ABSTRACT
This chapter discusses issues to address in designing and incorporating adequate viral clearance strategies during the production of biologicals and biopharmaceuticals. It focuses on safety assurance of continuous cell line (CCL)-derived products, the safety and addresses procedural considerations as applied to plasma-derived products. Endogenous retroviruses and retrovirus-like particles are associated with some CCLs; they are noninfectious but pose a theoretical safety concern due to their oncogenic potential. Humanized cell lines are derived from human B lymphocytes, which can harbor several viruses including retroviruses, hepatitis viruses, human herpesviruses, cytomegalovirus, and human papilloma virus. A key consideration for Protein A viral clearance validation is the fact that the low pH conditions used for product elution can also inactivate retroviruses. Careful process design and appropriate validation are critical for the successful implementation and performance of virus-retentive filters. Validation study design and virus load on the filter contribute to small virus breakthrough.
