Strategies To Address Mutagenic Impurities Derived from Degradation in Drug Substances and Drug Products

Autor:	Mark H. Kleinman, David P. Elder, Alan P. McKeown, Steven W. Baertschi, Mark D. Mowery, Andrew Teasdale
Rok vydání:	2015
Předmět:	Active ingredient Drug Potential risk Chemistry media_common.quotation_subject Organic Chemistry Computer based Forced degradation Ph range Organic chemistry Drug product Degradation (geology) Biochemical engineering Physical and Theoretical Chemistry media_common
Zdroj:	Organic Process Research & Development. 19:1447-1457
ISSN:	1520-586X 1083-6160
Popis:	This paper outlines strategies in alignment with ICH M7 for systematically assessing the potential risk posed by mutagenic degradants in active pharmaceutical ingredients (API) and formulated products. A mutagen risk assessment (MRA) process that involves degradation should include results from focused drug substance and drug product stress testing experiments (e.g., at elevated temperature, a wide pH range in solution, oxidative, and photolytic stress) as well as accelerated and long-term stability studies in the solid-state. While the MRA may include hypothetical (theoretically predicted) degradation products from computer based and/or knowledge-based approaches, investigations for numerous hypothetical degradation products whose significance have not been verified experimentally should not be initiated based on these results alone. Drug substance and drug product stress (forced degradation) studies should be designed to generate a comprehensive range of potential degradants that encompass all degradati...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::4651f405fe6af4483f271c29d8b5f63c https://doi.org/10.1021/acs.oprd.5b00091 Zobrazit plný text záznamu