“QUALITY CONTOL”

DEPARTMRNT

From

SERUM INSTITUTE of INDIA Ltd.

Training report submitted to University of Rajasthan, Jaipur in partial
fulfillment of the requirement for the degree of

Bachelor of Science in BIOTECHNOLOGY

Submitted by:

Miss Anamika Sud

Seedling Institute for Integrated Learning &

Advanced Studies, Jaipur, 2008
 CERTIFICATE-I

This is to certify that Anamika Sud has successfully completed

the Industrial Training from the “Quality Control” Department of
SERUM INSTITUTE OF INDIA Ltd. Her training report is
satisfactory for submission in partial fulfillment of the requirement
for B.Sc /M.Sc (Biotechnology) Integrated-IIIrd year of the
University of Rajasthan, Jaipur.

Supervisor
 CONTENTS

1. SPECIFICATION

2. DESIGN OF INDUSTRY

3. MANAGEMENT

4. PRODUCTS

5. MACHINE TYPE

6. ENVIRONMENT

7. QUALITY CONTROL

8. FACILITIES

9. MARKETING
 SPECIFICATION

1. LOCATION: SERUM INSTITUTE OF INDIA LTD.

212/2, Hadapsar,
Off Soli Poonawalla Road,
Pune-411028. INDIA

2. TYPE: Semi – govt.

3. SMALL SCALE/LARGE SCALE: Large scale

4. Pvt. Ltd

5. YEAR OF INSTALLING: 1966

Serum Institute is recognized as a reliable source of High Quality vaccines and

biological products. Their products have been supplied to International Health Agencies
like the WHO, UNICEF, PAHO and also to more than 140 countries across the globe.
The high service standards have resulted in several acknowledgements and
appreciation from International agencies and local governments and awards from Trade
authorities.

The production facilities of Serum Institute have the best in terms of equipment and
human resources; essential to ensure high quality vaccines. An interesting in-built
mechanism of continuous improvement is by practicing the concept of Quality Circles. It
empowers and encourages the employees at the grass-root level and at the same time
brings about upgradation of quality of all fronts. The case studies of our Quality Circles
have won many awards not only at State and national levels but also at the International
Level.
 DESIGN OF INDUSTRY
Serum Institute of India Ltd. has established it's self as the world's largest producer of Measles

and DTP group of vaccines. It is estimated that two out of every three children immunized in the

world is vaccinated by a vaccine manufactured by Serum Institute. In fact, their range of

products has been used in 140 countries across the globe.

Serum Institute of India was founded in 1966 with the aim of manufacturing life-saving immuno-

biologicals, which were in shortage in the country and imported at high prices. Thereafter,

several life-saving biologicals were manufactured at prices affordable to the common man and

in abundance, with the result that the country was made self-sufficient for Tetanus Anti-toxin

and Anti-snake Venom serum, followed by DTP (Diphtheria, Tetanus and Pertussis) group of

Vaccines and then later on MMR (Measles, Mumps and Rubella) group of vaccines. The

Philanthropic philosophy of the company still not only exists but has been proliferated to bring

down the prices of newer vaccines such as Hepatitis-B vaccine, Rabies vaccine, Combination

vaccine etc., so that not only Indian's, but the entire under- privileged children of the world, in

more than 140 countries are protected from birth onwards.

Serum Institute of India has recently set up Serum Bio Pharma Park, India's first biotech Special

Economic Zone (SEZ). The Park is adjoining Serum Institute's existing manufacturing unit and is

a sector-specific SEZ meant for biotechnology and pharmaceutical products. The SEZ will allow

Serum Institute of India to avail various tax benefits such as income tax, import duty on capital

goods etc. This has encouraged a lot of foreign companies to partner with Serum Institute of

India to avail and share these benefits.

