UTL

TO STUDY THE PRODUCTION OF SMALL VOLUME
PARENTERAL PRODUCTS (SVP) AND HOW TO CONTROL

QUALITY OF PRODUCT
A PROJECT REPORT
Submitted by
Rajkumar D. Patel
Roll no. 09078
Batch 2009 to 2011
To
Director (PGDM)
In partial fulfillment of the requirements of

Tolani Institute of Management Studies, Adipur
For the award of the degree of

Post Graduate Diploma in Management
Tolani Institute of Management Studies

Adipur- 370 025
July 2010
UNIMED TECHNOLOGIES LTD (UTL)
TABLE OF CONTENT
Sr. No. Title Page no.

01 Preface 08
02 Declaration 09
03 Acknowledgment 10
Chapter 1:- Introduction 11
04 Overview of Indian pharmaceutical industry 12
05 SWOT analysis of Indian pharmaceutical industry 14
06 Introduction of UTL 16
07 Introduction to parenteral formulation 17
08 Introduction to ophthalmic formulation 18
Chapter 2:- Objectives and Methodology 19
Chapter 3:- To study production of small volume parenteral product 22
09 ITM ERP 23
10 Flow of material throughout organization 24
11 P & A department 26
12 Store department 27
Engineering department 30
13.01 RO plant 31
13.02 WFI plant 31
13 13.03 Compressed air plant 32
13.04 Nitrogen plant 33
13.05 ETP (Effluent treatment plant) 33
13.06 AHU plant (Air handling unit) 34
Quality Assurance department 35
14 14.01 Change control 37
14.02 Market complain 38
Tolani Institute of Management Studies, Adipur Page 2

Sr. No. Title Page no.

Quality Control department 39
15
15.01 Various instruments of QC 40
Production department 42
16.01 Lay out 43
16.02 Chemist room 44
16.03 SOP 45
16.04 BMR 46
16.05 De-cartoning area 50
16.06 Ampoules/Vial washing area 50
16.07 Equipment washing area 51
16
16.08 Dress washing area 51
16.09 Autoclave and DHS area 52
16.10 Manufacturing area 53
16.11 Filtration area 54
16.12 Filling and capping area 54
16.13 Visual inspection area 56
16.14 Freeze dry area 58
16.15 Quarantine area 58
17 Packing department 61
Chapter 4:- How to control quality of products 64
18 Instrument qualification 66
19 Process validation 69
Chapter 5:- Finding and Interference 72
Chapter 6:- Recommendation and Suggestions 74
Chapter 7:- The reference 76
20 Bibliography 77

LIST OF TABLE
Sr. No. Table name Page no.
1 Top 10 Indian pharmaceutical companies, as of 2009 13
2 List of different ophthalmic formulation 18
3 Different status of raw materials in store department 28
4 Parameters control by AHU 34
5 Various function of QA department 36
6 List of instruments of QC department 40
7 Format of daily planning of production department 44
8 Distribution of activities in production department 44
9 Format of area label 45
10 Content of SOP 45
11 Content of BMR 47
12 Pressure limit of ampoule / vial washing machine 50
13 Batch size of different dose ampoules or vials 51
14 Different cycle of dress washing machine 52
15 Various cycles of Autoclave 53
16 Filling volume control limit 56
17 Various defect of visual inspection area 56
18 Format of statistical report of visual inspection area 57
19 Visual of plastic bottle 57
20 Format of FD schedule 58
21 Color code 59
22 Format of carton label 59
23 Sanitizing schedule of production department 60
24 Various packing line of packing department 61
25 Various defects of packing department 62
26 Content of BPR 63
27 Training schedule of packing department 63
28 Stages of instrument qualification 68
29 Content of process validation master plan 71
30 Execution process of process validation 71

LIST OF FIGURE
Sr. No. Figure name Page no.

1 Flow of material in organization 24
2 Various modules of HR application portal 26
3 Various sub units of store department 27
4 Material flow in store department 28
5 Activities of engineering department 30
6 Construction of RO plant 31
7 Construction of WFI plant 32
8 Construction of Compressed air plant 32
9 Construction of Nitrogen Plant 33
10 Mechanism of ETP 33
11 Construction of AHU 34
12 Procedure for change control 37
13 Procedure for Market complain 38
14 Layout of Production department 43
15 Movement of BMR throughout production department 48
16 Movement of material in packing department 49
17 Diagram of filtration process 54
18 Layout of Packing quarantine area 62

ABBREVIATIONS
Sr. No. Abbreviation Full form

1 AHU Air handling unit
2 API Active pharmaceutical ingredient
3 BKC Benzalkonium Chloride
4 BMR Batch manufacturing record
5 BOM Bill of material
6 BPR Batch packing record
7 CA Corrective action
8 CC Change control
9 CGMP Current good manufacturing practice
10 CQ Corporate quality
11 DHS Dry heat sterilization
12 DQ Design qualification
13 ETP Effluent treatment plant
14 FAT Factory acceptance test
15 FD Freeze dryer
16 FIFO First in first out
17 FO Filling operation
18 GC Gas chromatography
19 GMP Good manufacturing practice
20 GRN Goods receive note
21 HEPA High efficient particulate air
22 HPLC High performance liquid chromatography
23 HR Human resource
24 IQ Installation qualification
25 IPA Iso propyl alcohol

Sr. No. Abbreviation Full form

26 ITM Integrated trade & Manufacturing
27 LAF Laminar air flow
28 LPG Liquefy petroleum gas
29 OQ Operation qualification
30 PA Preventive action
31 pH pH = -log[H3O+]
32 PQ Performance qualification
33 PPM Primary packing material
34 QA Quality assurance
35 QC Quality control
36 QTY Quantity
37 RFID Radio frequency identification
38 RO Reverse osmosis
39 SAT Site acceptance test
40 SO Sterilization operation
41 SOP Standard operating procedure
42 SVP Small volume Parenterals
43 TLC Thin layer chromatography
44 UPLC Ultra performance layer chromatography
45 URS User requirement specification
46 UTL Unimed technologies ltd
47 UV Ultraviolet
48 WC Water column
49 WFI Water for injection
50 WHO World health organization

PREFACE
Project work is an essential part of the syllabus of PGDM program. In project work
student has to use his or her various skills like analytical skill, communication skill,
writing skill, etc. This is why included in PGDM program.
The proverb “Practical makes man perfect” means a lot to the manager. Success does
not come easily, one has to work hard for it and achieve it at each and every stage
of life.
Conceptual studies are always observed during the project study. It gives me the
complete understanding of the real life situation and happenings in the real world.
From the practical point of view a project plays an important role for the student.
Before I present this project, I would like to say that it is mirror image of a
reflection to whatever I have observed and have come through during my project
work.

DECLARATION
I hereby declare that the project work entitled “To study the production of
small volume parenteral Parenterals and how to control quality of products‟ submitted
to Tolani Institute of Management Studies, Adipur, is work of an original record done
by me under the guidance of Mr. Santosh Sawant, (HOD, HR department) This
project is not submitted for the award of any other degree/ diploma/ associate ship/
fellowship or similar award.
Signature:
Name: Rajkumar D. Patel
Date: July 2010
Place: Adipur

ACKNOWLEDGEMENT
I wish to express my gratitude to UNIMED TECHNOLOGIES LTD

management for giving me an opportunity to be a part of their esteem organization
and enhance my knowledge by granting permission to do my project under their
guidance.
I am grateful to Mr. Pushpendra Jain (Plant head), Mr. Santosh Sawant (HOD,
HR department), Mr. Samir shah & Mr. Jignesh Soni (HOD, Store department),
Mr.Bhadresh Parmar (HOD, Engineering department), Mr. Pramesh Kothari (HOD,
QC department), Mr.Nilesh Bhatt (HOD, QA department), Mr. Jagat Unadkat (HOD,
Production department), and all the employees of UNIMED TECHNOLOGIES LTD,
who guided me and provided their valuable guidance and cooperation during the
course of the project. They provided me all the information and support whenever
needed that has been instrumental in completion of this project.
At last but not the least I am grateful to all the staff members of UNIMED
TECHNOLOGIES LTD, for their kind cooperation and help during the course of my
project.
I am also thankful to Mr. Sushil Chaursiya and all staff members of my

college who helped me as and when required with his guidance.


