Determining the Number of Process Performance Qualification Batches

• Activity Number: 114
• Type: Topic Contributed
• Date/Time: Monday, August 4, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Richard Lewis*+ and Bill Henry and John Joseph Peterson and Paul McAllister
• Companies: GlaxoSmithKline and GlaxoSmithKline and GlaxoSmithKline and GlaxoSmithKline
• Keywords: Process performance qualification ; PPQ sample size

Abstract

In January 2011 the FDA issued a guidance document on drug process validation that introduces a three-stage product lifecycle concept: (1) process design, (2) process qualification, and (3) continued process qualification. The goal of process qualification is to determine whether or not the process is capable of reproducible commercial manufacturing, and a required component is process performance qualification (PPQ) at commercial scale. A key issue for manufacturers is determining the number of batches that are needed for process performance qualification. We review three approaches for determining PPQ sample size that have been proposed by the International Society for Pharmaceutical Engineering (ISPE), and propose an additional approach based on the probability of a batch successfully meeting all of its specifications. The batch success approach offers an intuitive and relatively simple methodology for determining PPQ sample size. In particular, it imposes no new process performance criteria, such as minimum values for process capability indexes, and naturally incorporates any number of specifications.