新药杂质评估03-Evaluating Impurities in Drugs 03.doc

Evaluating Impurities in Drugs (Part III of III) In Part III of a three-part article, the authors examine various degradation routes of APIs, impurities arising from interactions in formulations, metabolite impurities, various analytical methods to measure impuritie, and ways to control impurities. Apr 2, 2012By: Kashyap R. Wadekar,? Ponnaiah Ravi,? Mitali Bhalme,? S. Srinivasa Rao,? K. Vigneshwar Reddy,? L. Sampath Kumar,? E. BalasubrahmanyamPharmaceutical TechnologyVolume 36, Issue 4, pp. 76-86  Controlling and monitoring impurities in APIs and finished drug products is a crucial issue in drug development and manufacturing. Part I of this article, published in the February 2012 issue of Pharmaceutical Technology, discussed the various types of and sources of impurities with specific case studies (1). Part II, published in the March 2012 issue, examined chiral, polymorphic, and genotoxic impurities (2). In Part III, the authors examine various degradation routes of APIs, impurities arising from API–excipient interaction during formulation, metabolite impurities, various analytical methodologies to measure impurity levels, and ways to control impurities in pharmaceuticals. Definition of impurity The term impurity reflects unwanted chemicals that are present in APIs or that develop during formulation or upon aging of the API in the formulated drug product. The presence of such unwanted material, even in small amounts, could affect the efficacy and safety of pharmaceutical products. Several guidelines from the International Conference on Harmonization (ICH) address impurities in new drug substances, drug products, and residual solvents (3–6). As per the ICH guidelines on impurities in new drug products, impurities present below a 0.1% level do not need to be qualified unless the potential impurities are expected to be unusually potent or toxic (5). In all other cases, impurities should be qualified. If the impurities exceed the threshold limits and data a