“QUALITY ASSURANCE IN ARCH VITALIFE

LABORATORIES”

SUMMER INTERNSHIP REPORT (May’10- July’10)

Submitted for the partial fulfillment of

MBA (Biotechnology Management)

Degree of

AMITY UNIVERSITY, UTTAR PRADESH

EKTA SINGH

A0500109042

Under the supervision of

Mr. JITENDER SINGH
ARCH VITALIFE LABORATORIES

AMITY INSTITUTE OF BIOTECHNOLOGY

AMITY UNIVERSITY, UTTAR PRADESH
SECTOR-125, NOIDA, 201301
 CERTIFICATE

This is to certify that Ms. EKTA SINGH of Amity Institute of Biotechnology has done a
summer internship report entitled “QUALITY ASSURANCE IN ARCH VITALIFE
LABORATORIES” in the partial fulfillment of Master of Business Administration as
required under the rules of Amity University and has successfully completed it under the
guidance of Mr. JITENDER SINGH

Director General Signature Coordinator’s signature

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 DECLARATION

I, EKTA SINGH, declare that the project report entitled “QUALITY ASSURANCE IN
ARCH VITALIFE LABORATORIES” submitted to the Amity Institute Of
Biotechnology, Noida for the partial fulfillment for the award of the degree of MBA
(Biotechnology Management) is an authentic record of the work carried out by me under
the guidance of Mr. JITENDER SINGH General Manager (QA), Arch Vitalife
Laboratories. No part of this has been submitted for any degree, diploma title of
recognition before.

EKTA SINGH
A0500109042

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 ACKNOWLEDGEMENT

I am overwhelmed with respect and my deep sense of gratitude to my college for

assigning me such training opportunity which opened my vision towards practical
experience of the theory implications. I express my heartfelt thanks to my mentor in
college Ms. Sudha Balram (Program Coordinator) and all faculty members in my
institute and also my mentor in company Mr. Jitender Singh (General Manager, QA)
Arch Vitalife Laboratories, who has provided me with guidance, inspiration, perspective
and stimulating discussion throughout the writing of this project.

I would like to extend my sincere thanks to Mr. P.S. Raghav (Sr.Manager-HR &
Admin.), Mr. Manvendra Singh (Head, Microbiology lab.), Mr. Digvijay (Sr.
microbiologist, Microbiology lab) and all others in the company for acting as the constant
motivating force for, directing me towards right path and for the completion of the
project.

I have all my appreciation and respect for my parents whose unfailing inspiration, love
and support have enabled me to reach this level. And I would like to thank my friends
and all the people who are involved in this project report directly or indirectly.

EKTA SINGH

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 CONTENTS

• INTRODUCTION 6
• EXECUTIVE SUMMARY 8
• MISSION, VISION AND VALUES 9
• COMPANY OVERVIEW 10
• PRODUCTS OF THE COMPANY 11
• MANUFACTURING SITES 24
• FACILITIES 27
• CETIFICATES 29
• ENVIRONMENTAL, HEALTH AND SAFETY 31
• CORE STRENGTHS OF THE COMPANY 32
• QUALITY ASSURANCE 34
• QUALITY ASSURANCE SYSTEM 35
• QUALITY MANAGEMENT IN DRUG INDUSTRY 38
• QUALITY ASSURANCE PROCESSING 40
• GMP’s FOR PHARMACEUTICAL PRODUCTS 43
• QUALIFICATION AND VALIDATION 45
• QUALITY AUDITS 49
• DOCUMENTATIONS 53
• DOCUMENTS REQUIRED 55
• SOP’s AND RECORDS 62
• GOOD PRACTICES IN PRODUCTION 65
• GOOD PRACTICES IN QUALITY CONTROL 67
• QUALITY ASSURANCE STANDARDS 70
• CONCLUSION 72
• RECOMMENDATIONS 73
• REFERENCES 75

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 INTRODUCTION

Knowledge, experience, integrity and result!!!

This is on what, Arch Vitalife works. 40905126.doc
For early development to launch planning and life cycle management, that’s what Arch
brings to your small molecules API and drug intermediate goals.
Supported by eleven India-based certified facilities (including cGMP, US FDA, EDQM,
TGA and Japanese approved assets) and two state-of-the-art Process Technology Centres,
our 2,500 customer-centric Archers are helping global pharmaceutical companies to
efficiently and reliably transform their molecules into products, reducing costs and
growing profitability

Growth of Arch Pharmalabs Ltd in Pharma industry

The industry overall has been growing at a rate of 8-10% over the years. This could get
more pronounced in the wake of resizing of operations and migration of production to
India by major pharma companies in the US & Europe. Of course, this is based on the
premise that Indian companies gear up to challenges of a stricter regulatory and
environmental regime. The domestic market on the back of higher healthcare penetration,
insurance coverage and growth in lifestyle diseases is also exhibiting a robust growth

ARCH VITALIFE LABORATORIES

Founded in 1999,Arch Pharmalabs has gained recognition as a world-class provider of

small molecule process chemistry, custom synthesis services and full life-cycle API and
drug intermediates manufacture for the global pharmaceutical industry. Generating
revenues of USD 200 million, our India-based offering is supported by 2,400 customer-
centric Archers, eleven certified facilities (including cGMP-compliant, US FDA- and
EDQM-approved sites) and two state-of-the-art Process Technology centres.

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Arch Pharmalabs works tirelessly to deliver value, innovation and effective supply chain
solutions in the spirit of true partnership. Our large family of satisfied customers range
from emerging or specialty companies to global majors, many of whom have designated
Arch Pharmalabs as a Preferred Supplier or Strategic Partner. Arch Pharmalabs received
CNBC TV Emerging India 2006 Award as the No.1 Small or Medium Company in the
Pharmaceuticals and Chemicals category

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8
 EXECUTIVE SUMMARY

STATEMENT OF PROJECT

Project is to study the practical implications of quality assurance in the working of Arch
Vitalife Laboratories

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OBJECTIVE OF THE PROJECT
The main objective of the project is to know the practical impact and implication of the
theoretical knowledge of the quality assurance in the industry.
Initially, the report emphasizes on the history, business & latest developments of ARCH
VITALIFE LABORATORIES. It also emphasizes on the functioning of various
departments of Arch Vitalife including QC, Finance & Accounts department, Labs,
Engineering dept. etc.

Led by a diverse group of seasoned industry professionals, Arch Pharmalabs management

team brings a vast array of domain expertise and experience to developing innovative, yet
practical and cost-effective R&D and manufacturing solutions for our customers. Our
executives cherish customer-centricity as the cornerstone of a successful global business.

The systems are integrated in the whole organization to deliver good quality products or
services. This leads to improved quality and less rework. This results in more business for
the organization and further increasing profits.
The company has put an effort in working out with proper adoption of quality assurance
in the industry and to take full fledged benefit out of it.

MISSION, VISION AND VALUES

Arch Pharmalabs aims to be a world leader in the development, manufacture and supply
of Active Pharmaceutical Ingredients and intermediates across the life cycle for the
global drug industry. Our mission is to consistently exceed our customers’ expectations
through innovation, speed, low costs and high quality. Arch’s core strength comes from

10
our highly skilled and experienced customer-centric people, who are dedicated to
developing practical, rapid, quality-focused, yet highly cost-effective solutions for the
unique challenges of pharmaceutical product development and commercialization

We are committed to working transparently with our customers in the spirit of true
partnership and providing them with the best value, while delivering superior returns to
our shareholders. We take pride in being responsible, global corporate citizens and
stewards of the environment. Our colleagues are “Archers” and we create the best
atmosphere for them to hit the mark, while helping them to realize personal excellence
and growth goals. Integrity, results, accountability and a long-term approach are
cornerstones of our business philosophy. Working diligently to produce success for our
customers and partners across the world, Arch Pharmalabs is transforming the way
chemistry and manufacturing are outsourced

COMPANY OVER VIEW

PARTNERS AND CUSTOMERS

We service various customers with APIs and intermediates used in Pharmaceutical

industry. We have a "Zero Compete" position with our customers. Our service model is

11
founded on basic principle that "Our customers' success is our success". This is highly
customized business which combines various skills for value creation and sharing.