PHARMACEUTICAL INDUSTRY OVERVIEW
“Indian pharmaceutical industry can be defined as a success story providing

employment to millions and ensuring that essential drugs are available at affordable
prices to the vast population of Indian sub-continent”
-RICHARD GESTER
(Economist)
Accounting for two percent of the world's pharmaceutical market, the Indian
pharmaceutical sector has an estimated market value of about US $8 billion. It's at 4th
rank in terms of total pharmaceutical production and 13th in terms of value.
It is growing at an average rate of 7.2 % and is expected to grow to US $ 12

billion by 2010. Over the last two years the pharmaceutical market value has
increased to about US $ 355 million because of the launch of new products.
According to an estimate, 3900 new generic products have been launched in the past
two years. These have been by and large launched by big brands in the pharma sector.
And in the year 2005 Indian pharmaceutical companies captured around 70% of the
domestic market.
As in the present scenario, only a few people can afford costly drugs, which
have increased price sensitivity in the pharmaceutical market. Now the companies are
trying to capture the market by introducing high quality and low price medicines and
drugs. With the Product Patent Act, which came into action in January 2005, this
industry is able to attract big MNCs to India. Earlier these big firms had
apprehensions in launching new drugs in the Indian market.

At present, a large number of Indian pharmaceuticals companies are looking

for tie-ups with foreign firms for in-license drugs. GlaxoSmithKline is among the top
choices for the firms that wish to launch their product in India, but do not have any
branch over here. Contract research and pharmaceutical outsourcing are the new
avenues in the pharmaceutical market. Contract manufacturing is growing at a very
fast pace and is estimated to grow to US $30billion, whereas contract research is
estimated to reach US$6-10 billion.
Indian multinational companies like Dr.Reddy's Lab, Cipla, Ranbaxy, Sun

pharma etc have created awareness about the Indian market prospects in the
international pharmaceutical market. Approvals given by Foods and Drugs
Administration (FDA) and ANDA (Abbreviated New Drug Application)/DMF (Drug
Master File) have played an important role in making India a cost-effective and high
quality product manufacturer. Furthermore, the changes that took place in the patent
law, change of process patent to product patent, have helped in reducing the risk of
loss for intellectual property.
Rank Company Revenue 2009 (Rs crore)

1 Ranbaxy Laboratories 25196.48
2 Dr. Reddy's Laboratories 4162.25
3 Cipla 3,763.72
4 Sun pharmaceutical industries 2463.59
5 Lupin Labs 2215.52
6 Aurobinbo Pharma 2080.19
7 GlaxoSmithKline 1773.41
8 Cadila Healthcare 1613.00
9 Aventis Pharma 983.80
10 Ipca laboratories 980.44
Table 1: Top 10 Indian pharmaceutical companies, as of 2009

SWOT ANALYSIS OF INDIAN PHARMACEUTICAL

INDUSTRY:
STRENGTH
 Cost effective technology.
 Strong and well-developed manufacturing base.
 Clinical research and trials.
 Knowledge based low- cost manpower in science & technology.
 Proficiency in path-breaking research.
 High-quality formulations and drugs.
 High standards of purity.
 Non-infringing processes of Active Pharmaceutical Ingredients (APIs)
 Future growth driver.
 World-class process development labs.
 Excellent clinical trial centers.
 Chemical and process development competencies.
WEAKNESS
 Low Indian share in world pharmaceutical market (about 2%)
 Lack of strategic planning.
 Fragmented capacities.
 Low R&D investments.
 Absence of association between institutes and industry.
 Production of duplicate drugs.

OPPORTUNITIES
 Incredible export potential.

 Increasing health consciousness.
 New innovative therapeutic products.
 Globalization.
 Drug delivery system management.
 Increased incomes.
 Production of generic drugs.
 Contract manufacturing.
 Clinical trials & research.
 Drug molecules.
THREATS
 Small number of discoveries.
 Competition from MNCs.
 Transformation of process patent to product patent (TRIPS)
 Outdated Sales and marketing methods.

INTRODUCTION TO UNIMED TECHNOLOGIES LTD (UTL):
UTL has been established in 1990. UTL is situated above 36 km east from
Baroda & 6 km away from Halol. UTL is one of the leading companies, having an
asset of its quality products. UTL works under loan license of SUN pharma. It
manufactures various drugs, injections, eye drops etc.
UTL has 424 total employees, out of them 97 are permanent staff employees,
77 are permanent operators and 250 are contract (Casual) workers. UTL is currently
producing Parenteral, Ophthalmic and Hormone products. UTL has also engage with
construction of its new plant for production of ANDA “Abbreviated new drug
application” and also construct a gas based power plant to become self-reliable.
UTL has following departments:
P & A DEPARTMENT
STORE DEPARTMENT
ENGINEERING DEPARTMENT
UTL
QUALITY CONTROL DEPARTMENT
QUALITY ASSURANCE DEPARTMENT
PRODUCTION DEPARTMENT
PACKING DEPARTMENT

INTRODUCTION TO PARENTRAL FORMULATION
Definition:
Parenterals are defined as sterile dosage forms which are administered to patient by a
route other than alimentary canal. In other words, these preparations bypass the
gastrointestinal tract and liver. They directly enter into systematic circulation, these
preparations directly entered into blood vessels, tissues, body compartment.
Small volume Parenterals means parenteral preparation having volume 1 ml to 500

ml.
Advantages:
 Drugs can be administered to unconscious patient with ease.

 Drugs cannot be delivered through oral route can be administered through
parenteral route.
 Administration of drug to target area is ensured.
 Easily used in case of emergency.
Dis advantages:
 Self-medication is not possible; hence trained persons are required for proper
administration.
 Proper care should be taken during its manufacturing, filling, packaging and
strict sterility requirements are to be fulfilled.
 Parenteral products are quite expensive.
 Once administered, the drug cannot be retrieved in case of overdose.

INTRODUCTION TO OPHTHALMIC FORMULATION
Definition:
Ophthalmic is defined as the dosage form intended to be administered onto the

external surface of the eye, inside or adjacent to the eye or those used in combination
with ocular appliances.
The capacity of eye to accommodate dosage form is less. So they are administered in
small amounts. Only a small quantity of drug administered gets absorbed due to less
residence time of drugs in eye, caused by tear fluid drainage. Drugs which are
lipophilic penetrate the corneal layers easier than hydrophilic drugs.
Types of ophthalmic formulation:
Sr.
Types Description
No.
01 Eye drops Aqueous or oily solutions administered in form of drops.
Ophthalmic Drugs which are insoluble in water can be administered
02
suspension through suspension onto surface of eye.
Ophthalmic Anhydrous semisolid dosage form meant to apply inside
03
ointment lower eyelid to produce local effect.
Ophthalmic
04 Inject drugs through syringe in various parts of eye.
injection
Sterile solution which maintain cornea in hydrate and
05 Irrigation solution
clear state during an ocular surgery.
Devices containing drug reservoir enclosed by 2 release
06 Ocular insert
controlling membranes made up of copolymers.
Contact lenses care
07 Preparations are utilized for care of contact lenses.
solution
Table 2: List of different ophthalmic formulation


Objectives:
Primary objectives:-
 To understand all technicalities of production of small volume parenteral

products.
 To study facilities of limitation of plant (UTL)
Secondary objectives:-
 To get deep understanding of documentation of production process.
Methods of data collection:
Source of primary data:-
 One to one communication with employees of UTL.
Source of secondary data:-
 SOPs of company.
 BMR of company.
 GMP guideline.
 Internet.

