBJECTIVE:
The objective of this SOP is to describe the procedure for Approval and
Rejection of Packaging
Material.
2.0. RESPONSIBILITY:
2.1 The Chemist / Officer – Quality Control Packaging shall be:
2.1.1. Responsible for ensuring proper documentation of sampling and adequate number
of quantity sampled.
2.1.2. Responsible for carrying out analysis of packing material (s) accurately & precisely
by following specification and standard testing procedure.
2.1.3. Responsible for maintaining the Packaging Material Register.
2.1.4. Responsible for preserving the reserve sample along with Analytical Test Report.
2.1.5. Responsible for recording the correct results in the Analytical Test Report for every
PM in a stipulated time.
2.2 The Executive – Quality Assurance shall be:
2.1.1 Responsible for verify and review of the recorded results and of the
ensuring the results are within the
standard limits.
2.1.2 Responsible for updating the document as per regulatory requirement
2.1.3 Responsible for ensuring all laboratory instruments are calibrated and
working satisfactorily.
2.1.4 Responsible for final disposition of material under consultation with

Head – QA/QC.
2.1.5 Responsible for imparting training to sub-ordinates including Good

Laboratory Practice.
3.0. ACCOUNTABILITY:
Executive – Quality Assurance

4.0. PROCEDURE:
4.1. The sampling of the packaging material shall be carried out as per the SOP
4.2. Before starting the analysis take out Standards and Results Sheet from
Respective Product File and take out photocopy and get it issued from Sectional
Head by signing the space provided.
4.3. The sampled items shall be analysed as per respective laid down specifications
and general test procedure. The results shall be recorded in the Analytical Test
Report and compare for its limits.
4.4. Prepare Certificate Of Analysis in case the material is being used, to the
Regulated Market. (Refer Annexure – 1).
4.5. Then compile the results along with Sampler’s Remark and keep one Reserve
Sample for printed packaging material by affixing Reserve Sample Label on non-
printed part (Refer Annexure – 2 for Reserve Sample Label).
4.6. The Goods Receipt Note (GRN) along with complete analytical report shall be
checked thoroughly by another person.
4.7. Then this complete report shall be forwarded to the Head – QC or Executive – QC
for further disposition (Approval / Rejection).
4.8. The results are not within the specified limits and standards, the material shall be
rejected
4.9. If the material is rejected, the Material Rejection Note (Refer Annexure – 3) shall
be prepared and get it approved from Head – Plant Operation, Head – QA / QC.
4.10. If all parameters found within the prescribed range Executive or Head – QA shall
approve the Analytical Test Reports and GRN.
4.11. The report with regards to the disposition of the said consignment is then made &
the status label as whether it is APPROVED or REJECTED (Refer Annexure – 2) shall
be generated by using the computer System.
4.12. Affix the duly signed APPROVED / REJECTED label to the consignment.
4.13. Each approved pack of packing material shall be identified by affixing the small
green label (Refer Annexure – 2) having the A.R. No. for identity of the Consignment.
4.14. Forward the approved / rejected copies of GRN to Warehouse for further actions.
4.15. File the entire report along with Quality Control GRN Copy.
4.16. Then Warehouse personnel shall shift the Approved / Rejected material in the
designated areas.
4.17. The rejected consignment shall be shifted to the designated Rejected

Areas under lock and
Key.
4.18. The approved material is then used for Production as per requirement.
4.19. The shelf life of each individual packaging material is being work out, on the basis
of stability study of these materials. Till that time the shelf life of packing materials
is three years from the date of release of material.
6.0 TRAINING:
Trainees -- Chemist / Assistants - Quality Control Packaging
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : File Copy for Packaging Laboratory
Certified Copy No. 3 : Head – Plant Operation.

9.0 ANNEXURES:
Annexure – 1 : Format for Certificate of Analysis
Annexure – 2 : Approved, Rejected, Reserve Sample and A.R. No. Labels.
Annexure – 3 : Format for Material Rejection Form.
9.0 REFERENCES:
In house
ANNEXURE – 1
FORMAT FOR CERTIFICATE OF ANALYSIS
CERTIFICATE OF ANALYSIS
ALKEM
LABORATORIES LIMITED PACKAGING MATERIAL
(NAME)
DAMAN
Material name:
Item code: Batch No.:
Mfr. Name: Supplier Name:
Challan no.: Challan Date:
GRN No. : Date Received:
Quantity received: Containers Received:
Containers sampled: Date Of Sampling:
Sampled by: A. R. No.:
TESTS
RESULTS SPECIFICATIONS
APPROVED / REJECTED
Remarks: Sample COMPLIES / DOES NOT COMPLIES as per above Specification
ANALYST CHECKED BY APPROVED BY
(SIGNATURE / DATE) (SIGNATURE / DATE) (SIGNATURE / DATE)

K/QC/002/F-1/00
ANNEXURE – 2
FORMAT FOR APPROVED, REJECTED, RESERVE SAMPLE AND A.R. NO.

LABEL
Revision No.: 00 Page No.: 1
REF. SOP NO.: K/QC/002
Effective from: of 1
NAME
ITEM CODE
A.R. No. B. No.
G.R. No QTY.
POTENCY NO. OF CONTAINERS
RETEST DATE
SIGN. Date
ALKEM LABORATORIES LTD.. 333/1 KACHIGAM, DAMAN- 396210 ( U.T )
APPROVED
DOC/QC/001
ITEM CODE & NAME
A.R.NO B. NO.
G.R. NO. QTY.
POTENCY NO. OF
CONTAINERS
SIGN. Date
REJECTED
DOC/QC/002
RESERVE SAMPLE
Analytical Reference No.
A.R. No. : Sticker Label
G.R.N. No. :
Signature :
(149P – 2A/01)
Date :
ANNEXURE – 3
FORMAT FOR MATERIAL REJECTION NOTE

To
Head – Warehouse
Name Of Item:
Item Code No.: Rejection Note No:
Name Of Manufacturer/Supplier:
GRN. No./Date: A.R. No. :
Challan No. / Date: Qty. Received:
Batch No. : Qty. Rejected:
Date Of Analysis:
Reason For Rejection:
Remarks:
Prepared By. / Date Checked By/Date

Rejection Approved By/ Date
Head – QA / QC
(Executive – QA)
Carbon Copy To:
1. Head – Plant Operation.

2. Head – Purchase.
K/QC/002/F-2/00

 RETESTING OF PACKAGING MATERIALS
 REVIEW AND APPROVAL OF ANALYTICAL RAW DATA
 Responsibility of quality assurance in rejection.
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Responsibility of quality assurance in rejection.
1.0 Purpose : To provide instructions for responsibility of quality assurance in rejection.

Objective : To provide a documented procedure for role of quality assurance in the handling of
rejection
Scope : This procedure is applicable for the handling of rejection by quality assurance
department.
 Primary: QA-Officer
 Overall: QA-Manager
5.0 Procedure:
 Rejection of Raw Material:
 Supply Rejected by QC
o In case material does not meet specification parameters, QC raises an “Out of
Specification (OOS)” report along with attachments like report of analysis etc. and
forwards to QA for Approval, QA personnel will study available information / records /
documents of the material.
o If QA find that supply needs to be rejected, QA In-charge will approve the “Out of
Specification (OOS)”.
 Rejection due to manufacturing activities
o On receipt of “Online rejection note” from production department, inspect the rejection.
o Approve the rejection by signing on “Online Rejection Note”.
o If the quantity of rejection is very high, study the cause of rejection.
o Based on study QA, suggest the corrective action.
o If any corrective measures are required from the supplier, Inform to purchase
department for corrective actions.
Numbering system for Standard Operating Procedures and Index of Standard

Operating Procedure
0 Purpose: To provide instructions for numbering system for Standard Operating Procedures and
Index of Standard Operating Procedure. (SOPs).
0 Objective: To provide a documented procedure of numbering system for Standard Operating
Procedures and Index of Standard Operating Procedure. (SOPs)
3.0 Scope : This procedure is applicable for numbering system for Standard Operating Procedures
and Index of Standard Operating Procedure. (SOPs).
4.0 Responsibility:
 Primary: Officer–QA
 Secondary: Manager-QA
5.0 Procedure:
 SOP is prepared after studying total activities and interacting with all the concerned
Departments.
 SOP is classified into following six main groups.
Sr. No. Name of the Department. Department SOP No.
Code
1 Personnel and Administration PA ABC/XX/SOP/YYY
2 Production Department PR ABC/XX/SOP/YYY
3 Engineering Services MT ABC/XX/SOP/YYY
4 Quality Control Department QC ABC/XX/SOP/YYY
5 Quality Assurance QA ABC/XX/SOP/YYY
6 Store Department ST ABC/XX/SOP/YYY
 Each department’s SOPs having eleven digit code, e.g. ABC/XX/SOP/YYY

 Where,
o ABC = Name of City where plant located
o SOP = Indicates Standard Operating Procedure
o XX = Indicates department code (e.g. PA, PR, QC etc.)
o YYY = Indicates Serial number of SOP (e.g. 001, 002, etc.)
After preparation of all SOPs, circulate the SOPs to respective department and give
training
Analytical report numbering
1.0 Purpose : To provide an instruction for analytical report numbering procedure (AR No.)
2.0 Objective : To provide a documented procedure for analytical report numbering.
3.0 Scope : This procedure is applicable for analytical report numbering in QC department .
 Primary : QC Chemist / QC-Officer
 Secondary : Overall: QC-Officer
5.0 Procedure:
 Analytical Report Numbering for Raw Material
 Numbering of analytical report of raw material shall be in the form of R-XXX/YY/ZZ
For Raw material: R-XXX/YY/ZZ(e.g. R-001/09/09)
Where, R = raw material

XXX = serial no. (e.g. 001, 002,)
YY =month.
ZZ = year (e.g. 2009 as 09)
 Analytical Report Numbering for Packing Material
 Numbering of analytical report of packing material shall be in the form of P-XXX/YY/ZZ.
For Packing material: P-XXX/YY/ZZ (e.g. P-001/08/09)
Where, P = packing material
XXX = serial no. (e.g. 001, 002…)
YY = month. (e.g.01,02.. )
ZZ = year (e.g. 2009 as 09)
 Analytical Report Numbering for Intermediate
 Numbering of analytical report of intermediate shall be in the form of
I-WWW/XXX/YY/ZZ.
For Intermediate: I- WWW/XXX/YY/ZZ (e.g. I-001/001/01/09)
Where, I = Intermediate
WWW = product code (001, 002, ….)
XXX = serial no. (e.g. 001, 002, ….)
YY = month. (e.g.01,02.. )
ZZ = year (e.g. 2009 as 09)
 Analytical Report Numbering for Finished Product
 Numbering of analytical report of finished product shall be in the form of XXX or WWW or
WW//XXX/YY/ZZ
For Finished product: WWW or WW/XXX/YY/ZZ (e.g. MBZ/001/01/09)
Where, WWW or WW = Short name of product (001, 002, ….)

XXX = serial no. (e.g. 001, 002, ….)
YY = month (e.g.01,02.. )
ZZ = year (e.g. 2009 as 09)
 Analytical Report Numbering for Re-testing Raw Material
 Numbering of analytical report of re-test raw material shall be in the form of R-

XXX/ZZ/R1.
For re-test Raw material: R-XXX/ZZ/R1 (e.g. R-001/09/R1)
Where, R = raw material
XXX = serial no. (e.g. 001, 002, ….)
ZZ = year (e.g. 2009 as 09)
R1 = re-test first time (e.g. R1, R2, ….)
 Analytical Report Numbering for Re-testing Intermediate
I- WWW/XXX /ZZ/I1
For Intermediate: I- WWW/XXX/ZZ/I1 (e.g. I-001/001/09/I1)
Where, I = intermediate
WWW = product code (001, 002, ….)
XXX = serial no. (e.g. 001, 002, ….)
ZZ = year (e.g. 2009as 09)
I1 = re-test first time ( e.g. I1, I2, ….)

 Numbering system for Standard Operating Procedures and Index of Standard
Operating Procedure
 Code numbering system of packaging material
 Record maintained by Quality control department
 1.0 Purpose : To provide instructions for record maintained by quality control
department.
 2.0 Objective : To provide a documented procedure for record maintained by
quality control department.
 3.0 Scope : This procedure is applicable for record maintained by quality
control department.
 4.0 Responsibility :
  Primary : QC Chemist / QC Officer
  Secondary : Overall : QC In Charge
 5.0 Procedure :
  Following are control documents.
  Standard Operating Procedures of Quality Control Department..
  Specifications of Raw material.
  Specifications of Packing material.
  Specifications of In-process / intermediate.
  Specifications of Finished product.
  Standard Test Procedures of Raw material.
  Standard Test Procedures of Packing material.
  Standard Test Procedures of In-process / intermediate.
  Standard Test Procedures of Finished product.
  List of Instruments.
  Following are records.
  Raw materials testing records.
  Packing materials testing records.
  In-process / intermediates testing records.
  Finished products testing records.
  Instrument calibration records.
  Stability study records.
  Instrument calibration records.
  Glassware calibration records.
  Raw material inward logbook
  Raw material work sheet issuance logbook.
  Intermediate inward logbook.
  Intermediate work sheet issuance logbook.
  Finished product inward logbook.
  Finished product work sheet issuance logbook.
  In process samples inward logbook.
  Instrument uses logbooks.
  HPLC column logbook.
  Stability chamber logbook.
  Laboratory cleaning logbook.
  Volumetric solution logbook.
  Standard reagent solution logbook.
  Indicator logbook.
  Retention sample logbook.
  Logbook issuance logbook.
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Functions of Quality control department
1.0 Purpose : To provide an instruction for functions of quality control department.