INVESTORS

Arch Pharmalabs is backed by marquee investors ICICI Ventures (venture arm of

India's No.2 bank), Swisstec Ventures (venture arm of the Swiss Federal
Government) and IL&FS, who collectively own 58% of the Company

PRODUCTS OF THE COMPANY

1. API’s (Active Pharmaceutical Ingredients)

2. Pharma Intermediates

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 API’s (Active Pharmaceutical Ingredients)

Sr. No. Product Name Therapeutic Segment

1 Atorvastatin calcium (Amorphous) Lipid Lowering Agent
Atorvastatin calcium (Crystalline)
2 Amlodipine besylate Calcium Channel Blocker
3 Clopidogrel bisulphate (Form I) Anti Platelet Agent
Clopidogrel bisulphate (Form II)
4 Perindopril erbumine ACE Inhibitor
Trandolapril
5 Budesonide Anti Asthmatic
Ciclesonide
Fluticasone propionate
Mometasone furoate
Montelukast sodium#
6 Fluconazole Anti Fungal
7 Cetirizine dihydrochloride Anti Histamine
Levocetirizine dihydrochloride
Fexofenadine hydrochloride
8 Docetaxel anhydrous Anti Cancer
Gemcitabine hydrochloride
Paclitaxel hydrochloride
Capecitabine
9 Artesunate sodium Anti Malarial
Alpha beta arteether
Artemether
Lumefantrine
10 Chlorothiazide Diuretic
Hydrochlorothiazide
11 Zopiclone Sedative-Hypnotic
12 Citalopram hydrobromide Anti Depressant
Escitalopram oxalate
Duloxetine hydrochloride#

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 Milnacipran
13 Pregabalin Anti Convulsant

Efavirenz Anti Retroviral

14 Lamivudine
Stavudine
Zidovudine
Nevirapine
Ritonavir

15 Pantoprazole sodium Proton Pump Inhibitor

Rabeprazole sodium
16 Bromhexine hydrochloride Expectorant
17 Naproxen NSAIDs
Bromfenac
18 Ephedrine hydrochloride Decongestant
Pseudoephedrine hydrochloride
Ephedrine sulfate
Pseudoephedrine sulfate
19 Pramipexole dihydrochloride Anti parkinsonian
Monohydrate
entacapone
20 Ibuprofen NSAIDs
S (+) Ibuprofen
S (+) Ibuprofen DC
MeloxicamB
Piroxicam
Diclofenac sodium
Aceclofenac
MeFenamic acid
21 Loratadine Anti histamine
22 Isradipine Calcium channel blockers
Lacidipine

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PHARMA INTERMEDIATES

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Sr. EINECS
Intermediate CAS No. Structure End use
No. No.
Pharma Intermediates
1 CMIC Chloride: 25629- 247-137-4 Cloxacillin
3-(2-Chlorophenyl)-5-methyl 50-9
isoxazole-4-carbonyl chloride

2 DCMIC Chloride: 4462-55- 224-723-8 Dicloxacillin

3-(2,6 Dichlorophenyl)-5-methyl 9
isoxazole-4-carbonyl chloride

3 FCMIC Chloride: 69399- 273-987-0 Flucloxacillin

3-(2-Chloro-6-fluorophenyl)-5- 79-7
methyl isoxazole-4-carbonyl
chloride

4 PMIC Chloride: 16883- 240-915-4 Oxacillin

3-Phenyl-5-methyl isoxazole-4- 16-2
carbonyl chloride

5 EDPCC: 59703- 261-867-0 Piperacillin

4-Ethyl-2,3-dioxopiperazine 00-3
carbonyl chloride

6 EPCP: 63422- 264-133-8 Piperacillin

(R)-[[(4-Ethyl-2,3- 71-9
dioxopiperazin-1-
yl)carbonyl]amino]phenylacetic
acid

7 AOSA# 76855- 408-050-9 Carbapenem

New (3R,4R)-4-Acetoxy-3-[(R)-1- 69-1
(tert-butyl- (ELINCS)
dimethylsilyloxy)ethyl]azetidin-
16
2-one
8 Azacyclonol base: 115-46-8 204-092-5 Fexofenadine
 MANUFACTURING SITES

Arch has multi-locational manufacturing facilities in India. It has also augmented its
manufacturing strength through strategic alliances and co-marketing agreements. It
believes in teamwork that transcends organizational and geographic boundaries, to
cater to the changing needs of its customers worldwide.

All factories are equipped with proper effluent treatment and solvent recovery
systems in line with regulatory requirements

1. API manufacturing sites

2. Intermediates manufacturing sites

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 API -MANUFACTURING SITES

1. Vitalife site , Gurgaon - Located in northern India at Gurgaon near New Delhi,
this USFDA inspected, WHO-cGMP compliant site manufactures various APIs in
different therapeutic segments. This multipurpose facility handles diverse
chemistry range using n-BuLi, diethyl zinc and biocatalysts

2. Avon site , Solapur - Located in western India at Solapur, this USFDA inspected
site is the largest manufacturer of Ephedrine and Pseudoephedrine in India. In
addition to fermentation capabilities, this site has a multipurpose plant for
manufacturing APIs.

3. Sibra site, Hyderabad - Located in southern India at Hyderabad, this cGMP

compliant site has capability to manufacture various APIs in the Anti Retroviral
segment. The site handles biocatalysts, cyanides and azide based reactions.

4. Oncology site, Tarapur - Located in western India at Tarapur near Mumbai, this
cGMP compliant site handles various APIs in the oncology segment. The site has
state of the art isolation and containment systems in place to handle high potency
products

5. Dombivali site, near Mumbai - Located in western India at Dombivali near

Mumbai, this cGMP facility, with capabilities of handling complex chemical

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 reactions, is a USFDA, TGA and EDQM inspected site with over 15 APIs being
manufactured here.

INTERMEDIATES MANUFACTURING SITES

1. Merven site, Hyderabad - Located in southern India at Hyderabad, this site has
capacity to produce Isoxazole side chain intermediates in multiple ton quantities;
thus making Arch its largest producer in the world. In addition, it has capability to
handle diverse chemistries using n-BuLi, triphosgene and biocatalysts making it a
multipurpose facility to make advanced intermediates for various therapeutic
segments

2. Watsol site, Hyderabad - Located in southern India at Hyderabad, this site

manufactures Isoxazole based side chain intermediates and phosphorus chemicals
in multiple ton quantities

3. Avon site, Hyderabad - Located in southern India at Hyderabad, this site

manufactures diketene and its downstream intermediates. It is a multipurpose
facility to make various advanced intermediates.

4. Badlapur site, near Mumbai - Located in western India at Badlapur near

Mumbai, this site manufactures Intermediates and APIs. This multipurpose
facility is used for scale up and custom synthesis projects

5. Tarapur site, near Mumbai - Located in western India at Tarapur near Mumbai,
this site manufactures advanced intermediates for key APIs

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 6. Chromato site, Taloja - Located in western India at Taloja near Mumbai, this
site manufactures Intermediates and steroids (Class-III). This is a multipurpose
facility used for scale up and custom synthesis project

FACILITIES

PROCESS R&D
Working in state-of-the-art laboratories and supported by excellent in-house analytical
capabilities, our talented and experienced scientists work across multiple chemistry and
therapeutic categories to create scalable, robust and cost-effective processes. Arch
Pharmalabs provides flexible Full Time Equivalent (FTE) or per-project
arrangements to execute innovative route scouting, process R&D and rapid-response
custom synthesis of regulatory starting materials, advanced intermediates and APIs in
gram to multi kilo gram quantities as per customers' demand.

