Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators.

A workshop organized by the European Medicines Agency and the European Directorate for the Quality of Medicines and HealthCare was held in London, UK on November 28-29, 2013, to provide an overview of the current knowledge of the characterization of new factor VIII (FVIII) and factor IX (FIX) concentrates with respect to potency assays and testing of postinfusion material. The objective was to set the basis for regulatory authorities' discussion on the most appropriate potency assay for the individual products, and European Pharmacopoeia (Ph. Eur.) discussion on whether to propose revision of the Ph. Eur. monographs with respect to potency assays in the light of information on new FVIII and FIX concentrates. The workshop showed that for all products valid assays vs. the international concentrate standards were obtained and potency could be expressed in International Units. The Ph. Eur. chromogenic potency assay gave valid assay results which correlate with in vivo functionality of rFVIII products. For some modified rFVIII products and all modified rFIX products, one-stage clotting assay methods result in different potencies depending on the activated partial thromboplastin time reagent. As a consequence, monitoring of patients' postinfusion levels is challenging but it was pointed out that manufacturers are responsible for providing the users with appropriate information for use and laboratory testing of their product. Strategies to avoid misleading determination of patents' plasma levels, e.g. information on suitable assays, laboratory standards or correction factors were discussed.

European Regulatory guidance on virus safety of recombinant proteins, monoclonal antibodies and plasma derived medicinal products.

This article gives an overview of the principles of the European Regulatory guidance on virus safety and virus validation for products derived from mammalian cell lines (recombinant DNA products and monoclonal antibodies) and from human blood. It provides an insight of the current views of the European authorities on the virus safety aspects of these different kinds of products. For biotechnology (rDNA and mAb) products, the article elaborates on the experience gained within the centralised procedure and illustrates this by means of a survey of the virus validation studies of all biotechnology medicinal products authorised in the European Union from the beginning of 1995 to mid-2003. Trends in model viruses used in the virus validation studies and virus removal/inactivation steps for these products are identified in the survey. For plasma derivatives, this overview illustrates how EU regulatory guidance on the virus safety of plasma-derived medicinal products is kept under review and links to the topics discussed during the PDA-EMEA Virus Safety Forum.