2.0 Objective: To provide a documented procedure for functions of quality control
department.
3.0 Scope : This procedure is applicable for functions of quality control department.
 Primary: QC Chemist / QC-Officer
 Secondary : Overall: QC – In charge
5.0 Procedure :
 List of activities of quality control department.
 Testing and release or rejection of all incoming raw materials, packing materials, in-
process / intermediates and finished products as per specified specifications.
 Maintaining testing records as per standard procedures for raw materials, packing
materials, in-process / intermediates and finished products.
 Calibration of laboratory instrument / equipment.
 Performing stability study.
 Control sample storage.
 Analytical method validation.
 Preparation of standard volumetric solutions and maintain standardization record.
 Maintain Labeling procedure at all the stages and records.
 Maintain working / reference standard record of products.
 Analysis of complaint samples as and when required.
 To conduct technical audit / self-inspection.
 Follow safety norms at all the stage during handling of chemicals and using
instruments.
 Follow good laboratory practices.
 Labeling by Quality control department
 Cleaning of HPLC columns

 1.0 Purpose : To provide an instruction for washing of HPLC columns.
 2.0 Objective : To provide a documented procedure for washing of HPLC
columns.
 3.0 Scope : This procedure is applicable for washing of HPLC columns in
QC Department.
  Primary : QC Chemist / QC-Officer
  Secondary : Overall QC – In charge
 5.0 Procedure :
  After completion of analysis stop the pump, keep the reservoir in the distilled
& filtered water.
  Open the purging valve of the pump; purge the system for 3 to 5 minutes to
remove air bubbles. Close the purging valve by decreasing the flow rate up to
zero.
  Wash the HPLC column initial with HPLC grade water for about 15-20
minutes.
  Then wash the HPLC column with respective solvent mixtures (e.g. 50:50
Methanol: Water or Acetonitrile: Water) for minimum ½ hr to 1 hr.
  Finally wash the HPLC column with respective solvent (Acetonitrile /
Methanol) for about 15-30 minutes.
  Keep flow rate 0.5 ml / min or 1.0 ml / min. increase flow rate gradually.
  Check the pH of eluent on pH paper (it should be neutral)
  Store the HPLC column in solvent (acetonitrile or methanol).
  Disconnect the HPLC column and keep it at respective column storage box.
  Maintain the cleaning record in HPLC column logbook.
 1.0 Purpose : To provide an instruction for re-testing of raw materials and
intermediates.
 2.0 Objective: To provide a documented procedure for re-testing of raw
materials and intermediates.
 3.0 Scope : This procedure is applicable for re-testing of raw materials and
intermediates in QC department.
  Primary : QC Chemist / QC Officer
  Secondary : Overall: QC – Incharge
 Procedure:
  After the receipt of re-testing intimation note from store department, QC
Chemist takes its entry in the respective Re-testing logbook and gives AR No. to
raw materials or intermediate.
  AR No. Should be given as follows
 For Raw material: R-XXX/ZZ/R1 (e.g. R-001/08/R1)
 Where, R = raw material
 XXX = serial no. (e.g. 001, 002, ….)
 ZZ = year (e.g. 2008 as 08)
 R1 = re-test first time (e.g. R1, R2, ….)
 Collect samples as per sampling plan.
  After completion of sampling, do the necessary critical tests (e.g. assay, LOD,
water content, pH, specific optical rotation etc.) as per the Standard Analytical
Procedure.
  Raw material may also be approved on the basis of physical appearance.
  After completion testing, put the status of approved / rejected on the
containers.
  Re-testing of any raw materials should be four times only.
  Frequency of re-testing for raw material is every year, and for intermediate is
every six months.
  Re-testing should be performing on first come first out basis. The re-testing of
material should carry out, whose due date for re-test is earlier.
Dispensing of raw materials
1.0 Purpose : To define the procedure for dispensing of raw materials

2.0 Objective: To provide guidelines for dispensing of raw materials..
3.0 Scope : This procedure applies to dispensing of raw materials in stores
Department.
 Follow up : Officer – Stores
 Over all responsibility: Store Incharge.
5.0 Procedure :
 Stores Officer
 Receive the raw material issue requisition and record the serial number, material code
and date of receipt. Check for the entries in all the columns viz. Dept, Batch Size., Batch
No. and signatures for requisite by and authorizes by. If any of these columns is
missing, return the requisition to production.
 From the raw material stock register, check the quantities of material available and
quantities requested for. If any of the material in stock is less than the requisitioned
Quantity, inform to Stores Incharge.
 Stores Incharge.
 Check the materials in “Under Test” status. If the material requisitioned is
present in “Under Test” status, inform the Manager – Production and Asst
Manager – QC regarding the same. Hold the issue of the other materials
till the material is approved by QC.
 Stores Assistant
 Check the dispensing area for the following Cleanliness.
 No other material is present in the area
 The balance is clean and has been calibrated for the day.
 Availability of cleaned dispensing devices (scoops, etc.)
 Protective equipment has been worn as per the material safety data sheet.
 Check the details of the material on the Approved Label.
o Name of the Material
o Batch No.
o Batch size.
o A.R.No.
o Quantity
o No. of container.
o Tare Wt
o Gross Wt.
o Net Wt.
o Date
o Signature
 Check the tare weight of the empty container and note down on the dispensed label.
 Select the bulk raw material container of appropriate AR No as per FIFO system.
Check the retest date on the label. If the retest date falls in the month of issue, inform
QC regarding the retesting.
 Transfer the material to the dispensing area. Carefully transfer the material into the
container till the quantity required is transferred.
 Note down the final weight of the container and record on the dispensing label for
gross weight.
 Calculate the net weight and record on dispensing label and sign for issued by.
 Close the bulk raw material container and transfer back the bulk raw material container
to the original space.
 Repeat the steps for remaining materials of the raw l issue requisition one after the
other.
 Never keep more than one material in the dispensing area. Transfer the second
material only after the first has been dispensed and transferred back to its original
space.
 Always use clean dispensing devices and do not contaminate one with other material.
 Enter the details of issue into the raw material stock register for the material.
 Verify the quantities dispensed against the raw material issue requisition and sign for
Store officer.
 Inform the Asst. Manager – Production / Manager – Production regarding the checking
of the material.
 Material requisition will be made two copies. One copy will be kept in store department
and duplicate copy attach with B.M.R.
 Dispensing of packing materials
 Washing of dispensing tools
 Receiving Liquid Raw Materials
 Closing the Raw Material Stores
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Receiving Liquid Raw Materials
Purpose : To provide the procedure for receiving liquid raw materials in road
tankers.
bjective : To provide documented procedure for receiving liquid raw materials in road tankers.
Scope : This procedure defines instructions for receiving liquid raw materials in road tankers in
the stores department.
 Primary : Officer – Stores
 Secondary: Stores In charge/ Manager Store.
5.0 Procedure :
 Receive and verify the delivery documents (DC, Performa Invoice, Central Excise
Invoice, COA) and check for the Purchase Order copy for the material. The documents
shall essentially consist of the following information.
 Name of the material
 Name of the supplier
 Batch No. / Identification No.
 Manufacturing date
 Quantity of material including the units of measurement
 Number & date of Purchase order
 Contact the Purchase department, if PO copy for the material received is not available.
 Check for the security inward stamp on the delivery documents and the signature of the
security personnel along with the Security inward number.
 Inform QC Dept in writing about the arrival of tanker for tanking sample giving the
following details:
 Date
 Time of Reporting
 Name of the Product
 Name of the Supplier
 Name of the manufacturer
 Quantity
 DC / Invoice No. & Date
 If the sample from the tanker does not conform to the specification, inform the purchase
department regarding the “REJECTION”. Return back the tanker.
 On receipt of approval of the tanker from the QC, assign a Stores Asst. to the tanker
and send it to approved public weighing bridge for taking the gross weight.
 Instruct the tanker driver to position his vehicle near to the unloading point.
 Inform the engineering personnel to make arrangements for connecting the delivery
lines to the tanker, connect the earthing cable from the tanker outlet to the earthing point
to ensure the discharge of static electricity.
 Ensure all the safety precautions for unloading the material from the road tanker have
been taken.
 After the unloading is completed verify the compartments of the tanker by checking the
individual compartments and opening the outlet valves completely.
 Assign a store asst. and send the tanker for weighing to the weight bridge.
 On receipt of the weight of the empty tanker compute the net weight of the material
transferred. Check against the delivery documents and compute the difference if any.
 Enter in the raw material inward register including the actual content of the material
transferred.
 Sign for received on the delivery documents and retain the original copy.
 Return the duplicate copy to the driver and mention deviations observed for suppliers’
reference.
 Prepare the GRN and forward the same to the QC Dept for analysis of composite from
the storage tank.
 On receipt of report from QC, forward copy of the GRN to Accounts and Purchase
department.
 Dispensing of raw materials
 Raw material Weighing
nstructions for Engineering department as per safety and cGMP requirements
Purpose : To provide store management instructions for Engineering department as per safety and
cGMP requirements.
Objective : To provide documented procedure of store management instructions for engineering
department as per safety and cGMP requirements.
Scope : This procedure defines instructions for Engineering store management system. The SOP
specifies the responsibilities of staff for the various functions outlined here.
 Primary : Officer – Stores
 Secondary: Stores In charge/ Manager Store.
5.0 Procedure :
 Before raising the indents for material:
 Prepare the Bill of Quantity (BOQ) for the each job. Discuss with the contractor /
superiors and finalize it.
 Consider the physical stock of the quantities already exists / ordered.
 Procedure for indenting the material:
 If required, float the inquiry and invite the three quotations.
 Prepare cost comparative statements.
 Finalize the purchase order after negotiations.
 Prepare purchase order and hand over to the party.
 Procedure for Receiving the material:
 After getting the intimation, receive the material at the gate house.
 Check the material at gate house, as per delivery challan and quality of material i.e.
damage, scratches, finishing etc.
 Take the required quantity and use for it was indented.
 Procedure for releasing the intermediate payment of ordered material:
 After getting the Receiving Report (RR) from store department, check with the original
purchase order (PO).
 If okay, release the intermediate payment as per terms and condition mentioned in the
PO.
 Procedure for releasing the final payment of ordered material:
 If party has already completed all the terms and condition under his scope and supply,
then fill the certificate for “Final Payment”.
 Release the final payment as per PO.
 Types of filters in AHU as per safety and cGMP requirements
 Guidelines for Engineering & Maintenance
Cleaning of Sampling Area
1.0 Purpose : To provide a documented guideline for cleaning of sampling area.

2.0 Objective : To provide a guide line how and when to clean the sampling area.
3.0 Scope : Cleaning of sampling area in stores department.
 Cleaning : Work man
 Follow up : Officer – Stores
Over all responsibility : Store Incharge
5.0 Procedure :
 Floor
 Clean the floor using detergent solution after using disinfectant solution use. And
Using lint free cloth.
 If the sampling area is not in use then clean the floor once in a day using
detergent after using with lint free cloth.
 Walls -If the dispensing area is not in use then clean the walls once in a day
using Detergent after using disinfectant solutions and with lint free cloth.
 Door
 Clean the door using detergent after using disinfectant solution and mop with
Using lint free cloth. If the Sampling area is not in use then clean the door once
In a day using same procedure.
 Weighing balance
 Clean the surface of balance with slightly wet lint free cloth.
 Labeling
 After completion of cleaning, affix the “cleaned “label on equipment / area.
Frequency: Once in a day and whenever before starting the Batch.
Detergent / Disinfectant Brand Quantity

Detergent Teepol 0.6 % Detergent solution
Disinfectant Dettol 0.5 % Disinfectant solution
Disinfectant Savlon 0.5 % Disinfectant solution

 Cleaning of sampling tools
 Air sampling in Sterile area
 Cleaning & Sanitisation of Sampling room
 Monitoring Personnel of sterile area in Aseptic area
 Storage & Handling of Inflammables

 1.0 Purpose :To provide a documented guideline for Storage & Handling of Inflammables.
 2.0 Objective : To use for Storage & Handling of Inflammables.
 3.0 Scope : Stores
 · Follow up : Officer – Stores
 · Over all responsibility : Q.A. Incharge, Store Incharge
 5.0 Procedure :
 · Storage area of such inflammable solvents should be away from main building
of Plant &Warehouse with lock & Key arrangement. There should be restricted
entry in this area.
 · Inflammable solvents store should be well ventilated. The area must be
equipped with Latest & approve ate fire extinguisher system.
 · Ensure that the earthing system provide in the inflammable solvents stores is
proper and each & every drum and pump is covered by earthing connection.
 · Unload the material by Deduction of drums & checking for weight take the
drums to Inflammable solvent storage area.
 · While unloading of inflammable solvent ensures that there is leakage &
damage in drums.
 · While unloading or during storage, if leakage of damage observed, shift the
solvent in other empty drum with help of pneunimetric pressure pump. Empty
drum must have been used previously for the same solvent. Ensure that
earthinh connecting has been attached to the leak drum.
 · While issue use FIFO system.
 · Use protective equipments i.e. rubber gloves, spectacle, Transparent
facemask etc.
 · While opening the lid, unscrew it slowly so as to let the air / vapor’s pass out.
 · Ensure earthing connection to the pump. Put SS Pneumetric pump inside of
the
 drum. Switch on air pressure. Start pneumatric pump. Dispense the required
quantity of solvent in 25 liter GI Drums. Close the knob of pressurized air.
 · Put the lid on drum. Close it tightly. Mark the drum as “LOOSE” for
identification.
 · Switch off lights. Lock the Inflammable solvent storage room.
 · Put the filled 25 liter drums in a carrier trolley & carry to air lock of coating area
in properly closed condition.
Operation of Fire Extinguisher
1.0 Purpose : To provide a documented procedure for Operation of Fire

Extinguisher.
2.0 Objective : Operation of Fire Extinguisher
cope : This SOP is applicable for Operation of Fire Extinguisher.
 Primary: Technician Engineering
 Secondary: Manager Engineering
5.0 Procedure :
 Foam Type Fire Extinguisher:
 It should be used for fires involving solvents, oils, greases, fats, charcoals etc.
 As these articles being lighter than water, will float on water and are likely to splash
burning liquids on all sides.
 CO2 Gas Type Fire Extinguisher:
 This type of extinguisher can also be used for fires involving inflammable liquids such
as solvents, oils, greases etc.
 The only difference between foam type and CO2 type fire extinguishers must always be
used in the event of an electrical fire.
 Dry Chemical powder (DCP Type Extinguisher):
 These are recommended mainly for tackling petroleum/solvents fires.
 However they are suitable for gas fires
 Dispensing of raw materials
 Storage & Handling of Inflammables
 Coding of areas in Stores
 Operation of Air Compressor

 1.0 Purpose : To provide a documented procedure for Operation of Air
Compressor.
 2.0 Objective : Operation of Air Compressor.
 3.0 Scope : This SOP is applicable for Operation of Air Compressor.
  Primary: Technician Engineering
  Secondary: Manager Engineering
 5.0 Procedure :
  Before starting the compressor, check the water level of cooling tower tank, if
it is low, then add more water and make it full.
  Switch ‘ON’ the “main switch” on panel of the air compressor.
  Start the cooling tower pump and fan by pushing the green button from
starter.
  Remove the air bubble from the vent.
  Push the green color “Push Button” on panel to start the air compressor.
  Air compressor will start in “UNLOAD” condition and after 30 second it will
start in “LOAD” condition automatically.
  During “LOAD” condition air pressure in receiver will rise, once 7 Kg/cm 2 air
pressure is achieved, compressor will cut off automatically and run in “UNLOAD”
condition.
  Open the plant air supply valve of the receiver. Air pressure in receiver will
start to reduce and when air pressure is reduced to 6 kg/cm 2 the compressor will
start on “LOAD” condition.
  This cycle of “LOAD” and “UNLOAD” will continue and it depends on air
pressure requirement in the plant.
  If air pressure is not required in production then switches “OFF’ the air
compressor as per method given below.
  Close the plant air supply valve of air receiver, allow to run the compressor in
“UNLOAD” condition.
  Switch ‘OFF’ the “main switch” on panel of air compressor.
  Drain the pressure in receiver from drain valve and close the drain valve
when air pressure becomes zero.
  Switch ‘OFF’ the cooling tower pump and fan by pushing the red colour push
button on starter.
  Close the cooling water inlet valve of cooler and cylinder jacket.
  Drain the water in cylinder head jacket.
 Effluent Treatment Plant
 1.0 Purpose: To provide the procedure to be followed for the treatment of
effluent generated from production department.
 2.0 Objective : To provide a documented procedure to be followed for the
treatment of effluent generated from production department.
 3.0 Scope : It is applicable to treatment of effluent in effluent treatment
plant.
 § Primary : Officer – Safety and Environment
 § Secondary : Manager Safety and Environment
 § Overall responsibility: General Manager (PA)
 5.0 Procedure :
 · Effluent/sewage generated should be drained into the drainage system.