PROCESS TECHNOLOGY CENTRE

Located in Taloja (near Mumbai), Arch Pharmalabs Process Technology Centre
spearheads:
• Externally sponsored process R&D and custom synthesis of new chemical entities
• Continuous process improvement and expansion of our API portfolio

The site houses 150 process chemists and analysts and features professional project
management, state-of-the-art chemistry laboratories and analytical instrumentation. Kilo
laboratories and Pilot Plant assets enable rapid scale-up of APIs and intermediates for
timeline-sensitive pre-clinical animal GLP tox and Phase I human studies.

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CLINICAL TRIALS SUPPLIES MANUFACTURE
We fully understand the critical importance of time, quality and economics in
pharmaceutical development. Our customer-centric process R & D, QC analytics,
manufacturing teams and project champions work hand-in-hand with customer to
produce regulatory starting materials, intermediates and APIs for Phase I, II & III clinical
trials in kilo gram to metric tonne quantities. Arch Pharmalabs project management
systems enable transparent milestone tracking, communications and delivery.

PROCESS VALIDATION
Arch Pharmalabs product development and commercialization track record offers
customers and partners a unique opportunity to leverage our expertise and experience in
process validation and launch planning. Our New Product Introduction teams work
closely with customers to plan and execute a safe, cost-effective and risk-mitigated
validation strategy. Our regulatory team provides all API CMC- and / or DMF-related
supporting documentation and assistance to enable smooth filings

COMMERCIAL MANUFACTURE
Arch Pharmalabs offers multiple manufacturing locations and flexible assets in India to
provide our customers post-approval, market place requirements of regulatory starting
materials, intermediates and APIs in a reliable, quality-focused and economical manner.
Applying world-class best practices, our production, quality and supply chain teams work
diligently to enable customers' launch and post-approval commercial supply programs on
a global basis.

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CERTIFICATES

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INSPECTIONS AND COMPLIANCES CERTIFICATE

23
Arch Pharmalabs Avon GMP manufacturing facility (Solapur, Maharashtra) successfully
received a USFDA audit and is approved for supply of a bulk API. Our Vitalife GMP
manufacturing unit expects a USFDA inspection in 2009 and has successfully received
more than 7 full GMP / QA audits from global majors, including Top 10 companies. In
addition, Arch Pharmalabs routinely receives GMP / GLP / EHS audits in preparation for
site registration from current and prospective customers from across the world.

All Arch Pharmalabs sites have ISO 9001:2000 or ISO 140001 certifications as
authenticated by QA International Certification Ltd., UK or International Certifications
Ltd., New Zealand.

Arch Pharmalabs has submitted Type II DMFs with the following DMF Numbers to the
USFDA: 17693, 17954, 17953, 18215, 20444, 19744 and 20681.

ENVIRONMENTAL, HEALTH AND SAFETY

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Arch Pharmalabs has instituted an environmental, health and safety program to ensure
strict compliance with Local as well as Central Government regulations and industry best
practices, while maintaining safety, personnel health and continuous reinforcement of
principles through regular training.

We are firmly committed to the highest, internationally accepted manufacturing practices

and take special care in the handling and disposal of all potentially hazardous substances
and waste products per applicable codes. Arch Pharmalabs is dedicated to the protection
of the environment and safety of both employees and the public at large. Our sites have
effluent treatment plants ensuring zero discharge at point of manufacture and waste water
treatment to applicable standards, prior to release. Other available equipment includes
multiple effect evaporators, incinerators, scrubbers and solid waste management systems

Medical facilities and Physician check-ups are available either on-site or through nearby
hospitals. Large-scale production facilities maintain an on-site ambulance service 24
hours a day, 7 days a week..

Risk assessment is an integral part of scaling up new processes at Arch Pharmalabs.

These practices include hazard assessment, proper inventory control of hazardous
substances and easy access to fire extinguishers and other mitigation techniques
throughout our laboratory and production facilities. Our teams constantly reinforce these
principles through ongoing training programs.

CORE STRENGTHS OF COMPANY

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Our core strength is the ability to differentiate in a highly commoditised and fragmented
space. The differentiation is based on the following :

1. Multiple facilities with ability to handle complex reactions at various scales.

2. Reliance on R&D services which has helped us attract business from innovator
companies.
3. Assimilation of new technology on the back of our technical collaboration with
two partners viz. Codexis Inc ( USA) and DSM ( EU).
4. Offering of products in every therapeutic segment

Our positioning by way of market/co-market leadership in various products both globally

and in the domestic market.

EXPANSION PLANS OF THE INDUSTRY

The company has been at the forefront of consolidation in the Indian API industry. For
the year 2009, we will explore acquisitions either from a point of enhancement of
capacities , backward integration or therapeutic segment extension. Besides, the company
had finalised and embarked on expansion plans in the existing locations. The capital
expenditure during this period is expected to be around Rs1.5bn.

RECENT ACQUISITION BY THE COMPANY

We have acquired Benzochem Lifesciences Pvt. Limited. The company is engaged in

the manufacture of Oncology and Anti Malarial APIs. Based near Mumbai, the
acquisition offered an entry to Arch in the Oncology space. The company has been at the
forefront of consolidation in the Indian API industry. For the year 2009, we will explore
meaningful acquisitions either from a point of enhancement of capacities, backward
integration or therapeutic segment extension.

OPPORTUNITIES AND CHALLENGES

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The opportunities for the industry stem from a growing domestic market and demand.
This is in addition to the opportunities flowing in from the US & Europe where major
pharma companies are engaged in resizing their operations given the fact that we are
moving towards a growing generic market. Clearly India and China appear to be the
beneficiaries of these moves.

The challenges for the industry are primarily the following :

a. As the world goes " generic" , there are bound to be pressures on the realisations.
b. Highly fragmented industry in both India and China leading to overcapacity and
irrational pricing, at times. Higher investments in the face of stricter
environmental & regulatory compliances.
c. Shortage of skilled personnel, more so in the peripheral but highly critical
functions of documentation, quality control and assurance etc.

R&D BY INDUSTRY

Arch has two Corporate R&D centres besides Process Development labs at various
locations. The Corporate R&D centre focuses on offering services to both innovator and
generic companies. The services revolved around custom synthesis, offer of Full Time
Equivalence business model, scale up of hitherto untested processes and assist our
various manufacturing facilities for perpetual cost reduction programmes. Currently,
there are over 250 Chemists working in our R&D Centres and we expect to ramp up our
bench strength to over 350 in 2009. The Centres are equipped with state of the art
analytical equipment and built to international working and safety standards.

QUALITY ASSURANCE

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Quality assurance is a process in which steps are taken to make sure that a company's
products or services are of sufficiently high quality or are up to the mark of specified
values.
Definition often used interchangeably with quality control (QC), it is a wider concept that
covers all policies and systematic activities implemented within a quality system. QA
frameworks include –

• Determination of adequate technical requirement of inputs and outputs,

• Certification and rating of suppliers,

• Testing of procured material for its conformance to established quality,

performance, safety, and reliability standards,

• Proper receipt, storage, and issue of material,

• Audit of the process quality,

• Evaluation of the process to establish required corrective response, and

• Audit of the final output for conformance to -

1. technical
2. Reliability,
3. Maintainability, and
4. Performance requirements

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 QUALITY ASSURANCE SYSTEM

Quality Assurance System that is based on a continuous cycle of five stages:--

• data collection,
• data analysis,
• data and analysis dissemination,
• decision-making, and improvement and changes.
(Figure) depicts this cycle.

This system functions as an umbrella under which our quality efforts take place. By
following this cycle for activities such as program reviews other evaluations, practices a
culture of inquiry that allows the concern to learn more about itself and the services that it
provides. Additionally, such a system creates the path to make decisions based on well-
analyzed data, which in turn results in improved services. Depending on the nature of the
data source and the collection activity, different cycles are established.

