Professional Documents
Culture Documents
IR Nisha
IR Nisha
DHULIKHEL, KAVRE
SUBMITTED BY:
Nisha Joshi
SUBMITTED TO:
Rajani Shakya
Acting head of Department
Department of Pharmacy
Kathmandu Univerity
1
CERTIFICATION
This is to certify that the in-plant Training report entitled “IN-PLANT TRAINING“at
OhmPharmaceuticals Lab Pvt. Ltd, Tathali-8, Bhaktapur Nepal” submitted by Nisha Joshi
in partial fulfillment for the requirement of Bachelor in Pharmacy has been carried out under
my supervision.
This report has not been submitted to any university or institution earlier for the award of the
Bachelor in Pharmacy certificate.
……………………………
Phr.Sumit Chandra Shrestha
2
ACKNOWLEDGEMENT
I am highly indebted to Phr. Prashansa Shrestha (Deputy General Manager) for her valuable
guidance, suggestion during In-Plant training. I would also like to express my special thanks
to Phr. Anjana Shrestha (Assistant QA manager), Phr. Mribha Manandhar (Senior QA
officer), Phr. Dipendra Barta (QA Officer), Phr. Sushant Gelal (IPQA Assistant), Phr. Tulsi
Bade (Senior Production officer), Phr. Ashish Khadka (Production officer), Phr. Dhan Thapa (
Senior QC Officer), Mr.saroj Acharya (Assistant QC Manager), Mr.Dhurba Ojha
(Maintenance Supervisor) and Mr.Shree Krishna Prajapati (Store In-charge) and all QC and
QA staffs for the guidance during the period.
I am really thankful to all the operators, helpers and all other staffs enrolled in different
department of Ohm pharmaceutical Lab Pvt.Ltd for their hospitality, encouragement and
proper guidance.
3
ABSTRACTS
The in plant training program is a part of the final year practice of the bachelor program and it
has been our pleasure to be a member and spend four weeks here at Ohm Pharmaceutical
Laboratories Pvt. Ltd, the renowned company which has been established complying with the
class-A GMP & GLP requirements of WHO.
During this time period, we amassed knowledge from different departments namely Quality
control, Production, Quality Assurance, Engineering and store. Within this limited time
period we acquired practical knowledge on handling of the materials, the manufacturing
process, operation of equipment, packaging of finished products, and documentation of
activities performed, in process and finished product quality control. By the help of this
training we have also come to know about the commercial scale of drug manufacturing.
This internship period was really fruitful and also made us realize the roles and responsibility
of pharmacists in entire process of quality drug production in pharmaceutical company.
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ACRONYMS
AHU Air Handling Unit
BP British Pharmacopoeia
DT Disintegration Time
IP Indian Pharmacopoeia
IP C In-Process Control
OS Oscillating Granulator
PM Packaging Material
RH Relative Humidity
RM Raw Material
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RMG Rapid Mixing Granulator
RO Reverse Osmosis
UV Ultraviolet
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Contents
ACKNOWLEDGEMENT ...................................................................................................................... 3
ABSTRACTS .......................................................................................................................................... 4
ACRONYMS .......................................................................................................................................... 5
LIST OF FIGURES ................................................................................................................................. 8
1 INTRODUCTION ........................................................................................................................... 9
1.1 IN-PLANT BRIEFING ................................................................................................................. 9
1.2 OBJECTIVES ............................................................................................................................. 10
1.3 COMPANY PROFILE ................................................................................................................ 11
1.4 ORGANIZATIONAL STRUCTURE OF OPL .......................................................................... 12
1.5 OPL PRODUCTS ....................................................................................................................... 13
2. DIFFERENT DEPARTMENT OF OPL ........................................................................................... 14
2.1 STORE DEPARTMENT ............................................................................................................ 14
2.2 PRODUCTION DEPARTMENT ............................................................................................... 16
2.3 HORMONE SECTION ............................................................................................................... 25
2.4 QUALITY CONTROL AND ASSAURNCE DEPARTMENT (QCAD) .................................. 26
1. Quality Assaurance Department ................................................................................................ 26
2. Quality Control Department ...................................................................................................... 27
2.5 MAINTENANCE AND ENGINEERING DEPARTMENT ...................................................... 31
2.5.1 Heating, Ventilation and Air Conditioning Unit (HVAC system) ....................................... 31
2.5.2 Air Handling Unit................................................................................................................. 33
2.5.3 Water Purification System.................................................................................................... 34
2.5.4 Power Supply ....................................................................................................................... 37
2.5.5 Backup Power supply(generator) ......................................................................................... 37
2.5.6 Air compressor ..................................................................................................................... 37
2.6 RESEARCH AND DEVELOPMENT (R&D) DEPARTMENT ................................................ 37
3. CONCLUSION ................................................................................................................................. 39
4. ANNEX I....................................................................................................................................... 40
7
LIST OF FIGURES
8
1 INTRODUCTION
9
1.2 OBJECTIVES
The objectives of in-plant training are as follows:
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1.3 COMPANY PROFILE
Ohm Pharmaceuticals Laboratories Pvt.Ltd (OPL) was established on 2062 B.S. It is one of
the up growing pharmaceutical industries of Nepal with the motto of “Passion to Excellence”.
