Validation: Current approaches and considerations for viral clearance in cell and gene therapy

Assuring viral safety in cell and gene therapy (CGT) products poses a unique challenge as the viral vector is a key component of both in vivo and ex vivo gene therapies. Although viral clearance strategies for general biological drug manufacturing and vaccine production will apply to these products, there will be unique challenges and considerations for CGT modalities.

Regulatory authorities expect the viral safety and contamination controls for CGT manufacturing to be assured through the application of a comprehensive program of material sourcing, virus testing at appropriate stages of manufacturing, and removal and/or inactivation of adventitious viruses and helper viruses by the manufacturing process (the ‘three pillars’ approach). As with other biological products, such as monoclonal antibodies, viral clearance strategies can only be implemented if such processes do not impact product quality. Where viral clearance options are limited, the expectations for virus safety will focus on testing and controlling the raw materials and reagents and the manufacturing process.

This paper evaluates the applicability of the current understanding of viral clearance to the products and processes employed in CGT manufacture to assure the viral safety of these therapies. Unique considerations for preventing contamination through raw material risk mitigation are highlighted. Guidance on viral clearance strategies for inactivation and removal are also provided. This guidance focuses on adeno-associated viral vectors but may also apply to other viral vectors.

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• Create Date 12th June 2023
• DOI https://doi.org/10.46220/2023CGT004
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