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Veterinary vaccine testing and approval
Dr. Surajit Baksi
M. V. Sc., P. G. D. B. A. & Ph. D.
HESTER BIOSCIENCES LIMITEDwww.hester.in
• Testing and approval of the vaccines in India are crucialparts of manufacturing facilities.
• All the vaccines need to be tested strictly as per thepharmaceutical monographs and also to be exported asper the guidelines of international monographs.
• Following is the list of Indian and international guidelinesspecially emphasizing the testing of veterinary vaccines.
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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
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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
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Raw materials
SPF eggs/ Cell lines
Chemicals
Packing materials
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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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Chemicals testing
Description as per I.P./B.P./E.P./U.S.P
Solubility
Identification
Purity test (Assay)
Other physical and chemical parameters
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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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Packaging materials testing
Physical observation-
Size and weight
Mouth diameter
Body diameter
Total height
Neck height
Autoclave test-
Shape
Size
Colour
pH
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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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Inactivated antigen testing
Inactivation study
Sterility test
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Testing during blending
Swab test of all devices used in blending
Plate exposure in blending premises
Sterility testing of bulk
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Final product live vaccine
1. Identification test/ detection of extraneous pathogens bychicken 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/animalsof age and route prescribed in pharmacopoeia
Animals are observed for up to 21 days
No clinical signs and adverse effects attributable to vaccinestrain should be observed in the period
Inactivated vaccine-
Vaccines are inoculated in up to 2 doses in birds/animals ofage and route prescribed in pharmacopoeia
Animals are observed for up to 21 days
No clinical signs and adverse effects attributable to vaccinestrain should be observed in the period
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Potency test
Live vaccine-
One dose of vaccine is inoculated inbirds/animals of age and route prescribed inpharmacopoeia
Birds/animals are challenged as prescribed inpharmacopoeia and observed for up to 21 days
Vaccinated animals should be protected from thedisease and control animals should developdisease during observation period
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Potency test
Inactivated vaccine-
One dose of vaccine is inoculated inbirds/animals of age and route prescribed inpharmacopoeia
Birds/animals are challenged as prescribed inpharmacopoeia and observed for up to 21 days
Vaccinated animals should be protected from thedisease and control animals should developdisease during observation period
For many vaccines, serology test is alsoperformed after collecting blood samples fromthe vaccinated birds
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Serology test
Serology test is also performed after collecting bloodsamples from the vaccinated birds for many of theinactivated vaccines
After collecting blood samples post vaccination as perprescibed days in pharmacopoeia, serum isseparated
Haemagglutination-Inhibition, Agar Gel Precipitationor ELISA tests are perfomed to estimate specificantibodies produced against the vaccine antigen
Antibody titre is measured for passing limit mentionedin guidelines
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Formaldehyde estimation
Free formaldehyde of inactivated vaccines should not bemore than 0.05 % w/v
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Qualities of good emulsion
Homogeneous fine particles
Brownian movement
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Observation of good emulsion under microscope
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Observation of bad emulsion under microscope
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Moisture content
Moisture percentage of live vaccines should not be morethan
3.0 % w/w
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Pharmacopoeia Compliance for Live Vaccines
In-houseTest 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
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Inactivated Vaccines QC Testing Protocols
Pharmacopoeia Compliance for Inactivated Vaccines
In-houseTest 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
√ √ √ √ √
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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) andapplication for No Objection Certificate (NOC) is to besent to Department of Animal Husbandry, Dairying andFisheries (DADF).
• Apply for Test license (Form-30) to DCGI after gettingImport license and NOC.
• DCGI will provide test license (Form-29) for the vaccineand DADF will provide NOC for the same.
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General procedure for approval of veterinary vaccines
• Under test license, manufacturer has to manufacture 3test batches. These batches are tested as per theguidelines of pharmacopoeia, GMP and GLP. The testrecords are documented.
• After submitting application (Form-44) with results oftest batches, DCGI may give market authorization(Form-46).
• Under market authority, manufacturer will produceanother 3 commercial batches which are to be againtested and documented.
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General procedure for approval of veterinary vaccines
• After results are reported, DCGI may endorse thelicense of the vaccine to the manufacturer.
• Once, license has been endorsed by DCGI, samples ofbatches have to be submitted to Indian VeterinaryResearch Institute (IVRI).
• Manufacturer can sell the vaccine to market, once thebatch is passed from IVRI.
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Thank you
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