Demonstrating stability for clinical supplies should be driven by scientific knowledge gained in development as well a risk-based
assessment to guide efficient use of available resources. In early development, clinical efforts are often focused on relatively
simple products with short life cycles and the DS from which they are made are often produced by evolving chemical processes.
The efforts to determine the stability of the DS and drug product should be fit for this phase of development and are designed
to give the most basic stability information, namely, to ensure that the DS is of suitable quality when used to manufacture
product and that the drug product is of suitable quality while in the clinic. To make this assessment, simple stability studies
using ICH constructs and/or accelerated or stress data may be used. Other experimental data may be collected to increase the
scientific knowledge of the DS/DP.
It is our hope that providing the approaches to early phase stability outlined here, along with the approaches in this series
of white papers by the other focus areas of the IQ Early Phase GMPs working group, will provide a springboard to stimulate
discussions on these approaches within the industry and with worldwide health authorities.
To encourage further dialogue, this IQ working group is planning a workshop in the near future to promote robust debate and
discussion on these approaches. These discussions will hopefully provide improved alignment between development, QA oversight,
and regulatory within the pharmaceutical industry, and most importantly with worldwide health authorities. Agreement between
industry and health authorities regarding acceptable approaches to stability studies in early phases of drug development would
clearly be beneficial to development scientists and allow for a more nimble and flexible approach to better address the dynamic
environment typically encountered during the early phases of clinical development, while still providing appropriate controls
to ensure patient safety.
This article represents the opinion of the authors and not necessarily those of their respective companies.
Bruce Acken is in Analytical Sciences at Merck & Co. Inc. (Summit, NJ); Mark Alasandro is in Pharmaceutical Analysis and Microbiology at Allergan (Irvine, CA); Stephen Colgan is at Pfizer Global Research and Development (Groton CT); Paul Curry is in NCE Analytical R&D at Abbott Laboratories (Abbott Park, IL); Frank Diana is in Pharmaceutical Development at Endo Pharmaceuticals (Chadds Ford, PA); Q. Chan Li is in Analytical Development US, and Z. Jane Li is in Pharmaceutical Development, both at Boehringer Ingelheim Pharmaceuticals (Ridgefield, CT); Tony Mazzeo* is in Analytical and Bioanalytical Development at Bristol-Myers Squibb Company (New Brunswick, NJ); Andy Rignall is in Analytical Science at Astra Zeneca R&D (Macclesfield, UK); Z. Jessica Tan is in Analytical R&D at Amgen (Thousand Oaks, CA); and Robert Timpano is at Pfizer Global R&D (Groton, CT).
*To whom all correspondence should be addressed.
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