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ABSTRACT:
Forced degradation studies are used to facilitate the development of analytical methodology, to gain a better understanding of active pharmaceutical ingredient (API) and drug product (DP) stability, and to provide information about degradation pathways and degradation products. The objective of the review article is to furnish comprehensive portrayal of the forced degradation studies as per the regulatory guidelines that are associated with various regulatory agencies. This article recapitulates the collective views of industry practices on the topic of forced degradation studies. This article reiterates a practical interpretation and summary of the available guidance and some suggestions for best practices for conducting forced degradation studies.
KEYWORDS: Active pharmaceutical ingredient (API), Drug product (DP), Forced Degradation, ICH, FDA guidance, Validation, Method Development.
INTRODUCTION:
All pharmaceutical substances un-avoidably contain impurities and the role of ethical pharmaceutical industry is to define an impurity profile that is acceptable for the intended use of a given drug, without compromising its therapeutic safety and efficacy. The stability of a drug product or a drug substance is a critical parameter in which may affect purity, potency and safety.1,2 Changes in drug stability can risk patient safety by formation of a toxic degradation product(s) or deliver a lower dose than expected. Therefore it is essential to know the purity profile and behavior of a drug substance under various environmental conditions which could be possible by stability testing. 1,2
Stress testing is defined as the stability testing of drug substances and drug products undertaken to elucidate intrinsic stability attributes. Stress testing is performed by exposing drug substances and drug products to extreme conditions, such as pH, photolysis, oxidation and temperature, over a very short time period. It also referred to as forced degradation studies.3,4
Pharmaceutical companies perform forced-degradation studies during preformulation to help select compounds and excipients for further development, to facilitate salt selection or formulation optimization, and to produce samples for developing stability-indicating analytical methods.
Stress testing provides information about degradation mechanisms and potential degradation products. This information then can be used to develop manufacturing processes or to select proper packaging. It may also help in preparing reference material of identified degradation products. Although preformulation work is part of earlyphase drug development, stress testing often is repeated when manufacturing processes, product...