Ruepp Robin, Frötschl Roland, Bream Robert, Filancia Maria, Girard Thomas, Spinei Andrei, Weise Martina, Whomsley Rhys
European Medicines Agency, Human Medicines Division, Amsterdam, Netherlands.
Licensing Division 2, Federal Institute for Drugs and Medical Devices (Bundesinstitiut für Arzneimittel und Medizinprodukte), Bonn, Germany.
Front Med (Lausanne). 2021 Nov 19;8:782536. doi: 10.3389/fmed.2021.782536. eCollection 2021.
The unexpected detection of nitrosamine impurities in human medicines has recently seen global regulators act to understand the risks of these contaminations to patients and to limit their presence. Over 300 nitrosamines are known, many of which are highly potent mutagenic carcinogens. Regulators first became aware of the presence of nitrosamines in EU medicines in 2018, with reports of detection of -nitroso-dimethylamine (NDMA) in valsartan from one manufacturer. A subsequent EU review of all valsartan medicines was triggered by the European Medicines Agency (EMA) and was later extended to other angiotensin receptor blockers/sartans. A separate review was also started for ranitidine medicines. This was followed by an EU-wide examination of the risk of presence of nitrosamines in all human medicines. This article reflects on the investigation of the EU regulatory network into the presence of nitrosamines and the scientific knowledge informing recommendations for developers on how to limit nitrosamines in medicines.
近期，在人类用药中意外检测到亚硝胺杂质，这促使全球监管机构采取行动，以了解这些污染物对患者的风险并限制其存在。已知的亚硝胺有300多种，其中许多是极具诱变作用的致癌物。监管机构于2018年首次意识到欧盟药品中存在亚硝胺，当时有报告称一家制造商生产的缬沙坦中检测到N-亚硝基二甲胺（NDMA）。随后，欧洲药品管理局（EMA）启动了对所有缬沙坦药品的欧盟审查，该审查后来扩展到其他血管紧张素受体阻滞剂/沙坦类药物。雷尼替丁药物也开始了单独审查。随后在欧盟范围内对所有人类用药中存在亚硝胺的风险进行了检查。本文反思了欧盟监管网络对亚硝胺存在情况的调查，以及为药品开发商提供如何限制药品中亚硝胺的建议所依据的科学知识。