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30
Quality Assurance Cycle

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QUALITY MANAGEMENT IN DRUG INDUSTRY

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Philosophy and essential elements-
In the drug industry at large, quality management is usually defined as the aspect of
management function that determines and implements the “quality policy”, i.e. the
overall intention and direction of an organization regarding quality, as formally expressed
and authorized by top management. The basic elements of quality management are:--

• an appropriate infrastructure or “quality system”, encompassing the organizational

structure, procedures, processes and resources;
• systematic actions necessary to ensure adequate confidence that a product (or service)
will satisfy given requirements for quality. The totality of these actions is termed
“quality assurance”.

Within an organization, quality assurance serves as a management tool. In contractual

situations, quality assurance also serves to generate confidence in the supplier.

The concepts of quality assurance, GMP and quality control are interrelated aspects of
quality management. They are described here in order to emphasize their relationship and
their fundamental importance to the production and control of pharmaceutical products.

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QUALITY ASSURANCE CYCLE

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 QUALITY ASSURANCE PROCESSING

“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 those outside the scope of this guide such as product design and development.

The system of quality assurance appropriate to the manufacture of pharmaceutical

products should ensure that:

• pharmaceutical products are designed and developed in a way that takes account of
the requirements of GMP and other associated codes such as those of good laboratory
practice (GLP) and good clinical practice (GCP);

• production and control operations are clearly specified in a written form and GMP
requirements are adopted;

• managerial responsibilities are clearly specified in job descriptions;

• arrangements are made for the manufacture, supply and use of the correct starting and
packaging materials;

• all necessary controls on starting materials, intermediate products, and bulk products
and other in-process controls, calibrations, and validations are carried out;

• the finished product is correctly processed and checked, according to the defined
procedures;

• pharmaceutical products are not sold or supplied before the authorized persons have
certified that each production batch has been produced and controlled in accordance

35
 with the requirements of the marketing authorization and any other regulations
relevant to the production, control and release of pharmaceutical products;

• satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical

products are stored by the manufacturer, distributed, and subsequently handled so that
quality is maintained throughout their shelf-life;

• there is a procedure for self-inspection and/or quality audit that regularly appraises
the effectiveness and applicability of the quality assurance system;

• regular evaluations of the quality of pharmaceutical products should be conducted

with the objective of verifying the consistency of the process and ensuring its
continuous improvement.

The attainment of this quality objective is the responsibility of senior management and
requires the participation and commitment of staff in many different departments and at
all levels within the company, the company’s suppliers, and the distributors. To achieve
the quality objective reliably there must be a comprehensively designed and correctly
implemented system of quality assurance incorporating GMP and quality control. It
should be fully documented and its effectiveness monitored. All parts of the quality
assurance system should be adequately staffed with competent personnel, and should
have suitable and sufficient premises, equipment, and facilities.

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37
 GOOD MANUFACTURING PRACTICES FOR
PHARMACEUTICAL PRODUCTS
(GMP)

Good manufacturing practice is that part of quality assurance which ensures that products
are consistently produced and controlled to the quality standards appropriate to their
intended use and as required by the marketing authorization.

GMP are aimed primarily at diminishing the risks inherent in any pharmaceutical
production. Such risks are essentially of two types:-- cross-contamination (in particular of
unexpected contaminants) and mix-ups (confusion) caused by, for example,- false labels
being put on containers.
Under GMP:--
• all manufacturing processes are clearly defined, systematically reviewed in the
light of experience, and shown to be capable of consistently manufacturing
pharmaceutical products of the required quality that comply with their
specifications;
• qualification and validation are performed,
• all necessary resources are provided, including:-
(i) appropriately qualified and trained personnel;
(ii) adequate premises and space;
(iii) suitable equipment and services;
(iv) appropriate materials, containers and labels;
(v) approved procedures and instructions;
(vi) suitable storage and transport;
(vii) adequate personnel, laboratories and equipment for in-process controls;

• instructions and procedures are written in clear and unambiguous language,

specifically applicable to the facilities provided;
• operators are trained to carry out procedures correctly;

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 • records are made (manually and/or by recording instruments) during manufacture
to show that all the steps required by the defined procedures and instructions
have in fact been taken and that the quantity and quality of the product are as
expected; any significant deviations are fully recorded and investigated;
• records covering manufacture and distribution, which enable the complete history
of a batch to be traced, are retained in a comprehensible and accessible form;
• the proper storage and distribution of the products minimizes any risk to their
quality;
• a system is available to recall any batch of product from sale or supply;
• complaints about marketed products are examined, the causes of quality defects
investigated, and appropriate measures taken in respect of the defective products
to prevent recurrence.

SANITATION AND HYGIENE

A high level of sanitation and hygiene should be practised in every aspect of the
manufacture of drug products. The scope of sanitation and hygiene covers personnel,
premises, equipment and apparatus, production materials and containers, products for
cleaning and disinfection, and anything that could become a source of contamination to
the product. Potential sources of contamination should be eliminated through an
integrated comprehensive programme of sanitation and hygiene.

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 QUALIFICATION AND VALIDATION

In accordance with GMP, each pharmaceutical company should identify what

qualification and validation work is required to prove that the critical aspects of their
particular operation are controlled .

The key elements of a qualification and validation programme of a company should be

clearly defined and documented in a validation master plan.

Qualification and validation should establish and provide documentary evidence that:-

• the premises, supporting utilities, equipment and processes have been designed in
accordance with the requirements for GMP (design qualification, or DQ);
• the premises, supporting utilities and equipment have been built and installed in
compliance with their design specifications (installation qualification, or IQ);
• the premises, supporting utilities and equipment operate in accordance with their
design specifications (operational qualification, or OQ);
• a specific process will consistently produce a product meeting its predetermined
specifications and quality attributes (process validation, or PV, also called
performance qualification, or PQ).
• Any aspect of operation, including significant changes to the premises, facilities,
equipment or processes, which may affect the quality of the product, directly or
indirectly, should be qualified and validated.
• Qualification and validation should not be considered as one-off exercises. An on-
going program should follow their first implementation and should be based on an
annual review.
• The commitment to maintain continued validation status should be stated in the
relevant company documentation, such as the quality manual or validation master
plan. The responsibility of performing validation should be clearly defined.
• Validation studies are an essential part of GMP and should be conducted in
accordance with predefined and approved protocols.

40
 • A written report summarizing the results recorded and the conclusions reached
should be prepared and stored.
• Processes and procedures should be established on the basis of the results of the
validation performed.
• It is of critical importance that particular attention is paid to the validation of
analytical test methods, automated systems and cleaning procedures.

COMPLAINTS
• All complaints and other information concerning potentially defective products
should be carefully reviewed according to written procedures and the corrective
action should be taken.
• A person responsible for handling the complaints and deciding the measures to
be taken should be designated, together with sufficient supporting staff to assist
him or her. If this person is different from the authorized person, the latter should
be made aware of any complaint, investigation or recall.
• There should be written procedures describing the action to be taken, including
the need to consider a recall, in the case of a complaint concerning a possible
product defect.
• Special attention should be given to establishing whether a complaint was caused
because of counterfeiting.
• Any complaint concerning a product defect should be recorded with all the
original details and thoroughly investigated. The person responsible for quality
control should normally be involved in the review of such investigations.
• If a product defect is discovered or suspected in a batch, consideration should be
given to whether other batches should be checked in order to determine whether
they are also affected. In particular, other batches that may contain reprocessed
product from the defective batch should be investigated.
• Where necessary, appropriate follow-up action, possibly including product recall,
should be taken after investigation and evaluation of the complaint.

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 • All decisions made and measures taken as a result of a complaint should be
recorded and referenced to the corresponding batch records.
• Complaints records should be regularly reviewed for any indication of specific or
recurring problems that require attention and might justify the recall of marketed
products.
• The competent authorities should be informed if a manufacturer is considering
action following possibly faulty manufacture, product deterioration,
counterfeiting or any other serious quality problems with a product.

