Determination of Acceptance Criteria for Statistical Equivalence Testing in CMC Applications

• Activity Number: 133
• Type: Contributed
• Date/Time: Monday, August 5, 2013 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Richard Burdick*+ and Leslie Sidor
• Companies: Amgen Inc. Co. and Amgen, Inc
• Keywords: Equivalence ; Comparability ; Similarity

Abstract

Regulatory bodies recognize and accept change as a normal part of manufacturing in a cGMP environment. A statistical technique used to demonstrate comparability between pre- and post change processes is statistical equivalence testing. This approach is used to demonstrate that the difference between means of the pre- and post-change processes is less than an amount deemed to be scientifically important. This scientifically important value is called the equivalence acceptance criterion (EAC). The EAC is established by a subject matter expert (SME) based on safety and efficacy considerations, as well as knowledge of the analytical method and the expected process variation.

In this presentation, the role of the statistician in helping the SME establish a science-based EAC is considered. In particular, we consider the following conditions: 1. Processes for which specifications are available, 2. Characterization testing where specifications are not defined, and 3. Stability data where non-Arrhenius behavior of the protein degradation mechanism requires criteria with no direct linkage to product specifications.