Regulatory background
Safety assurance practices are required to assure regulators and ultimately patients and the public that the final medicinal product is safe. In the 1990’s, the International Conference on Harmonization (ICH) promulgated “Q5A: Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin” (ICH 1998) which established a world-wide standard for viral safety. ICH Q5A describes a multi-tier scheme for testing and clearance validation to achieve this goal. The testing program focuses on cell banks, raw materials and bioreactor harvests, informed by a product risk analysis. Beyond testing, ICH Q5A mandates an evaluation of downstream purification, as a fail-safe in case of undetected contaminants upstream. The clearance validation assures that if any virus that evades the testing regime, it can be removed and/or inactivated before it ends up in the final medicinal product.