FDA Control of Nitrosamine Impurities in Human Drugs Guidance for Industry

标准简介

标准截图

标准文档说明

标准部分原文

Control of Nitrosamine Impurities in Human Drugs 1

Guidance for Industry This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page. I. INTRODUCTION This guidance recommends steps manufacturers of APIs and drug products should take to detect 2 3

and prevent unacceptable levels of nitrosamine impurities in pharmaceutical products. The guidance also describes conditions that may introduce nitrosamine impurities. The recent unexpected finding of nitrosamine impurities, which are probable human carcinogens, in drugs 4 5 6 7

such as angiotensin II receptor blockers (ARBs), ranitidine, nizatidine, and metformin, has made clear the need for a risk assessment strategy for potential nitrosamines in any pharmaceutical product at risk for their presence. This document revises the guidance of the same title issued in September 2020. This revision extends the time period for preparing initial risk assessments to March 31, 2021 (i.e., within 7 months of publication of the original guidance). 1

This guidance has been prepared by the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. You may submit comments on this guidance at any https:/regulations.gov/docket/FDA-2020-D-

time. Submit comments to Docket No. FDA-2020-D-1530 (available at 1530) (see the instructions for submitting comments in the docket). 2

The term nitrosamine as used in this guidance means N-nitrosamine. 3

New drug application (NDA) and abbreviated new drug application (ANDA) holders or sponsors, drug master file (DMF) holders, and owners of marketed products that are not the subject of approved NDAs or ANDAs (such as compounded products or products marketed under an over-the-counter (OTC) drug monograph) who are not also the manufacturer of the drug products and APIs should work with their contract manufacturers to take the steps recommended in this guidance. This applies to drug products currently available on the U.S. market as well as those with pending applications. 4

The first nitrosamine detected in ARBs was N-nitrosodimethylamine (NDMA), which is a genotoxic and carcinogenic agent in animals and is classified as probably carcinogenic to humans (Class 2A carcinogen) by the World Health Organization’s (WHO’s) International Agency for Research on Cancer (IARC). Other nitrosamines, including N-nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutanoic acid (NMBA), have also been detected in various ARB products. 5

https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-

ranitidine 6

See footnote 5. 7

https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-metformin

网盘链接

百度网盘：https://pan.baidu.com/s/1pFzArjWB4R_-Ncm7pv7XWA
提取码：33pz