PRODUCT RECALL
There should be a system to recall from the market, promptly and effectively, products
known or suspected to be defective. The authorized person should be responsible for the
execution and coordination of recalls. He/she should have sufficient staff to handle all
aspects of the recalls with the appropriate degree of urgency.

• There should be established written procedures, which are regularly reviewed and
updated, for the organization of any recall activity. Recall operations should be
capable of being initiated promptly down to the required level in the distribution
chain.
• An instruction should be included in the written procedures to store recalled
products in a secure segregated area while their fate is decided.
• competent authorities of all countries to which a given product has been
distributed should be promptly informed of any intention to recall the product
because it is, or is suspected of being, defective.
• The distribution records should be readily available to the authorized person, and
they should contain sufficient information on wholesalers and directly supplied
customers (including, for exported products, those who have received samples for
clinical tests and medical samples) to permit an effective recall.
• The progress of the recall process should be monitored and recorded. Records
should include the disposition of the product. A final report should be issued,

42
 including a reconciliation between the delivered and recovered quantities of the
products.
• The effectiveness of the arrangements for recalls should be tested and evaluated
from time to time.

CONTRACT PRODUCTION AND ANALYSIS

Contract production and analysis must be correctly defined, agreed and controlled in
order to avoid misunderstandings that could result in a product or work or analysis of
unsatisfactory quality.

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 QUALITY AUDITS

The purpose of self-inspection is to evaluate the manufacturer’s compliance with GMP in

all aspects of production and quality control. The self inspection programme should be
designed to detect any shortcomings in the implementation of GMP and to recommend
the necessary corrective actions. Self-inspections should be performed routinely, and may
be, in addition, performed on special occasions, e.g. in the case of product recalls or
repeated rejections, or when an inspection by the health authorities is announced. The
team responsible for self-inspection should consist of personnel who can evaluate the
implementation of GMP objectively. All recommendations for corrective action should
be implemented. The procedure for self-inspection should be documented, and there
should be an effective follow-up programme.

PERSONNEL
The establishment and maintenance of a satisfactory system of quality assurance and the
correct manufacture and control of pharmaceutical products and active ingredients rely
upon people. For this reason there must be sufficient qualified personnel to carry out all
the tasks for which the manufacturer is responsible. Individual responsibilities should be
clearly defined and understood by the persons concerned and recorded as written
descriptions.

Key personnel responsible for supervising the manufacture and quality control of
pharmaceutical products should possess the qualifications of a scientific education and
practical experience required by national legislation. Their education should include the
study of an appropriate combination of:--
• chemistry (analytical or organic) or biochemistry;
• chemical engineering;
• microbiology;
• pharmaceutical sciences and technology;
• pharmacology and toxicology;
• physiology;

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 • other related sciences.

The person responsible for approving a batch for release should always ensure that the
following requirements have been met:--
• the marketing authorization and the manufacturing authorization requirements
for the product have been met for the batch concerned;
• the principles and guidelines of GMP, as laid down in the guidelines published
by WHO, have been followed;
• the principal manufacturing and testing processes have been validated, if
different;
• all the necessary checks and tests have been performed and account taken of the
production conditions and manufacturing records;
• any planned changes or deviations in manufacturing or quality control have been
notified in accordance with a well defined reporting system before any product is
released. Such changes may need notification to, and approval by, the drug
regulatory authority;
• any additional sampling, inspection, tests and checks have been carried out or
initiated, as appropriate, to cover planned changes and deviations;
• all necessary production and quality control documentation has been completed
and endorsed by supervisors trained in appropriate disciplines;
• appropriate audits, self-inspections and spot-checks are carried out by experienced
and trained staff;
• approval has been given by the head of quality control;
• all relevant factors have been considered, including any not specifically
associated with the output batch directly under review (e.g. subdivision of output
batches from a common input, factors associated with continuous production
runs).

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TRAINING
• The manufacturer should provide training in accordance with a written
programme for all personnel whose duties take them into manufacturing areas or
into control laboratories (including the technical, maintenance and cleaning
personnel) and for other personnel as required.
• Besides basic training on the theory and practice of GMP, newly recruited
personnel should receive training appropriate to the duties assigned to them.
Continuing training should also be given, and its practical effectiveness
periodically assessed. Approved training programmes should be available.
Training records should be kept.
• Personnel working in areas where contamination is a hazard, e.g. clean areas or
areas where highly active, toxic, infectious or sensitizing materials are handled,
should be given specific training.
• The concept of quality assurance and all the measures which aid its
understanding and implementation should be fully discussed during the training
sessions.
• Visitors or untrained personnel should preferably not be taken into the production
and quality control areas. If this is unavoidable, they should be given relevant
information in advance (particularly about personal hygiene) and the prescribed
protective clothing. They should be closely supervised.
• Consultant and contract staff should be qualified for the services they provide.
Evidence of this should be included in the training records.

PREMISES
Premises must be located, designed, constructed, adapted, and maintained to suit the
operations to be carried out. The layout and design of premises must aim to minimize the
risk of errors and permit effective cleaning and maintenance in order to avoid cross
contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality
of products.

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EQUIPMENT
Equipment must be located, designed, constructed, adapted, and maintained to suit the
operations to be carried out. The layout and design of equipment must aim to minimize
the risk of errors and permit effective cleaning and maintenance in order to avoid cross-
contamination, build-up of dust or dirt, and, in general, any adverse effect on the quality
of products.

MATERIALS
The main objective of a pharmaceutical plant is to produce finished products for patients’
use from a combination of materials (starting and packaging).
• Materials include starting materials, packaging materials, gases, solvents, process
aids, reagents and labelling materials.
• No materials used for operations such as cleaning, lubrication of equipment and
pest control, should come into direct contact with the product. Where possible,
such materials should be of a suitable grade (e.g. food grade) to minimize health
risks.
• Starting materials should be purchased only from approved suppliers and, where
possible, directly from the producer. It is also recommended that the
specifications established by the manufacturer for the starting materials be
discussed with the suppliers.
• It is of benefit that all critical aspects of the production and control of the starting
material in question, including handling, labelling and packaging requirements as
well as complaints and rejection procedures, are contractually agreed between the
manufacturer and the supplier.
• All incoming materials should be checked to ensure that the consignment
corresponds to the order. Containers should be cleaned where necessary and
labelled, if required, with the prescribed information. Where additional labels are
attached to containers, the original information should not be lost.

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 DOCUMENTATION

Good documentation is an essential part of the quality assurance system and, as such,
should exist for all aspects of GMP. Its aims are to define the specifications and
procedures for all materials and methods of manufacture and control; to ensure that all
personnel concerned with manufacture know what to do and when to do it; to ensure that
authorized persons have all the information necessary to decide whether or not to release
a batch of a drug for sale, to ensure the existence of documented evidence, traceability,
and to provide records and an audit trail that will permit investigation. It ensures the
availability of the data needed for validation, review and statistical analysis. The design
and use of documents depend upon the manufacturer. In some cases some or all of the
documents described below may be brought together, but they will usually be separate.

• Documents should be designed, prepared, reviewed and distributed with care.

They should comply with the relevant parts of the manufacturing and marketing
authorizations.
• Documents should be approved, signed and dated by the appropriate responsible
persons. No document should be changed without authorization and approval.
• Documents should have unambiguous contents: the title, nature and purpose
should be clearly stated. They should be laid out in an orderly fashion and be easy
to check. Reproduced documents should be clear and legible. The reproduction of
working documents from master documents must not allow any error to be
introduced through the reproduction process.
• Documents should be regularly reviewed and kept up to date. When a document
has been revised, a system should exist to prevent inadvertent use of the
superseded version. Superseded documents should be retained for a specific
period of time.
• Where documents require the entry of data, these entries should be clear, legible
and indelible. Sufficient space should be provided for such entries.

