ANNEX II

Technical requirements for supply of concentrated inactivated monovalent foot-and-mouth disease virus antigen and its formulation into vaccine 1. Availability of concentrated inactivated antigen suitable for storage in liquid nitrogen, or by a method giving at least equivalent stability. 2. Availability of antigen corresponding to each of the sub-types specified in Annex I. The antigen must also be suitable for the preparation of oil emulsion vaccines for pigs, in which case ;/6 of a dose volume must protect at least 5 out of 10 pigs if challenged by intrapodal injection of 1 000 ID50. 3. Full information should be provided on the tests conducted by the producer on seed virus, cells and other materials used in the production. Samples of each master seed virus must be submitted to the CCI for confirmatory tests of identity and purity. Samples of the cells used to produce the virus should be submitted to the CCI. 4. The manufacture and quality of antigen must be consistent with the generally accepted standards for good manufacturing practice in Europe. The vaccines to be produced on the basis of the antigen must comply with the requirements of the European Pharmacopoeia. In addition: the antigen shall have been inactivated before concentration using a first order inactivant. For each batch of antigen the kinetics of inactivation must be followed and documented by the producer. The range of inactivation must be such that the batch as a whole is free from infective virus, and the safety margin should be in the range of about 3 log10 (based on extrapolation); and (b) the mixture of virus preparation/inactivant must have been transferred to a second sterile container when half of the inactivation time has elapsed in such a manner as to prevent contamination; an equivalent method could, however, be acceptable; and (c) subsequent processing of the antigen should be carried out in a non-contaminated environment (FMD virus free). Polyethyleneglycol (PEG) precipitation, polyethyleneoxide (PEO) precipitation, ultrafiltration or a combination of these are permitted methods for the concentration of inactivated antigen; and (d) before and during the performance of innocuity tests, the inactivated antigen should be stored in a sealed container, in a quarantine area, outside the restricted (high-security) area; and (e) the concentrated product containing the inactivated antigen should be in a volume at least 100 times less than that used for formulation of conventional vaccines. The producer must indicate the number of vaccine doses per volume unit of concentrated material; and (f) the main bulk of the inactivated antigen should be supplied in containers suitable for storage over liquid nitrogen and divided into volumes to be agreed between the producer and the CCI. In consultation with, and under the supervision of, the CCI, the producer must also provide 20 representative samples containing at least 1 mg each of concentrated 146S antigen for periodic in vitro and in vivo tests; and (g) the producer must provide relevant information about the antigen and its formulation into vaccine for consideration by the CCI. 5. (a) On receipt, each batch of concentrated inactivated antigen will be checked by the CCI for possible residual infective virus in vitro and in cattle using the method prescribed for vaccine in the European Pharmacopoeia; and (b) potency of the vaccines prepared from the concentrated antigen will be tested by the CCI. Vaccines will be formulated according to the prescription of the producer. Vaccines for pigs will be formulated as oil emulsions. For cattle, aluminium-hydroxide-, saponin- or oil-adjuvanted vaccines may be used. Any batches found to be unsatisfactory when tested immediately upon reconstitution following deposit in the antigen bank will be rejected and be replaced at the producer's expense. The cost of testing the replacement batch will be met by the producer; (c) components of the concentrated antigen must not interfere with the preparation and stability of the oil-emulsion vaccines. 6. The antigen as provided by the producer should have an expected stability of at least five years. 7. (a) The concentration and quality of the vaccine adjuvants will be agreed with the CCI. (b) The producer should also specify the expected shelf-life of the product after formulation into vaccine. This shelf-life should be at least four months. 8. Vaccines which have exceeded their expiry date must not be used; this date can be checked and if necessary reviewed by the CCI. 9. Formulated vaccines must be kept under cool temperature conditions as specified in the European Pharmacopoeia. Care should be taken to maintain the correct temperature during distribution, until administered.

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Source: EUR-Lex (Cellar) · retrieved 2026-11-08 · Text as adopted (Official Journal); later amendments are not incorporated in this text.