Counteracting the Virus Threat

Recent years have seen a shift in the paradigm for virus safety, away from an assumption that each pillar of the safety triangle (see Figure 1) contributes equally to the overall virus safety profile of a product, towards a view that virus inactivation and/or removal may play a more important role in assuring the safety of the product (1). The degree to which this is apparent is product-dependent, and this shift in paradigm has been most noticeable in the human plasma products industry. The actual contribution to risk reduction by donor selection, donor screening and virus inactivation/removal can be mathematically modelled and shows that donor screening and donor testing each contribute in the order of a 1-2 log10 reduction in measurable risk for viruses such as HIV or HCV (1,2).

In contrast, the incorporation of two steps into the manufacturing process, each providing in the order of 5.0 log10 inactivation or removal, can provide a risk reduction in the order of 10 log10. Such data has resulted in ever-increasing scrutiny of the manufacturing process, in particular ensuring that the design of the virus inactivation study and presentation of the data is such that the reduction factors claimed for a manufacturing process can be relied upon. This article looks at a number of aspects of virus clearance study design that have proven critical in ensuring that the design and interpretation complies with current regulatory requirements.

HOW MANY VIRUS INACTIVATION/REMOVAL STEPS DO I NEED?

This question can only be answered by first understanding the nature of the product. It is almost certain that any manufacturing process that includes two to three dedicated and effective virus inactivation/removal steps is likely to meet even the most stringent of regulatory reviews. The extent to which a process will be viewed as having sufficient viral clearance will depend on the various strategies adopted during the design phase of the product.