 Flow of the effluent:

 Source of Production à Equalization Tank à Neutralization Tank à Flocculation
Tankà Primary Settling Tank à Aeration Tank-1 à Aeration Tank-2 à Secondary
Settling Tank à Treated Effluent Collection Sump à Carbon Filter-1 à Carbon
Filter-2 à GIDC Drainage.
 · Equalization Tank:
 Ø Initially effluent from different stream is being collected in under ground and
above the ground Equalization Tank.
 Ø Pump out the effluent from Equalization tank to Neutralization Tank by electric
pump.
 · Neutralization Tank:
 Ø The effluent pump from Equalization Tank is collected in Neutralization Tank.
 Ø In Neutralization Tank effluent is adjusted to proper pH .
 · Flocculation Tank:
 Ø Neutral effluent is send to the flocculation Tank from Neutralization Tank.
 Ø Flocculating agent are added here which emphasis fast settling in the
Primary Settling Tank.
 · Primary Settling Tank;
 Ø The effluent after pH adjustment & addition of flocculants is being feed in to
Primary Settling Tank.
 Ø Sludge is settled in Settling Tank due to flocculating agent.
 Ø This sludge is removed from the bottom of the primary settling tank and
sends in sludge bed.
 Ø The top supernatant is being sent in Aeration Tank.
 · Aeration Tank:
 Ø In Aeration Tank, the surface aerator maintains & keeps the effluent mix liquid
in suspension & supply dissolved oxygen to biomass.
 Ø The organic matter is decomposed in this tank by bacteria, which convert it
into CO2 and H2O.
 Ø The effluent from aeration tank is being transferred to Secondary Settling
Tank.
 · Secondary Settling Tank:
 Ø In Secondary Settling Tank Biomass is being settled down.
 Ø It is being recycled to aeration tank for maintaining MLSS & MLVSS of the
Aeration Tank.
 Ø Excess sludge is being transferred to the Sludge Drying Beds.
 Ø The treated effluent is being collected in Treated Water Sump.
 · Carbon Filter:
 Ø Finally, effluent is being given Tertiary Treatment in Carbon Filter.
 Ø The filter reduces the color of the treated effluent having almost colorless and
less COD.
 Ø Discharge into GIDC drain.
Accident Prevention Guidelines
urpose : To provide a documented procedure for preventing accident & Recording accident.
2.0 Objective : To maintain safety aspects
3.0 Scope : Preventing accident & Recording accident
 Follow up : Concern department head
 Over all responsibility: Personnel & Administration Manager.
5.0 Procedure :
 Accident Prevention
 Workman shall engage themselves in the duties which have been assigned to them.
The execution of their duties must be in the safe manner laid down in S.O.P. for the
operation, of the machine or duty concerned.
 Removal of guards or safety devices, cleaning of machines which they are
Running, etc., are expressly forbidden.
 Workmen working beyond the height of 10 feet shall wear the safety belt.
 If any employee / work man working beyond the height of 10 feet on ladder shall work
with one additional work man / employee to hold ladder.
 Safety instructions given or posted on Notice Boards are to be followed.
 Workman shall not keep sharp edge tools into their pocket.
 Any employee / workman working with electricity shall wear safety shoes &
Sock proof gloves.
 Any workman working with hazardous chemicals / acid shall wear the safety
Wears like goggles, gloves etc.
 Speed of vehicle inside the factory premises shall not exceed 20 km / hr.
 When welding work is to be carried out in closed area, extra fire extinguisher
Shall be provided.
 After working with oil, floor shall be cleaned thoroughly to wipe out the oil.
Solvents shall be stored in tight closed container.
 Used drums of solvent / chemicals shall be discarded by skilled workman.
 Sufficient emergency light shall be provided.
 Entry into transformer yard / explosive storage yard shall be restricted to selected
Personnel.
 Machine which is under maintenance shall be labeled as “Under Maintenance”.
 Workman shall enter into water tank, drainage, septic tank only after permission Of
Personal & Administration department.
 Workman shall carry out repairing work of high pressure line / high temperature Line /
or any explosive line only after permission of Engineering In charge.
 Wear earplugs near high noise area.
ecording of Accident
 Accident shall be recorded into Accident Register.
 The accidents are categorized as critical major and minor depending on the
 Seriousness of the incident.
 Action taken upon Accidents:
 The First aid, if required, after the accident shall be provided at the earlier marked
Locations and trained persons are available.
 The telephone no. of fire station, doctor, ambulance shall be displayed in all the
Departments to call upon in an emergency.
 The affected employee shall be immediately rushed to the hospital, if needed and is
provided the required medical help.
 Personnel Hygiene
 First Aid
 Security Personnel
 Uniform of Employees
LinkWithin
Appraisal of Employee
1.0 Purpose : To provide a documented procedure for appraisal of employee.

2.0 Objective : To evaluate performance of employee.
3.0 Scope : Employees
 Follow up : Personnel & Administration In charge
 Over all responsibility : General Manager (Adm)
5.0 Procedure :
 Performance Appraisal is carried out to inform employees about his performance
To identify where he / she stands against the expectation of company.
 First employees shall be called for Appraisal and Appraisal form to be given to
Employee for self appraisal and personal discussion.
 Strength & Weakness of the employees shall be discussed with examples.
 Employee shall be informed well in advance for Appraisal so that she / he can
Prepare for the discussion.
 Employees shall be ask specifically for any hindrances, or any other problems
Related to his performance.
 Rating System :
 Poor
 Normal
 Good
 Very Good
 Out Standing
Note: In case of Poor: give the reason behind that.
In case of Out Standing: give the reason behind that.
Frequency : Once in year
 Explanation of points covers in the performance appraisal form.
 Appraisal panel
 Department head
 Personnel & Administration In charge
 General Manager
 Appraisal Form
Name of employee
Department
Designation
Job carried out
Best performance by employee
Best output
Sign
Commitment
By Department Head opinion Sign
Commitment

 Medical check up of Employees
Appraisal of Employee
1.0 Purpose : To provide a documented procedure for appraisal of employee.

2.0 Objective : To evaluate performance of employee.
3.0 Scope : Employees
 Follow up : Personnel & Administration In charge
 Over all responsibility : General Manager (Adm)
5.0 Procedure :
 Performance Appraisal is carried out to inform employees about his performance
To identify where he / she stands against the expectation of company.
 First employees shall be called for Appraisal and Appraisal form to be given to
Employee for self appraisal and personal discussion.
 Strength & Weakness of the employees shall be discussed with examples.
 Employee shall be informed well in advance for Appraisal so that she / he can
Prepare for the discussion.
 Employees shall be ask specifically for any hindrances, or any other problems
Related to his performance.
 Rating System :
 Poor
 Normal
 Good
 Very Good
 Out Standing
Note: In case of Poor: give the reason behind that.
In case of Out Standing: give the reason behind that.
Frequency : Once in year
 Explanation of points covers in the performance appraisal form.
 Appraisal panel
 Department head
 Personnel & Administration In charge
 General Manager
 Appraisal Form
Name of employee
Department
Designation
Job carried out
Best performance by employee
Best output
Sign
Commitment
By Department Head opinion Sign
Commitment

 Medical check up of Employees
 Good Laboratory Practices

 1.0 Purpose : To provide instruction good laboratory practices.
 2.0 Objective : To provide a documented procedure for good laboratory
practices.
 3.0 Scope : This procedure is applicable for good laboratory practices
follow.
  Primary: Chemist : Officer of respective department.
  Overall Responsibility : Respective department Head.
 5.0 Procedure :
 Following types of laboratory facilities are necessary for assuring the quality of
Active pharmaceutical products:
  Premises :
  Control labs should be well designed, equipped, maintained and has
sufficient space to suit the operation to be performed in them.
  There should be provisions for writing, recording, storage of control
samples, chemicals and documents.
  A separate room is necessary to keep sensitive instruments free from
temperature humidity variations and dust particles.
  Chemical, and Microbiological labs should be separate from each other.
  Equipments :
  Control lab should be fully equipped with appropriate instruments for the
testing procedures.
  Equipments and instruments should be serviced and calibrated at suitable
and calibrated at suitable specified intervals of time and readily available.
Records should be maintained of the same. The records should indicate the next
calibration date.
  Defective equipment should be withdrawn from use until the fault has been
rectified.
  Cleanliness :
  Control lab should be kept clean in accordance with the written procedure.
  A written procedure for cleaning the glass apparatus of chemical assay
should be available.
  Personnel should wear clean, protective clothing appropriate to duties
being performed.
  Sampling:
  Samples should be taken in such a manner that they should be
representative samples in accordance with their written sampling procedure. For
this statistical control norms can be adopted.
  The sampling procedure should include:
  Method of sampling.
  Equipment to be used.
  Amount of sample taken.
  Any special precautions or instructions to be followed.
  Raw materials are to be collected as per the lot numbers or batch numbers
given by the manufacturer.
  Each container should bear a label indicating:
  Name of the material.
  Date of collection / receipt.
  Batch / Lot number.
  Name of the manufacturer and supplier.
  Date of manufacturing / expiry.
  Status label: ‘UNDER TEST’, ‘APPROVED’, AND ‘REJECTED’.
  Documentation:
  It indicates the test procedure, specification, standards, limits and detailed
analytical reports.
  Raw material analysis record indicating:
  Name of the material with code number and reference number.
  Date of receipt, date of sample collected, date of analysis, completion data
  Number of containers received and number of samples collected.
  Detailed analytical report indicating standards and specification, status of
sample, with approved signature.
  Finished product record indicating:
  Name of the material with code number and reference number.
  Date of receipt, date of sample collected, date of analysis, completion data.
  Number of containers received and number of samples collected.
  Detailed analytical report indicating standards and specification, status of
sample, with approved signature.
  Record of in-process materials / intermediates.
  Record of standard / normal solution indicating periodically its validity, with
date and authorized signature.
  Reference standard records determining the potency / purity periodically
with date and signature.
  Records of water analysis used for analytical purpose.
  Control sample record showing its location, date of receipt, quantity
received, date of removal indicating the reason and the product details with the
authorized signature should be maintained.
  List of various chemicals used.
  Stability data of all products.
  Market complaint record indicating the details:
  Nature of the product.
  Manufacturing
  Nature of complaint.
  Region from which complaint received.
  Quality Assurance Department investigation / remark / action.
  Instrumentation and Calibration :
  Analytical balance should be checked at least annually against weights
traceable to National Bureau of Standards Calibration.
  The accuracy of the calibration of pH meter should be checked using
known buffers.
  Spectrophotometers should be checked with regard to their photometric
accuracy, reproducibility, resolution, and wavelength.
  Thermometers should be checked against Standard Thermometer of
National Bureau of Standards Calibration.
  Water baths, refrigerators, incubators should be checked for their
distribution of uniform temperature by a calibrated thermometer.
  Controls :
  CHEMICAL: Specially prepared test solution should be used for checking
the accuracy of various tests.
  Karl Fischer Moisture Test: Test one or more hydrated compound to
compare the theoretical water content obtained.
  Infra- red and UV Identity: Maintain spectra of each active ingredient of
reference standard.
  Checking all the manufacturing and in-process data along with the
analytical data before the final release.
  The transfer of entries from the note books to the final records is to be
cross checked by the authorized person.
  Specifications:
  Specifications approved by Quality Control should be available for:
  Starting material
  Finished products
  Packing material
  Intermediates.
  Facilities:
  Fuming chamber / exhaust fan
  Vacuum line.
  Cross ventilation / air conditioning facilities.
  Lock room facility to store poisonous material.
  Chemical and glass ware storage.
  Fire extinguishers.
  Returned Goods and Reprocessing Goods:
  A finished product returned from the depot or market may be relabeled,
provided there is no risk to the product quality and therapeutic value.
  Mix-up during relabeling should be avoided.
  Additional tests of reprocessed product should be considered.
  Training :
  Chemists, analysts, lab assistants, should be trained to know the
importance and technical importance of all GMP norms.
Good Documentation Practices
1.0 Purpose : To provide instruction good documentation practices.