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• Any alteration made to a document should be signed and dated; the alteration
should permit the reading of the original information. Where appropriate, the
reason for the alteration should be recorded.
• Records should be made or completed when any action is taken and in such a way
that all significant activities concerning the manufacture of pharmaceutical
products are traceable. Records should be retained for at least one year after the
expiry date of the finished product.
• Data (and records for storage) may be recorded by electronic dataprocessing
systems or by photographic or other reliable means.
• Master formulae and detailed standard operating procedures relating to the
system in use should be available and the accuracy of the records should be
checked.
• If documentation is handled by electronic data-processing methods, only
authorized persons should be able to enter or modify data in the computer, and
there should be a record of changes and deletions;
• access should be restricted by passwords or other means and the entry of critical
data should be independently checked.
• Batch records stored electronically should be protected by back-up transfer on
magnetic tape, microfilm, paper print-outs or other means. It is particularly
important that, during the period of retention, the data are readily available.

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 DOCUMENTS REQUIRED

LABELS
• Labels applied to containers, equipment or premises should be clear,
unambiguous and in the company’s agreed format. It is often helpful in addition
to the wording on the labels to use colours to indicate status (e.g. quarantined,
accepted, rejected, clean).
• All finished drug products should be identified by labelling, as required by the
national legislation, bearing at least the following information:
(a) the name of the drug product;
(b) a list of the active ingredients;
(c) the batch number assigned by the manufacturer;
(d) the expiry date in an uncoded form;
(e) any special storage conditions or handling precautions that may be necessary;
(f) directions for use, and warnings and precautions that may be necessary;
(g) the name and address of the manufacturer or the company or the person
responsible for placing the product on the market.
• For reference standards, the label and/or accompanying document should
indicate potency or concentration, date of manufacture, expiry date, date the
closure is first opened, storage conditions and control number, as appropriate.

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SPECIFICATIONS AND TESTING PROCEDURES
• Testing procedures described in documents should be validated in the context of
available facilities and equipment before they are adopted for routine testing.
• There should be appropriately authorized and dated specifications, including tests
on identity, content, purity and quality, for starting and packaging materials and
for finished products; where appropriate, they should also be available for
intermediate or bulk products. Specifications for water, solvents and reagents
(e.g. acids and bases) used in production should be included.
• Each specification should be approved, signed and dated, and maintained by
quality control, quality assurance unit or documentation centre. Specifications for
starting materials, intermediates, and bulk, finished products and packaging
materials are referred to in sections.
• Periodic revisions of the specifications may be necessary to comply with new
editions of the national pharmacopoeia or other official compendia.
• Pharmacopoeias, reference standards, reference spectra and other reference
materials should be available in the quality control laboratory.

Specifications for starting and packaging materials

• Specifications for starting, primary and printed packaging materials should
provide, if applicable, a description of the materials, including:
(a) the designated name (if applicable, the INN) and internal code reference;
(b) the reference, if any, to a pharmacopoeial monograph;
(c) qualitative and quantitative requirements with acceptance limits.
• Depending on the company’s practice other data may be added to the
specification, such as:
(a) the supplier and the original producer of the materials;
(b) a specimen of printed materials;
(c) directions for sampling and testing, or a reference to procedures;
(d) storage conditions and precautions;
(e) the maximum period of storage before re-examination.

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 • Packaging material should conform to specifications, and should be compatible
with the material and/or with the drug product it contains. The material should be
examined for compliance with the specification, and for defects as well as for the
correctness of identity markings.
• Documents describing testing procedures should state the required frequency for
re-assaying each starting material, as determined by its stability.

Specifications for intermediate and bulk products

• Specifications for intermediate and bulk products should be available. The
specifications should be similar to specifications for starting materials or for
finished products, as appropriate.

Specifications for finished products

• Specifications for finished products should include:
(a) the designated name of the product and the code reference, where applicable;
(b) the designated name(s) of the active ingredient(s)
(c) the formula or a reference to the formula;
(d) a description of the dosage form and package details;
(e) directions for sampling and testing or a reference to procedures;
(f) the qualitative and quantitative requirements, with acceptance limits;
(g) the storage conditions and precautions, where applicable;
(h) the shelf-life.

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MASTER FORMULAE

• A formally authorized master formula should exist for each product and batch size
to be manufactured.
• The master formula should include:--
1. the name of the product, with a product reference code relating to its
specification;
2. a description of the dosage form, strength of the product and batch size;
3. a list of all starting materials to be used (if applicable, with the INNs),
with the amount of each, described using the designated name and a
reference that is unique to that material (mention should be made of any
substance that may disappear in the course of processing);
4. a statement of the expected final yield with the acceptable limits, and of
relevant intermediate yields, where applicable;
5. a statement of the processing location and the principal equipment to be
used;
6. the methods, or reference to the methods, to be used for preparing and
operating the critical equipment, e.g. cleaning (especially after a change in
product), assembling, calibrating, sterilizing, use;
7. detailed step-wise processing instructions (e.g. checks on materials,
pretreatments, sequence for adding materials, mixing times, temperatures);
the instructions for any in-process controls with their limits;
8. where necessary, the requirements for storage of the products, including
the container, the labelling, and any special storage conditions;
9. any special precautions to be observed.

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PACKAGING INSTRUCTIONS
• Formally authorized packaging instructions should exist for each product, pack
size and type. These should normally include, or make reference to:
1. the name of the product;
2. a description of its pharmaceutical form, strength and, where applicable,
method of application;
3. the pack size expressed in terms of the number, weight or volume of the
product in the final container;
4. a complete list of all the packaging materials required for a standard batch
size, including quantities, sizes and types, with the code or reference
number relating to the specifications for each packaging material;
5. where appropriate, an example or reproduction of the relevant printed
packaging materials and specimens, indicating where the batch number
and expiry date of the product have been marked;
6. special precautions to be observed, including a careful examination of the
packaging area and equipment in order to ascertain the line clearance
before and after packaging operations;
7. a description of the packaging operation, including any significant
subsidiary operations, and equipment to be used;
8. details of in-process controls with instructions for sampling and
acceptance limits.

BATCH PROCESSING RECORDS

• A batch processing record should be kept for each batch processed. It should be
based on the relevant parts of the currently approved specifications on the record.
The method of preparation of such records should be designed to avoid errors.
(Copying or validated computer programmes are recommended. Transcribing
from approved documents should be avoided.)
• Before any processing begins, a check should be made that the equipment and
work station are clear of previous products, documents, or materials not required

54
 for the planned process, and that the equipment is clean and suitable for use. This
check should be recorded.
• During processing, the following information should be recorded at the time each
action is taken, and after completion the record should be dated and signed by the
person responsible for the processing operations:-
1. the name of the product;
2. the number of the batch being manufactured;
3. dates and times of commencement, of significant intermediate stages, and of
completion of production;
4. the name of the person responsible for each stage of production;
5. the initials of the operator(s) of different significant steps of production and,
where appropriate, of the person(s) who checked each of these operations (e.g.
weighing);
6. the batch number and/or analytical control number and the quantity of each
starting material actually weighed (including the batch number and amount of any
recovered or reprocessed material added);
7. any relevant processing operation or event and the major equipment used;
8. the in-process controls performed, the initials of the person(s) carrying them out,
and the results obtained;
9. the amount of product obtained at different and pertinent stages of manufacture
(yield), together with comments or explanations for significant deviations from
the expected yield;
10. notes on special problems including details, with signed authorization for any
deviation from the master formula.

BATCH PACKAGING RECORDS

• A batch packaging record should be kept for each batch or part batch processed. It
should be based on the relevant parts of the approved packaging instructions, and
the method of preparing such records should be designed to avoid errors.
(Copying or validated computer programmes are recommended. Transcribing
from approved documents should be avoided.)