It has been devoted to provide its remarkable service to health care aspects of Nepal since
May 2009. It is located in Tathali-9, Bhaktapur with the infrastructure designed to fulfill the
latest requirement for Good Manufacturing Practices (GMP). It is the first company to
receive WHO GMP for its Hormone Section.
OPL is one of the much talked company, in the pharmaceuticals fraternity of Nepal because
of heavy investment done in the project with capabilities of producing different dosage form
(Tablets, Capsules, Liquid).The company gives first priority to the quality as it has the policy
of “Quality should be in-built”.Moreover, OPL owns the collection of professional expertise
to offer the excellence to all of its valued customers through the integrity and teamwork.
OPL has a passion to excellence in every regard to serve the Nepalese Pharmaceuticals
Industry and Health Sector to its best.
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1.4 ORGANIZATIONAL STRUCTURE OF OPL
BOARD OF DIRECTORS
MANAGING DIRECTOR
OPERATION DIRECTOR
QA OFFICERS
Asst. QC Officer
Asst. Production
officer
Operators
Supervisior
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1.5 OPL PRODUCTS
OPL manufactures drug of different therapeutic categories which are as follows:
Tablets
Capsules
Dry syrups
Suspensions
Syrups
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2. DIFFERENT DEPARTMENT OF OPL
OPL has following departments:
Store Department
Production Department
Hormone Section
Non Penicillin Section
Cephalosporin Section
Packaging And Finished Product Storage Department
Quality Control Department
Quality Assurance Department
Research And Development(R&D) Department
Maintenance And Engineering Department
Check the availability of raw material and packaging material i.e. Inventory control.
Keeping record of the materials available in the store.
Holding and Keeping record of the materials that arrive at the store.
Requesting QC for sampling.
Storing of the passed material as per specification.
Preparing dispensing slip.
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Informing QA about the rejected materials.
Maintaining different levels on raw materials.
Store is concerned with the storing and documentation activities which are as follows:
Materials enter into the store directly from the manufacturer or supplier.
Materials enter de-dusting area and required information like control no, invoices no, batch
details, manufacturing date, expiry dates are documented in Good Receiving Note (GRN).
Request for analysis is sent to QC for sampling and analysis, orange colored “Under Test
“label is tagged to each sample.
After approval of QA, green colored “QA Approved Label” is tagged and AR no is given for
respective material. Rejected Samples are labeled “QC Rejected” and removed from the
quarantine to rejection store.
Approved materials based on the storage conditions are stored as per location log book. Log
book includes name, store no, rack no, step no, corner.
As per the requisition from the Production Department, raw material based on FIFO are
dispensed in the dispensing booth strictly according to the BMR record under the supervision
of QA personnel and id then documented.
Primary and Secondary packaging materials are dispensed as per requisition from the
concerned department.
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2.2 PRODUCTION DEPARTMENT
Production comes under grey zone and is maintained under class III grey area i.e. particles in
this zone should not be greater than 0.5 micron and should not exceed 100,000 per cubic feet.
