Depts. of Biological Process Sciences, Statistical Sciences, and Biopharmaceutical Manufacturing and Development, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, 19406, King of Prussia, PA, USA.
Cytotechnology. 1995 Jan;18(1-2):21-5. doi: 10.1007/BF00744316.
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.
对于源自连续细胞系的产品，世界各地的监管机构都要求对其纯化工艺进行验证，以确保其能够去除或灭活潜在的污染物，如病毒和类病毒颗粒。新的指南建议对这些研究进行统计评估，但该行业尚未制定此类标准。估计过剩产能的任务也因可变检测、在单元操作中清除估计值的变异性积累、清除能力对操作参数的依赖性以及实验费用而变得复杂。我们提出了一种实验策略，以确定生物制药工艺的过剩清除能力，并以有效的方式提供过剩容量的统计估计。为每个正交单元操作计算清除估计值及其方差，并将估计值组合起来，形成整体工艺清除能力的区间估计。泊松回归被建议作为清除研究数据分析的有效技术。我们相信，这种方法应该以具有成本效益的方式满足监管指南，同时阐明在设定要求时定性和定量成分的作用。
