End-product testing cannot be used to assure viral safety of clotting factor concentrates.
The testing used for screening plasma for viral agents, whether performed on individual donations or pools of donations, and whether serologic or molecular, is not designed or validated for testing end products. Using these tests for end products is highly inappropriate and adds nothing to the assurance of safety of the products. Its application may lead to incorrect assessments of product quality and safety and hold up product release.
The major regulatory agencies that oversee much of the production of recombinant clotting factor concentrates – the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) – do not test those final products for viral safety because such testing has no additional value. Instead, they review the entire manufacturing process.
Crucial for viral safety of plasma derivatives are selection of healthy donors, testing of donations for virus markers and appropriate manufacturing processes. For example, in Europe, all relevant information about the source plasma must be compiled in a certified plasma master file (PMF), and the plasma pools used for production are re-tested for virus markers in official medicine control laboratories (OMCL), co-ordinated by the European Directorate for Quality of Medicines and Health Care (EDQM).
For recombinant and plasma-derived clotting factor concentrates, product quality depends on ensuring that testing methods and release criteria are approved as part of the overall review process and are subject to all the requirements of good manufacturing practice (GMP). It is important to emphasize that the overall process is what builds quality and safety into a product; it is not possible to compensate for any GMP deviations by testing final products.