Corridor is the cleanest zone and must be maintained at positive pressure difference of 15
Pascal (±5) than that of the room so as to prevent cross-contamination. The walls and ceilings
are painted by epoxy emulsion. . The pressure difference is monitored by the Standard
Magnehelic pressure Gauges. Rooms are cleaned periodically by disinfectants like Isopropyl
alcohol, Sodium hypochlorite, and Savlon to prevent resistance to microorganism
contamination. The end of walls are curved which facilitates cleaning and prevent dust
accumulation. Air handling unit log sheet, machine log sheet, temperature and humidity
record and sanitation record is maintained for every product. There are clearly written SOPS
for each instrument and the SOPS are reviewed in every two years interval. The major
machines in the production section in OPL are of latest design and automated.
Production area is generally divided into following area and consists of following equipments:
1. Dispensing room:
Dispensing of raw material is carried out in the dispensing room and it consists of dispensing
booth. Dispensing booth is maintained with Class 100 by the help of laminar air flow, primary
filter, intermediate filter and HEPA filter. There was perforated stainless steel table, clean
stainless scoops, weighing balance and negative pressure in dispensing booth. The air flow
was a vertical laminar air flow. As per the requirements of various departments materials are
requested by filing the requisition form stating the type and quantity of materials. Dispensing
of raw material is carried out by the store personnel as per requisition form in the presence of
QA personnel. All the dispensed materials are labelled properly and signed by QA officer.
Raw materials are dispensed on the basis of FIFO (First in First Out) and sometimes on the
basis of FEFO (First Expiry First Out) as necessary. The dispensed materials are then
dispatched to carry out production or transferred to pre-dispensing room for storage until the
production is carried out. The equipments in dispensing room are:
Weighing balance
Dispensing booth
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2. Granulation Room:
In this room granulation of the materials in the large batches is carried out. Mixing, milling,
sieving and drying are carried out in this room. Granulation is carried out by using 2 different
methods in OPL. They are as follows:
Direct compression
This type of granulation is frequently used and used for moisture and heat sensitive
materials.
Wet granulation
Wet granulation is a widely employed method for the production of compressed tablets.
Tray drier
Mass Mixer
Mechanical sifter
Oscillating granulator ( OG )
4. Compression room: Granules or powders are blended in one of the compression room
containing
5. Coating Room: Coating room is used either for enteric or film coating of tablets with the
following sets of equipments;
Coating pan
Hot air blower
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Spray gun
Exhaust
Stirrer
Batch requisition
(Line clearance)
Manufacturing
18
Dry screening
Compression IPQC
(QC Analysis)
Coating
Quarantine
(QC Analysis)
Secondary Packaging
(QC Analysis)
QA Analysis
Market Dispatch
6. Suspension preparation Room: In this room suspension for coating is prepared which
contain
Colloid mill
Stirrer I
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7. Blending Room:
Drum Blender
8. Liquid Manufacturing Room: This room is used to prepare liquid dosage. It has
following machineries:
9. Liquid Filling Room: This room is used to prepare liquid dosage form where the bottle is
washed, filled and sealed as an inline process.
QC Analysis
Sieving
Volume make-up
Homogenization
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PH adjustment
QC Release
Storage Tank
Bottle Washing
Storage
Dispatch
21
10. Capsule filling room:
This room is used to fill blended powders or granules or pellets into capsules. This room is
used to fill blended powders or granules or pellets into capsules. At high moisture capsules
become soft/tacky and at low moisture they become brittle, so, temperature and relative
humidity should be maintained at 22±2◦C and 45±5% respectively.
Packaging
Dispatch
Fig 2.2.3 General steps of capsule manufacturing
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The machine used during capsule filling are:
11.IPQC Room:
Under this the intermediate and finished products are checked against their defined
specifications at the time of processing or packing which aims to ensure that process is under
control throughout the manufacturing. The IPQC lab functions under the production
department. The different task carried out by IPQC personnel are:
IPQC of granules
To check Moisture content bulk density of dried granules
To check Percentage of fines
IPQC of Tablet
To take average weight of 20 tablets and individual weight
To check the thickness, individual weight variation, friability, hardness,
disintegration time of tablet and capsule.