Methodology:
 I have completed my summer training in following sequence:
PHASE ACTIVITY DAYS

Introduction to P&A, Store department 01
Introduction to engineering department 01
Primary Introduction to QC department 01
Introduction to QA department 01
Introduction to Production department 01
De-cartoning & Washing area 02

DHS & Autoclave area 02
FD & Quarantine area 01
Manufacturing & Filtration area 02
Secondary
Filling & Capping area 02
Visual inspection area 02
Hormone area 02
Packing area 02
SOP reading 06
Conversion of SOP into vernacular language 01
BMR understanding 04
Modification & Correction of BMR 04
Advance
Planning of production schedule
04
To study factors affecting cycle time of BMR
Instrument qualification 02
Process validation 02
Holidays (Weekly off) 06
Total days 49
Time period: From 03rd May 2010 to 20th June 2010


ITM – ERP
 UTL is currently using ITM (Integrated trade and manufacturing) “Enterprise

resource planning” software to cover all activities of different departments of
UTL.
 ITM automates business processes and manage information of business house
involved in trading and manufacturing activities.
 Management oriented design of ITM goes hand to hand with business process
re-engineering. Activities carried out by organization should be made process
oriented rather than department oriented.
 To obtain best result from software, way business is done has to be looked at
from ITM point of view. Each employee’s contribution and accountability
must be made transparent to system.
 Business processes should be mapped to system in a right way, which require
deep knowledge of ITM. (All modules)
 Software is tightly integrated across various modules and functional area of
organization. All modules work as one system, sharing information across
organization.
 ITM has following modules. Each module has number of sub-functions.
Help
Adminstration
Manufacturing
ITM
Supply Chain Managment
Finance
System

FLOW OF MATERIAL THROUGHOUT ORGANIZATION
Receive raw
Verify document Unload materials
materials from
of received goods from vehicle
supplier
GRN (Goods
Verify quantity of De dusting of
receive note) in
materials containers
ERP
If quality is up to
Sampling by QC
mark, affix green
Kept in store (Affix Yellow label)
label and approve
quarntine room "Under process
for use, otherwise
status"
"Reject"
Sampling by QC, Manufacturing, Issue to

approve and release Filtration, Filling, production
for packing, Capping, Visual department for
otherwise hold it inspection manufacturing
Dispatch to
BMR released by Release a batch to
company ware -
QA store department
house
Fig 1: Flow of material in organization

P & A DEPARTMENT
[HOD- MR. SANTOSH SAWANT]
Introduction:
"If you want 10 days of happiness, grow grain. If you want 10 years of
happiness, grow a tree. If you want 100 years of happiness, grow people."
Human resources are the most valuable and unique assets of an organization.
The successful management of an organization's human resources is an exciting,
dynamic and challenging task, especially at a time when the world has become a
global village and economies are in a state of flux. The scarcity of talented resources
and the growing expectations of the modern day worker have further increased the
complexity of the human resource function. Even though specific human resource
functions/activities are the responsibility of the human resource department, the actual
management of human resources is the responsibility of all the managers in an
organization.
It is therefore necessary for all managers to understand and give due

importance to the different human resource policies and activities in the organization.
Human Resource Management outlines the importance of HRM and its different
functions in an organization. It examines the various HR processes that are concerned
with attracting, managing, motivating and developing employees for the benefit of the
organization.
The specialist role of the HR professional takes a number of forms: the

auditor's role, the executive's role, the facilitator's role, the consultant's role and the
service-provider's role. HRM objectives should be in alignment with the
organizational objectives, and should balance them with the individual and social
goals.

Activities:
 P & A department follow systematic procedure for collecting, storing,
maintaining, retrieving and validating data needed by organization about its
human resource.
 It is also responsible for discovering of potential applicants for actual or
anticipated organizations vacancies.
 Also responsible for picking individuals, out of pool of job applicants.
 It also organizes training and development sessions for enhancing specific
skill, abilities, knowledge of employees.
 It assists performance of individual in a systematic way for increment in
salary.
 Once in a year, it organizes camp of 2 days for medical checkup of employees
of company.
HR application portal:
Welcome User manual
Leave
Attendance
HR portal
HR application
Salary slip
Digital signature
Bonus statment
Change password
Entry & Exit time of

Calender view
month
Appraisal
Fig 2: Various modules of HR application portal

STORE DEPARTMENT
[HOD- MR. SAMIR SHAH & MR. JIGNESH SONI]
Introduction:
It is a link between industry and external environment market. Store is only

department which deals with acceptance of raw material for production and dispatch
of finished goods. Store department is also responsible for storage of raw materials
and finished products as per requirement in suitable environment.
The store department is responsible for stocking all the necessary tools, spares,
raw materials and equipments which required for manufacturing process. When
source is unreliable, buffer stocks will need to be kept and the use of computerized
stock control systems helps keep stocks at a minimal but necessary level for
production to continue unhindered.
Store department is further divided into following 4 sub units:
STORE
DEPARTMENT
Secondary
Raw material Primary packing Finished product
packing storage
storage area storage area storage area
area
Ampoules, Vials, Labels, cartons,

API, excipient
Rubber stoppers gum tap
Fig 3: Various sub units of store department
Store department is currently using FIFO (First in First out) method. Store
department has facility of cold room to store products at 20C to 80C

In store department, materials are divided in 3 major categories as per following:
Sr. Types of
Description
No. material
Quarantine Material waiting for approval of QC, cannot issue to
1
material production department “Affix Yellow label”
Approved Material approved by QC, can be issued to production
2
material department “Affix Green label”
Rejected Material having any discrepancy, never issue to production
3
material department “Affix Red label”
Table 3: Different status of raw materials in store department
Material movement in store department:
Verify document
Receive raw
Gate pass in store
materials at gate
department
Dedusting of Material receive Entry in inward

materials at receiving bay register
Transfer to
Goods inward Request to QC
respective
memo quarantine area for sampling
Dispensing from
dispensing area Material move to
Approved by QC
to production approved area
area
Fig 4: Material flow in store department

Advantages of store department:
 RFID technology helps to locate the place of stored material in store

department.
 Different color labels are used to differentiate stage of production.
 It has well developed SOP.
 It has well developed layout & sufficient space.
 100% sampling. (1 sample form each container)
 Equipments are calibrated regularly by third party.

ENGINEERING DEPARTMENT
[HOD- MR. BHADRESH PARMAR]
Activities of engineering department:
ENGINEERING
DEPARTMENT
WATER SYSTEM AIR SYSTEM
RAW WATER LOW PRESSURE HIGH PRESSURE

HIGH VOLUME LOW VOLUME
UNDERGROUND
AHU (AIR Compressed air,
TANK
HANDLING UNIT) Nitrogen gas
GERMICIDE PROCESSED
SAND FILTER
DOSING WATER
OVERHEAD
TANK
UTILITY AREA RO PLANT

SEND FILTER
PURIFY WATER PURE STEAM WFI

SEND FILTER SEND FILTER SEND FILTER
Figure 5: Activities of engineering department

RO plant: (RO = Reverse osmosis)
 It is also called demineralized water.

 Generally Purify water is used for washing of primary packing materials like
Ampoules, Vials, Equipments or tanks also used for utility at canteen.
 Purify water is continuously recirculating, because stagnant water is source of
contamination.
Pump provide
Pass through
Processed water high pressure to
filter
flow ahed
Pass through Pass through

Pass through Mixed
Anion bed, for Cation bed, for
bed, for removal of
removal of -ve removal of +ve
remaining ions
ion ion
Purify water,
having <0.1
conductivity
Fig 6: Construction of RO plant
WFI Plant: (Water for Injection)

 It is also called de-pyrogenated water. (Pyrogen free)
 Widely used in manufacturing process as a vehicle of formulation.
 Also used for washing of primary packing material like ampoules, vials.
 It is also re-circulated continuously at 80 0C.

RO water Stem having 143 0C
Pass through
Multicolumn Pure stem
plant
AUTOCLAVE Condenser
Utility loop at
WFI
80 0C
Fig 7: Construction of WFI plant
 In multi column plant steam having temperature of 1430C, only to remove

pyrogen (O-) from water. (Pyrogen is responsible for causing pain at site of
injection)
Compressed air plant:
Pass through DD
Air Blower filter, absorb Oil
droplets
Pass through QD Pass through PD

Compressed air filter, absorb filter, absorb
hazardous gases moisture
Fig 8:Construction of Compressed air plant

 It is used in washing of primary packing materials like Ampoules, Vials.

 Also used in pneumatic pressure for opening & closing door of autoclave.
Nitrogen plant:
Air (78% N2 + 21%

O2 +1% other Blower
gases)
Pass through CMC

Nitrogen gas material, absorb
(NMT 0.5% O2) O2 and other
gases
Fig 9: Construction of Nitrogen Plant
 It is used in pre & post filling of parenteral products.

