Viral validation strategy for recombinant products derived from established animal cell lines

For products derived from continuous cell lines, regulatory agencies worldwide require that the purification process be validated for its ability to remove or inactivate potential contaminants such as viruses and virus-like particles. New guidance suggests a requirement for statistical evaluation of these studies but the industry has yet to develop such standards. The task of estimating excess capacity is also complicated by variable assays, accumulation of variability in clearance estimates over unit operations, dependence of clearance capacity on operating parameters, and expense of experiments. We propose an experimental strategy to determine the excess clearance capacity of a biopharmaceutical process and to provide statistical estimation of excess capacity in an efficient way. Clearance estimates and their variances are calculated for each orthogonal unit operation and estimates are combined to form an interval estimate of overall process clearance capacity. Poisson regression is suggested as an efficient technique for data analysis of clearance studies. We believe that this approach should meet regulatory guidelines in a cost effective way, while clarifying the roles of qualitative and quantitative components in setting requirements.