Risk assessment and management of genotoxic impurities in pharmaceuticals
作者单位：Division of Genetics and MutagenesisNational Institute of Health Sciences
会议日期：2013年
学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学]
摘 要：Residential impurities resulting from manufacturing and formulation,or from degradation of the active pharmaceutical ingredient may be present in synthetic pharmaceutical products.A subset of these impurities may present a potential for genotoxicity and therefore pose an additional safety concern to clinical subjects and *** ICH guidance on impurity evaluation(Q3A/B) provides guidance on how to identify genotoxic impurities but give no guidance on the acceptable *** EMEA and FDA currently have available guidance on genotoxic impurities in *** revealed the widely acknowledged deficiency regarding impurity assessment in ICH-Q3A/B and initiated the development of a new ICH *** new ICH-M7 guidance,Assessment and Control of DNA-Reactive(Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk is now *** addresses a variety of ways to characterize the mutagenic hazard of impurities in pharmaceuticals,to assess their risk,and reduce the potential lifetime cancer risk associated with patient exposure to genotoxic impurities both during clinical development and after *** is now widely accepted the concept of Threshold for Toxicological Concern(TTC),at which the majority of non-threshold direct acting mutagens exposed less than 1.5μg per day are not a safety *** M7 guidance allows the excess of the TTC level considering less than life time exposure and chemicals *** also proposes(Q)SAR approaches for the initial assessment of the *** proposal has resulted in the recent advance of in silico(Q) SAR tools which can robustly as well as accurately predict Ames *** ICH-M7 Guideline recommendations provide a state-of-the-art approach for assessing mutagenic impurities to have mutagenicity and ensure that such impurities are controlled to safe levels.