 Also used in pre & post integrity test of filter.
ETP (Effluent treatment plant):
 All hazardous waste will be processed at NANDESARI common disposal

plant and then release waste by converting it non-hazardous.
Upper layer for

Water of plant Add Alum, 2 layers
reuse, reject lower
sewage will be seprate out
layer
Fig 10: Mechanism of ETP

AHU (Air handling unit):

 AHU controls following parameters:
Sr.
Parameter Limit Description
No.
01 Humidity NMT 55% With help of de humidifier.
02 Temperature NMT 270C With help of chilled water coil.
Cycle time in which complete air of area will
03 Air chain 1.5 min
change.
Depend on Differential (-Ve) pressure, so air cannot enter
04 Pressure
area inside from outside area.
Table 4: Parameters control by AHU
Construction of AHU:
Fresh air filter * Chilled water

Pre filter of 5
through 10 coil, for lowering
micron temperature of air
microne filter
Micro pre filter

De humidifier Blower
of 3 micron
Connection to
HEPA filter of 0.3 Terminal HEPA areas where
micron of 0.3 micron controlled air is
required
* Further send Each area has

to Chilled water duct to suck
coil controlled air
Fig 11: Construction of AHU

QUALITY ASSURANCE DEPARTMENT
[HOD- MR. NILESH BHATT]

Introduction:
Quality assurance is a part of quality management which represents a complex

process focused on creation of the confidence that the corresponding requirement to
quality is kept, and includes all the factors and the actions needed for achievement of
the appropriate quality level of products and services. Many enterprises have Quality
assurance departments (QAD) which provide, develop and maintain a system of
quality assurance management. Such system covers not only processes of sampling,
working with specifications and organizing researches, but also development of
documentation and techniques which guarantee satisfactory quality of products and
services.
The work of QAD is focused, first of all, on preventing the claims from
customers. In case of receiving such claims on quality of provided products and
services, the department starts searching the reasons and effects of the revealed
discrepancies. Quality Assurance means the completion of a project in accordance
with the previously agreed specifications and functionality required without defects
and possible problems.
The general objective of quality assurance department is an enhancement of

product and service quality and an increase of customer satisfaction. To achieve this
objective, QAD should reach the following goals:
 Continuous and consistent development, implementation and maintenance of

quality assurance management system
 Staff training and compliance with the requirements of the quality assurance
management
 Quality control over provided products and services in accordance with the
rules and standards of the company
 Developing and making arrangements for enhancing the quality of provided
products and services
 Control over product output

 Investigation of customer claims

 Organizing and conducting internal audit of the quality assurance management
system
 Organizing and controlling corrective and preventing actions of quality
management
 Control over equipment and production process
There are mainly 5 functions of Quality Assurance department:
Function Sub function Description

Daily QA
Modification of SOPs & follow GMP
observation
Internal audit Documentation like SOPs & BMR
External audit Audit from WHO & GMP
Audit
Action to be taken to eliminate a cause of
Corrective action
previous non conformity
Action to be taken to ensure that, non-
Preventive action
conformity will not repeat again.
Departmental
Find out responsible area
investigation
Cross functional
Find out dependent effect
Event investigation
investigation Root cause
Find out responsible person
investigation
Preventive action Modification in SOPs to avoid such
plan problem
Means any batch has been proved to be defective and withdraw
Product recall
from market
Change control Means any temporary or permanent change is taken into BMR.
Market
Drug violate standard of authorized agency
complain
Table 5: Various function of QA department

Procedure for Change control:
 Means any temporary or permanent change is taken into BMR.

 On the request of Production department, QA department will issue CC form,
which shall be filled by production and submit to QA, then after approval of
QA, Change control became valid.
Fig12: Procedure for change control
Initiate change
Temporary change Permanent change
Lot no / Batch no Assign change control no
Impact analysis Evaluate requirement of change
Approve for execution Review of recommendation
Update BMR or SOP Conclusion Evaluation

Procedure for Market complain
 Means any drug violate standard of authorized agency of respective country.

 At the time of market complain, QA will start event investigation.
Fig13: Procedure for Market complain
Receipt of complain by Receipt of complain by

corporate quality (CQ) other than CQ
Arrangement for Send copy to CQ and

investigation of retain original one
complain
Send to responsible plant Investigation of complain
Investigation report Prepare action plan
Review of report Ensure that CA to be taken as

report
Close complain

QUALITY CONTROL DEPARTMENT
[HOD- MR. PRAMESH KOTHARI]
Introduction:
There is always a need for a separate quality control department in any

pharmaceutical unit. Quality Control Department is required to keep a check on
pharmaceutical machineries and equipment. The main responsibilities and priorities of
the department are to ensure an updated check of the equipment. The department has
the authority to approve or reject all closures, in-process materials, components,
labeling, drug product containers, packaging material and drugs. Moreover,
department can actually find out the review production records to assure that no errors
have occurred. If errors have occurred, they are completely investigated and sorted
out. Apart from certain authorities, quality control department has also certain
responsibilities to handle, reject or approve drug products manufactured, packed, or
held under contract by another company.
Adequate laboratory facilities are required in the department for the testing
and approval (or rejection) of components used in the process of manufacturing. The
quality control department has the responsibility for either approving or rejecting all
procedures or specifications impacting on the purity of the drug product, quality,
strength and identity of the product. The responsibilities and procedures applicable to
the quality control department will be in written form.
Every individual of the department is properly trained which enable him to

perform the assigned functions. Moreover, his or her education and experience is kept
in account while providing training for the desired purpose. Training is conducted in
the particular operations that the employee performs and in current good
manufacturing practice. To make the employees remain familiar with CGMP

requirements applicable to them, training is given by qualified individuals on a

continuing basis.
 QC department is fully equipped with latest technology device as per

followings:
Area name Instrument name Purpose of Instrument

HPLC Find out concentration of drug in sample
Instrument room Working standard
Maintenance of standard solution
no. 1 cabinet
Incubator Maintenance of sample solution
Similar to HPLC, but require small
UPLC
volume of sample & Solvent
Karl fisher Find out amount of moisture in sample
Infra-Red For identification of sample drug
Instrument room
De humidifier For removal of moisture
no. 2
UV meter For identification of sample drug
Shaker Provide mechanical shaking to apparatus
Bottle rotating
Provide mechanical rotation to apparatus
apparatus
Solvent preparation
Instrument room For storage of solvents
apparatus
no. 3
Dissolution apparatus To find out dissolution rate
Centrifugation Used for separation of 2 layers from
machine sample
Hot air oven Used for drying
Vacuum oven Provide drying and vacuum also
Hot zone Melting point
For melting point measurement
apparatus
Lick test apparatus To check leakage of ampoules
Sonigator Removal of air bubble from sample
Water bath For heating of thermolabile materials

Furnace Used to produce ash of sample

pH meter Find out pH
Potentio meter Find out conductivity of sample
Polari meter To check polarization of sample
Chemical testing Miliquo For preparation of water for HPLC
room Disintegration Find out Disintegration time
TLC For sample Identification
Viscometer Find out viscosity
Magnetic stirror For proper mixing
Chemical stock room Maintain stock of reagents
GC room Find out concentration of drug in sample
Micro lab Check microbial & pyrogen content
Document record room For storage of BMR
Store drug sample up to expiry date of
Stability room
batch
Table 6: List of instruments of QC department

PRODUCTION DEPARTMENT
[HOD- MR. JAGAT UNADKAT]
Introduction:
Production is the functional area responsible for turning inputs into finished
outputs through a series of production processes. The Production Manager is
responsible for making sure that raw materials are provided and made into finished
goods effectively. He or she must make sure that work is carried out smoothly, and
must supervise procedures for making work more efficient and more enjoyable.
In a manufacturing company the production function may be split into

following sub-functions:
 The production and planning department will set standards and targets for
each section of the production process. The quantity and quality of products
coming off a production line will be closely monitored. In businesses focusing
on lean production, quality will be monitored by all employees at every stage
of production, rather than at the end as is the case for businesses using a
quality control approach.
 The works department will be concerned with the manufacture of products.

This will include the maintenance of the production line and other necessary
repairs. The works department may also have responsibility for quality control
and inspection.