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• Before any packaging operation begins, checks should be made that the
equipment and work station are clear of previous products, documents or
materials not required for the planned packaging operations, and that equipment is
clean and suitable for use. These checks should be recorded.
• The following information should be recorded at the time each action is taken,
and the date and the person responsible should be clearly identified by signature
or electronic password:--
1. the name of the product, the batch number and the quantity of bulk
product to be packed, as well as the batch number and the planned
quantity of finished product that will be obtained, the quantity actually
obtained and the reconciliation;
2. the date(s) and time(s) of the packaging operations;
3. the name of the responsible person carrying out the packaging operation;
4. the initials of the operators of the different significant steps;
5. the checks made for identity and conformity with the packaging
instructions, including the results of in-process controls;
6. details of the packaging operations carried out, including references to
equipment and the packaging lines used, and, when necessary, the
instructions for keeping the product unpacked or a record of returning
product that has not been packaged to the storage area;
7. whenever possible, samples of the printed packaging materials used,
including specimens bearing the approval for the printing of and regular
check (where appropriate) of the batch number, expiry date, and any
additional overprinting;
8. notes on any special problems, including details of any deviation from the
packaging instructions, with written authorization by an appropriate
person;
9. the quantities and reference number or identification of all printed
packaging materials and bulk product issued, used, destroyed or returned
to stock and the quantities of product obtained to permit an adequate
reconciliation.

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 STANDARD OPERATING PROCEDURES (SOP’s) AND RECORDS

Standard operating procedures and associated records of actions taken or, where
appropriate, conclusions reached should be available for:-
1. equipment assembly and validation;
2. analytical apparatus and calibration;
3. maintenance, cleaning and sanitization;
4. personnel matters including qualification, training, clothing and hygiene;
5. environmental monitoring;
6. pest control;
7. complaints;
8. recalls;
9. returns.

• There should be standard operating procedures and records for the receipt of each
delivery of starting material and primary and printed packaging material.
• The records of the receipts should include:--
1. the name of the material on the delivery note and the containers;
2. the “in-house” name and/or code of the material if different from (a);
3. the date of receipt;
4. the supplier’s name and, if possible, manufacturer’s name
5. the manufacturer’s batch or reference number;
6. the total quantity, and number of containers received;
7. the batch number assigned after receipt;
8. any relevant comment (e.g. state of the containers).
• There should be standard operating procedures for the internal labelling,
quarantine and storage of starting materials, packaging materials and other
materials, as appropriate.
• Standard operating procedures should be available for each instrument and piece
of equipment (e.g. use, calibration, cleaning, maintenance) and placed in close
proximity to the equipment.

57
• There should be standard operating procedures for sampling, which specify the
person(s) authorized to take samples.
• The sampling instructions should include:--
1. the method of sampling and the sampling plan;
2. the equipment to be used;
3. any precautions to be observed to avoid contamination of the material or
any deterioration in its quality;
4. the amount(s) of sample(s) to be taken;
5. instructions for any required subdivision of the sample;
6. the type of sample container(s) to be used, and whether they are for aseptic
sampling or for normal sampling, and labelling;
7. any specific precautions to be observed, especially in regard to the
sampling of sterile or noxious material.
8. There should be a standard operating procedure describing the details of
the batch (lot) numbering system, with the objective of ensuring that each
batch of intermediate, bulk or finished product is identified with a specific
batch number.
• The standard operating procedures for batch numbering that are applied to the
processing stage and to the respective packaging stage should be related to each
other.
• The standard operating procedure for batch numbering should ensure that the
same batch numbers will not be used repeatedly; this applies also to reprocessing.
• Batch-number allocation should be immediately recorded, e.g. in a logbook. The
record should include at least the date of allocation, product identity and size of
batch.
• There should be written procedures for testing materials and products at different
stages of manufacture, describing the methods and equipment to be used. The
tests performed should be recorded.
• Analysis records should include at least the following data:--
1. the name of the material or product and, where applicable, dosage form;

58
 2. the batch number and, where appropriate, the manufacturer and/or
supplier;
3. references to the relevant specifications and testing procedures;
4. test results, including observations and calculations, and reference to any
specifications (limits);
5. date(s) and reference number(s) of testing;
6. the initials of the persons who performed the testing;
7. the date and initials of the persons who verified the testing and the
calculations, where appropriate;
8. a clear statement of release or rejection (or other status decision) and the
dated signature of the designated responsible person.
• Written release and rejection procedures should be available for materials and
products, and in particular for the release for sale of the finished product by an
authorized person.
• Records should be maintained of the distribution of each batch of a product in
order, e.g. to facilitate the recall of the batch if necessary.
• Records should be kept for major and critical equipment, as appropriate, of any
validations, calibrations, maintenance, cleaning, or repair operations, including
dates and the identity of the people who carried these operations out.
• The use of major and critical equipment and the areas where products have been
processed should be appropriately recorded in chronological order.
• There should be written procedures assigning responsibility for cleaning and
sanitation and describing in sufficient detail the cleaning schedules, methods,
equipment and materials to be used and facilities and equipment to be cleaned.
Such written procedures should be followed.

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 GOOD PRACTICES IN PRODUCTION

Production operations must follow clearly defined procedures in accordance with

manufacturing and marketing authorizations, with the objective of obtaining products
of the requisite quality.

• All handling of materials and products, such as receipt and cleaning, quarantine,
sampling, storage, labeling, dispensing, processing, packaging and distribution,
should be done in accordance with written procedures or instructions and, where
necessary, recorded.

• Any deviation from instructions or procedures should be avoided as far as

possible. If deviations occur, they should be done in accordance with an approved
procedure. The authorization of the deviation should be approved in writing by a
designated person, with the involvement of the quality control department, when
appropriate.

• Operations on different products should not be carried out simultaneously or

consecutively in the same room or area unless there is no risk of mix-up or cross-
contamination.

• At all times during processing, all materials, bulk containers, major items of
equipment, and where appropriate, the rooms and packaging lines being used
should be labelled or otherwise identified with an indication of the product or
material being processed, its strength (where applicable) and the batch number.
Where applicable, this indication should also mention the stage of production. In
some cases it may be useful to record also the name of the previous product that
has been processed.

• Normally, non-medicinal products should not be produced in areas or with

equipment destined for the production of pharmaceutical products.

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• In-process controls are usually performed within the production area. The
performance of such in-process controls should not have any negative effect on
the quality of the product or another product (e.g. cross-contamination or mix-up).

• Contamination of a starting material or of a product by another material or

product must be avoided. This risk of accidental cross-contamination arises from
the uncontrolled release of dust, gases, particles, vapours, sprays or organisms
from materials and products in process, from residues on equipment, from
intruding insects, and from operators’ clothing, skin, etc.

• Cross-contamination should be avoided by taking appropriate technical or

organizational measures

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 GOOD PRACTICES IN QUALITY CONTROL

Quality control is the part of GMP concerned with sampling, specifications and testing,
and with the organization, documentation and release procedures which ensure that the
necessary and relevant tests are actually carried out and that materials are not released for
use, nor products released for sale or supply, until their quality has been judged to be
satisfactory. Quality control is not confined to laboratory operations but must be involved
in all decisions concerning the quality of the product.
• The independence of quality control from production is considered fundamental.
• Each manufacturer (the holder of a manufacturing authorization) should have a
quality control function. The quality control function should be independent of
other departments and under the authority of a person with appropriate
qualifications and experience, who has one or several control laboratories at his or
her disposal.
• Adequate resources must be available to ensure that all the quality control
arrangements are effectively and reliably carried out. The basic requirements for
quality control are as follows:--
1. adequate facilities, trained personnel and approved procedures must be
available for sampling, inspecting, and testing starting materials,
packaging materials, and intermediate, bulk, and finished products, and
where appropriate for monitoring environmental conditions for GMP
purposes;
2. samples of starting materials, packaging materials, intermediate products,
bulk products and finished products must be taken by methods and
personnel approved of by the quality control department;
3. qualification and validation must be performed;
4. records must be made (manually and/or by recording instruments)
demonstrating that all the required sampling, inspecting and testing
procedures have actually been carried out and that any deviations have
been fully recorded and investigated;

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 5. the finished products must contain ingredients complying with the
qualitative and quantitative composition of the product described in the
marketing authorization; the ingredients must be of the required purity, in
their proper container and correctly labelled;
6. records must be made of the results of inspecting and testing the materials
and intermediate, bulk and finished products against specifications;
product assessment must include a review and evaluation of the relevant
production documentation and an assessment of deviations from specified
procedures;
7. no batch of product is to be released for sale or supply prior to certification
by the authorized person(s) that it is in accordance with the requirements
of the marketing authorization. In certain countries, by law, the batch
release is a task of the authorized person from production together with the
authorized person from quality control;
8. sufficient samples of starting materials and products must be retained to
permit future examination of the product if necessary; the retained product
must be kept in its final pack unless the pack is exceptionally large.

