A Stress Testing Benchmarking Study

portant part of the drug development process, and the pharmaceutical industry’s considerable interest in this topic has led to the publication of an article by the Pharmaceutical Research and Manufacturer’s of America (PhRMA) in Pharmaceutical Technology (1). Although the concept of stress testing is not new to the pharmaceutical industry, the procedure was not clearly defined until the International Conference on Harmonization (ICH) provided a definition in its guidance on stability. The ICH guideline indicates that stress testing is designed to help “determine the intrinsic stability of the molecule by establishing degradation pathways in order to identify the likely degradation products and to validate the stabilityindicating power of the analytical procedures used” (2). Because the ICH definition leaves the details of the investigations to the pharmaceutical researcher, the practices that companies use to conduct stress testing studies can vary tremendously and therefore have a significant effect on the quality of the analytical methodology used throughout the industry. The intent of this study about stress testing is to survey stress testing practices in the industry and to provide a thorough comparative analysis of approaches to stress testing. The authors hope that these survey results will provide further guidance about stress testing to the industry. Stress testing is a critical component of drug development. By generating key stress-testing samples (i.e., partially degraded samples stressed under various conditions), predictive degradation information can be obtained early in the process and can be of significant value to a drug company in terms of time and money. In addition, stress testing can help in the selection of more-stable drug substance salt forms and drug formulations. Stress testing also is becoming increasingly important in testing new molecules. Methods developed by stress testing and the stability information gained from those methods can have a significant effect on the actual compound selected for development. Therefore, to understand the current state of stress testing in the pharmaceutical industry, a benchmarking survey focusing on the methods and practices was conducted in November 2001. The survey was sponsored by Eli Lilly and Company (Indianapolis, IN) and Pfizer Inc. (Groton, CT). KMR Group, Inc. (KMR, Chicago, IL), a management consulting firm that specializes in benchmarking, conducted the study.