Viral safety is essential in the manufacturing of biopharmaceuticals and required to ensure patient safety. Assurance of viral clearance can be difficult, however, during production of vectors such as adeno-associated viruses (AAV) used for the purpose of gene delivery. The need to define and deploy an appropriate and robust viral clearance strategy for a process that inherently aims at purifying a virus for therapeutic purposes can be particularly challenging without an overarching strategy in place.
A manufacturing process designed with viral safety as a goal should include specific robust virus inactivation and removal steps, as well as purification unit operations that provide additional viral reduction. Risk mitigation through the careful choice and extensive testing of source materials will help prevent introduction of adventitious viruses while rigorous testing procedures for raw materials, cell banks, virus seed stocks, bulk harvests and drug substances, and assessment of the manufacturing process for inactivation and removal of viruses ensure another layer of safety throughout the process.
This whitepaper describes an approach to adventitious viral risk mitigation which encompasses this multifaceted approach defined as “prevent, detect, remove”. Best practices and advanced technologies to help assure viral safety are also presented.