Lay out:
VISUAL INSPECTION ROOM
DE
CARTOONI
NG ROOM
VIALS MANUFA
CAPPING CTURING
AMP / FILLING ROOM
LINE
VIAL LINE
WASHING
ROOM
FILTRATION AREA
EQUIPME
NT AUTOCLA
WASHING
VE & DHS
ROOM COOLIN
DE
MALE G AREA HORMONE
CARTOONING
CHANGE
ROOM
BOTTLENECK
AREA
ROOM
FD
PLASTIC FILTRATIO
STERILIZE LOADIN
FEMALE BOTTLE N ROOM
D ROOM G AREA
CHANGE FILLING
ROOM LINE
MANUFACT MANUFAC FD
HOD CAPPING URING TURING CHAMBE
OFFICE LINE ROOM R
ROOM
VISITOR
CHEMIST EQUIPME QUARNTINE ROOM
CHANGE
OFFICE NT ROOM
ROOM
Fig14: Layout of Production department

Chemist room:
 It is an area where all workers, machine operators and officers meet daily at
the starting time of their respective shift to plan complete schedule and
allocate work activities.
 In the room, one white board displays 1 month projected manufacturing
schedule of production department in following format:
Sr. Mfg. Filling Product Batch

Batch No. Remarks
No. Date Date name Size
1 15/05/10 16/05/10 Lotepred LS HKMJ0522 200 liter Domestic
2 16/05/10 16/05/10 Tropicamet + HKMJ0513 100 liter Export
Table 7:Format of daily planning of production department
 All staff members have highly dedicated work, means they have to perform
same task every day. (Repetitive task)
Sr. No. Activity Responsible Persons

1 Planning & co ordination Mr. Jagat & Mr. Malay
2 Documentation & SOP Mr. jaymin
3 BMR & Visual inspection Mrs. Rachna & Mr. Anil
4 Washing & Quarantine Mr. Sailendra & Mr. Dilip
5 Autoclave & DHS Mr. Kiran, Mr. Mitesh, Mr. Vishal
6 Manufacturing Mr. Rajesh, Mr. Suresh & Mr. Darshan
7 Filling & Capping Mr. Amit, Mr. Trupesh & Mr. Hemant
8 Hormone department Mr. Nirvesh & Mr. Bharat
9 Training Mr. Hansdeep, Mr. Vishal
10 New plant documentation Mr. Niraj & Mr. Birju
Table 8: Distribution of activities in production department

 All officers have been affix label on glass window of concern area, to
demonstrate current operation of area in following fix format.
BATCH IN PROCESS
DATE:__/ __/ 201_
PRODUCT NAME
BATCH NUMBER
BATCH SIZE
MANUFACTURING SIZE
EXPIRY DATE
STAGE
CHECKED BY
Table 9:Format of area label
SOP {Standard Operating Procedure}:

 It is a document which prescribes an ideal procedure for each & every activity
of pharmaceutical company. It strictly follows GMP (Good manufacturing
practice)
 Content of SOP:
Sr. No. Title Description

1 Title It is expressive of subject of SOP
2 CC no. Change control number
3 Supersedes Mention previous SOP no.
4 Effective date Date on which SOP become effective
5 Purpose Mention intended use of SOP
6 Scope Application of SOP
7 References Detail of any reference used
8 Attachment Desired supportive documents attach with SOP
9 Annexure Documents serve as informative guidance
10 Distribution Area in which copy will be send to department
11 Definition of terms Define in Lehman language, easy for understanding
12 Procedure Systematic procedure as per GMP
13 History Any previous incident or abnormalities

14 Stamp It represent green colored stamp and copy number

Table 10:Content of SOP
 Primary phase training of any new joining is read SOPs, at the end test will be
conducted has passing criteria of 60%.
 As per the suggestion of WHO (World Health Organization) UTL also
translate all SOPs in vernacular language (Gujarati) for easy understanding of
Workers & Operators.
BMR {Batch Manufacturing Record}:

 It is a file which contains all the details of batch starting from raw material
receiving to finish good dispatch.
 BMR is preserved for 1 year more than expiry date of batch.
 Content of BMR:
Sr.
Title Description
No.
1 Product name Brand name of product
2 Generic name Generic name of drug
3 Strength Content of API
4 BMR status Tentative or final or Scale up
5 Effective date Date on which BMR become effective
6 Supersedes BMR number of previous master BMR
8 Batch size In terms of liter & Kg
9 Material pick up list Analytical Report no, Quantity of material
10 Detail of raw material, procedure & condition of
Master formula
manufacturing
11 Name, designation of person who fill, check or
Signature log
verify BMR
12 Verification sheet AR no. Primary Packing Material (PPM) detail
13 Washing of PPM Used equipment code, pressure control limit
14 Mfg process detail Used equipment or tank code & timing

15 Filtration detail Used filter code & result of integrity test

16 Filling detail FO number, Syringe code
17 Sterilization detail Filled SO no. (Sterilization operation number)
18 Calculation Practical yield calculation, comply with limit or not
19 Accountability % Output including non-recoverable rejection
20 Yield % Actual good output
21 Visual inspection Reject ampoules or vials having visual defect
record
22 History date Any abnormalities
23 Taken time from receipt of materials to dispatch of
Cycle time
final goods
Table 11:Content of BMR

Route of BMR:
Production QA issue BMR to

department send Store department
production, based
request to QA for prepare pick up list
on Master BMR
BMR
Production
Production Raw material issue
department start
department send in to production
manufacturing as
process sample to department for
per procedure of
QC for approval manufacturing
BMR
After approval, Filling of products to

primary packaging Visual inspection /
filtration will be materials like Post Sterilization
carried out Ampoules /Vials
Send finish
Start secondary
Verify BMR product sample to
packing
QC for analysis
Dispatch complete
Observation & Release a batch of batch of drug to
Remarks by QA drug company
warehouse
Fig15: Movement of BMR throughout production department

Material movement in production area:
Store department issue

materials to production
department
Drugs & Excipients Primary packaging Secondary

materials packaging
Materials
Manufacturing room De cartooning

room
Filtration room
Washing room
Autoclave & DHS

Filling room
Capping room Visual inspection
Quarantine area Issue to packing

department
Fig16: Movement of material in packing department

De-cartoning Area:
 It has normal room temperature and humidity.
 It receives primary packing materials like Ampoules & Vials.
 Officer always check that, received material must be approved by QC, means
cartons of material have green color label.
 Generally UTL use Ampoules or Vials consist of Type 1, borosilicate glass.
Because Type 1 glass is highly resist to leaching process during sterilization
process.
 Here workers arrange ampoules or vials into perforated plate. Plates are
directly sent to washing area through Hatch. (Hatch means window has
differential pressure, dynamic pass box)
 Plates are made up of Stainless Steel.
Ampoules/Vials Washing Area:

 Temperature of washing area should NMT 27 0C and pressure NLT 0.4 mm of
WC. (WC = water column)
 UTL has multi jet washing machine of PRO-TECH Company.
 Machine wash ampoules or vials in batch process.
 It provides 2 types of wash.
 Inner wash: By help of Purify water, Water for Injection, Compressed air one
by one.
 Outer wash: By help of Purify water & Water for injection one by one.
Sr. No. Media Pressure (Kg/cm2)

1 Purify water 1.5 to 2.5
2 Water for injection 2.5 to 3.0
3 Compressed air 3.0 to 4.0
Table 12: Pressure limit of washing machine
 Batch size of materials will vary with their size.

Ampoule size Batch size Time Vial size Batch size Time
(ml) (Second) (ml) (Second)
1 58.5 2&3 78
2 67 5 288 nos. 95.5
4 79 10 104
288 nos.
5 87.5 20 127
10 103 30 208
80 nos.
20 208 50 208
100 416
Table 13: Batch size of different dose ampoules or vials
 One sample from one batch sends to visual department for fiber testing.
 Washed ampoules or vials have been shifted to DHS room for sterilization,
within 16 hrs. otherwise re wash it.
 Materials have been shifted under movable LAF (Laminar Air Flow) to
maintain pressure between 5 to 20 mm of WC, helps to reduce cross
contamination.
 Movable LAF is from AIR-PAC company.
Equipment washing area:

 Temperature of washing area should NMT 27 0C and pressure NLT 0.4 mm of
WC. (WC = water column)
 Here parts of equipment or tanks has to be cleaned with help of purify water
and then water for injection.
 Generally one worker is sufficient to perform task.
Dress washing area:

 It has normal room temperature and humidity.
 Clothes or gowns are used in sterilized area has to be washed in this area.
 Gowns have to be washed & dried before sterilization.

 Equipment has capacity to process 30 pairs of dress at once.