The Industry is divided into following sections:-

1. PRODUCTION SECTION
• Hepatitis-B, Combo-vaccines, Polysaccharide Conjugate vaccine.
• Biosimilar protein {EPO, GCSF, IFN}
• Viral vaccines{Rabies}, Bacterial Vaccines, Anti-cancer products

2. QUALITY CONTROL LABORATORY

3. SPECIAL ECONOMICAL ZONE [SEZ]

4. MICROBIOLOGY LAB {Media preparation/ Sterilization}

5. ENVIRONMENTAL MONITORING DEPARTMENT

6. IN-PROCESS & FINISHED PRODUCT TESTING

7. ANIMAL HOUSE

8. PACKAGING DEPARTMENT

9. SALES AND MARKETING SECTION

 MANAGEMENT

CADRE

CHAIRMAN & MANAGING DIRECTOR

Dr. CYRUS S POONAWALLA

Executive Director, Operations

Mr. ADAR C POONAWALLA

International Marketing Division

Mr. S.M. Dodwadkar

Domestic Marketing Division

Mr. Masad Ahmed

Finance Division
Mr. Satish Deshpande

Human Resources
Mr. Rammesh Patil

MICROBIOLOGY LAB
Dr. A.G. Gawande

ENVIRONMENTAL MONITORING
 Mr. K.B. Satpute
Mr. A.V. Pereira

Bacterial Vaccines Viral Vaccines

Below is a list of products that Serum Institute intends to manufacture in the near future.

Vaccines

• Meningococcal A Conjugate Vaccine

• Meningitis A, Y, C, W-135 Quadrivalent Vaccine
• Bladder Cancer Vaccine
• Pneumococcal Polysaccharide & Conjugate Vaccine

Recombinant Products

• Recombinant Granulocyte Colony Stimulating Factor

• Interferon Alpha
• Recombinant Erythropoietin

Production department referred to the area where all the vaccines components were
produced from their microbial or viral sources. All the vaccine components had their
specific production departments, where they were extracted from their respective
sources. The production facilities of Serum Institute have the best in terms of equipment
and human resources; essential to ensure high quality vaccines. The manufacturing
facilities conform to WHO current Good Manufacturing Practice (cGMP) requirements
and are approved by WHO, Geneva. The unique large bioreactors for DTP group of
vaccines have a huge batch size to produce millions of doses.
The company also produces hundreds of millions of doses of the Measles, Mumps and
Rubella group of vaccines annually. Serum Institute meets 100 % requirements for
Measles vaccine of the Government of India and also the global requirements.
An interesting in-built mechanism of continuous
improvement is by practicing the concept of Quality Circles. It empowers and
encourages the employees at the grass-root level and at the same time brings about
upgradation of quality of all fronts. The case studies of our Quality Circles have won
many awards not only at State and national levels but also at the International Level.

It goes without saying that Serum Institute's work ethic ensures that every safeguard is
instituted, every norm of cGMP is scrupulously observed, and every procedure followed.
Among the latest acquisitions is the state-of-the-art EDP system, which provides instant
information on every aspect of production, from stocks, inventory, quantity of vaccines
in the pipeline, Q.C. results of each batch, to sales, product dispatch and destinations.

MACHINE TYPE

Continuous Plasmapheresis Machine

This is a fully computerized blood separator designed for humans. Concern for the
health and well-being also of animals has prompted Serum Institute scientists to modify
the machine and adapt it for animals. Serum Institute is the first and only laboratory in
the world where the Cobe Spectra is used for plasmapheresis of immunized equines.

Recombinant Vaccine Production

State-of-the-art Recombinant Vaccine Manufacturing Facility

It’s in our DNA! Required for producing vaccines needing high end technology at a high
level of quality.
 Rabies Vaccine Manufacturing
Because there is No Second Chance! The scientists toiled to develop affordable 'Gold
Standard' HDC rabies vaccine with a unique advantage - adsorption.

Lyophilisation
Serum Institute has the largest computerized facility in India for Lyophilisation of
parenterals; this complex process of freeze-drying is universally accepted as the best
option for the preservation of biologicals. It increases the shelf-life and stability of the
products.

