Appendix XV K (Vet) 2. Evaluation of Efficacy of Veterinary Vaccines and Immunosera

The term ‘product’ means either a vaccine or an immunoserum throughout the text.

During development of the product, tests are carried out to demonstrate that the product is efficacious when administered by each of the recommended routes and methods of administration and using the recommended schedule to animals of each species and category for which use of the product is to be recommended. The type of efficacy testing to be carried out varies considerably depending on the particular type of product.

As part of tests carried out during development to establish efficacy, the tests described in the Production section of a monograph may be carried out; the following must be taken into account.

The dose to be used is that quantity of the product to be recommended for use and containing the minimum titre or potency expected at the end of the period of validity.

For live vaccines, use vaccine containing virus/bacteria at the most attenuated passage level that will be present in a batch of vaccine.

For immunosera, if appropriate, the dose tested also contains minimum quantities of immunoglobulin or gammaglobulin and/or total protein.

The efficacy evidence must support all the claims being made. For example, claims for protection against respiratory disease must be supported at least by evidence of protection from clinical signs of respiratory disease. Where it is claimed that there is protection from infection this must be demonstrated using re-isolation techniques. If more than one claim is made, supporting evidence for each claim is required.

Vaccines The influence of passively acquired and maternally derived antibodies on the efficacy of a vaccine is adequately evaluated. Any claims, stated or implied, regarding onset and duration of protection shall be supported by data from trials.

Claims related to duration of immunity are supported by evidence of protection. The test model described under Immunogenicity and/or Potency is not necessarily used to support claims regarding the duration of immunity afforded by a vaccine.

The efficacy of each of the components of multivalent and combined vaccines shall be demonstrated using the combined vaccine.

Immunosera Particular attention must be paid to providing supporting data for the efficacy of the regime that is to be recommended. For example, if it is recommended that the immunoserum needs only to be administered once to achieve a prophylactic or therapeutic effect then this must be demonstrated. Any claims, stated or implied, regarding onset and duration of protection or therapeutic effect must be supported by data from trials. For example, the duration of the protection afforded by a prophylactic dose of an antiserum must be studied so that appropriate guidance for the user can be given on the label.

Studies of immunological compatibility are undertaken when simultaneous administration is recommended or where it is a part of a usual administration schedule. Wherever a product is recommended as part of an administration scheme, the priming or booster effect or the contribution of the product to the efficacy of the scheme as a whole is demonstrated.

LABORATORY TESTS

In principle, demonstration of efficacy is undertaken under well-controlled laboratory conditions by challenge of the target animal under the recommended conditions of use.

In so far as possible, the conditions under which the challenge is carried out shall mimic the natural conditions for infection, for example with regard to the amount of challenge organism and the route of administration of the challenge.

Vaccines Unless otherwise justified, challenge is carried out using a strain different from the one used in the production of the vaccine.

If possible, the immune mechanism (cell-mediated/humoral, local/general, classes of immunoglobulin) that is initiated after the administration of the vaccine to target animals shall be determined.

Immunosera Data are provided from measurements of the antibody levels achieved in the target species after administration of the product, as recommended. Where suitable published data exist, references are provided to relevant published literature on protective antibody levels and challenge studies are avoided.

Where challenges are required, these can be given before or after administration of the product, in accordance with the indications and specific claims to be made.

FIELD TRIALS

In general, results from laboratory tests are supplemented with data from field trials, carried out, unless otherwise justified, with untreated control animals. Provided that laboratory tests have adequately assessed the safety and efficacy of a product under experimental conditions using vaccines of maximum and minimum titre or potency respectively, a single batch of product could be used to assess both safety and efficacy under field conditions. In these cases, a typical routine batch of intermediate titre or potency may be used. Where laboratory trials cannot be supportive of efficacy, the performance of field trials alone may be acceptable.