KATHMANDU UNIVERSITY

DHULIKHEL, KAVRE

A REPORT ON IN PLANT TRAINING

AT
OHM PHARMACEUTICALS LABORATORIES PVT.LTD
IN PARTIAL FULFILLMENT OF THE REQIREMENT FOR THE DEGREE
OF
BACHELOR’S OF PHARMACY

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

General Manager (Technical)

Ohm Pharmaceuticals Lab Pvt.Ltd.

Tathali, Bhaktapur, Nepal

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 ACKNOWLEDGEMENT

I would like to express my profound gratitude to Department of Pharmacy, Acting Head of

Department Dr. Rajani Shakya for arranging 1 month in-plant training.

I would like to express my heartfelt gratitude to Phr.Sumit Chandra Shrestha, General

Manager (Technical Department) of Ohm Pharmaceuticals Lab Pvt. Ltd. for granting
permissions to do in-plant training at Ohm Pharmaceuticals Lab Pvt. Ltd.

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

API Active Pharmaceutical Ingredient

BMR Batch Manufacturing Record

BP British Pharmacopoeia

BPR Batch Packaging Record

DDA Department of Drug Administration

DMW De-Mineralized Water

DT Disintegration Time

FBD Fluidized Bed Drier

FG/FP Finished goods/ Finished Products

GLP Good Laboratory Practice

GMP Good Manufacturing Practice

HDPE High Density Polyethylene

HEPA High Efficiency Particulate Air

HPLC High Performance Liquid Chromatography

HVAC Heating Ventilating and Air Conditioning

IP Indian Pharmacopoeia

IP C In-Process Control

IPQC In-Process Quality Control

IPA Isopropyl Alcohol

ISO International Organization for Standardization

OS Oscillating Granulator

PM Packaging Material

PPM Parts per Million

PVC Polyvinyl Chloride

RH Relative Humidity

RM Raw Material

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RMG Rapid Mixing Granulator

RO Reverse Osmosis

RPM Revolution per Minute

R&D Research and Development

SOP Standard Operating Procedure

USP United State Pharmacopoeia

UV Ultraviolet

WHO World Health Organization

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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

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 LIST OF FIGURES

Fig 1.4.1 organizational structure of OPL 11

Fig 1.3.1 Site of OPL 12

Fig 2.1.1 flowchart of handling of materials in store 15

Fig 2.2.1 Flowchart of Tablet Manufacturing Process 19

Fig 2.2.2 Flowchart of Overall Liquid 20-21

Fig 2.2.3 General Steps of Capsule Manufacturing Process 22

Fig 2.5.1.1 Schematic Diagram of HVAC System 32

Fig 2.5.2.1 Flowchart of Air Handling Unit 33

Fig 2.5.3.1 Water Purification System 36

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 1 INTRODUCTION

1.1 IN-PLANT BRIEFING

The in-plant training was received to fulfill the completion of Bachelor degree of Pharmacy
program of Kathmandu University, Dhulikhel ,kavre at Ohm Pharmaceuticals Laboratories
Pvt.Ltd (OPL),Tathali, Bhaktapur. One month training was received at OPL as the partial
fulfillment of the course curriculum. During the course of training we were placed at various
sections of manufacturing plant like production, quality control and assurance, primary and
secondary packaging area, store department and engineering and maintenance department.
Those 4 weeks were very fruitful and was proved to be very much worthy in our pharmacy
career. The in-plant training gave a clear picture about what industrial scenario is all about
and what activities are performed there on day to day basis in context to production and
quality of pharmaceutical products.

Training Period: September 10 to October 18.