 Generally one person is sufficient.
 There are specific sequence for washing activity as follow:
Equipment Solution to be Required time Temperature

Cycle no.
name used (Min) (0C)
Hemptop soap
1 15
solution
Washing
2 Dettol solution 15 50
machine
3 15
Purify water
4 15
Tumbler
5 NA 30 55
dryer
Table 14: Different cycle of dress washing machine
Autoclave & DHS Area:

 It has temperature NMT 27 0C and humidity NMT 55%.
 Materials or equipment used for preparation of parenteral products must pass
through Autoclave or DHS, for sterilization.
 DHS means “Dry heat sterilization”.
 This process leads to denaturation of protein of bacteria, result in death of
bacterias.
 There are mainly 2 cycles for DHS operation.
 General drying cycle:
 160 0C for 2 hours.
 Depyrogenation cycle:
 205 0C for 2 hours or 230 0C for 1.5 hours.
 Temperature will be automatically recorded and printed at regular interval of 3
minutes.
 2 DHS are from Bombay engineering & Machine fabric.
 Autoclave will lead to coagulation of protein of bacteria.
 There are 2 different types of autoclaves.

o Rapid cooling with ventilator system

o Double door hinge sterilization
 There are 7 different cycle for different materials.
Sr. Jacket
Cycle name Purpose Temperature Time
No. pressure
1 Sterilization of 15 + 15
Tanks
equipment min
2 Depend on
Vacuum drying Rubber stopper
products
1210C
3 8 /15/40
Rapid cooling Fast exhaust
min
4 Garment &
Dresses 30 min 1.2
Component
Kg/Cm2
5 Leak test of Ampoules or
< 400C
Ampoule or vial vials
6 Chamber 15 min
vacuum leak 950C
Calibration of
test
Autoclave
7 Post terminal
1210C 8 / 30 min
sterilization
Table 15: Various cycles of Autoclave
Manufacturing area:
 It has temperature NMT 27 0C & humidity NMT 55%.
 Here active ingredients & excipient of final product have been mixed
according to procedure of BMR.
 Mixing will be takes place in various size of tanks based on batch size.
 Sometimes special dedicated tanks have been used for particular drugs.
 Manufacturing area has to send in process sample of 30 ml for approval of QC
department.
 Area has to mention following parameters very strictly:

 Temperature (For proper dissolution), Humidity (To avoid microbial

contamination), pH (For stability), Order of mixing (For proper dissolution),
Time (To achieve proper physical characteristic), status and temperature of
WFI.
Filtration area:
 Bulk solution or suspension is filtered through membrane or cartilage filter by
help of Nitrogen gas with pressure of 0 to 2 Kg/cm2.
 Efficiency of filter is calibrated by Bubble point test.
 Before starting of filtration, filter is checked by pre filtration integrity test &
after completion of filtration post integrity test should be carried out.
 Integrity test will check pore size of filter, by observing pressure of Nitrogen
gas.
 Products pass from sterilized silicon tube to filling tank via filter.
Fig17: Diagram of filtration process
Filling & Capping area:

 In filling area Product is filled in respective containers.
 There are 3 different types of filling tube Stainless steel, Glass & Silicon.

 Tubes have been washed by ultrasonic machine. (By help of vibration)

 Initial 5 vials or ampoules have been discard in following cases:
 Initial machine startup.
 Completion of maintenance work.
 Replacement of syringe & needle.
 Shift change.
 Each & every carton contain FO number (Filling operation)

 FO number will be changed in following cases:
 Any interruption.
 Take more than 1 day for filling
 Power failure of more than 30 minutes.
 Breakdown for more than 120 minutes.
 Change in filling syringe.
 Change in fill volume.
 In the filling process control limit (Standard of company) is +/- 1.5% and
tolerance limit (Standard of industry) is +/- 2%.
 In UTL, excess amount of drug is filled than labeled volume in pharmaceutical

industry as follows:
Labeled size Recommended excess volume

Sr. no.
(ml) Mobile liquid (ml) Viscous liquid (ml)
1 0.5 0.1 0.12
2 1 0.1 0.15
3 2 0.15 0.25
4 2.5 0.17 0.3
5 3 0.20 0.35
6 4 0.25 0.4
7 5 0.30 0.5
8 10 0.50 0.7
9 20 0.60 0.9

10 30 0.80 1.2
11 50 2% 3%
Table 16: Filling volume control limit
Ampoules filling machine:

 This machine performing both Filling & sealing activity at once.
 There are 4 heads for ampoules filling and 8 jets for sealing of ampoules.
 Jet used LPG: O2 in ratio of 2:1.
Tube filling machine:

 UTL has only one product “Eye mist Gel” in tube form.
 It has 1 head; output rate is 60 tubes/min.
Visual inspection area:

 In this area each & every ampoules or vials have been checked by trained
workers manually.
 Each worker gets target to complete within one shift, target is depend on type
of product.
 Visual department require minimum 22 workers.
 Each worker has to be submitting eye report from government hospital.
 Each worker gets 20 minute break after every 2 hours.
 Workers have to be properly trained properly for 1 week.
 Company takes on test for 100 ampoules, in which qualifying criteria is 97%
accuracy.
 Upto one week 100% cross checking is takes place.
 Workers are generally reject products having following errors:
Fiber NMT 2 Low dose Improper sealing Damaged bottle

Black particle High dose Without seal Melt cake
White particle Black oil Without rubber stopper Others
Table 17: Various defect of visual inspection area

 At the end of visual of any batch, area has to prepare statistical sorting report
in following format:
No.
Container Inspected Sample No. of Sorted Types of Re
of
no. by qty. rejection by rejection mark
units
1 294 DJV 3 Nil SAM NA NA
2 294 SRV 3 Nil SAM NA NA
Table 18: Format of statistical report of visual inspection area
 Visual department has to be mention following reports:

 Temperature measurement record.
 Sequential log sheet.
 Daily visual inspection record.
 Manpower attendances register.
 Training record file.
 Here plastic bottles are non-transparent, so it is only checked for high or low
dose mechanically by applying compressed air pressure at capping process.
 Different air pressure is required for different dose of product as follows:
Air pressure (Kg/cm2)

Dose Weight of filled bottle
Jet 1 Jet 2
2 ml 7.5 gram 1 1.2
3 ml 8.5 gram 1.2 1.4
5 ml 10.5 gram 1.6 1.8
10 ml 16.5 gram 2.2 2.4
Table 19: Visual of plastic bottle
 RAPIFOL is only product which requires 2 times visual inspection, because it

has property to generate black fiber after 15 days of manufacturing.

Freeze dry area:

o It works on principle of “Lyophilization & Sublimation”
o This process has capacity to remove moisture from product by converting
moisture in ice and then directly convert to vapor by passing liquid stage.
o Freeze dryer is from “Lyovac company”.
o Product has been load at 5 0C at loading temperature.
o In first stage freeze dryer lower temperature up to -40 0C, so moisture in
product will be converting to ice.
o Silicon oil is used to lower and maintain temperature up to -40 0C, because
structure of silicon oil will remain same from -56 0C to +260 0C.
o Now in second stage temperature will increase at uniform rate.
o Vacuum of 0.05 millibar will be applied to remove vapor of moisture.
o Cycle time & temperature will vary with types of product.
o This freeze dryer has 200 liter capacity.
o EX: Lupride depot is freeze dried product; UTL is only Manufacturer
Company in India.
o FD area has planning schedule on the board in following format:
Sr. Product FD load FD unload Batch no. Batch Remark

No. name date date size
Lupride
1 08/5/10 10/5/10 HKMJ0482 500 gm Primary
depot
2 Ivepred 40 10/5/10 15/5/10 HKMJ0486 20 kg NA
Table 20: Format of FD schedule
Quarantine area:
 After completion of visual inspection, products are placed in this area.
 From this area, packing department will receive products for labeling &
secondary packing with help of “Batch transfer note”.
 There are different color codes for different stages of products.
 Purpose of color code is to identify product at each & every stage and to avoid
a mix up of materials.