2.0 Objective : To provide a documented procedure for good documentation practices.
3.0 Scope : This procedure is applicable for good documentation practices follow.
 Primary: Chemist/ Officer of respective department.
 Overall: Respective department Head.
5.0 Procedure:
 All information related to activities should be recorded clearly and easy to read.
 Abbreviated date should be recorded by Day/Month /Year.
 All documents should be made in black ball pen / ink pen only.
 Data should be specific and as far as possible numerical value.
 Scrap paper should not be used for recording the data.
 Document should be made online.
 If any error is found immediately after recording the data, cross out incorrect information
with a single line and not by using erasable pens or Corrective fluids. Enter correct data,
sign and date near correction.
 Information should be recorded on proper forms, laboratory notebooks, cleaning
records, immediately after actions are completed. Entries of signatures or initials and
dates must be made at the same time.
Overwrite should not acceptable in any documents
 Good Laboratory Practices
 Good Manufacturing Practices
 Numbering system for Standard Operating Procedures and Index of Standard Operating
Procedure
 Restart The Activities After Power Failure / Breakdown

 1.0 Purpose : To provide a documented procedure for Procedure For Restart
The Activities After Power Failure / Breakdown.
 2.0 Objective : Procedure For Restart The Activities After Power Failure /
Breakdown.
 3.0 Scope : This SOP is applicable for. Restart The Activities After Power
Failure / Breakdown.
  Primary: Technician Engineering
  Secondary: Manager Engineering
 5.0 Procedure :
  Power failure:
  Check the main power circuit panel for voltage and break down.
  Start the D.G. Set and check the voltage and frequency, it should be 430 V
and 50 HZ.
  Then changeover the power supply from G.E.B. to D.G. Set for normal
operation.
  After resuming the power supply from G.E.B. check the voltage and
frequency.
  Before changing over power supply from D.G. Set power supply inform the
critical
  Processing areas personnel and switch. the power supply for normal
working.
  BREAKDOWN :
  In case of breakdown of power supply, confirm the nature of breakdown.
  Start the D.G. Set
  Check the voltage and frequency; it should be 430 V & 50 HZ.
  Change over the power supply from G.E.B. to D.G. Set for normal working.
  After attending the breakdown of power supply, restore the power supply and
check the voltage and frequency of mains.
  Before change over the power supply from D.G. Set to G.E.B. power supply
inform to critical activities area personnel for normal working.
 Issuance of Labels and Reconciliation
 1.0 Purpose : To provide instructions for Issuance of labels and
reconciliation.
 2.0 Objective : To provide a documented procedure for Issuance of labels
and reconciliation.
 3.0 Scope : This procedure is applicable for Issuance of labels and
reconciliation for QA.
  Primary: Officer – QA / Officer – Production
  Secondary: Production In-change
 5.0 Procedure:
  On receipt of labels issuance request intimation / note from production
department, QA shall enter the entry in label issue register.
  QA shall enter the information related to label, like Name of Product, Product
Code, Product Stage, Batch Number, Manufacturing Date, Expiry Date, and
required labels quantity.
  QA shall issue required quantity of labels with one extra label for BMR.
  QA shall take a receiver signature in labeling issuance register.
  Maintain the issuance record with updating labels quantity.
  If any mistake occur during filling the data on label, issue another new label
and destroyed the incorrect label
  Maintain record of destroyed labels in label issue register.
 Instructions for Supervision of Analysis
 1.0 Purpose : To provide instructions for supervision of analysis.
 2.0 Objective : To provide a documented procedure for supervision of
analysis.
 3.0 Scope : This procedure is applicable for supervision of analysis in QC
department.
  Primary: Officer – QA / Officer-Store
  Secondary: Officer – QA Manager.
 5.0 Procedure:
  Spot-check once a week all registers, reagents and volumetric standard
solutions.
  Frequently observe the actual testing done by the chemist.
  Review analytical reports and before signing check and confirm for:
  Complete entries in to the logbooks, test data sheets etc.
  Reagents should be stored in bottles.
  Reference / working standards stored in desiccators should be checked for
details like name, date of preparation, date of expiry, purity.
  Whether analysis has been done as per the specified pharmacopoeia or in-
house specifications (if specified).
  If not found to comply, necessary action to rectify / modify the procedure can
be taken.
HANDLING OF SAMPLE FOR ANALYSIS
1.0 OBJECTIVE
To lay down a procedure for Handling of Samples for Analysis of Raw Materials./ Formulations.
2.0 RESPONSIBILITY
Quality Control Officer.
3.0 ACCOUNTABILITY
Quality Control Manager.
4.0 PROCEDURE
4.1 RAW MATERIALS
4.1.1 The Quality Control Officer shall receive the samples along with the GRN and
‘sampler’s
check list.
4.1.2 The samples shall be kept in the tray labeled ‘Under Test Raw Material, till those are
allocated for analysis.
4.1.3 The samples shall be handled carefully to avoid cross contamination.
4.1.4 The samples shall be allocated for analysis by Quality Control Manager and relevant
details
shall be mentioned in the register.
4.1.5 The excess samples shall be destroyed after completion of analysis.
4.1.6 The samples for destruction shall be kept in a container labeled as “samples for
destruction”
and shall be destroyed as mentioned below,
4.1.8 Raw material shall be removed from their container.
4.19. The container shall be destroyed by breaking (in case of glass), by cutting (in case of
plastic).
4.1.10 Collected material shall be destroyed by putting the material in water , but the cephalosporin
materials shall be destroyed by putting the material in 2% w/v solution of sodium
hydroxide.
Then all the collected material closed properly and send to the burning pit.
4.2 FORMULATIONS
4.2.1 The Quality Control Officer shall receive the samples along with the sample request
form and he
shall ensure intactness of the samples by visual checking.
4.2.2 The entries of the samples shall be made in the respective register by the Quality Control Officer.
4.2.3 Sample shall be kept in the tray labeled as ‘Under Test formulation till those are allocated for analysis.
4.2.4 The samples shall be handled carefully to avoid cross contamination.

4.2.5 The samples shall be allocated for the analysis by the Quality Control Manager. The relevant details of
allocation and green sheet number shall be mentioned in the respective registers.
4.2.6 The excess samples shall be destroyed after completion of analysis .
4.2.7 The samples for destruction shall be kept in a container labeled as ‘Samples for destruction and shall be
destroyed as mentioned below.
4.2.8 Tablets, capsules, dry syrups and powder of vials shall be removed from their respective pack.
4.2.8 Packaging material shall be destroyed by burning at burning pit and product shall be
destroyed by burning at burning pit after breaking.
4.3 All Formulations / Raw Material Samples of Cephalosporin group of products shall be disposed off after
treating with 2% w/v Sodium Hydroxide solution.
4.4 No samples shall Under Test for more than 60 days. Any sample found pending for analysis
for more than 60 days shall be investigated for delay in analysis & documented.
4.5 ABBREVIATIONS
SOP = Standard Operating Procedure

GRN = Goods Receipt Note
W/v = Weight by Volume

6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:

8.0 ANNEXURES:
Nil
9.0 REFERENCES:
In house.
 CONTROL OF ISSUANCE OF RECORD OF ANALYSIS
 Sending sample to contract lab
 Sampling of Raw Material
 PROCEDURE FOR OPERATING OF SONICATOR


 1.0 OBJECTIVE :

 The objective of this SOP is to lay down the procedure for giving Analytical Reference Number
(A.R. No.) for Raw Material, Packaging Material, Finished Product, Blend and Validation
samples.

 2.0 RESPONSIBILITY

 Executive – Quality Control

 3.0 ACCOUNTABILITY

 Head – Quality Control

 4.0 PROCEDURE

 4.1 RAW MATERIAL

 The A.R. No. is a unique code having 10 digits.
 For example: 5RA0028001
 First digit stands for the Year. specified Raw material
 Second to Seventh Digit stands for code of the specified Raw material.
 The eighth to tenth digit is serial number of consignment starting with “001”

 4.2 PACKING MATERIAL

 For example: 5PA0028001
 First digit stands for the Year. Specified Packing material
 Second to Seventh Digit stands for code of the specified Packing material.
 The eighth to tenth digit is serial number of consignment starting with “001”

 4.3 FINISHED PRODUCT:
 For example : 02C-5A/30156
 First two digits stands for the month of manufacturing.
 Third digit stands for the dosage forms i.e. C for Capsules, S for Dry Syrups, T for Tablets, I for
Injection,
 The fourth digit is “-“
 Fifth digit “5” stands for Year 2005.
 Sixth digit “A” stands for ALKEM LAB LTD,
 “G” stands for GALPHA LAB LTD,
 “I” stands for INDICHEMI HEALTH SPECILIETIES .
 Seventh digit is “/”.
 Then the advice sheet No.(Who is having five digits) shall be followed.

 4.4 BLEND /INPROCESS:
 For example : 2BC-5A/30156 / 2IC-5A/30156
 First digits stands for months for manufacture.
 Second digit stand for Blend /Inprocess.
 Third digit stands for the dosage forms i.e. C for Capsules, S for Dry Syrups, T for
Tablets, I for
 Injection
 The fourth digit is “-“
 Fifth digit “5” stands for Year 2005.
 Sixth digit “A” stands for ALKEM LAB LTD.
 “G” stands for GALPHA LAB LTD ,
 “I” stands for INDICHEMI HEALTH SPECILIETIES
 Seventh digit is “/”.
 Then the advice sheet No.(Who is having five digits) shall be followed.

 4.5 VALIDATION SAMPLES:

 After location code there is “/” followed by “V”, which stands for validation sample followed by
 “/ ” and batch No.


 4.6 LOCATION CODE :-

 INJ- Injection
 TAB- Tablet
 BET- Betalactum
 CAP- Capsules
 DRY- Dry syrup
 5.0 REASON FOR REVISION
 Harmonization of format.

 6.0 TRAINING:
 Trainer -- Head – Quality Control
 Trainees-- Quality Control Chemists & Assistants
 Period -- One day
 7.0 DISTRIBUTION:

 Certified Copy No. 1 : Head of Department – Quality Control
 Original Copy : Head – QUALITY ASSURANCE.

 8.0 ANNEXURES:

 Nil

 9.0 REFERENCES:

 In house.

SAMPLING OF STERILE RAW MATERIAL
1.0. OBJECTIVE
To lay down a procedure for aseptic sampling of sterile Raw

Material so as to get a
representative sample of the whole lot for analysis.
2.0. RESPONSIBILITY
Micobiologist .
3.0. ACCOUNTABILITY
Quality Control Manager.

4.0 PROCEDURE
4.1 Generate Sampler’s checklist-RM as per the Batch Number mentioned in the
Under Test list and decide the number of containers to be sampled as per sampling
plan (Annexure – I).
4.2 Check and reconcile number of containers and the total quantity as
shown in Under Test.
Compare the details like manufacturing date, expiry date and

pharmacopoeial status
mentioned on Sampler’s checklist-RM with that mentioned on

manufacturer’s label. Ensure
that each container is affixed with ‘UNDER TEST’ label. In case of

any discrepancies
inform to Quality Control Manager / Ware-House Manager.
4.3 Check the packing condition of the containers for any damages.
Physically damaged
containers shall not be considered for sampling and the same shall
be Rejected..
4.4 In case of material received in triple laminated bags, the sample

container received alongwith
the material shall be used for microbiological and chemical testing.
4.5 In case of sterile material received in aluminium containers, follow

the procedure given
below,
4.5.1. Select the containers to be sampled and inform Ware-House Officer to
transfer these containers to the raw material storage area of production block.
4.5.2 Sterilize and dehydrogenate all sampling accessories as mentioned in point no.
5.0.
4.5.3 Prepare label for individual container sample, with details of name of the
material, Batch no., and container number.
4.5.4. Total number of labels to be prepared shall be equal to the number of containers
to be sampled.
4.5.5. Prepare labels (annexure-II ) for Sample for Analysis, microbiology test and
control sample.
4.5.6. Transfer the containers to the buffer zone. Follow the SOP on ‘Raw material
receipt, storage, and transfer to sterile area’.
4.5.7. Enter into the sterile area following gowning and degowning procedure for sterile
area.
4.5.8. Transfer the container to be sampled to the Quality Control Microbiology Lab
( Sterile Area.)
4.5.9. Ensure that temperature inside the room is less than 25 deg.C. & RH is less than
40% or as specified on Manufacturer’s label.
4.5.10. Place one container under LAF. Peel off the outer tape/seal from the mouth of the
container and open the lid of the container aseptically.
4.5.11. Withdraw an appropriate quantity of sample aseptically into a piece of

depyrogenated aluminium foil.
4.5.12. Observe carefully the physical appearance of the material for any abnormalities
like discolouration, lumps, foreign matter and physical heterogenicity.
4.5.13. If any abnormalities are observed, collect the sample in two separate vial, for
separate evaluation.
4.5.14. Plug all vials with sterilised rubber plugs.
4.5.15. Close the lid of the container tightly, wrap the mouth with adhesive tape and
remove the container from LAF booth.
4.5.16. Mark the sample containers using glass marker with batch number and container
number in case of individual sample and only batch number in case of pool, control
sample & micro sample.
4.5.17. Mark containers / packs which are selected for sampling with marker as N/1/n,
N/2/n….N/S/n (‘N’ stands for total number of packs / containers, ‘S’ for serial number
of container selected for sampling and ‘n’ for total number of containers taken for
sampling).
4.5.18. Similarly sample the rest of the containers aseptically. Refer annexure-II for total
quantity to be sampled.
4.5.19. Seal all the vials with aluminium tear off seals.
4.5.20. Transfer all the containers to Air lock-1.
4.5.21. Transfer all the samples & sampling aids in the Air lock-1.
4.5.22. Clean the LAF bench and room and leave the sterile area alongwith the samples.
4.5.23. Label all the collected sample vials.
4.5.24. Affix ‘SAMPLED’ labels (Annexure – III) duly signed with date of sampling on the
container.
4.5.25. Record all observations in the Sampler’s checklist-RM (Annexure-IV).
4.5.26. Give the samples along with the Sampler’s checklist-RM, Supplier’s COA (if
available) to Quality Control Laboratory for Chemical Analysis.
4.5.27. Inform the Ware-House Officer to shift all the containers back to Stores ‘UNDER
TEST STORAGE’ area after performing decontamination of external surfaces.
4.6 Preparation of sampling accessories
4.6.1. Vials : Follow washing, drying, sterilizing and depyrogenation procedure as

followed in normal production.
4.6.2. Rubber Stopper : Follow washing steam sterilization and drying procedure as
followed in normal production run.
4.6.3. Spoons : Wash the spoon dry and wrap in 3 layers of aluminium foil,
depyrogenate in Dry Heat Sterilizer at 250 degree Celsius for one hour.
4.6.4. Aluminium Foil : Cut pieces of aluminium foil of approximately 10cm.sq.area,

wrap them in triple layer of aluminium foil and depyrogenate in Dry Heat Sterilizer
at 250 degree Celsius for one hour.
4.6.5. After depyrogenation of sampling accessories, transfer them to
production block hatch.
Remove outer layer of wrap here, from this hatch transfer the
accessories to aseptic area
hatch. Remove the second layer of the wrap and transfer them to
buffer zone LAF.
4.7 ABBREVIATIONS :
COA = Certificate of Analysis.
5.0 REAVISION FOR REVISION:
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION
Certified Copy No. 2 : For Display in microbiology Dept.
Original Copy : Head – QUALITY ASSURANCE