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1.2 OBJECTIVES
The objectives of in-plant training are as follows:

 To have a concept of implementation of the WHO-GMP principle in the

pharmaceutical industry.
 To be familiar with the structure, organization, departments and their role and
functioning in a pharmaceutical company.
 To have an idea about the Building Design & Constructions Pharmaceutical Industry.
 To know the sequence of Procurement, Processing, Production, Handling
Documentation & Quality Assurance during the various steps from Raw Materials to
Finished Products.
 To be familiar with the different Equipments & Instruments used for the
manufacturing of the drugs in the pharmaceutical industries including their working
principle.
 To know the different Process of Quality Control and In-Process control of Raw
Materials & Finished Products.
 To have an idea about Water purification system and engineering of the AHU.
 To have an idea on waste management system in pharmaceutical industry.

10
1.3 COMPANY PROFILE

Fig 1.3.1 Site of OPL

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.

11
 1.4 ORGANIZATIONAL STRUCTURE OF OPL

BOARD OF DIRECTORS

MANAGING DIRECTOR

OPERATION DIRECTOR

PURCHASE GENERAL MANAGER

DEPARTMENT

QUALITY ASSURANCE MANAGER R&D

QA OFFICERS

PRODUCTION QUALITY CONTROL STORE MAINTENANCE

Sr.Production officer Sr. QC officer In charge Supervisor

PRODUCTION OFFICERS MAINTENANCE

QC OFFICERS STAFFS

Asst. QC Officer
Asst. Production
officer

Operators
Supervisior

Fig 1.4.1 organizational structure of OPL

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1.5 OPL PRODUCTS
OPL manufactures drug of different therapeutic categories which are as follows:

 Non-Steroidal Anti-Inflammatory Drugs(NSAIDS)

 Antipyretic
 Anti-Cold
 Anti-Tussives
 Anti-Histamines
 Proton Pump Inhibitors
 Anti-microbial
 Antispasmodics
 Laxatives
 Vitamins
 Hormones

These drugs are found in different dosages form which are;

 Tablets
 Capsules
 Dry syrups
 Suspensions
 Syrups

List of OPL products are given in ANNEX I

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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

2.1 STORE DEPARTMENT

Storage is the process of keeping or holding goods in a systematic way preserving its quality
and store is the place where goods are kept safely for future use. It is the body concerning
with the storing of all required materials and chemicals which may be API, excipients,
packing materials or any materials which may find use in near future and documentation of
such materials. . Since, store is the first point of entry of material into the factory, it should
therefore be properly maintained to prevent deterioration, contamination of stored goods till
theirs shelf life.
OPL store has following sections
 Documentation Cabinet
 Dedusting Area
 Raw material store
 API Store /Cold area
 Quarantine
 Rejected material store
 Area for supplying for dispensing.

The major activity of store is:

 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 are crossed checked based on the details provided in invoice.

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.

Fig 2.1.1 flowchart of handling of materials in store.

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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

16
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.

The machines used here are:

 Mechanical sifter
 Multi mill
 Rapid mixing granulator
 Fluidized Bed Drier ( FBD )
 Paste kettle

3. Mini Granulation Room:

 Tray drier
 Mass Mixer
 Mechanical sifter
 Oscillating granulator ( OG )

4. Compression room: Granules or powders are blended in one of the compression room
containing

 Double Hopper 35 station rotary tablet press

 Double Hopper 27 station rotary tablet press
 Single Hopper 20 station rotary tablet press
 Tablet Deduster

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

17
  Spray gun
 Exhaust
 Stirrer

General Step of tablet Manufacturing:

Batch requisition

Batch Manufacturing Record (BMR) issued by QA

Weighing and Dispensing of raw material (in presence of QC or QA personnel)

Counter checking by the production pharmacist

(Line clearance)

Manufacturing

Sieving in vibroshifter with different mess size

Milling (if required)

Mixing in RMG use impellors and chopper, blending

Granulation (wet granulation)

(Starch paste with Binding solution)

Granulation/ kneading in RMG

Wet screening (if necessary in oscillating granulator)

Drying (FBD/tray drier)

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 Dry screening

Lubrication of the final product

Bulk product formation

(Storage in quarantine until QC clearance)

Compression IPQC

(QC Analysis)

Coating

Quarantine

(QC Analysis)

Primary Packaging (blister or strip) IPQC (Leak Test)

Secondary Packaging

Finished Product Analysis

(QC Analysis)

QA Analysis

Market Dispatch

Fig 2.2.1 Flow chart of tablet manufacturing process

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:

 Sugar melting vessel

 Manufacturing Tank 2000 ltr
 Transfer Pump
 Storage Tank
 Suction motor
 Filter Press

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.

