The Bio-virus safety committee, one of the committees of the Parental Drug Association Japan (PDA Japan), has discussed various concerns on biopharmaceuticals from scientific, technical and regulatory perspective. One of the most significant concerns is the risk of viral contamination into the products. This risk should be addressed, as required per the international regulations, by minimizing to use raw materials sourced from animal origin and by performing viral clearance studies in order to evaluate capability of purification processing to reduce and/or inactivate known and/or adventitious viruses. The Bio-virus safety Committee has reported the conclusions of discussion how to prepare and qualify cell bank system as one of raw materials and how much Log Reduction Value (LRV) should be targeted in virus clearance studies in the annual conference of the PDA Japan in 20051). The Bio-virus safety committee has discussed the practical experimental procedures for viral clearance studies since 2006 and reported the conclusions in the annual conference of the PDA Japan in 2007. In this report, standardized and practical experimental procedures for viral clearance studies are shown, considering not only requirements for submission to regulatory agencies but also experimental technique. In addition, trouble shooting based upon experiences of the members, information regarding Contract Research Organizations (CROs), reference of international guidelines, and worksheets of viral clearance study are provided.
Recently diseases caused by “prion” are well known as BSE (Bovine Spongiform Encephalopathy) and CJD (Creutzfeldt-Jakob disease). In manufacture of pharmaceuticals, there is potential risk of contamination of “prion” if bovine derived materials or human blood plasma are used as raw materials. Various provisions against this risk, enactment of specific regulations, development of assay method and measures in manufacture of pharmaceuticals for example, have been performed in regulatory authorities, academic organizations and pharmaceutical industry. In this article, content and the present situation of these provisions in pharmaceuticals, especially in bio-pharmaceuticals are described. Occurrence of BSE has been obviously decreased by the provisions like restriction of source of food for bovine, and occurrence of vCJD (variant CJD) in UK caused by BSE also seems to have been decreased. However, we can not have optimistic view regarding issues of vCJD yet. Because BSE still continues to occur in Japan, and infection risks from human to human have not been swept away. In addition, there are still scientifically unknown issues like variety of vCJD, difference of sensitivity and latent period of vCJD based on human genotypes. In short effective provisions are not clear yet. In these situations, pharmaceuticals manufacturing companies recognize risk of contamination, and are taking preventative measures, usage of safe raw materials for example, as good as possible. In order to make preventative measures more effective, clarification of disease mechanism, development of analytical method with high sensitivity enough to detect and to control infective substance, and development of reliable evaluation method regarding removal of possible contaminants of infective substance in manufacture process are essential. Aggressive and persevering cooperation effort among industry, regulatory and academic in long term is quite important in order to resolve these issues.
Single-use technologies are one of the most accelerated trends in biopharmaceutical and vaccine industry. Users of disposables and single-use systems are steadily increasing and feeling comfortable with the concept. While the industry is coming together to explore the challenges of disposable processing, this has resulted in the need to establish industry consensus guide for the use of single-use technologies. This article describes recent topics in this field and presents some examples of single-use products including biocontainer, sterile connectors and membrane chromatography, which can be useful for risk assessment study.