药品中N-尼托胺杂质的建议可接受摄入量限制的确定:致癌效能分类方法 (CPCA) 的开发和应用
Naomi L Kruhlak1, Marianne Schmidt2, Roland Froetschl3
1US Food and Drug Administration (US FDA), Silver Spring, MD, USA.
Regulatory toxicology and pharmacology : RTP
|May 16, 2024
概括
一种新的致癌潜能分类方法 (CPCA) 提供了与尼胺药物相关杂质 (NDSRI) 的AI极限. 这种方法有助于制药杂质控制,而无需特定化合物的数据.
科学领域:
- 制药化学 制药化学 制药化学
- 毒理学 毒理学 毒理学
- 药品安全 药品安全
背景情况:
- 胺杂物,包括NDSRI,对制药业和全球药物供应构成重大挑战.
- 许多NDSRI缺乏建立可接受摄入量 (AI) 限制的经验数据,使杂质控制复杂化.
- 现有的交叉阅读方法受到NDSRI的替代物可用性和结构多样性的限制.
研究的目的:
- 提出一种新的框架,即致癌效能分类方法 (CPCA),用于确定尼托胺的推AI限值.
- 提供一种科学支持的方法来评估尼特胺的致癌性,并设定AI的极限.
主要方法:
- CPCA是一种基于结构-活性关系的方法,将尼托胺分为5个强度组.
- 它分析了结构特征,包括α-分布和激活/失活组,影响代谢激活.
- 这种方法预测了致癌效应,以赋予相应的AI极限.
主要成果:
- 由于缺乏经验数据,CPCA提供了一种快速的方法,用于AI对缺乏经验数据的尼托胺的极限确定.
- 它简化了基于结构特征的致癌活性评估.
- 该方法已被国际药物监管机构采用.
结论:
- CPCA提供了一种实用和简化的方法,用于为尼托胺剂设定AI推的限制值.
- 它解决了NDSRI有限的经验数据的挑战,改进了杂质控制策略.
- 该框架作为对尼托胺杂质的监管评估的起点.
关键词:
可以接受的摄入量 (AI) 极限致癌功效分类方法 (CPCA) 的方法.致癌性的强度可能是致癌性.药物杂质是药物的杂质.药物安全 药物安全致变性 致变性 致变性N-尼托胺是一种N-Nitrosamine.氨酸药物物质相关杂质 (NDSRI)药品制造业 药品制造业 药品制造业 药品制造业监管合作 监管合作监管科学是一种监管科学.结构与活动关系 (SAR)更多相关视频
08:41Integration of Miniaturized Solid Phase Extraction and LC-MS/MS Detection of 3-Nitrotyrosine in Human Urine for Clinical Applications
Published on: July 14, 2017
9.3K
08:59An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
7.9K
相关概念视频
01:25Mutagenicity and Carcinogenicity
1.2K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.2K
01:25Drug Regulation
1.4K
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
1.4K