Flow chart for overall Process of Liquid Production

RM Requisition from Production

QC Analysis

QC Release RM Dispensing Supervised by QA

by Store

Sieving

Primary Syrup/Base preparation

Mixing of Active and other excipients

Color and Flavor added

Volume make-up

Homogenization
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 PH adjustment

QC Release

Filtration in Filter press Colloidal Mill for Suspension passed

for Syrup Through mess 60 or 40

Storage Tank

Bottle Washing

Empty Bottle Inspection

Bottle Filling & Sealing

(IPQC Volume check-up )

Filled bottle Visual Inspection

Labeling & Packing

Storage

Dispatch

Fig 2.2.2 Flowchart of overall liquid production

It consists of the following machineries:

 Manufacturing tank 5000 ltr

 Automatic Volumetric Liquid Bottle Filling Machine
 Sealing Machine
 Bottle Inspection Machine
 Semi automatic filling machine(dysfunctional stage)
 Stirrer

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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.

General step of Capsule Manufacturing

Raw materials dispensed: received by production

Sieving using sieve of suitable size

Geometrical mixing: As per BMR

(QC Analysis)

Hard gelatin capsule loading in automatic capsule

Capsule filling and sealing using manual capsule filling machine

Capsule polishing and sorting

(QC Analysis)

Packaging

Finished Product Stored

(QC Analysis)

Dispatch
Fig 2.2.3 General steps of capsule manufacturing

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The machine used during capsule filling are:

 Semi Automatic capsule filling machine

 Capsule inspection and sorting
 Manual capsule filling machine
 Capsule Loader

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

This room consists of following equipment:

 Digital hardness tester
 Digital vernier caliper- For thickness, diameter and length
 Weighing balance
For weight variation of 20 caps: Limit- <300mg-7.5% & ≥300 mg-5%
 Friability testing apparatus
 Disintegration apparatus
 Bulk density apparatus
 Moisture Balance
 pH meter- For liquids

12. Packaging room;

Packaging is the final step of Drug production. Packaging is a means of presenting product to
the customer protecting its quality. Packaging section consists of following two areas:
1. Primary packaging area
2. Secondary packaging area

Primary Packaging Room:

In primary packaging, the product comes in direct contact with the packaging materials. It is
the final step carried out in grey area.
After the drugs are packed into primary packaging, they are sent to the black area for
secondary packaging. Before that, the following are checked:
a. printing mistake
b. broken tablets inspected visually
c. unfilled packs (strips, blisters, bottles)
d. Particles, improper seals in bottles

 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.

Liquid filling and sealing:

Liquids after mixing are filled and sealed in bottles with the liquid filling and sealing room.
Primary packaging materials used in OPL for liquid includes amber colored glass bottle,
plastic bottle and PP cap. After the drugs are packed into primary packaging, they are sent to
the black area for secondary packaging. Before that, the following are checked:

a. proper seals in bottles

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

2.3 HORMONE SECTION

This unit is mainly focused on manufacturing of hormones. This is a separate and segregated
unit thus the access door, aprons and other allied material are different for this section.

This room is equipped with:

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

 Disintegration test apparatus

 Friability test apparatus
 Weighing balance

2.4 QUALITY CONTROL AND ASSAURNCE DEPARTMENT (QCAD)

1. Quality Assaurance Department

Quality assurance is a wide-ranging concept covering all matters that individually or

collectively influence the quality of a product. It is the totality of the arrangements made with
the object of ensuring that pharmaceutical products are of the quality required for their
intended use. Quality assurance therefore incorporates GMP and other factors, including
product design and development.