Sr. No. Color code Stage of product

1 Yellow Ready for packing
2 Pink Ready for visual
3 Orange Ready for leak test
4 Blue Ready for Sterilization
5 Red Ready for Rejection
Table 21:Color code
 Format of label:
UNDER PROCESS APPROVAL

DRUG NAME VISCOMET INJ 5 ml
STAGE READY FOR VISUAL INSPECTION
BATCH CODE HKMJ 0555 BATCH SIZE 100 LT
MFG DATE 05/2010 EXP DATE 04/2012
CONTAINER NO. 1 OUT OF 50
BARCODE
Table 22:Format of carton label
Crushing area:
 Once in 15 days, all non-recoverable rejected final products have been crushed
here.
 Production area is responsible for maintaining records of crushing activity.
Sanitizing Activity:
 Each & every area of production department sanitize regularly by different
solution.
 Even company sanitizes each drain point by using 2.5 liter of sanitizing
solution daily.
 Company has to change sanitizing solution after every week, because of
“Development of resistant in microorganism”

Week Sanitizing solution

1st 0.8% Benzalkonium chloride (BKC)* in 70% Iso propyl alcohol (IPA)
2nd 2% V/V Aceptik in 70% IPA
3rd 4% V/V Hydrogen peroxide in water for injection
4th 1% V/V of Gramicid solution
*BKC is not used at time of Viscomet drug production
Table 23:Sanitizing schedule of production department
Media plate:
 In each & every area, QA department kept one plate having media of agar to
ensure sterility of area.
 If sterility is not proper then, growth of microorganism in media will be
observed.
Particle counter:
 Once in month, QA department check particle count in area A, by help of

particle counter machine.

PACKAGING DEPARTMENT
[HOD- MR. BIRJU PATEL]

Introduction:
 There are 6 different types of packing line in packing department for

secondary packing.
 Secondary packing includes following boxes.
Sr. Work
Line name Use Machines
No. stations
Labeling machine
(Maharshri company)
Plastic bottle packing Plastic Cartonator machine
01 9
line bottle (Pam Pac company)
Check weigher machine
(Techno four company)
Labeling machine
(Maharshri company)
Check weigher machine
02 Vial packing line Vial 14
Online coding machine
(PIC electronics)
Ampoule packing line Same as “Vial packing
03 Ampoule 14
(2 line) line”
Single wrapping machine
Single pack show box Single
04 8 Check weigher machine
over wrapping line show box
Multi wrapping machine
Multi pack show box Multi show
05 8 Check weigher machine
over wrapping line box
Table 24: Various packing line of packing department
 There are mainly 2 types of products.

 Physician sample & General sell products.

 After completion of batch, final products are transferred to store of company.

 Layout of packing department quarantine:
Fig18: Layout of Packing quarantine area
 In packing department following defects have been observed:

Double label Improper label Damaged cartoon
Twisted label Torn label Partial printing
Tip break Dirty label Missing leaflet
De shaped ampoule Cartoon without bottle
Table 25: Various defects of packing department
BPR (batch packing record):
 It is a file which contains all details of packing materials like batch number,
type of label, show box, ply box, corrugated box.
 Content of BPR:
Sr.
Title Description
No.
1 Product name Brand name of product
2 Generic name Generic name of drug
3 Strength Content of API

4 BPR status Tentative or final or Scale up

5 Effective date Date on which BMR become effective
6 Supersedes BMR number of previous master BMR
8 Batch size In terms of liter & Kg
Name, designation of person who fill, check or verify
9 Signature log
BPR
10 BOM Bill of material containing overages of batch
Verification
11 AR no. Secondary Packing Material (SPM) detail
sheet
12 Calculation Practical yield calculation, comply with limit or not
13 History date Any abnormalities
Taken time from receipt of materials to dispatch of final
14 Cycle time
goods
Table 26: Content of BPR
Training procedure:
Phase Stage Activity Duration

General guideline, GMP, SOP, Movement of
1 3 days
document, common packing techniques
Line clearance, In process check, Handling of cold
Primary 2 3 days
chain products
3 Machine setup 2 days
4 Instrument principle, Operating techniques 2 days
Handling of deviation, Change control, Plant
modification, Handling of market complain,
Advance On job
Investigation of records, Preparation of protocol &
reports
Conformation Candidate has to score greater than or equal to 60%. N.A.
Table 27: Training schedule of packing department


The pharmaceutical industry relies on the precision and accuracy of analytical

instruments to obtain valid data for research, development, manufacturing, and quality
control. Indeed, advancements in the automation, precision, and accuracy of these
instruments parallel those of the industry itself.
Through published regulations, regulatory agencies require pharmaceutical

companies to establish procedures assuring that the users of analytical instruments are
trained to perform their assigned tasks. The regulations also require the companies to
establish procedures assuring that the instruments that generate data supporting
regulated product testing are fit for use.
So in pharmaceutical industry, quality of product is controlled by 2 following ways:
 By instrument qualification (Control instrument or product)

 By process validation (Control process)

INSTRUMENT QUALIFICATION:
Qualification of instruments is not a single, continuous process but instead results

from many discrete activities. For convenience, these activities have been grouped
into 7 phases of qualification. These phases are described below:
Sr. No. Steps Description

1 URS User requirement specification
2 DQ Design qualification
3 FAT Factory acceptance test
4 SAT Site acceptance test
5 IQ Installation qualification
6 OQ Operation qualification
7 PQ Performance qualification
Table 28: Stages of instrument qualification
These qualification phases were used because of their wide acceptance within the
community of users, manufacturers, and quality assurance. Some of these
qualification phases have their roots in manufacturing process validation.
User requirement Specification (URS)
URS is a protocol which will be prepared by user or Customer Company. This

protocol reflects all necessities of User. This protocol contains all types of
configuration of the machine. Ex: Speed, Capacity, Dimension etc. After preparation
of URS, user will send this protocol to manufacturer.
Design Qualification (DQ)
The Design Qualification activity is most suitably performed by the instrument

manufacturer. However, users should ensure that instruments are suitable for their
intended applications and that the manufacturer has adopted a quality system for
developing, manufacturing, and testing as per URS. Users should also establish that

manufacturers adequately support installation, service, and training. Methods for

ascertaining the manufacturer’s design qualification and an instrument's suitability for
its intended use depend on the nature of the instrument. Informal personal
communications and networking with peers at technical or user group meetings
significantly inform users about the suitability of instrument design for various
applications and the quality of vendor support services. Informal site visits to other
user to obtain data on representative samples using the specified instruments also are
a good source of information regarding the suitability of the instrument design for
intended use.
Factory Acceptance Test (FAT)
Once design qualification protocol approved by user than manufacturer start to make
machine and when machine will completed than user will go to supplier place to do
FAT. In this test user will check that whether machine is made according to DQ
which has been provided by supplies & user has to check all the parts of machine.
Site Acceptance Test (SAT)
After completion of FAT, Sat will be performed. The SAT protocol contains the most
probably same information as FAT protocol. Mainly SAT is done when machine
comes to user site. The main purpose of doing site acceptance test is to check machine
on the bases of URS and also to check that same machine has come to site which one
is inspected during FAT.
Installation Qualification (IQ)
Installation Qualification is a documented collection of activities needed to install an

instrument in the user’s environment. IQ applies to a new, pre-owned or an existing
onsite. The activities and documentation associated with IQ are as follows:
• System Description: Provide a description of the instrument, including its

manufacturer, model, serial number, software version, etc.

• Instrument Delivery: Ensure that the instrument, software, manuals, supplies,

and any other accessories arrive with the instrument as the purchase order
specifies and that they are undamaged.
• Utilities/Facility/Environment: Verify that the installation site satisfactorily

meets manufacture specified environmental requirements.
• Network and Data Storage: Some analytical systems require users to provide
network connections and data storage capabilities at the installation site. If this
is the case, connect the instrument to the network and check its functionality.
• Assembly and Installation: Assemble and install the instrument and perform
any initial diagnostics and testing. Assembly and installation of a complex
instrument are best done by specialized engineers, whereas users can assemble
and install simple ones. For complex instruments, vendor-established
installation tests and guides provide a valuable baseline reference for
determining instrument acceptance.
• Installation Verification: Perform the initial diagnostics and testing of the

instrument after installation. On obtaining acceptable results, the user and
(when present) the installing engineer should confirm that the installation was
successful before proceeding with the next qualification phase.
Operational Qualification (OQ)
After a successful IQ the instrument is ready for OQ testing. The OQ phase may
consist of these test parameters:
• Fixed Parameters: These tests measure the instrument's non-changing, fixed

parameters such as length, height, weight, etc. If the vendor-supplied
specifications for these parameters satisfy the user, he or she may waive the
test requirement. However, if the user wants to confirm the parameters, testing
can be performed at the user’s site.
• Secure Data Storage, Backup, and Archive: When required, secure data
handling, such as storage, backup, and archiving should be tested at the user
site according to written procedures.