To check moisture content and bulk density of dried granules
To check shape size of tablet
To check spray rate, rpm of coating pan, tablet bed temperature, average
weight of tablet before and after coating
Problems associated with tablet manufacturing like Capping, lamination,
mottling etc.
IPQC of oral liquids
Suspension: To check PH, Physical appearance, Fill volume, leak test etc.
Syrup: To check Clarity, pH, Physical appearance, Fill volume, leak test etc
IPQC of Capsule
To take average weight of 20 capsules
To check Individual weight variation of capsule
To check disintegration time
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Record of room temperature and relative humidity
Blister packaging room: Tablets or capsules after compression or coating or filling are
then blister packed in this room with the :
Automatic Blister pack Machine (BP 102, Pam Pack)
It is used for the products that are not sensitive to light and moisture.
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Packaging materials:
PVC foil
PVDC foil
Aluminum foil
Strip packaging: Tablets or capsules after compression or coating or filling are then strip
packed in this room with the Automatic strip pack Machine.
b. visual inspection of particles under white and black background light for liquids
Secondary Packaging
The drug does not come into direct contact with the secondary packaging material. The drugs
which are packed from primary packaging (strip, blister and filled bottles) are then conveyed
to secondary packaging area by conveyer belt. While passes through conveyer belt, integrity
of packing, batch coding, visible defects, leak test and printing mistake are observed and if
found any, they are rejected. During secondary packaging, blister and strips are packed in
carton and they are also packed in corrugated carton, and are released only after obtaining a
release certificate from QA.
Following materials are used for secondary packaging:
Printed carton
Duplex box or corrugated box or packaging
Printed label
Measuring cap
Middle plate
1. Dispensing Room
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Dispensing Booth
Weighing Balance
2. Granulation
Tray drier
Mass mixer
Sifter
23 station single hopper rotary tablet press
3. Packing
Blister packing
4. IPQC room
The QA department is responsible for monitoring the overall quality; the ultimate aim being
providing standard quality drugs to the people by monitoring, developing, implementing &
improving the quality of the product according to the WHO GMP guidelines & DDA
regulations.
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Activities performed by QA are:
Documentation
Dispensing
Line Clearance
Validation
Fulfillment of the regulatory requirement.
Monitor the specific processes and conditions to be followed in the production.
Follow the specifications and control procedures for all starting materials, intermediate and
finished products.
Finished Product Inspection
Batch release
Internal Audit
Batch or Lot Disposition
Handling quality crisis
Making Recall Decisions
Drug is a very important component of the health care system. Once the drugs are taken, the
pharmacodynamic effect shown by the drug can’t be reversed; the poor quality drug doesn’t
only cause therapeutic failure but also shows various toxic effects, so drugs need special
attention in regard to quality, efficacy and safety.
''Quality is never an accident'',To build quality in the end product, overall control should be
maintained right from the starting material to the manufacturing processes, building design,
equipment and personnel involved. In order to deliver quality drug to the people, OPL has
been implementing Good Manufacturing Practice which ensures that products are consistently
produced and controlled according to the quality standards.
Quality control is a part of GMP concerned with sampling, specification, testing, and with the
reorganization, documentation and release procedures which ensure that the necessary and
relevant tests are actually carried out and that materials are not released for use or products
are released for sales or supply, until their quality has been judged to be satisfactory. The
team of qualified pharmacy and analyst work together for improvement of quality of product,
in QC department located on the 1st floor of Ohm Pharmaceutical laboratories. In QC
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department to assure that all the processes and practices meets GMP requirements, OPL has a
well-equipped and maintained department called Quality Control Department consisting of
sophisticated instruments, facilities and reagents and highly skilled manpower.
QC department of Ohm Pharmaceutical Laboratories performs analysis as per the official
pharmacopoeias especially IP and BP, USP and other validated procedures like In-House
Specification ( IHS) to check if the tested materials meet the specification or not.
2. SWAB analysis
3. Water analysis
5. Microbiological analysis
6. Stability testing
All the raw materials on arrival in RM store are sampled and analyzed by QC department.