Robotic Arm
Every advancement is quickly adopted like using Robots to handle our tissue culture -
they are efficient with no room for error.
 ENVIRONMENT
POLLUTION CONTROL

Serum Institute considers the protection of the environment as direct responsibility and
all processes and technologies incorporate this feature. A clean and a green
environment is an absolute necessity and they ensure this by using state-of-the-art
Effluent Treatment Plant for all the waste generated. Its sprawling green campus
houses a large percentage of employees.

Environment

(1) The immediate surroundings shall be free from refuse, rubbish, overgrown
vegetation, and waste materials, to prevent harborage of rodents, insects, and other
vermin.

(2) A suitable drainage system shall be provided which will allow rapid drainage of all
water from plant buildings and driveways including surface water around the plant and
on the premises and all such water shall be disposed of in such a manner as to prevent
an environmental or health hazard.

Pollution Prevention and Control

Good pollution prevention practices in the drug industry include:
• Reduction of product losses by better production control.
• Use of disposable packaging instead of bottles where feasible.
• Optimization of use of water and cleaning chemicals; recirculation of cooling waters.
• Segregation of effluents from sanitary installations, processing, and cooling (including
condensation) systems; this facilitates recycling of wastewater.
• Use of high-pressure nozzles to minimize water usage.

Industry Description and Practices

The industry involves manufacturing of drugs such as vaccines, antibiotics,

antibacterials, Immuno-biologicals and Pharmaceuticals.
Treatment Technologies
Treatment of effluents consists of screening, flow equalization, neutralization,
and air flotation; it is normally followed by biological treatment. If space is available, land
treatment or pond systems are potential treatment methods. Other possible biological
treatment systems include trickling filters, rotating biological contactors, and activated
sludge treatment. Pretreated dairy effluents can be discharged to a municipal sewerage
system, if capacity exists, with the approval of the relevant authority. Odor control by
ventilation and scrubbing may be required.

Monitoring and Reporting

Monitoring of the final effluent for the parameters listed above is carried out at least
once per month or more frequently if the flows vary significantly. Monitoring data is
analyzed and reviewed at regular intervals and compared with the operating standards
so that any necessary corrective actions can be taken. Records of monitoring results
are to be kept in an acceptable format. The results are reported to the responsible
authorities and relevant parties, as required.

Effluent Treatment Plant –

This plant is helpful in reducing operating costs and environmental pollution.

Most companies operate effluent treatment plants to reduce the potential for pollution of
receiving waters and to comply with discharge consent conditions. Effective
management and control of the processes used for effluent treatment will help you to:

o Reduce your operating costs and thus increase profits.

o Achieve more effective compliance with legislation.
o Improve your company's public image

Pollution Prevention and Control

Every effort should be made to replace highly toxic and persistent ingredients with
degradable and less toxic ones.
Recommended pollution prevention measures are as follows:
• Meter and control the quantities of active ingredients to minimize wastage.
• Reuse by-products from the process as raw materials or as raw material substitutes in
other processes.
• Recover solvents used in the process by distillation or other methods.
• Give preference to the use of nonhalogenated solvents.
• Use automated filling to minimize spillage.
• Use “closed” feed systems into batch reactors.
• Use equipment washdown waters and other process waters (such as leakages from
pump seals) as makeup solutions for subsequent batches.
• Recirculate cooling water.
• Use dedicated dust collectors to recycle recovered materials.
• Vent equipment through a vapor recovery system.
• Use loss-free vacuum pumps.
• Return toxic materials packaging to the supplier for reuse, or incinerate/destroy it in an
environmentally acceptable manner.
• Minimize storage time of off-specification products through regular reprocessing.
• Find productive uses for off-specification products to avoid disposal problems.
• Minimize raw material and product inventory to avoid degradation and wastage.
• Use high-pressure hoses for equipment cleaning to reduce wastewater.
•Provide storm water drainage and avoid contamination of storm water from process
areas.