• Quality control as a whole will also have other duties, such as to establish,
validate and implement all quality control procedures, to evaluate, maintain, and
store the reference standards for substances, to ensure the correct labelling of
containers of materials and products, to ensure that the stability of the active
pharmaceutical ingredients and products is monitored, to participate in the
investigation of complaints related to the quality of the product, and to participate
in environmental monitoring. All these operations should be carried out in
accordance with written procedures and, where necessary, recorded.

CERTIFICATES

Certificates must contain at least the following information:--

• identification (name and address) of the issuing supplier;

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• signature of the competent official, and statement of his or her qualifications;
• the name of the material tested;
• the batch number of the material tested;
• the specifications and methods used;
• the test results obtained;
• the date of testing.

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 QUALITY ASSURANCE STANDARDS

Quality Assurance Standard for ISO 9001

Quality assurance standard is a written set of instructions and guidelines followed by
various industries in order to maintain the quality of their products or services. Big as
well as small businesses adopt these quality standards worldwide and get certification
after audit from the authorized body that ensures the company and its manufacturing or
service delivery steps and procedures are in compliance with the laid down standards and
polices. This certification enhances the brand value of the organization, its products or
services and it also instills confidence in the customers. Some QA standard documents
are industry specific while some apply to all organizations. One such universal standard
that applies to all types of organizations is ISO 9001.

What Is ISO 9001

ISO stands for International Organization for Standardization. ISO standards for quality
are recognized worldwide and hence ISO certified organizations have far better
opportunities to trade in the international market. ISO 9001, quality assurance standard
can be followed by any kind of industry, whether it is service or manufacturing industry.
Each organization should develop its own quality management system in order to adhere
to ISO 9001 guidelines. To get ISO 9001 certification, the organization has to undergo
three audits. The first audit is conducted by the quality monitoring and inspection
professional from within the organization i.e. internal auditor. The second such audit is
conducted by the customers using the product or service in question, and the third audit is
conducted by the organization that is authorized to grant ISO certifications for quality
maintenance.

Benefits Of ISO 9001 2008

The ISO 9001 standard was first published in 1987. The latest edition of the standard is
ISO 90012008, which was released in December 2008. This edition has minor changes as
compared to the earlier one i.e., ISO 90012000.

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Systematic Approach
The standard helps the organizations to function in a more systematic manner. There are
defined systems, processes, and procedures in the organizations to do each and every
task. Teams are designated to perform these tasks. Hence, it results in more organized
and systematic approach to work which improves employee satisfaction and retention

Improved Quality
The systems are integrated in the whole organization to deliver good quality products or
services. This leads to improved quality and less rework. All this helps the organization
to reduce wastage and increase margins.

Customer Satisfaction
The customers trust the organizations that are ISO 9001 certified because this QA
standard certification offers a sort or an assurance of the good practices and systems in
organizations. When customers get good products or services in accordance to their
requirements, their loyalty towards the organization increases. This results in more
business for the organization. The profits of the organization also increase.

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 CONCLUSION

In evaluating data gathered and systematic analysis of the reports in the course of the
study regarding the impact of QUALITY ASSURANCE on corporate performance and
productivity in the Arch Vitalife laboratories, the following conclusion can be drawn: --

• There are signs that QUALITY ASSURANCE concepts improves the

performance of an organization in terms of cost reduction, increase in corporate
performance and productivity, profitability and market shares, competitiveness
and customer satisfaction;

• The concept of QUALITY ASSURANCE has been highly welcomed in the

company as a way of life for customer satisfaction, making the customer
delighted as well as staff and in achieving corporate goals and objectives.

• Finally, the importance of QUALITY ASSURANCE in achieving business

success can hardly be denied Quality is therefore the best assurance of customer
allegiance, strongest defence against competition and the only path to Sustained
company growth and earnings.

• Involvement of all members of the company in the system is crucial if

improvement in the performance and productivity is ever to be achieved with the
adoption of QUALITY ASSURANCE.

• Though, this is not easy to achieve but it must come from personal example and
commitment. In addition, there must be consistency in the system, as this can help
change the entire process and maintain the competitive edge which the company
seeks to attain.

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 RECOMMENDATIONS

Based on the research findings and the above conclusion, on the impact of QUALITY
ASSURANCE on corporate performance and productivity, the following are highly
recommended towards improving QUALITY ASSURANCE in the sector:

• The practice of QUALITY ASSURANCE should be regarded as an activity. As

long as there are new ideas, innovations, developments, there should be no end to
QUALITY ASSURANCE process, so as to be able to cope with the dynamism of
the modern world;

• There is need for top management to be more committed to QUALITY

ASSURANCE, as well as providing an enabling environment to incorporate all
within the system in the QUALITY ASSURANCE process. Similarly, there
should be QUALITY ASSURANCE awareness campaign a well as QUALITY
ASSURANCE meetings where programmes/ideas can always be discussed.

• The company should intensify efforts on cost reduction exercise. This can be
done by providing regular staff training programmes for the staffs as this will
help increase their knowledge, skills and prepare them for future challenges

The benefits of QUALITY ASSURANCE should not be over stated , rather the whole
quality effort should be dedicated to and judged by predetermined results. Hence, there
should be reasonable focus in setting strategic objectives and building organizational
routing that link many units and levels as much as possible. And there should be no
organizational barriers between departments and managerial operational procedure within
the company.

• The QA approach to any process should be based on the requirements of

external customers for the sake of their satisfaction because if the QUALITY

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 ASSURANCE activities are not geared towards customers’ satisfaction, the
concept will fail.
• Finally, management of organizations, irrespective of size, structure, and
operations should bear in mind that success only comes to firms that can fully
internalize and adopt QUALITY ASSURANCE strategies to their own business
environment. It is only those that maximize quality to their customers while at the
same time meeting the needs of its staffs that will succeed.
• It must also be borne in mind, that it is not just implementation of QUALITY
ASSURANCE that matters. The recipes for success require enhanced
organizational staff cooperation for improved customers/clients satisfaction. This
is what adds to product and quality services, reduces or increases revenue.
• Internalization of QUALITY ASSURANCE strategies is also the recipes that
provide long-term approach to improving shareholders value by ensuring
corporate survival and growth. Success requires the company literally builds
customers needs and expectations (including meeting of these needs and
expectation) into daily organizational routines with the aim of enhancing
corporate performance and increase productivity in the market.

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 References

BOOKS

• Godfrey, A. B., "Juran's Quality Handbook", 1999

• Ishikawa, Kaoru. 1982.Guide to Quality Control. Tokyo: Asian Productivity

Organization

• James & james, 2001 “Total quality”, south western

• Dale H. Besterfield, “Quality Control”

WEBSITES

• www.qualityassurancemag.com

• www.quality-assurance-solution.com

• http://www.asq.org/

• www.archvitalife.com

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