8.0 REFERENCES
USP 25 Page no.:- 1878 , E.P: - Page no. 125 , 2.6.1
9.0 ANNEXURES:
Annexurer-1 Attached
ANNEXURE – I
SAMPLING PLAN
Revision No.: 00 Page No. : 1

of 1
Effective from: 10.01.2005
MINIMUM NUMBER OF CONTAINERS RECOMMENDED TO BE TESTED (AS PER E.P)
Number of items in the batch Minimum no. of containers to be sampled
Not more than100 containers 10% or 4 containers, whichever is greater
More than 100 but not more than 10 containers

500 containers
More than 500 containers 2% or 20 containers, whichever is least
ANNEXURE – II
QUANTITY TO BE SAMPLED
Tests Sample Quantity (Approx.)
Chemical 40g (in two vials)
Microbiology (sterility & endotoxin) 20g
Control sample 20g
Total quantity 80g
ANNEXURE- III
SAMPLED
SING. /DATE
CLEANING OF LABORATORY GLASSWARE
1.0 OBJECTIVE
To define the cleaning procedure for glassware used during analysis.
2.0 RESPONSIBILITY
Quality Control Chemist

3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 Cleaning of General Glassware
4.1.1 Dip the used glassware in a basin of water containing detergent.
4.1.2 Brush each item thoroughly, to remove stains and or grease.
4.1.3 Rinse thoroughly with RO water.
4.1.4 Final rinsing given with purified water.
4.1.5 Dry in an oven and store in designated areas.
4.2 Microbiological Glassware
4.2.1 Follow step No. 4.1.1 to 4.1.3
4.2.2 Final rinsing given with water for Injection.
4.2.3 Glass ware used for Sterility / Endotoxin purposes must be sterilized /
depyroginated for 30 minutes at 250º C .
4.2.4Glass ware used for microbiological analysis etc. must be sterilized by heating
for 30 minutes at 120º C .
4.3 New Glassware

4.3.1 After routine cleaning treat for 24 hours with 5 % solution of sodium carbonate
followed by soaking in hydrochloric acid for 24 hours. Wash thoroughly with R.O
water & final rinsing is given with purified water.
4.4 Greasy Glassware
4.4.1Treat with 5% sodium carbonate solution or few ml of acetone or

chromic acid solution.
4.5 CAUTION
4.5.1 While preparation of chromic acid solution ensure that must wear
gloves and goggles.
4.5.2 Chromic acid solution is extremely corrosive and hygroscopic and

should be Stored in a glass -
stoppered bottle in a safe place.
4.5.3When the mixture acquires a green colour , discard under continuously

flowing water.
* Preparation Of Chromic Acid Solution
Dissolved 100 gm of sodium dichromate in 50 ml water, add slowly with constant

stirring 750 ml of sulphuric acid . Allow to cool.
4.6 Glassware With Adhering Precipitate

4.6.1Use nitric acid, aquaregia or fuming sulphuric acid .
4.7CAUTION
4.7.1 These materials are extremely corrosive. Wear gloves and goggles
when using.
4.8 ABBREVIATIONS
RO- Reverse Osmosis
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : Display in Glassware Washing Room.

8.0. ANNEXURES:
Nil
9.0. REFERENCES:
IP/BP/USP
CLEANING OF QUALITY CONTROL LABORATORY
1.0 OBJECTIVE
To lay down the procedure for cleaning of quality control laboratory.
2.0 RESPONSIBILITY
Hygiene supervisor
3.0 ACCOUNTABILITY
Quality Control Chemist
4.0 PROCEDURE
4.1 Broom the floor of all the sections including the staircase, daily and then
mope with wet mope.
4.2 Clean all the tables and reagent racks with dry mopping.
4.3 Empty the dust bins, clean them and keep them at place.
4.4 Clean all the instruments with a cotton duster.
4.5 Once in a week clean all the fixtures with dry mopping.
4.6 Clean all the racks in chemical stores once every week .
4.7 Clean all the walls and ceiling once every week .
4.8 After cleaning the area by workmen, check the cleanliness of the area and
put the Yes in
the cleaning record as per the ANNEXURE I
4.1. Frequency :
S.No Activity Frequency

.
A Brooming and general cleaning Two times a day
B Mopping Two times a day
C Dustbin Cleaning Two times a day
D Instrument cleaning Once a day
E Walls and Ceiling Once a week.
F Reagent racks in chemical stores Once a week
Note: - trained workmen should do Instrument cleaning.

5.0. REASON FOR REVISION
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 1: Head of Department – Quality Control
8.0 ANNEXURES:
ANNEXURE – I, For QC Cleaning Record.
9.0 REFERENCES:
In house
ANNEXURE I
Q.C. CLEANING RECORD

of 1
Effective from:
CLEANING RECORD
QC Lab : Wet chemistry lab / Instrument rooms / chemical stores / Control sample room.
Brooming Mopping Dustbin Instrument Walls Reagent Checked

and Cleaning cleaning and racks in by.
general Ceiling chemical
cleaning stores
Frequency Two times Two Two Once a day Once a Once a

a day times a times a week. week.
Date day day
 CLEANING OF LABORATORY GLASSWARE

 LABORATORY DISCIPLINE IN QC LAB
OPERATION AND CALIBRATION OF HPLC SYSTEM (SIMADZU)
1.0. OBJECTIVE:
The objective of this SOP is to ensure that the instrument performs satisfactorily
and gives accurate and reproducible data.
2.1 The Chemist/ Executive - Quality Control shall be:
2.1.1. Responsible for operating the HPLC as per the SOP.
2.1.2. Responsible for timely calibration of HPLC System as per the SOP.
2.1.3 Responsible for ensuring the adherence of SOP.
4.0. PROCEDURE:
4.1 PROCEDURE FOR GENERAL CLEANING:
4.1.1 Ensure that the power supply to the instrument is switched off and main cord is
removed from supply.
4.1.2 Clean the instrument with a clean dry cloth everyday. A wet cloth dipped in dilute
soap solution may be used occasionally.
4.1.3 Precaution must be taken to clean the instrument immediately with dry cloth.
4.2 OPERATING INSTRUCTIONS:
4.2.1 Ensure that the instrument is properly connected to the power supply.
4.2.2 Fix the column and prepare the mobile phase.

4.3 PREPARATION OF MOBILE PHASE
4.3.1 Use HPLC grade solvent / water & AR/Excel/ HPLC grade reagent only.
4.3.2 Filter the mobile phase through 0.45 membrane filter after mixing it in required
proportion and de-gas on ultrasonic bath for about 5 minutes.
4.4 PROCEDURE TO GET STARTED
4.4.1 Switch on pump, auto injector, detector and then system controller.
4.4.2 Turn the drain valve knob to 180 in anticlockwise to open the drain valve to run
the purge system.
4.4.3 After the purge is over close the drain valve.
4.4.4 Set desired flow rate by pressing function key.
4.4.5 Press pump key. The pump will run and indicator will glow.
4.4.6 Purge the auto injector by pressing purge key on auto sampler display.
4.4.7 Enter the desired wavelength on detector using function key
4.5 PROCEDURE TO OPERATE CLOSE UP
4.5.1 Switch on the computer monitor and printer.
4.5.2 Double click on the main Menu of SHIMADZU Icon.
4.5.3 It will show Confrigration, Real Time, and Sample Shedule & Post Run Analysis.
4.5.4 Open Real Time.
4.5.5 From the “file menu” create a new method or load the existing method.
4.5.6 Create a new sample shedule and feel sample name, batch number,,sample
volume , method name and file name ,after then save the shedule .
4.5.7 Run Sample Shedule .

4.5.8 For system suitability test, inject six continuous injections of same standard and
RSD should not be more than 2.0 %, otherwise it is specified in standard test
procedure.
4.5.9 After every ten injection of sample (5 samples in duplicate), the standard solution
shall be injected 3 times and the RSD shall be calculated and ensure that it is within
the limit.
4.6 SHUT DOWN PROCEDURE
4.6.1 Close Sample Shedule, Real Time and then CLASS LC 10 to Software.
4.6.2 From Start button select “Shut down” and click yes.
4.6.3 Switch-off the computer.
4.6.4 Switch-off CBM.
4.6.5 Switch-off Detector then, auto sampler.
4.6.6 Stop pump by pressing, “Pump” key and switch off the pump module.
4.7 CALIBRATION PROCEDURE.
4.7.1 FOR PUMP:
4.7.1.1 Disconnect the column and connect the inlet and outlet tubing’s with a union.
4.7.1.2 Prime all the lines at 5 ml/min flow rate with water and ensure that flow line is
free from air bubbles.
4.7.1.3 Set the flow rate at 1ml / min and collect the mobile phase (water) in a dry
preweighed beaker and collect the mobile phase for 10 min. weigh the beaker to get
the weight of mobile phase.
4.7.1.4 Calculate the flow rate by dividing the weight obtained with weight per ml and 10
(run time).
4.7.1.5 Calculate the corresponding flow rate. Carry out the experiment in duplicate.
4.7.1.6 Repeat the same procedure for Pump- B

4.7.1.7 Record the observation in Annexure -1
4.7.1.8 Acceptance criteria: Flow rate should be in between 0.99 to 1.01 ml / min..
4.7.2 FOR GRADIENT VALVE:
4.7.2.1 Install union in place of column & flush solvent lines (A&B) at flow rate of 2ml/min
with water.
4.7.2.2 Prepare the mobile phase.
4.7.2.3 Prepare 0.3% acetone with HPLC grade water.
4.7.2.4 Fill reservoir A with 100% HPLC grade water & reservoir B with 0.3% acetone in
HPLC grade water as mobile phase.
4.7.3 INSTRUMENT SET UP:
4.7.3.1 Enter the following time program:
TIME FUNCTION VALUE
0.01 B CONC 10
10.00 B CONC 10
10.01 B CONC 50
20.00 B CONC 50
20.01 B CONC 90
30.00 B CONC 90
30.01 B CONC 100
40.00 B CONC 100
40.01 B CONC 0
50.00 B CONC 0
4.7.3.2 Use detector at wavelength of 254 nm.
4.7.3.3 Record the printout of gradient valve test as per Annexure - 2.

4.7.3.4 The gradient valve test shall be accepted if actual concentration with ±1% of set
concentration.
4.7.4 CALIBRATION OF INJECTOR:
CHECK FOR PRECISION: Purge the injector system with 100% water to ensure the
complete washing of injector.
4.7.5 STANDARD PREPARATION:
4.7.5.1 Transfer about 50 mg of Uracil to a 250ml volumetric flask. Add 100ml of

Methanol, sonicate to dissolve and make up the volume with Methanol to obtain a
solution containing about 0.02 mg/ml of Uracil.
4.7.5.2 Filter the solution through 0.45m membrance filter.
4.7.5.3 Use HPLC grade Methanol as the mobile phase.
4.7.5.4 Instrumental Set Up
Column : Hypersil ODS or equivalent 150 x 4.6 mm, 5.0m
Flow rate : 1.0 ml/min
Injector Volume : 20m litre
Detector : 254 nm
4.7.5.5 Inject the standard preparation six times in the system. The peak areas observed
shall be consistent.
4.7.5.6 The relative standard deviation for area counts calculated shall not be more than
1.0%.
4.7.5.7 Record the observation in the format as mentioned in Annexure – 3.
4.7.6 CHECK FOR LINEARITY:
4.7.6.1 Inject 10, 20, 30, 40 & 50m litre of standard preparation in duplicate. Calculate
the average area counts corresponding to each set of injection.
4.7.6.2 Tabulate the average area against each injection. Plot a graph for area counts vs
mlitre the resulting graph shall be linear.
4.7.6.3 The correlation coefficient calculated shall be not less than 0.99.
4.7.6.4 Record the observation as per the Annexure - 3.
4.7.7 CALIBRATION OF DETECTOR:
4.7.7.1 Standard preparation. Mobile phase, Instrument set- up same as mentioned in

calibration of Injector.
4.7.7.2 Run the chromatograph at different wavelength (252 nm – 262 nm with 2 nm

increment)
4.7.7.3 The largest peak response shall be at 258 nm ± 2nm.
4.7.7.4 Record the results in the detection calibration record as per the Annexure - 4.
4.7.7.5 Affix a calibration status label on the instrument containing “Calibrated On”,
“Due On” and “Signature”.
4.7.7.6 Report to Head – QC, if any discrepancy observed during calibration or operating
the instrument and affix ‘Under Maintenance’ label on the instrument.
UNDER MAINTENANCE
EQUIPMENT :
SINCE :
SIGNATURE:
4.7.8 FREQUENCY OF CALIBRATION:
4.7.8.1 Detector : Once in three months and after each maintenance job.
4.7.8.2 Pump : Once in three months and after each maintenance job.
4.7.8.3 Injector : Once in six months and after each maintenance job.
4.7.8.4 Gradient : Once in six months and after each maintenance job in the pump.
6.0 TRAINING:
Trainees -- Quality Control Chemists and Assistants
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : File copy in HPLC Calibration Data
Reference Copy No. 3 : Display copy Near HPLC System
8.0 ANNEXURES:
Annexure – 1 : Format For Calibration Record Of Pump (Flow Rate)
Annexure – 2 : Format For Calibration Record Of Gradient Proportionate Valve
Annexure – 3 : Format For Calibration Record Of Injector
Annexure – 4 : Format For Calibration Record Of Detector
9.0 REFERENCES:
In house.
ANNEXURE – 1
FORMAT FOR CALIBRATION RECORD OF HPLC

Revision No.: 00
Effective from:
Calibration Record : High Performance Liquid Chromatograph
Instrument No. :
Make And Model :
Calibration Date :
Calibration Due On :
Calibration Of Pump (Flow Rate):
Observed weight in gm.