Pollution Reduction Targets

Implementation of cleaner production processes and pollution prevention measures can
yield both economic and environmental benefits. Specific reduction targets for the
different processes have not been determined. In the absence of specific pollution
reduction targets, new plants should always achieve better than the industry averages
quoted in the section on Waste Characteristics.
Vapor recovery systems should be installed to control air emissions. Wastewaters and
treated effluents should be recycled to the extent feasible
 QUALITY CONTROL
Serum Institute is recognized as a reliable source of High Quality vaccines and
biologicals. Our products have been supplied to International Health Agencies like the
WHO, UNICEF, PAHO and also to more than 140 countries across the globe. The high
service standards have resulted in several acknowledgements and appreciation from
International agencies and local governments and awards from Trade authorities.

Quality is the buzzword. The assurance of quality starts from the Raw Material itself as
soon as it enters the premises. It goes without saying that Qualification studies are
mandatory for all equipment and all production and analytical procedures are validated.
The stringency of control can be adjudged by the challenge that the production of
Measles vaccine poses, as it is totally preservative free.

The Quality Assurance department is well equipped with a huge investment in men and
machines. The entire process is managed with the State-of-the-art EDP system, which
controls and provides instant information on every aspect of Production and Quality
Control. The QC of massive batches of MMR and DTP group of vaccines is a challenge
in itself. All this has been possible with the high work ethic that ensures that every
safeguard is instituted and every norm of cGMP is scrupulously followed.

Regular training of our 64 FDA approved Production experts and 45 FDA approved
Testing experts through continuous professional development has played a significant
role in this direction. Many of our experts are regularly sent for training to USA, UK,
France, Netherlands, etc. This ensures that the latest advances in production and
quality testing standards are quickly incorporated in our processes.

Complementing our team of competent and experienced personnel is the wide array of
sophisticated analytical equipment. With this, scientists have developed and adapted
special tests, ensuring Total Quality Management.
 Quality control (QC) is a procedure or set of procedures intended to ensure that
a manufactured product or performed service adheres to a defined set of quality criteria
or meets the requirements of the client or customer. The quality control unit is defined
as the Lab where testing of sample is done. The dairy Quality Control Unit was
established in 1908. SERUM has a modern, fully-equipped laboratory. They conduct
tests including biological, chemical, physical, labeling, packaging, organic and inorganic
contamination for drugs and Services are used by drug manufacturers, associations,
government and non government institutions. Some of the tests been performed are:

Bacterial Endotoxin Test by Kinetic Turbidometric Test

The LAL (Limulus Amoebocyte test Lysate) test is the most sensitive and specific
method available to detect and measure Endotoxin, a fever producing by-product of
G-ve bacteria commonly known as Pyrogen. Endotoxin initiates opaque gel by
modifying coagulogen, a clotting protein in LAL to form an insoluble matrix.

Preparation of Control Std. Endotoxin (CSE)

↓
Dilution of CSE for Std. curve- 5.0EU/ml, 0.5EU/ml, 0.05EU/ml
↓
Preparation of LAL
↓
Preparation of Sample Dilution

Dilution = Sample potency (mg/ml) X Endotoxin limit (EU/mg)

Mid point/ lowest conc. of Std. curve
Spore Count
Culture content was added to sterile Tween 80 solution
↓
Homogenized by a metal spatula
↓
Solution was poured in a stock container
↓
A serial dilution of spore suspensions was prepared with 0.01% of Tween 80 solution
↓
Cover of the counting chamber was applied so that both counting areas to be covered
↓
A drop of suspensions was spread over both niches of the counting camber with the
help of pipette
↓
The counting chamber was fitted on the microscope table and the objective
Lens (10x and 40x) was adjusted
↓
Image was focused on overlapped lines under the objective lens
↓
Only the spores dwelling within the 25 squares of counting area was counted
↓
The spore number of each side of the counting chamber was recorded
↓
200 spores were selected for counting