Raw material, active and inactive, are sampled and tested for identification tests, purity
test, assayed for their content and checked for their specifications. Physical characteristics
such as color, odor and foreign material particle size, heavy metal content, arsenic,
selenium, water content, microbial limit, residue on evaporation and pH are tested.
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If a sample passes the QC test then the sample is labeled as “QA Approved”(green
sticker) by QC otherwise labeled as “QA REJECTED”(red sticker). The parameters to be
checked depend upon the materials and as stated in official pharmacopoeias.
Intermediate products such as granules and powders are analyzed before advancing to
further steps of production.
All the packaging materials are tested for specified standard by QC department. Length,
breadth, thickness, correctness of printed text, coating of aluminum strip etc. is tested and
then approval or rejection release is issued based on the result.
Bottle
Duplex box
Label
Aluminum foil
Measuring cap
PVC
PP cap
QC in OPL consists of hot zone, Wet lab chemistry, sophisticated instrument, microbiology
lab. And it consists of following instruments:
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Disintegration test apparatus:
Dissolution test apparatus
Friability test apparatus
Vernier caliper
Precision Melting point apparatus
Magnetic stirrer
Digital PH meter
Sonicator
Water bath
Centrifuge machine
Weighing balance
Desiccator
UV fluorescence Analysis
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2.5 MAINTENANCE AND ENGINEERING DEPARTMENT
Engineering department in the Ohm pharmaceutical industry is associated with assembling
and maintenance of machineries, arranging services and sanitation so as to facilitate smooth
production and favorable environment. The major function of this department is routine
management of HVAC system, water plant system, electricity supply, power-backup
generator, compressed air supply, etc. The major units are described below:
Double skin AHU is located inside mezzanine floor and air cooled chiller located on terrace is
dedicated to each critical area in order to avoid cross contamination. Control panel along with
thermostat is located on terrace near chiller plant. All manufacturing and primary packing
areas are provided with HVAC system. Temperature and relative humidity is maintained by
the HVAC system as per the requirement of production being processed in the rooms. The air
is passed through double skin AHU with blower and then series of the filters and numerous
rows of heating and cooling coils. Air distribution is through low particle shedding GI ducting
system insulated with arm flex insulation material. The Return air is collected from rooms and
20% fresh air is added to the system, filtered, cooled/heated and supplied to dedicated areas.
Ventilation system complies with 2 staged filters 10µprefilter, followed by 5µ bag filter.
Supply grill is production area have terminal 0.3µ superfine HEPA filters. 100% exhaust is
ensured in the powder processing area. HVAC system is designed to maintain an environment
of 20⁰C-24⁰C and RH 45%±5% in case of manufacturing area. In all, the return air duct 10µ
filters are provided to avoid powder contamination. Dehumidifier along with AHU is
provided at all critical location of tablet and capsule manufacturing.
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Damper Filter section Coil section Blower section
Supply Duct
HEPA Filter
Production
Area
Return Filter/Course Filter
Return Duct
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2.5.2 Air Handling Unit
Re-circulated Air-
Fresh Air- 85%
15%
Mixing Chamber
Pre-filter (10µ) Bag Filter (5µ)
33
Working of an AHU:
The air inlet section consists of a funnel shaped inlet duct from where air enters the AHU.
From this place about 25% fresh air and 75% re-circulated air is transferred. The fresh air and
re-circulated air gets mixed in the mixing chamber. The so mixed air gets filtered through
various filters in the filter section. The filter section contains pre-filter, bag filter, supply filter
and return filter. The pre filter is of 10µ in its pore size and is washable while the bag filter is
of 0.5µ and is disposable. The supply filter is kept at inlet of rooms. The filtered air is passed
through conditioning unit where the temperature and humidity is maintained at about 15-30 ºC
and 20-60% respectively. Then the air is supplied to the blower section which supplies the air
to the supply ducts. Each room and the corridors are provided with the inlet of air, which
consists of HEPA filter of pore size 0.3µ size, and corridor is positively pressurized which is
in accordance with WHO GMP which is double plus for corridor and plus for rooms. Each
room is provided with inlet of air at the top of the room and outlet at the opposite side at the
bottom of the room. Pressure cascade corridor must be positive to operating room with 15
Pascal’s difference. Air change per hour must be 20-25 cycles. Standard Magnehelic
Pressure Gauge is installed in every door to monitor the pressure difference.