Limit in ml
Flow rate adjusted to 1.0 ml / min. Mean wt. / Mean
1 2 / min.
min Vol. / min
Pump-A
Weight of beaker + water after 10

min. (W2)
0.99 to
Weight of beaker (W1) 1.01
(W2 – W1) / 10
Pump-B
Weight of beaker + water after 10

min. (W2)
0.99 to
Weight of beaker (W1) 1.01
(W2 – W1) / 10
Weight per ml of water = ________ gm.
Calibrated By: Checked By:
Date Date :
ANNEXURE – 2

Revision No.: 00
Effective from:
Instrument No. :
Make And Model :
Calibration Date :
Calibration Of Gradient Proportionate Valve

Parameters :
Mobile Phase : Reservoir A 100% Water with HPLC
Reservoir B 0.3% Acetone HPLC
Wavelength : 254 nm.
Flow rate : 2 ml / min.
Height From Base Line

Tine Value Actual Value Set In
To B Concentration
Range Obtained The Program
Peak.
0.01 To (Lt: 9.9 To
10.0 10.1)
10.01 To (Lt: 49.5 To

20.0 50.5)
20.01 To (Lt: 89.1 To

30.0 90.9)
Value : Height of B Concentration
--------------------------------------
Height of a 100 % Concentration
Remarks: Satisfactory / Not Satisfactory
Date Date :
ANNEXURE – 3

Revision No.: 00
Effective from:
Instrument No. :
Make And Model :
Calibration Date :
Calibration Of Injector : 1. Check for Precision:
Standard Preparation:
Take ______ mg of Uracil (about 50 mg)  250 ml.  5ml  50ml with Methanol.
Parameters:
Mobile Phase : Methanol HPLC grade. Column : ODS (150 mm x 4.6 mm. 5
micron)
Wavelength : 254 nm. Flow rate : 1 ml / min. Injection volume : 20 l.
Inject six replicate injection of standard solution and calculate RSD for area of main
peak.
Injection no. Area % of RSD Limit
3
Not More Than 1.0 %
4
2.Check for Linearity :
Correlation coefficient
Sr. Injection
Area Mean Observed
No. volume Limit
results
1 10 l. i) Not less than

0.99
ii)
i)
2 20 l.
ii)
i)
3 30 l.
ii)
i)
4 40 l.
ii)
i)
5 50 l.
ii)
Remarks: Satisfactory / Not satisfactory.
Date Date :
ANNEXURE – 4

Revision No.: 00
Effective from:
Instrument Sr. No. :
Make And Model :
Calibration Date :
Calibration Of Detector
Standard Preparation:
Take _____ mg of Uracil ( about 50 mg.) 250 ml.  5ml  50ml with Methanol.
Parameters:
Mobile Phase: Methanol HPLC grade Column: ODS (150 mm x 4.6 mm. 5
micron)
Wavelength: 252- 264 nm with 2 nm increment. Flow Rate: 1 ml / min.

Injection Volume: 20 l.
Sr.No. Wavelength (nm) Area Mean
1)
1 252
2)
1)
2 254
2)
1)
3 256
2)
1)
4 258
2)
1)
5 260
2)
1)
6 262
2)
1)
7 264
2)
Largest peak response is observed at __________ nm. (Limit: 258 nm ± 2

nm)
Remarks: Satisfactory / Not Satisfactory
Date Date :

 OPERATION AND CALIBRATION OF POLARIMETER
 OPERATION AND CALIBRATION OF MICROPIPETTE
 OPERATION AND CALIBRATION OF ANALYTICAL BALANCE
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DESTRUCTION OF ANALYTICAL SAMPLES AFTER TESTING
1.0. OBJECTIVE:
The objective of this SOP is to describe a procedure for the destruction of balance
analytical samples after analysis and control samples.
2.1 Chemist Quality Control shall be responsible for Destruction of the remaining
unwanted Analytical samples after analysis.
2.2 Head - Quality Assurance shall be responsible for ensuring the destruction of
samples as per the procedure.
Head – Quality Control
4.0. PROCEDURE:
NOTE: 2% w/v solution of sodium hydroxide shall be used to inactivate

samples before Disposal.
4.1 Tablets and Capsules:
Blend Analysis
After analysis, discard the balance sample of the tablets and capsules into a wet bin
containing 2 % w/v solution of sodium hydroxide. Deface the label of poly bag and
discard the bag into waste bin after treating it with 2 % w/v solution of sodium
hydroxide
4.2 Bulk Analysis
After analysis, discard each and every capsule or tablet into the wet bin containing
2 % w/v solution of sodium hydroxide. Deface the label of poly bag and discard the
bag into waste bin.after treating it with 2 % w/v solution of sodium hydroxide.
4.3 Finished product control samples:
Cut the blisters / strip packs and take out the tablets / capsules and discard them
into the wet bin containing 2 % w/v solution of sodium hydroxide. Discard the empty
blisters / strip packs into waste bin. after treating it with 2 % w/v solution of sodium
hydroxide.
4.4 Dry syrups / powders and oral liquids.
Discard the powders / liquids in wet bin containing 2% w/v solution of sodium
hydroxide. Deface the label on the bottle. Glass bottle shall be treated with 2 % w/v
solution of sodium hydroxide before disposal to the vial / bottle crusher.
4.5 Raw Materials
After analysis, discard balanced sample of raw material into the wet bin containing
2 % solution of sodium hydroxide. Deface the label of polybag and discard into the
waste bin.
4.6 Packaging Materials
4.6.1 After analysis, cut the material into pieces and it to scrap yard.
4.6.2 At the end of the day remove the wet bin from the laboratory premises and send
it to the ETP to discard the waste.
5.0. TRAINING:
Trainee -- All departmental heads / Quality Control Personnel
Period -- One day
6.0. DISTRIBUTION:
Certified Copy No. 2 : Excutive – Micro
Certified Copy No. 3 : For Display In IPQA
7.0. ANNEXURE:
Nil.
8.0. REFERENCE:
In-House
 STORAGE OF HAZARDOUS CHEMICALS & DESTRUCTION AFTER ANALYSIS

 Analytical report numbering
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OPERATION AND CALIBRATION OF MICROPIPETTE
1.0 OBJECTIVE
To lay down a procedure for operation and calibration of micropipetter.
2.0 RESPONSIBILTY
Microbiologist / Q.C Executive
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 For 0-200l micropipetter. (carry out all the activities at Temperature 25°C )
4.1.1 Adjust micropipetter to 50l by rotating the adjusting scale at clockwise or

anticlockwise direction.
4.1.2 Insert the micro-tip tightly to the micropipetter.
4.1.3 Pipette out in previously tared beaker on weighing balance and note the reading.
4.1.4 Carry out the procedure twice and note the weight displayed on the balance,
calculate the mean and standard deviation of three readings and record it in the
format as given in annexure-I.
4.1.5 The weight per ml of water at 25°C when weight in air is 0.99602 g .Divide the
mean with weight per ml to get the volume dispensed.
4.1.6 Carry out similar procedure by setting micropipetter to 100l and 200l .
4.2 For 200l to 1000l micropipetter
4.2.1 Repeat the same procedure as above by setting 200, 500 & 1000l
quantity.
4.2.2 Note the observations in the format given in Annexure-I
4.3 ACCEPTANCE CRITERIA :
4.3.1 Standard deviation between three readings should not be more than
1%.
4.3.2 The volume dispensed should not vary by more than 1% of the set
volume.
4.4 FREQUENCY OF CALIBRATION
Quarterly
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : For Display Near The Micropipetter
8.0 ANNEXURES:
Annexure 1. Format for Clibration of Micropipetter
9.0 REFERENCES:
In house.
ANNEXURE –I
FORMAT FOR CALIBRATION OF MICROPIPETTER

Revision No. : 00
Effective Date:
CALIBRATION DATE:-
MAKE / MODEL:-
CALIBRATION DUE:-
Weight per ml of water : ____________ Temperature of water =
VOLUME STANDARd OBSERVE LIMITS

DEVIATION D
DISPENSED WEIGHT RECORDED MEAN (l )
VOLUME
(l ) ( NMT- 1% )
(l )
I II III
0 – 200 l
50 49.5-
50.5
100 99.0-101
200 198-202
200 – 1000 l
200 198-202
500 495-505
1000 990-1010
CONCLUSION: The Micropipetters are working within / out of specified limit.
Frequency of calibration – Quarterly once
Done by:
Checked
by:
Sign.& Date
Sign.& DatE

 Operation and Calibration of Heating-Blocks
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CULTURE MEDIA PREPARATION FOR MICROBIAL TEST
1.0 OBJECTIVE
To lay down a procedure for preparing of media for microbiological tests.
2.0 RESPONSIBILTY
Microbiologist./ Q.C Executive.
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 INTRODUCTION
4.1.1 Before employing any dehydrated media for analysis ensure that the growth
promotion test has been performed for that particular batch or lot or any new media
procured.
4.1.2 Media for Microbiological testing should be prepared as per

requirements.
4.1.3 For preparing any culture media (Solid or Liquid) take properly cleaned glass
container of different volumes as per requirement.
4.1.5 Select the glass container such that the medium volume be prepared, is half of its
capacity.
4.1.6 Follow the instructions given by the manufacturer for preparing the culture media
(Name of the Mfr.).
4.1.7 Weigh the media powder as mentioned on the label of the container and Annexure
II . Reconstitute with distilled water and mix the powder stirring with glass rod.
4.1.8 Warm the powder mixed distilled water, if required, to dissolve the
powder
Completely & check the pH of the solution with the help of pH

indicator strips.
4.1.9 Plug the mouth of the container by non-absorbent cotton and wrap butter paper
/Alue. Foil to prevent any Contamination and label.
4.1.10 Boil or sterilize the media at 121°C for 20 min, as per manufacturer
instruction and
check the pH after aterilization.
4.1.11 After completion of all the above procedures label each media containers with
media name, media lot no. date of preparation, and Use before date on the
container . Pre-incubation must be done at 30-35C
for at least 48 hrs before taken for use. In case if the medium is
required to be use
immediately, keep appropriate negative and positive control to

ensure the proper
sterilization and fertility of the medium.
4.1.12 Record the media preparation and pre-incubation details in Media

preparation record
as mentioned in Annexure I.
4.1.13 Prepared media can be used within 1month period if properly sealed and stored at
temperature < 25°C.
4.1.14 Whenever new bottle is opened write the date of opening , Date of growth
promotion test and signature on the bottle.
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : For microbiology Department.
Certified Copy No. 3 : For Display in Media preparation Room
8.0 ANNEXURES:
Annexure –I
9.0 REFERENCES:
Himedia Manual
ANNEXURE –I
LIST OF MEDIA
Revision No. : 00
Effective Date :
Sl.n Media Gms. /L pH Procedure for

o. preparation
1. Soyabean Caesin Digest 30.00 7.3 ± Sterilization at 1210C

Media (SCDM), 0.2 for 20 min
2. Fluid Thioglycollate Media 29.75 7.1 ± Sterilization at 1210C

(FTGM), 0.2 for 20 min
3. Soyabean Caesin Digest Agar 40.00 7.3 ± Sterilization at 1210C

(SCDA) 0.2 for 20 min
4. Brilliant Green Agar (BGA), 58.00 6.9 ± Sterilization at 1210C

0.2 for 20 min
5. Bismuth Sulphite Agar(BSA) 52.33 7.7 ± Boiling

0.2
6. Deoxycollate Citrate Agar 70.52 7.5 ± Boiling

(DCA) 0.2
7. Selinite Broth (SCB), 23.00 7.0 ± Boiling

0.2
8. Tetra thionate Broth (TTB), 77.4 / -- Boiling

980ml
9. Mac Conkey Broth Purple 35.0 7.3 ± Sterilization at 1210C

(MB), 0.2 for 20 min
10. Xylose Lysine Deoxycholate 56.68 7.4 ± Sterilization at 1210C

Agar (XLDA), 0.2 for 20 min
11. Mac ConkeyAgar (MA), 48.5 7.1 ± Sterilization at 1210C

0.2 for 20 min
12. Sabaurud Dexterose Agar 65.0 5.6 ± Sterilization at 1210C

(SDA), 0.2 for 20 min
13. Azide Dextrose Broth (AZB), 34.7 7.2 ± Sterilization at 1210C

0.2 for 20 min
14. Vogel Jhonson Agar (VJA) 61.0 7.2 ± Sterilization at 1210C

0.2 for 20 min
15. Urea Broth (UB), 18.7/50 6.8 ± Sterilization at 1210C

ml DW 0.2 for 20 min
16. Manitol Salt Agar (MSA), 111.0 7.4 ± Sterilization at 1210C

0.2 for 20 min
17. Baired Parker Agar (BPA), 63.0 7.0 ± Sterilization at 1210C

0.2 for 20 min
19. Nutrient Broth (NB), 13.0 7.4 ± Sterilization at 1210C

0.2 for 20 min
20. Cetrimide Agar (CA) 45.3 7.2 ± Sterilization at 1210C

0.2 for 20 min
21. Antibiotic assay medium no.-3 17.5 7.0 ± Sterilization at 1210C

0.2 for 20 min
22. B12 assay agar 51.5 7.2 ± Sterilization at 1210C

0.2 for 20 min
23. B12 culture agar 37.85 7.0 ± Sterilization at 1210C

0.2 for 20 min
24. Triple sugar iron agar 65.0 7.4 ± Sterilization at 1210C

0.2 for 20 min
 FERTILITY ( GROWTH PROMOTION ) TEST FOR MEDIA.

OPERATION AND CALIBRATION OF BULK DENSITY APPARATUS
1.0 OBJECTIVE
To lay down procedure for operating of bulk density apparatus.
2.0 RESPONSIBILITY
Q.C. Chemist / Q.C Executive.
3.0 ACCOUNTABILITY
Manager Q.C.
4.0 PROCEDURE
4.1. OPERATION
4.1.1. The apparatus consist of following switches.
MAIN SET NXT CHK

STRT
4.1.2. Connect the instrument to a 230 V supply.
4.1.3. Switch ON the instrument.
4.1.4. Weigh atleast 10 g of sample and transfer it to 50 ml (or 25ml which is

suitable) measuring cylinder. Put stopper on it .
4.1.5. Fix the measuring cylinder on the Bulk density stand.
4.1.6. Set the apparatus to the required strokes by adjusting switches.
4.1.7. Put on STRT switch.
4.1.8. The apparatus starts working and stroke rate displayed on the
screen.
4.1.9. After the completion of the specified stroke .The apparatus will go OFF
automatically with a buzzer.
4.1.10. For repeating the analysis. Press STRT .
4.1.11. Switch off the MAIN after the analysis.

