Determination of acceptance criteria and sample sizes for accelerated stability comparability studies for biologics

摘要

Changes of manufacturing processes are common. It is required by the regulatory agencies that manufacturers establish adequate and appropriate comparability between pre-change and post-change products. The goals of comparability assessments are to demonstrate the comparability and consistency of product quality before and after change and to demonstrate that the changes do not have an adverse effect on safety and efficacy of the drug products. Accelerated or stressed stability studies may shed light on drug quality under stressed environmental conditions and on product differences in the degradation pathways. Comparability of accelerated stability data may provide further evidence on the impact of process change. Equivalence test has been recommended to demonstrate the comparability of stability profiles for accelerated stability studies. Selection of appropriate acceptance criteria for determining comparability is one of the most challenging steps in the comparability studies. Because of the inherent heterogeneity of biologics, the stability profiles may vary considerably from batch to batch. It is more challenging to set the acceptance criteria for comparing the accelerated stability data for biologics. In this article, we present an approach for determining the acceptance criteria and necessary sample sizes for accelerated comparability studies for biologics. (C) 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.