ABSTRACT
There are specific regulatory recommendations regarding the design, conduct, and use of stability studies that should be performed to support
• Investigational new drug applications (INDs) (21 CFR 312.23(a)(7))
• New drug applications (NDAs) for both new molecular entities and non-new molecular entities, new dosage forms (21 CFR 314.50(d)(1))
• Abbreviated new drug applications (ANDAs) (21 CFR 314.92-314.99)
• Supplements and annual reports (21 CFR 314.70, and 601.12)
• Biologics license application (BLAs) and product license applications (PLAs) (21 CFR 601.2)
Given below is a comprehensive description of the principle established in International Conference on Harmonisation (ICH) Q1A-that information on stability generated in any one of the three areas of the European Union, Japan, and the U.S. would be mutually acceptable in both of the other two areas. Also included here is a discussion of biological products and products submitted to the Center for Biologics Evaluation and Research (CBER). (Note that effective July 2003, the U.S. Food and Drug Administration has transferred several therapeutic proteins to the Center for Drug Evaluation and Research [CDER] from CBER.)
Given below are recommendations for the design of stability studies for drug substances and drug products that should result in a statistically acceptable level of confidence for the established retest or expiration dating period for each type of application. The applicant is responsible for confirming the originally established retest and expiration dating periods by continual assessment of stability properties (21 CFR 211.166). Continuing confirmation of these dating periods should be an important consideration in the applicant’s stability program. The choice of test conditions defined in this guidance is based on an analysis of the effects of climatic conditions in the European Union, Japan, and the U.S. The mean kinetic temperature in any region of the world can be derived from climatic data (Grimm, W.,
Drugs Made in Germany
, 28:196-202, 1985, and 29:39-47, 1986). [ICH Q1A]
Information on the stability of a drug substance under defined storage conditions is an integral part of the systematic approach to stability evaluation. Stress testing helps to determine the intrinsic stability characteristics of a molecule by establishing degradation pathways to identify the likely degradation products and to validate the stability, indicating the power of the analytical procedures used.