4.1.12 Calculate the bulk density of the sample by measuring the volume of the
sample on measuring cylinder , occupied after setting it specified strokes.
Wt. of sample
B.D = ---------------- X gm / c.c
Volume
4.2. CALIBRATION PROCDURE
4.2.1. Put ON the mains.
4.2.2. Set the apparatus for 50 strokes by adjusting the push button.
4.2.3. Put STRT the switch.
4.2.4. Counter the number of strokes.
4.2.5. Change the setting to the following number of strokes and

check actual strokes.
50 : 49-51
75 : 73-77
100 : 98-102
4.2.6. Report the results in the format given in Annexure I.

4.2.7. If the calibration is not proper then report to the department
head for an appropriate action.
4.3. FREQUENCY
Monthly.
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2. : For Display near the Bulk Density Test Apparatus
8.0 ANNEXURES:
Annexure 1., formats for calibration of Bulk Density Apparatus

9.0 REFERENCES:
In house.
ANNEXURE – I
CALIBRATION OF BULK DENSITY APPARATUS

of 1
Effective from:
Name of Bulk Density Apparatus Instrument Id

Instrument
Make Model
Calibration Next Calibration Due

date on
SET STROKE OBSERVED STROKES LIMITS ( STROKES )

50 50 ± 1
75 75 ± 2
100 100 ± 2
CALIBRATED BY CHECKED BY
 Bulk Density Apparatus

 OPERATION AND CALIBRATION OF KARL FISCHER APPARATUS
 Calibration of Disintegration test apparatus
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OPERATION AND CALIBRATION OF POLARIMETER
1.0 OBJECTIVE
To lay down a procedure for operation & calibration of polarimeter.
2.0 RESPONSIBILITY
Q.C. Chemist / Q.C Executive.
3.0 ACCOUNTABILITY
Manager Q.C.
4.0 PROCEDURE
4.1 OPERATION
4.1.1.Following are the keys present on the instrument:
STOP Print FILE HELP Zero START
4.1.2. Switch on the instrument power supply, and wait for few minutes.
4.1.3. As soon as the power is switched on ,the monitor shows the company’s name and go on
initializing For 5.13 minutes.
4.1.4 After that the Instrument is in the "READY" mode for automatic operation indicated by
READY. Display :
4.1.5. Lift the door of the sample compartment and place the sample cell filled with media in which
sample is prepared (ensure that no air bubbles are there ). Push ZERO keys for zero clearing.
4.1.6. Push EDIT key and enter identification and concentration of sample .
4.1.7. Place the sample cell filled with sample solution ( ensure that no air bubbles are there ) and
press START key. Take the reading displayed on the digital screen .
4.2. CALIBRATION :
4.2.1. Prepare the standard solutions of sucrose in distilled water of different concentrations
from 10 %
To 50 % and sonicate if necessary . Use distilled water as a blank and operate the
instrument as
Per SOP.
4.2.2. Clean the sample cell with distilled water and check the reading . Press ZERO to get
the zero of the distilled water blank. Place the sucrose solution one after
another from 10 % to 50 % and measure the optical rotation for each solution which should be
comparable with values given below:-
CONCENTRATION ANGLE OF ROTATION
10 % 13.33
20 % 26.61
30 % 39.86
40 % 53.06
50 % 66.23
Check that instrument is clean and free from dust.

4.3. FREQUENCY : Three months
4.4. If the Calibration is not proper then report the results to the Department Head for an
appropriate
Action.

STERILITY TESTING
1.0 OBJECTIVE
To lay down a procedure for STERILITY TESTING
2.0 RESPONSIBILTY
Microbiologist/ Q.C Executive
3.0 ACCOUNTABILITY
4.0 PROCEDURE
4.1 MEMBRANE FILTERATION METHOD
4.1.1 Enter the area as per SOP
4.1.2 Carry out environmental monitoring test as per SOP
4.1.3 Follow S.O.P for transferring materials inside the sterile area.
4.1.4 Disinfect LAF station wth 70% filtered IPA solution & check the
manometer reading (i.e
between 10-
15 mm of water) then rinse hands with 70% filtered IPA solution

followed by drying hands
under the LAF before proceeding for testing.

For dry powder injections-Inject 5-10ml of sterile peptone water
into each vial of
injection(powder) by a sterile syringe after opening the flip-off seal

of the vial and dissolve
powder of the vial to be tested under RLAF & suck out the sample.
For liquid injections-Suck out the sample with a sterile syringe after opening the
flip-off seal of the vials to be tested under LAF.
4.3 Collect the sample in a empty sterile flask.
4.4 Place the sterilized filtration units on the filtration assembly under the RLAF which
is connected to a a collecting flask and with a vacuum pump by a tubing tightly
fitted with it.
4.5 Open the filtration units (A suitable unit consist of closed reservoir and receptacle
between which a properly supported membrane of Pore size of 0.22 and a
diameter of approx. 47 mm. At flow rate of 55 to 75ml of water per minute at a
pressure of 70 cm of mercury) carefully and pour the collected sample in the sterile
filtration assembly and filter the sample.
4.9 Start the vacuum pump as per SOP No. K/QC/092
4.10 Rinse the membrane filter with 3 x 100ml of peptone water.
4.11For sterility testing for STERILE WATER FOR INJECTION or any

liquid injections, rinse thoroughly
the outer portion of 20 nos. of ampoules/ vials and suck out water with the
help of sterile syringe.
4.12 Collect the sample in a sterile conical flask and filter it through 0..45
membrane filter and rinse the
membrane filter with 100ml of 0.1%sterile peptone water and in case of
liquid injections ,rinse the
membrane filter with 3 x 100ml of 0.1%sterile peptone water.
4.13 After completion of filtration ,cut the membrane filter into two with the help
of sterile scissor and
forceps and inoculate each half portion of it into sterile 100ml SCDM and
FTGM
4.14 After inoculation, close the mouth of the container tightly and incubate
SCDM tubes at 20-25C and
FTGM at 30-35C.
4.15 Hold the incubated tubes at the above mentioned temperature in incubator
for duration as mentioned in
pharmacopoeia .
4.16 Note the observations in the format as in annexure-I. For any adverse
result inform Manager QC &
follow SOP no.- K/QC/087.
5.0 ABBREVIATIONS :
6.0 REFERENCES
USP 25 Page no.:- 1878 , E.P: - Page no. 125 , 2.6.1
7.0 ANNEXURES : Annexure I & II
ANNEXURE- I
QUANTITIES OF THE PRODUCT TO BE EXAMINED IN THE TEST OF STERILITY (AS PER
E.P)
Type of Quantity per Minimum qty to be used for each
preparation container medium ,unless otherwise justified &
authorized
Parenteral
Liquids
preparations
Less than 1 ml The whole content of each container
1 ml or more Half the content of each container but not more

than 20ml
Solids
Less than 50 The whole content of each container

mg
50 mg or more Half the content of each container

but less than
300 mg
300 mg or 150 mg
more
MINIMUM NUMBER OF ITEMS RECOMMENDED TO BE TESTED(AS PER E.P)
Number of items in the batch Minimum no. of items to be tested

for each medium
Not more than100 containers 10% or 4 containers, whichever is greater
More than 100 but not more than 500 10 containers

containers
More than 500 containers 2% or 20 containers, whichever is least
ANNEXURE -II
STERILITY TEST REPORT
(MEMBRANE FILTRATION METHOD)

Page 01 of 02
AR. NO./GR. NO. TEST REPORT NO. SAMPLE QTY.
SAMPLE
BATCH NO. MFG. DATE EXP. DATE
QTY./BATCH SIZE DATE OF SAMPLED BY

SAMPLING
DATE OF TEST DATE OF REPORT ANALYZED BY
MEDIA PREPARATIONS
SOYABEAN CASEIN DIGEST MEDIUM FLUID THIOGLYCOLLATE MEDIUM
.DATE OF PREPARATION .DATE OF PREPARATION
MEDIA BATCH NO. MEDIA BATCH NO
MEDIA LOT NO. MEDIA LOT NO.
TEST RESULT
NAME OF SOYABEAN CASEIN DIGEST MEDIUM

MEDIA INCUBATION TEMP. 20-25C
NO. OF DAYS  1 2 3 4 5 6 7 8 9 10 11 12 13 14
GROWTH
OBSERVED
NAME OF FLUID THIOGLYCOLLATE MEDIUM

NO. OF DAYS  1 2 3 4 5 6 7 8 9 10 11 12 13 14
GROWTH
OBSERVED
NEGATIVE CONTROLS
NAME OF SOYABEAN CASEIN DIGEST MEDIUM

NO. OF DAYS  1 2 3 4 5 6 7 8 9 10 11 12 13 14
GROWTH
OBSERVED
NAME OF FLUID THIOGLYCOLLATE MEDIUM

NO. OF DAYS  1 2 3 4 5 6 7 8 9 10 11 12 13 14
GROWTH
OBSERVED
POSITIVE CONTROLS
MEDIA  SOYABEAN CASEIN DIGEST FLUID THIOGLYCOLLATE
MEDIUM MEDIUM
DAYS  1 2 3 4 5 6 7 1 2 3 4 5 6 7
S. aureus NA - +v +v +v +v +v +v
ve e e e e e e
C albicans/A - - +v +v +v +v +v NA
niger ve ve e e e e e
C. sporogenes NA - +v +v +v +v +v +v
ve e e e e e e
INFERENCE: SAMPLE PASSES / DOES NOT PASSES IN STERILITY TEST AS PER

IP/BP/USP/IH
-ve : - No growth and +ve : - Growth
MICROBIOLOGIST SIGN / DATE
MANAGER QA/QC SIGN / DATE
 Swab sampling and testing for clean rooms

 DESTRUCTION OF ANALYTICAL SAMPLES AFTER TESTING
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PROCEDURE FOR CHECKING THE CORRECTNESS OF COMPUTERISED

FORMULATION ORDER ISSUE SYSTEM
1.0 OBJECTIVE
To lay down the procedure for checking correctness of the computerized formulation order issue
system.
2.0 RESPONSIBILITY
Production Planning Supervisor / Quality Control Chemist
3.0 ACCOUNTABILITY
Production Planning Manager / Quality Assurance Manager
4.0 PROCEDURE
4.1. Print computerized Formulation Order.
4.2. Check the Formulation Order for
4.2.1. Manufacturing Date

4.2.2. Expiry Date
4.2.3. Master Formula
4.2.4. “First in First out” system
4.3. Manufacturing Date
4.3.1. Check the formulation order for the manufacturing date.
For example:-
The formulation order printed in the month of Jun’2005 shall have the manufacturing
date
as “Jun 2005”.
4.3.2. Expiry Date
Check the expiry date of active Ingredient(s), against Analytical Report Number (AR. No.)
Mentioned in the formulation order. Check the correctness by comparing with expiry date
mentioned in COA. Following guideline shall be followed while assigning Expiry for the
product.
4.4. Domestic Products
The expiry date of the Finished Product shall be as per the expiry date of the product or expiry
date of its active Ingredient (s), whichever is earlier. Products having multiple active
ingredient(s) shall have expiry of Raw Material having the least expiry.
4.5. Export Products
The expiry date of the Finished Product shall be as per the Shelf life assigned in Master
Formula.
4.6. MASTER FORMULA
4.6.1. Check the Formulation Order against the master formula issued by Product Development
Laboratory for following.
4.6.1.1. Code No.

4.6.1.2.Ingredient(s)
4.6.1.3.Batch Quantity
4.6.1.4. Actual Quantity Issued
4.6.2. Calculation of active Ingredient(s) and Filler
4.6.2.1. Collect potency and moisture data of the active ingredients issued in the formulation order by
referring to the Certificate of Analysis from Quality Control and check the same with the
formulation order.
4.6.2.2. Calculate the actual quantity of active ingredients to be issued by referring to the
formula
specified in the Master Formula given by Product Development Laboratory and
the quantity of
the Filler.
4.6.2.3. Check the correctness of the quantity by comparing with quantity mentioned in Formulation
order.
4.7. “First in-First out” system
4.7.1. Check the “ First in – First out” System for any two ingredients issued in Formulation
order.
4.7.2. In case of active ingredients, Check for the material in stock having less expiry
than that of the issued material. If there is no stock of material having less
expiry, the “ First out” system shall be followed.
4.7.3. After taking out the Formulation Order, check Analytical Report Number wise stock on
computer screen. In case of other ingredients, If there is no stock of previous Analytical Report
Number in the system, the “First in-First out” principle shall be considered to be followed.
4.8. In case of any discrepancy, a team comprising of
4.8.1. Production Planning Manager

4.8.2. Quality Assurance Manager
4.8.3. Manager InfoTech
4.8.4. VP (Operation)
Shall investigate the matter and take corrective action. The investigation report shall be
documented.
Details of the investigation shall be documented as per Annexure-1.
4.9. FREQUENCY OF VALIDATION
Five Formulation Orders of different products shall be checked during each Calendar Month
4.10. ABBREVIATIONS:
AR No. = Analytical Reference Number

COA = Certificate of analysis
6.0. TRAINING:
Trainer -Head – Quality Control

Trainees-- Production Planning Supervisor / Quality Control Chemist
Period -- One day
7.0. DISTRIBUTION:

8.0. ANNEXURES :
Annexure I – Investigation report.
Annexure II– General Check List.
9.0. REFERANCE
In-house
ANNEXURE-1
Investigation report
Revision No.: 00
Effective from:
Date
Product Batch Number
Market Batch Size
F.O. Serial No. Date
Sl. Ingredients AR. Data Manual As per Sign Remarks

No. No from Calculation formulation
Actual
Quantity
Potency Moisture Expiry Quantity
Date
POTENCY MOISTURE CORRECTION AND FILLER ADJUSTMENT
ANNEXURE - II
2. GENERAL CHECKLIST
Revision No.: 00
Effective from:
ITEM CHECKED SIGN
A. Manufacturing Date
B. Expiry Date
C. Master Formula
DONE BY CHECKED BY