• Instrument Functions Tests: Test important instrument functions to verify that

the instrument operates as intended by the manufacturer and required by the
user. The user should select important instrument parameters for testing
according to the instrument's intended use. Vendor-supplied information is
useful in identifying specifications for these parameters. Tests should be
designed to evaluate the identified parameters. Users, or their qualified
designees, should perform these tests to verify that the instrument meets
vendor and user specifications.
Performance Qualification (PQ)
After the IQ and OQ have been performed, the instrument’s continued suitability for
its intended use is proved through performance qualification. The PQ phase includes
these parameters:
• Performance Checks: Set up a test or series of tests to verify an acceptable

performance of the instrument for its intended use. PQ tests are usually based
on the instrument’s typical on-site applications.
PQ tests are performed routinely on a working instrument, not just on a new

instrument at installation. Therefore, PQ specifications can be slightly less
rigorous than OQ specifications.
PQ tests should be performed independent of the routine analytical testing

performed on the instrument. Testing frequency depends on the ruggedness of
the instrument and criticality of the tests performed. Experience with the
instrument can influence this decision.
• Preventive Maintenance and Repairs: When PQ test(s) fail to meet

specifications, the instrument requires maintenance or repair. For many
instruments a periodic preventive maintenance may also be recommended.
Relevant PQ test(s) should be repeated after the needed maintenance or repair
to ensure that the instrument remains qualified.
• Standard Operating Procedure for Operation, Calibration, and

Maintenance: Establish standard operating procedures to maintain and
calibrate the instrument. Use a logbook, binder, or electronic re-cord to
document each maintenance and calibration activity.

PROCESS VALIDATION
Definition:
 It is defined as documented evidence that a process will produce a product

meeting its predetermined specification and quality attributes.
 3 batches of commercial batch size taken as prospective validation.
 Samples shall be withdrawn from different stages of manufacturing process
like follows:
 From Ampoules or Vials washing machine.
 From Autoclave or DHS.
 From filling & capping or sealing machine.
 From SIP tank.
 From freeze dryer.
Content of Process validation master plan:
Sr.
Content Description
No.
01 Training (date) It shall be provided to all concern persons
02 Objective Purpose of validation study
03 Design & Scope Philosophy of process validation
04 Responsibility An individual’s responsibility in protocol
05 Mfg process flow chart Flow of batch & its significant stage of Mfg
06 Evaluation of formulation Manufacturing formula of batch
ingredients
07 Demonstrate comparison of raw material
Evaluation of raw materials
utilized with vendor name
08 Evaluation of equipment Comparison of equipment utilized during batch
09 Conformation regarding equipment
Equipment qualification
qualification
10 Manufacturing process
11 Filtration process Sampling detail & result of test
12 Filling process

13 Freeze dried process

14 List of content those are supposed to be
Documentation
recorded during validation studies
15 Stability Result of stability study test
16 Approval Final approval of protocol
Table 29: Content of process validation master plan
Execution of process validation:
Sr.
Stage Description
No.
Prepare by QA
Preparation, Review & Review by QC head, Production head
01
approval Approved by quality head, plant head,
Corporate quality head
QA head issue photocopy to officer
Officer monitor manufacturing process
02 Execution of protocol
Report deviation
Record raw data like process parameters
Officer shall prepare validation report
03 Report preparation Review by head of production, QC & QA
Approved by corporate quality head
Quality head shall justify and authorized any
04 Deviation
deviation
Table 30: Execution process of process validation
Storage of process validation:
 Retain in separate file in QC.

 QC department ensure security.
Review of process validation:
 After every 2 years.


 In production department, most critical part is filling of BMR. Because it

requires great attention and accuracy also. But as I seen generally officers are
so much busy with their work (instructing to operators and workers).
 So definitely, BMR has some correction after observation of QA department.
 Generally BMR has some hand written details as well as work order generated
from ITM software also. So it may create error also.
 Sometimes products are ready for next stage process, but because of remaining
correction in BMR, next stage process is delayed until BMR is released by QA
department. Still UTL is able to manage cycle time less than standard cycle
time of company.
 In packing department, there is a thumb rule that remaining packing material

(after complete packing of batch) has to be destroyed, because ITM has no
function to create material return note to store department.
 Basically, construction of UTL was specially designed for manufacturing of

tablet and capsule, so UTL has some limitation to accept modern automatic
technology.
 Cost of one batch of product is too high, so to reduce chance of batch failure,
UTL use in process sampling, means after approval of QA, batch has been
send to next stage process.


 As I discussed that BMR is not accurate, So I suggest that company has to use
on line BMR program, which has following benefits:
 Increase accuracy.
 System properly followed.
 Save time of officers.
 Easy to preserve for (2 to 3 years) long time.
 Easy to retrieve data from any BMR.
 All statistical calculation became automatic.
 Also help to planning activities of different areas.
 In my project duration, I observe so many waste or misuse of stationaries;

employees blindly print material which they want.


BIBLIOGRAPHY
BOOKS
 Krajewski L, Ritzman L, Malhotra M, Operation Management: Process and

value chain, (8th ed: Pearson Hall, 2009)
 Standard operating procedures of UTL.
 BMR of UTL.
 BPR of UTL.
WEBSITES
 www.sunpharma.co.in
 www.pamindustries.com
 www.fundoodata.com/advance_search.php
 http://www.training-management.info/
 http://www.pharmainfo.net/luckypharmacist/top-10-indian-pharma-companies
 http://www.aapspharmscitech.org
 http://www.gmpqualityup.org

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TO STUDY THE PRODUCTION OF SMALL VOLUME

PARENTERAL PRODUCTS (SVP) AND HOW TO CONTROL

In partial fulfillment of the requirements of

For the award of the degree of

Tolani Institute of Management Studies

Sr. No. Title Page no.

Tolani Institute of Management Studies, Adipur Page 2

Sr. No. Title Page no.

Tolani Institute of Management Studies, Adipur Page 3

Tolani Institute of Management Studies, Adipur Page 4

Sr. No. Figure name Page no.

Tolani Institute of Management Studies, Adipur Page 5

Sr. No. Abbreviation Full form

Tolani Institute of Management Studies, Adipur Page 6

Sr. No. Abbreviation Full form

Tolani Institute of Management Studies, Adipur Page 7

Tolani Institute of Management Studies, Adipur Page 8

Name: Rajkumar D. Patel

Date: July 2010

Tolani Institute of Management Studies, Adipur Page 9

I wish to express my gratitude to UNIMED TECHNOLOGIES LTD

I am also thankful to Mr. Sushil Chaursiya and all staff members of my

Tolani Institute of Management Studies, Adipur Page 10

Tolani Institute of Management Studies, Adipur Page 11

PHARMACEUTICAL INDUSTRY OVERVIEW

“Indian pharmaceutical industry can be defined as a success story providing

It is growing at an average rate of 7.2 % and is expected to grow to US $ 12

Tolani Institute of Management Studies, Adipur Page 12

At present, a large number of Indian pharmaceuticals companies are looking

Indian multinational companies like Dr.Reddy's Lab, Cipla, Ranbaxy, Sun

Rank Company Revenue 2009 (Rs crore)

Tolani Institute of Management Studies, Adipur Page 13

SWOT ANALYSIS OF INDIAN PHARMACEUTICAL

Tolani Institute of Management Studies, Adipur Page 14

 Incredible export potential.

Tolani Institute of Management Studies, Adipur Page 15

INTRODUCTION TO UNIMED TECHNOLOGIES LTD (UTL):

UTL has following departments:

QUALITY CONTROL DEPARTMENT

QUALITY ASSURANCE DEPARTMENT

Tolani Institute of Management Studies, Adipur Page 16

INTRODUCTION TO PARENTRAL FORMULATION

Small volume Parenterals means parenteral preparation having volume 1 ml to 500

 Drugs can be administered to unconscious patient with ease.

Tolani Institute of Management Studies, Adipur Page 17

INTRODUCTION TO OPHTHALMIC FORMULATION

Ophthalmic is defined as the dosage form intended to be administered onto the

Types of ophthalmic formulation:

Tolani Institute of Management Studies, Adipur Page 18

Tolani Institute of Management Studies, Adipur Page 19

 To understand all technicalities of production of small volume parenteral

 To get deep understanding of documentation of production process.

Methods of data collection:

Source of primary data:-

 One to one communication with employees of UTL.

Source of secondary data:-

Tolani Institute of Management Studies, Adipur Page 20

PHASE ACTIVITY DAYS

De-cartoning & Washing area 02

Holidays (Weekly off) 06