veterinary vaccine testing and approval

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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