QA refers to planned and systematic; production processes that provide confidence in a

product’s suitability from its intended purpose. It is a set of activities intended to ensure that
products satisfy customer requirements in systematic, reliable fashion. QA has important role
of monitoring right from the handling of the raw materials to the production of the finished
product.

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.

26
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

2. Quality Control Department

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

27
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.

QC department of Ohm pharmaceutical Laboratories is involved in carrying out the following

major activities:

1. Routine analysis and documentation.

 Raw material Analysis(active ingredient and excipients)

 Intermediate products analysis (Lubricated granules) for further processing
 Bulk Products
 Finished Products analysis for their release
 Packaging Materials analysis (both Primary & Secondary)

2. SWAB analysis

3. Water analysis

4. In process sample analysis

5. Microbiological analysis

6. Stability testing

7. Environmental monitoring of production area (Checking for bioburden level)

8. Routine calibration and standardization of laboratory equipment

9. Record of laboratory reagents

10. Maintaining quality control records

 Raw material analysis ( Active and inactive)

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.

28
 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 product analysis

Intermediate products such as granules and powders are analyzed before advancing to
further steps of production.

 Finished product analysis

Finished goods are analyzed before starting the packaging process.

 Packaging material analysis

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:

1. The instrument of Hot zone in QC lab are:

 Fume Hood
 Hot air oven
 Muffle furnace

2. The instrument in Wet lab chemistry are:

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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

3. The instruments in sophisticated instrumentation section are:

 Double beam UV spectrophotometer:

 HPLC
 Polarimeter
 Potentiometric titrator
 Karl-Fischer titration
 Digital PH meter
 Desiccator
 IR
3. Instruments in microbiology laboratory are:
 Autoclave: It is used for sterilization by application of moist heat under pressure. It is
operated at 1210C for 15 minutes under pressure of 15 lbs. per square inch.
 Incubator: It is operated at 370C. Main objective is to maintain suitable temperature
for the growth of inoculated microorganism
 Laminar Air flow cabinet: It is used to carry out the microbiological procedures
under aseptic conditions. It is based on the principle of laminar airflow.
 Colony counter: It is used to count the bacterial colony.
 Refrigerator: It is used to cool culture medium, agar and preservation of reagent

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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:

2.5.1 Heating, Ventilation and Air Conditioning Unit (HVAC system)

HVAC plays an important role in ensuring the manufacturing of quality pharmaceutical
products. A well design HVAC system will also result in operator comfort. HVAC system
design influences architectural layouts with regard items such as airlock positions, doorways,
and lobbies. The architectural components have an effect on room pressure differentials
cascades and cross contamination control. The prevention of contamination and cross
contamination is an essential design consideration of the HVAC. Temperature, relative
humidity, particle count and ventilation should be appropriate and should not adversely affect
the quality of the pharmaceutical product during their manufacture and storage or the accurate
functioning of the HVAC system.

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

Pre- filter. Bag filter

HEPA Filter

Production
Area
Return Filter/Course Filter

Return Duct

Fig2.5.1.1Schematic diagram of HVAC System

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2.5.2 Air Handling Unit

Different parts of AHU include:

 Air inlet
 Mixing chamber
 Filter section
 Conditioning unit
 Blower section
 Chilling units of different capacity

Re-circulated Air-
Fresh Air- 85%
15%

Mixing Chamber
Pre-filter (10µ) Bag Filter (5µ)

Blower/ Heater (Solenoid Coil) Condensing Unit (Chiller)

Fan

Controller HEPA Filter/ Biopack Room

filter (0.3µ)

Biopack Filter Return Filter

(10- 20µ)

Fig 2.5.2.1 Flow chart of Air Handling Unit

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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.