Formula Used:
Spores per ml (N) = Z x 1/10 -4 x 1/Y
Where, Z = average of spores count / 16 small squares
10 -4 = overall volumes of 25 squares of the Neubauers counting chamber (ml)
Y = utilized dilution
 FACILITIES

Poonawalla Stud Farms was established (as the Poona Stud Farm) in 1946 by the late
Soli. A. Poonawalla with approximately a dozen mares and one stallion, Fitz Clarence
(GB). From its very first crop the farm produced the Indian 2000 Guineas winner in
Fitzcall. Today, Poonawalla Stud Farms stands as the Leading Stud Farm in the
country, with 8 "Champion Breeders' Awards", 4 times in successive years since the
awards' inception only 13 years ago. Among other numerous achievements, the farm
has bred 305 Classic winners (all India) to date December 2008, including winners of 8
Indian Derbies and 64 Indian Classics. It is the highest stakes earning establishment in
the country with over 237 home breeds earning stakes in excess of Rs. 1 million.

School: Education is the cradle of a successful developing nation and Serum

committed to it by managing an educational trust.

Recreation /Sports: Serum offers diverse recreational facilities for the employees and
their families. A well-equipped gymnasium is available inside the township. From
playing table tennis, badminton, lawn tennis and cricket, employees can do just what
they like to get fresh and rejuvenated. Serum also organizes ‘Intra Company' sports
events from time to time. Since the very inception, the Serum has built houses, parks,
schools and market for the employees, their families and others residing nearby. The
beautiful Landscape of Township covers huge area and has quarters for all its
employees. Modern amenities such as Gas Pipeline, electricity, water, sanitation and
welfare facilities like super markets, Educational institutions, near by it has a well
equipped hospital, cricket ground, parks, post office, ATMs, Banks etc make the
township self sufficient. Guesthouse facility is also provided for the outsiders. As
corporate office is inside the township, the commutation has made the life far simpler for
Serum employees. They also have Employees' cooperative society, which provides
loans at subsidized rate of interest on contribution of monthly amount.
ACHIEVEMENTS

Several official awards and marks of recognition have been showered on Serum Institute of
India.

• Certificate of Merit awarded by CHEMEXCIL, Mumbai, for outstanding export

performance in 1994-95.
• First Award under the Drugs and Pharmaceuticals panel from CHEMEXCIL, Mumbai, for
sterling export performance in 1995-96.
• Certificate for Export Recognition (1st Rank) under the Export House category, from the
Government of Maharashtra for export achievement in 1996-97.
• Vikas Bharati Award received in 1997 from International Council for Business Promotion,
New Delhi, for outstanding achievements and contribution in the chosen field of
activities, towards promotion and maintaining quality and standard of products/ services
through innovative strategies.
• Certificate of Merit awarded by the Government of India, Ministry of Commerce for
outstanding export performance in 1996-97.

Export Excellence Award for 1996-97 and 1997-98 awarded to TOP TEN EXPORTERS from
Pune Region by the Joint Director General of Foreign Trade, Pune and Mahratta Chamber of
Commerce, Industries and Agriculture

The Health-education Film "Snakebite" is a blend of action-packed drama,

interesting information and stunning snake photography that enthralls and educates.
Superstitions and ignorance continue to kill thousands of victims of snakebite and unfortunately,
life-saving Anti-Snake Venom Serum remains virtually unknown and unavailable in rural India.
The lore, the mystery, the facts and the demystification of snakes and snakebites have all been
captured in "Snakebite". The message is that the best protection is knowledge.

The film has won several prestigious awards:

• The "Best Professional" film award at the Ninth International Film Festival held in U.S.A.
in 1986:
• The British Medical Association Film Competition Gold Award in 1987;
• The Cine Golden Eagle Award by the Council on International Non-theatrical Events,
1987