2. HESTER BIOSCIENCES LIMITED
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• Testing and approval of the vaccines in India are crucial
parts of manufacturing facilities.
• All the vaccines need to be tested strictly as per the
pharmaceutical monographs and also to be exported as
per the guidelines of international monographs.
• Following is the list of Indian and international guidelines
specially emphasizing the testing of veterinary vaccines.
3. HESTER BIOSCIENCES LIMITED
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Indian Pharmacopoeia, 2014
British Pharmacopoeia, 2016
European Pharmacopoeia, 8th edition
US Pharmacopoeia, 2016
Japanese Pharmacopoeia, 17th edition
Title 9 of Code of Federal Regulations
OIE manual for vaccines, 2016
4. HESTER BIOSCIENCES LIMITED
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Quality control measures used in manufacturing of
Vaccines
• Testing of raw and packaging materials
• Testing of in-process materials
• Testing of final product
6. HESTER BIOSCIENCES LIMITED
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SPF egg testing
Weight of the eggs
Quality of the egg shell e.g. porosity and thickness of shell
Fertility of the eggs
Egg surface swab test
Egg incubator environment monitoring
Cell line testing
Quality of cells
Mycoplasma contamination test
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Testing of water used in manufacturing
Appearance, Colour, Odour, Taste
pH, Conductivity, TOC
Acidity and alkalinity
Ammonium, calcium, magnesium, heavy metal, chloride,
nitrate and sulphate test.
Microbial testing for total bacterial and coliform count.
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In-process testing
Sterility testing of media, stabilizer, adjuvant, bulk
Sterility testing of inoculums
Environment monitoring through air sampler
Finger dab, contact plate testing
Settle plate exposure during critical activities
Swab tests
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Live antigen testing
Sterility test
Titration of virus by EID 50 or TCID 50
Titration of bacteria by CFU
Detection of mycoplasma contamination
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Final product live vaccine
1. Identification test/ detection of extraneous pathogens by
chicken embryo inoculation test/ virus inactivation study
2. Sterility test
3. Titre estimation by CFU or EID 50 or TCID 50
4. Safety test
5. Potency test
6. Moisture determination
7. Detection of mycoplasma contamination
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Final product inactivated vaccines
1. Sterility test
2. Monitoring for extraneous antigen in SPF chicks
3. Safety test
4. Potency test
5. Serology test
6. Formaldehyde estimation
7. Emulsion test
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Safety test
Live vaccine-
Vaccines are inoculated in up to 10 doses in birds/animals
of age and route prescribed in pharmacopoeia
Animals are observed for up to 21 days
No clinical signs and adverse effects attributable to vaccine
strain should be observed in the period
Inactivated vaccine-
Vaccines are inoculated in up to 2 doses in birds/animals of
age and route prescribed in pharmacopoeia
Animals are observed for up to 21 days
No clinical signs and adverse effects attributable to vaccine
strain should be observed in the period
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Potency test
Live vaccine-
One dose of vaccine is inoculated in
birds/animals of age and route prescribed in
pharmacopoeia
Birds/animals are challenged as prescribed in
pharmacopoeia and observed for up to 21 days
Vaccinated animals should be protected from the
disease and control animals should develop
disease during observation period
18. HESTER BIOSCIENCES LIMITED
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Potency test
Inactivated vaccine-
One dose of vaccine is inoculated in
birds/animals of age and route prescribed in
pharmacopoeia
Birds/animals are challenged as prescribed in
pharmacopoeia and observed for up to 21 days
Vaccinated animals should be protected from the
disease and control animals should develop
disease during observation period
For many vaccines, serology test is also
performed after collecting blood samples from
the vaccinated birds
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Serology test
Serology test is also performed after collecting blood
samples from the vaccinated birds for many of the
inactivated vaccines
After collecting blood samples post vaccination as per
prescibed days in pharmacopoeia, serum is
separated
Haemagglutination-Inhibition, Agar Gel Precipitation
or ELISA tests are perfomed to estimate specific
antibodies produced against the vaccine antigen
Antibody titre is measured for passing limit mentioned
in guidelines
25. HESTER BIOSCIENCES LIMITED
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Pharmacopoeia Compliance for Live Vaccines
In-house
Test Protocols
9CFR (2014)
EU
Pharmacopoeia
(Volume 8.0)
Indian
Pharmacopoeia
Vet. (2014)
British
Pharmacopoeia
Vet. (2015)
OIE Manual of
Diagnostic Tests
& Vaccines for
Terrestrial
Animals
Physical
Parameter
√ √ √ √ √
Identification
Test
√ √ √ √ √
Titre Estimation √ √ √ √ √
Sterility Test √ √ √ √ √
Safety Test √ √ √ √ √
Moisture
Determination
√ √ √ √ √
Detection of
Mycoplasma
Contamination
√ √ √ √ √
Live Vaccines QC Testing Protocols
26. HESTER BIOSCIENCES LIMITED
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Inactivated Vaccines QC Testing Protocols
Pharmacopoeia Compliance for Inactivated Vaccines
In-house
Test Protocols
9CFR (2014)
EU
Pharmacopoeia
(2014)
Indian
Pharmacopoeia
(2014)
British
Pharmacopoeia
(2015)
OIE Manual of
Diagnostic Tests
& Vaccines for
Terrestrial
Animals
Physical
Parameters
√ √ √ √ √
Identification
Tests
√ √ √ √ √
Sterility √ √ √ √ √
Safety √ √ √ √ √
Potency √ √ √ √ √
Residual
Formaldehyde Test
√ √ √ √ √
27. HESTER BIOSCIENCES LIMITED
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General procedure for approval of veterinary
vaccines
• Apply (Form -12) for the import license (Form-11)
from Drug Controller General of India (DCGI) and
application for No Objection Certificate (NOC) is to be
sent to Department of Animal Husbandry, Dairying and
Fisheries (DADF).
• Apply for Test license (Form-30) to DCGI after getting
Import license and NOC.
• DCGI will provide test license (Form-29) for the vaccine
and DADF will provide NOC for the same.
28. HESTER BIOSCIENCES LIMITED
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General procedure for approval of veterinary
vaccines
• Under test license, manufacturer has to manufacture 3
test batches. These batches are tested as per the
guidelines of pharmacopoeia, GMP and GLP. The test
records are documented.
• After submitting application (Form-44) with results of
test batches, DCGI may give market authorization
(Form-46).
• Under market authority, manufacturer will produce
another 3 commercial batches which are to be again
tested and documented.
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General procedure for approval of veterinary
vaccines
• After results are reported, DCGI may endorse the
license of the vaccine to the manufacturer.
• Once, license has been endorsed by DCGI, samples of
batches have to be submitted to Indian Veterinary
Research Institute (IVRI).
• Manufacturer can sell the vaccine to market, once the
batch is passed from IVRI.
