Regulatory Experiences with Root Causes and Risk Factors for Nitrosamine Impurities in Pharmaceuticals

被引:22
|
作者
Horne, Stephen [1 ]
Nagavelli, Laxma R. [2 ]
Sayeed, Vilayat A. [2 ]
Heckman, Laurel [2 ]
Johnson, Deborah [2 ]
Berger, Dan [2 ]
Yip, Yean Yean [4 ]
Krahn, Carolina Lopes [5 ]
Sizukusa, Leticia Oyamada [5 ]
Rocha, Nayrton Flavio Moura [5 ]
Ludwig, Joachim [7 ]
Keire, David A. [3 ]
Condran, Gary [1 ]
Vera, Matthew D. [2 ]
Bream, Robert N. [6 ]
机构
[1] Hlth Canada, Ottawa, ON K1A 0K9, Canada
[2] US FDA, Silver Spring, MD 20993 USA
[3] US FDA, St Louis, MO 63110 USA
[4] Hlth Sci Author HSA, Singapore 138667, Singapore
[5] Agencia Nacl Vigilancia Sanit ANVISA, Brasilia, DF, Brazil
[6] European Med Agcy EMA, EU, Amsterdam, Netherlands
[7] Bundesinst Arzneimittel & Med Prod BfArM, Bonn, Germany
关键词
N-nitrosamines; Nitrosation; Regulatory science; Regulatory co-operation; Root causes; Risk factors; Risk mitigation; Pharmaceutical quality; Mutagenic; Impurities; VOLATILE N-NITROSAMINES; NDMA FORMATION; NITRITE ION; PRODUCTS; NITROSATION; RANITIDINE; DRUGS; IDENTIFICATION; DEGRADATION; DIMETHYLNITROSAMINE;
D O I
10.1016/j.xphs.2022.12.022
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
N-Nitrosamines (also referred to as nitrosamines) are a class of substances, many of which are highly potent mutagenic agents which have been classified as probable human carcinogens. Nitrosamine impurities have been a concern within the pharmaceutical industry and by regulatory authorities worldwide since June 2018, when regulators were informed of the presence of N-nitrosodimethylamine (NDMA) in the angioten-sin-II receptor blocker (ARB) medicine, valsartan. Since that time, regulatory authorities have collaborated to share information and knowledge on issues related to nitrosamines with a goal of promoting convergence on technical issues and reducing and mitigating patient exposure to harmful nitrosamine impurities in human drug products. This paper shares current scientific information from a quality perspective on risk fac-tors and potential root causes for nitrosamine impurities, as well as recommendations for risk mitigation and control strategies.(c) 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:1166 / 1182
页数:17
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