Division 2.1 Starting materials of biological originF1

The description shall be given in the form of a monograph.

Whenever possible, vaccine production shall be based on a seed lot system and on established cell seeds. For the production of immunological veterinary medicinal products consisting of serums, the origin, general health and immunological status of the producing animals shall be indicated and defined pools of source materials shall be used.

The origin, including geographical region, and history of starting materials shall be described and documented. For genetically engineered starting materials this information shall include details such as the description of the starting cells or strains, the construction of the expression vector (name, origin, function of the replicon, promoter enhancer and other regulator elements), control of the sequence of DNA or RNA effectively inserted, oligonucleotidic sequences of plasmid vector in cells, plasmid used for cotransfection, added or deleted genes, biological properties of the final construct and the genes expressed, copy number and genetic stability.

Seed materials, including cell seeds and raw serum for anti-serum production shall be tested for identity and extraneous agents.

Information shall be provided on all substances of biological origin used at any stage in the manufacturing procedure. The information shall include:

• details of the source of the materials,

• details of any processing, purification and inactivation applied, with data on the validation of these process and controls during production,

• details of any tests for contamination carried out on each batch of the substance.

If the presence of extraneous agents is detected or suspected, the corresponding material shall be discarded or used in very exceptional circumstances only when further processing of the product ensures their elimination and/or inactivation; elimination and/or inactivation of such extraneous agents shall be demonstrated.

When cell seeds are used, the cell characteristics shall be shown to have remained unchanged up to the highest passage level used for the production.

For live attenuated vaccines, proof of the stability of the attenuation characteristics of the seed has to be given.

Documentation shall be supplied to demonstrate that the seed materials, cell seeds, batches of serum and other material originating from animal species relevant for the transmission of TSE comply with the Note for Guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products, as well as with the corresponding monograph of the European Pharmacopoeia . Certificates of Suitability issued by the European Directorate for the Quality of Medicines and HealthCare, with reference to the relevant monograph of the European Pharmacopoeia , can be used to demonstrate compliance.

When required, samples of the biological starting material or reagents used in the testing procedures shall be provided to enable the competent authority to arrange for check tests to be carried out.