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stored in storage tank and which then enters to mixed bed de-ionizer to maintain conductivity
below 0.3µ Siemens/cm (In-house limit). Mixed bed de-ionizer has mixed resins both cationic
and anionic, which removes anions and cations of water respectively. Anionic resins are
recharged with HCl whereas NaOH is used to recharge Cationic resins. Then after, the
purified, de-mineralized water is passed through UV light system to kill microorganisms and
then through the 0.2µ sized cartridge filter and collected into the distribution tank.
Distribution of water in every section occurs through PVP pipes.
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Undergro Raw
NaCl Recharge
und Raw water
water storage
Storage tank
tank Sand Activated Soft
(150000 Filter Carbon ener
ltrs.) Filter
Soft water
Supply to Storage Tank De-
Production scalant
for cleaning Dosing
5µ Cartridge filter
Tank
RO Water
Regeneration Storage Tank
Tank
RO
Rejected
RO Plant Water
UV Treatment MIX
BED Supply to
Washroom,
Garden
DM Water Supply to
0.2µ Cartridge filter Storage Production
Tank
Transfer pump
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2.5.4 Power Supply
Electric Power
The electricity in the industry is obtained from Nepal electricity supply board.
For identifying feasibility, methodology for the development of new formulation, dosage
form and different dose, R& D department of pharmaceutical industry plays the vital role.
Experts, researchers and well trained pharmacist in this department involved in designing and
manipulation of different excipients and active drug give new formulation or improve existing
formulation which could be more effective than present available formulation.
Functions of R & D
New formulation development
Upgrading of existing product
Analytical method development
In house specification development
Stability study
Troubleshooting during production
Coordination with DDA and other authorities
Procedure:
The marketing planning department (MPL) of the company conducts surveys and researches
to find out what sort of formulation and dosage form has higher demand and higher scope in
the market. The R &D department conducts the literature review, the production department
checks whether such formulation is feasible in the company or not, whether they have
sufficient instruments and machines or not. Finally, if it is concluded that the product can be
produced in the company then the company applies for the Product Registration Form in the
37
DDA. Then after getting the manufacturing license the R & D starts its work in small scale
producing different formulation changing the excipients and other ingredients and sends it to
QC for the effectiveness of the formulation. Side by side the stability test of the formulation is
conducted. The stress testing is conducted to find out the shelf life. After satisfactory result
from the different trials the formulation is produced is large scale. Then some samples are
sent to the NML and after its approval, the company applies for marketing permission. The
real time stability test is also initiated right from the scale up production. Then large scale
production stars after the approval letter from DDA.
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3. CONCLUSION
In-plant training at OPL has been very helpful to us. It helped us gather practical knowledge
regarding the Industrial pharmacy and its practices, those of which we had only theoretical
knowledge of. We got the opportunity to see different processes involved in store, production,
QC, QA and engineering departments. We saw the actual working of BMR, BPR, SOP’s and
how it acted along in the production of a pharmaceutical product, maintaining GMP.
OPL staffs are friendly, helpful, supportive, dedicated and honest to their duties. The co-
operation we got from all the staffs, had been very motivational. We got to learn from them,
how to handle a problem in a real setting, that which wouldn’t be found in books. Their
guidance and support were always valuable for us, which helped us to understand the basic
and practical aspects of pharmaceutical manufacturing. This training has indeed been a boost
for our career. We felt really glad to have the opportunity of completing my internship or in-
plant training under the competitive personnel of the Nepalese pharmaceutical field. We wish
OPL a great march towards the pharmaceutical excellence always.
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4. ANNEX I
40
42. Sidaze 10 Serratiopeptidase
43. Unwanted Tab Levonorgestrel
44. Uroxate Flavoxate
45. Vertin 8 Tab Betahistine
46. Vertin 16Tab Betahistine
47. Vertin 24Tab Betahistine
48. Xifim 100 DT Cefixime
49. Xifim 200 Tab Cefixime
50. Xifim Dry Syrup Cefixime
51. Zolben 400 CT Albendazole
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