2.5.3 Water Purification System

Water is stored in an underground reservoir tank of capacity 150000 liters, which is then
transferred to a raw water storage tank located at the roof of the building Potable water is first
passed through sand filter to remove any suspended particulate matter. Sand filter consists of
different size of particle, smaller size at upper bed and larger size towards bottom. Sand filter
is rinsed daily, cleaned by back-pass of water and drain through bypass. Then, it is passed
through Activated Carbon filter (water softener), mainly to de-chlorinate water by adsorption
and also remove any odor or color. It is changed in every two weeks. Water coming out of
carbon filter is passed through water softener tank to reduce hardness of water by removing
Ca, Mg, and other metals with help of resins. Resins are recharged with iodine free NaCl
weekly or in 15 days. Resins are changed as required, usually after 2 years. Then this water
can be used as tap water, also it is dosed with descalent to remove any scale forming salts. It
prevents scale formation in RO membrane and it’s choking. The descalent dosed water passes
through 5µ cartridge filter and then through 5 serial RO plant of 0.3 µ sized membrane pore.
From RO plant, two lines of water are separated; one of concentrated water which can be used
in gardening and washroom, another line of RO water is for pharmaceutical use which is

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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

Fig 2.5.3.1 Water Purification System

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2.5.4 Power Supply
Electric Power
The electricity in the industry is obtained from Nepal electricity supply board.

2.5.5 Backup Power supply(generator)

As for the alternate source of electricity company is facilitated by two diesel based generators
of 360KV and 20KV capacities in case of power cut.

2.5.6 Air compressor

Compressed air is required during various unit operations in production area such as coating,
Fluidized Bed Drier (FBD), compression, capsule separation and polishing, Blister packing,
to run chopper of RMG, bottle dedusting, etc. Air compressor filters, collects, dehumidifies
and supplies compressed air where it is needed. Currently OPL has one air compressor.

2.6 RESEARCH AND DEVELOPMENT (R&D) DEPARTMENT

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

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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

Product list of Ohm Pharmaceutical Laboratories Pvt. Ltd.

S.N. NAME OF THE PRODUCTS COMPOSITION

1. ACC Tab Paracetamol + Chlorpheniramine
maleate + Phenylephrine
2. ACC Suspension Paracetamol + Chlorpheniramine
maleate + Phenylephrine
3. AGT 500 Tab Tinidazole
4. AGT 1000 Tab Tinidazole
5. Alert Tab Cetrizine
6. Alert Syrup Cetrizine
7. Alofen 100 Tab Acelofenac
8. Azicare 500 Tab Azithromycin
9. Azicare 250 Tab Azithromycin
10. B-COM Cap Vitamin B
11. B-COM Syrup Vitamin B
12. Biospan 10 Tab Hyoscine butylbromide
13. Biospan 20 Tab Hyoscine butylbromide
14. Cofsy-D Levodropropizine
15. Evalax 100 Lactulose
16. Evalax 200 Lactulose
17. Hepact 150 Urosodeoxycholic acid
18. Hepact 300 Urosodeoxycholic acid
19. Ibosyn Mebiverine
20. Kestine 10 Ebastine
21. Kestine 20 Ebastine
22. Leflox 250 Levofloxacin hemihydrate
23. Leflox 500 Levofloxacin hemihydrate
24. Lotemp Suspension Paracetamol
25. Mecobal 0.5 Methylcobalamine
26. Mecobal 1.5 Methylcobalamine
27. Mistol Misoprostol
28. Obeslim Orlistat
29. Omflam Tab Ibuprofen + Paracetamol
30. Omflam Suspension Ibuprofen + paracetamol
31. Omni Tab Nimesulide
32. Opiflox 250 Ciprofloxacin
33. Opiflox 500 Ciprofloxacin
34. Panom 40 Pantoprazole
35. Pregno Mefipristone
36. Pregalin 75 Pregabalin
37. Proton 20 Omeprazole
38. Prostam 0.4 Tamsulosine
39. Quinflox 200 Ofloxacin
40. Quinflox 400 Ofloxacin
41. Sidaze 5 Serratiopeptidase

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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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