 Numbering system for Standard Operating Procedures and Index of Standard Operating
Procedure
 PROCEDURE FOR OPERATING OF SONICATOR
 Issue and entry of Batch Manufacturing Records
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OPERATION AND CALIBRATION OF pH METER
1.0 OBJECTIVE :
To lay down a procedure for operating of pH meter.
2.0 RESPONSIBILITY
Chemist / Executive.
3.0 ACCOUNTABILITY
Manager Q.C
4.0 PROCEDURE
4.1. OPERATION
4.1.1. Ensure the cleanliness of the instrument.
4.1.2. Clean the electrodes with purified water and wipe with tissue paper.
4.1.3. Switch ON the main power.
4.1.4. To check the pH of the sample by dipp electrode in the sample solution taken in a suitable
container.
4.1.5. .Push “READ” bottom ,it beep .When reading be stable by showing [A]
record the results.
4.1.6. Remove the electrode from the sample solution, wash with purified water and place in a
beaker of fresh purified water.
NOTE : ENSURE THAT THE TEMPERATURE OF THE SOLUTION IS
WITHIN 23°C - 27 °
4.2. PREPARATION OF STANDARD BUFFER SOLUTION
4.2.1. In three, dry separate beakers take 1 buffer tablet of pH 4.0, 7.0 and 9.2
respectively.
4.2.2. Add 70 ml of Distilled Water to dissolve the tablets.
4.2.3. Transfer the preparation from beakers to clean 100 ml volumetric flasks
separately.
4.2.3. Rinse the beakers with distilled water and transfer to the volumetric
flasks.
4.2.4. Make the volume accurately to 100 ml with Distilled Water in each case.
4.2.5. Transfer the prepared buffer solutions of pH 4.0, pH 7.0, pH 9.2, in three
different
bottles, appropriately labeled.
4.2.6. Affix the labels on the bottles indicating the USE BEFORE---- Date of solution.
4.2.7. Prepared buffer solution is valid up to 7 days from the date of preparation.
4.3. CALIBRATION OF PH METER
4.3.1. Clean the electrode with purified water and wipe excess water with tissue
paper.
4.3.2. Deep electrode in pH 4.0 buffer and push “CAL” bottom, after stabule ,record the result
.Repeat the process with pH 7.0 and pH 9.2 buffers .
4.3.3. While checking the pH of buffer 4.0, 7.0 and 9.2 clean the electrode with purified water
every time.
4.4.4. After use keep the electrode dipped in the purified water .
4.4.5. Record the results in the format attached – Annexure-1.

4.4.6. If the results of calibration are not conforming to the specified limits report to eh department
head for an appropriate action.
4.5. FREQUENCY
Daily
4.6. ACCEPTANCE CRITERIA
± 0.05 pH

6.0 TRAINING:
Trainer Head – Quality Control
Period -- One day
7.0 DISTRIBUTION:

Certified Copy No. 2: or Display near the pH Meter.
8.0 ANNEXURES:
Annexure – I. Format for calibration of pH meter.
9.0 REFERENCES:
Manufacturer’s Manual. / IP.

ANNEXURE – I
FORMAT FOR pH METER CALIBRATION
Revision No. : 00
Effective Date:
MAKE : SERIAL No :
MODEL : Ref. SOP :
DATE CLEANLINESS STANDARD BUFFERS DONE BY CHECK

BY
4.0 7.0 9.2
Limits 4.0 ± 7.0 ± 9.2 ±

0.05 0.05 0.05

 pH Meter
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OPERATION AND CALIBRATION OF ANALYTICAL BALANCE
1.0 OBJECTIVE
To lay down the procedure for operation and calibration of Analytical

balance .
2.0 RESPONSIBILITY
Quality Control Officer / Quality Assurance Officer.
3.0 ACCOUNTABILITY
Quality Assurance Manager / Quality Control Manager.
4.0 PROCEDURE
4.1.0 Clean the pan thoroughly prior to calibration.

4.1.1 Check that the air bubble is in the center of the level & if necessary adjust the
level by turning the leveling screws.
4.1.2 Switch ON the balance & allow it to stabilise for 15 mins.
4.2 Calibration Procedure :
4.2.0 Internal calibration
4.2.1 Ensure that the balance pan is not loaded & the doors of the weighing chamber is
closed properly.
4.2.2 Press the ” Set up ” button ,the balance will display ‘ CAL ‘
4.2.3 Press ‘ Enter ‘ button the balance will displays ‘ CAL TYPE '
4.2.4 Then press ‘ Enter ‘ button the balance will display ‘ CAL TYPE ' ‘InCAL ‘
4.2.5 Then again press ‘ Enter ‘ button the balance will display ‘INCAL
After a few seconds the balance will display ‘ CAL SET ‘ & then return to WEIGH
mode & displays as WEIGH 00000.
4.3 DAILY VERIFICATION OF BALANCE PERFORMANCE:
4.3.1 After internal calibration is completed verify the performance of the balance by
weighing 50 mg,
100 mg , 1g , 10 g and 50 g . Record the results in the format given in

Annexure I
4.4 CALIBRATION FOR MEASUREMENT UNCERTAINTY
4.4.1 Place 500mg standard calibrated weight on the pan.
4.4.2 Record the display of the weight.
4.4.3 Remove the weight & again place the weight on the pan & record the
display once again.
4.4.4 Repeat the above operation to get ten readings Calculate the standard
deviation of ten readings.
4.4.5 The measurement uncertainty shall be considered satisfactory if three times of

standard deviation of not less than 10 replicate weighing divided by amount weight
does not exceed 0.001.
Record the observations in the calibration record as per Annexure-II.
4.4.6 Affix a ‘ Calibration label’ on the instrument.
4.4.7 Report any discrepancy noted at the time of calibration to Q.C Manager &
notify the defect to rectify the instrument. & affix an ‘ UNDER MAINTENANCE ‘ label
on the instrument.
4.5 FREQUENCY OF CALIBRATION:
4.5.1.The frequency of calibration shall be mentioned as below :
Internal Calibration - Daily

4.5.2.Verification of Balance Performance - Daily and after every
maintenance job.
4.5.3.Calibration of measurement uncertainty - Monthly and after every

maintenance job.
6.0 TRAINING:
Period -- One day
7.0 DISTRIBUTION:
Certified Copy No. 2 : For Display Near Analytical Ballance
9.0 ANNEXURES:
ANNEXURE -I Attached.
ANNEXURE -II Attached.

9.0 REFERENCES:
In house/Manufacturer Manual
ANNEXURE -I
FORMAT FOR BALANCE CHECKING
Revision No. : 00
Effective Date:
MAKE :
MODEL :
SERIAL No :
DAT CLEANLIN STANDARD WEIGHTS DONE CHECKE

E ESS BY D BY
50 mg 100 mg 1 gm 10 gm 50 gm
Limits 50mg 100mg 1g ± 10g ± 50g ±
± 0.1 ± 0.1 1mg 10 mg 50 mg
ANNEXURE -II
FORMAT FOR CALIBRATION FOR MEASUREMENT UNCERTAINTY
Revision No. : 00
Effective Date:
Name of : Analytical Balance

Instrument
Instrument Ser. :
No.
Make & Model :
Calibration date :
MEASURED UNCERTAINTY : Weight = 500 mg.
S.No. Displayed weight

(X)
3
4
10
Standard deviation ( ) =
3 x 
Measured Uncertainty = ----------------
Wt measured
Acceptance Criteria: Measured uncertainty should not more 0.001.
REMARKS: Satisfactory / Not satisfactory.
CALIBRATED BY APPROVED BY
 Analytical balance-Libror
 Analytical balance- Mettler Toledo
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OPERATION AND CALIBRATION OF BURSTING STRENGTH TESTER
1.0. OBJECTIVE:
The objective of this SOP is:
1.1 To describe the operation procedure of Bursting Strength Tester.
1.2 To describe the calibration procedure of Bursting Strength Tester.
2.1 The Chemist - Quality Control shall be:
2.1.1. Responsible for carrying out the analysis as per the procedure.
2.1.2. Responsible for interpretation of the results obtained
2.1.3. Responsible for timely calibration of the equipment.
2.1.4. Responsible for intimating any abnormal observation to Manager – Quality

Control for necessary corrective actions.
Manager – Quality Control .
4.0. PROCEDURE:
4.1. CLEANING PROCEDURE:

4.1.1. Switch OFF Power Supply of the equipment before cleaning. Clean the
equipment with a dry cloth every day.
4.1.2. If necessary wet cloth shall be used for effective cleaning it shall be dried
immediately using a dry cloth.
4.2. OPERATING INSTRUCTIONS
4.2.1. Switch On the mains. This will bring the plunger to its starting positions. If the
plunger is already at its starting position, motor will not start on switching ON main.
4.2.2. A representative sample of the material to be tested shall be placed over the
diaphragm. The sample size shall be cut to 10 X10 cm.
4.2.3. Place the sample specimen on the Platform.
4.2.4. The tripod plate shall tightened to apply sufficient clamping pressure in such a
way that sample does not slip.
4.2.5. Select the gauge [II] for 3 ply shippers and partitions and gauge [I] for 5 ply and
7 ply shippers.
4.2.6. Set the maximum hand of the gauge at zero or a point on the scale below the
point at which bursting will occur.
4.2.7. Push the RED push button and keep it pressed so that plunger will start rotating
in clockwise direction till sample bursts. The push button is released as soon as the
sample bursts. Note down the gauge reading in Analytical Test Reports.
4.2.8. Release the pressure on the test piece by rotating the clamp wheel in anti-cock
wise direction and remove the sample specimen.
4.3. CALIBRATION PROCEDURE
4.3.1. Clean the equipment using a clean cloth.
4.3.2. Check the glycerin level [this bursting strength tester is a hydraulic unit and its
accuracy depends on a completely filled hydraulic system. Inadequate glycerin
quantity affects the accuracy of the gauge readings]
4.3.3. Take the standard Aluminium foil of 5.4 Kg / cm 2 for Gauge II and 9.5 kg / cm 2
for Gauge I provided by the manufacturer.
4.3.4. Operate the instrument as per operating procedure mentioned above.
4.3.5. Record the observations in the calibration record as per the Annexure - 1, in
case of any discrepancy observed, affix an “Under Maintenance” label on the
instrument and report to Executive - Quality Assurance to take necessary corrective
actions.
4.3.6. After calibration affix the calibration status label.
4.3.7. Acceptance Criteria
4.3.7.1. For Gauge I : 9.0 to 10.0 Kg / cm2
4.3.7.2. For Gauge II : 5.2 to 5.6 Kg / cm2
4.4. Frequency of calibration:
4.4.1. Quarterly.
6.0. TRAINING:
Trainer Manager – Quality Control
Trainee -- Quality Control Packaging Personnel
Period -- One day
7.0.DISTRIBUTION:

Certified Copy No. 2 : File copy in Packaging Laboratory
Certified Copy No. 3 : For Display near the Bursting Strength Tester.
8.0.ANNEXURE:
Annexure – 1 : Format for Calibration Record of Bursting Strength

Tester
9.0.REFERENCE:
Manufacturer’s Manual.
ANNEXURE – 1
FORMAT FOR CALIBRATION RECORD OF BURSTING STRENGTH TESTER
Revision No.: 00 Page No.: 1

REF. SOP NO.:
Effective from: of 1
Instrument no. :
Name of instrument : Bursting Strength Tester
Frequency : Quarterly
Observed bursting Strength of standard

foils
Da Calibrate Checke Rema
te Gauge I Gauge II d by d by rks
(Lt. 9.0 to 10.0 (Lt. 5.2 to 5.6

kg /cm2) kg /cm2)
 OPERATION AND CALIBRATION OF SHORE HARDNESS TESTER

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Idoc - Pub - Audit Checklist For Store Department

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Audit Checklist for Store Department

Sr. Check points Observation Recommendatio Action

Posted by Quality Assurance and GMP and ICH at 12:56 PM 0 comments

Self Audit Checklist for Quality Control Department

Sr. Check points Observation Recommendation Action

21 Check the stability chamber record.

32 Check the environment where control

36 Is the sample in QC lab well labeled?

40 Is glassware breakage log book maintained?

Internal Audit Plan as per GMP

Self Audit Checklist for Production Department

Sr. Check points Observation Recommendation Acti

20. Check the cleaning of dryer and drying area.

24. Check the cleaning of sifting area.

37. Is ECR available?

38. Check the ECR.

39. Check the condition of fluid bed dryer.

Vendor Audit for Validation

1.1 Building Maintenance

1.3 Administrative Block/O

1.4 Utility Block

3 PLANT & BUILDING :

3.1 : Well equipped and sufficient area for Storages

a) : Raw Material ____________

b) : Packing Material ____________

d) : Finished Goods ____________

e) : Cleaning / Schedule ____________

f) : Cleaning of used equipment

3.3 Separate canteen area

3.5 HVAC are providing for critical operation.

3.6 Drain is properly sanitized for critical area.

3.7 Water purification system

3.10 Area is product dedicated or group of products

3.12 Area cleaning procedure

3.13 Procedure of handling of rejected material.

3.14 Lighting level

3.15 Handling of sewage and waste

3.16 Sanitization of process equipments

3.17 Pest control system

a) Design MOC of contact parts

4.2 : Written Manufacturing Procedure

4.3 : Deviation Control Procedure

4.4 : Means of Communication

4.5 : Status label for rejected / released material

4.6 : Used container control

5.4 : If NO Please Specify:-

6.1 : Material issue control ________________

6.2 : Equipment Log ________________

6.3 : Process Record ________________

6.4 : In-Process Results ________________

7. RAW MATERIAL CONTROL:

7.2 : Approved Material Segregation __________________

7.3 : Rejected Material Control __________________

8.1: Raw Material Specification / Test Procedure & its control_______

8.2: Calibration Record ______

8.3: Finished Product Analysis & Release control _______

8.4: Testing facilities _______

9. INFORMATION RELATED TO OTHER PRODUCT MANUFACTURED:

9.1: List of product manufactured (Attach Sheet)

9.2: Product change over control (Cleaning Validation) _______

10. FILING SYSTEM:

10.1 Retrievable ______________

11. NON CONFORMANCES IF ANY: