Nitrosamines in Human Drugs: FDA Guidance and USP Chapter

Understanding FDA and USP Standards for Nitrosamines in Pharmaceuticals
About this Event

Date: Oct 20,2024

Time: 1 PM -2:30 PM ET

Duration: 90 Mins

Description

In September 2020, FDA issued a final guidance on the "Control of Nitrosamine Impurities in Human Drugs” This guidance was issued both in the response to the finding of nitrosamine impurities, several of which are classified as probable human carcinogens, in such drugs as angiotensin II inhibitors (e.g., valsartan), ranitidine, nizatidine and metformin. Nitrosamines have subsequently been found in fixed-combination hypertension products, and it has been noted that nitrosamine impurity formation is possible even in drug substances where it would seem unlikely, due to potential contamination from impurities in some solvents, catalysts or reagents. This has led FDA to conclude that a risk assessment strategy is needed for any drug at risk of the presence of nitrosamines.

FDA set a timeline of having the industry complete a risk assessment for their products by March 31, 2021 (EMA March 31, 2021, for chemical medicines and July 1, 2021, for biologics) and, where necessary, completing confirmatory testing of drug products and submission of required changes in the drug applications by October 1, 2023 (EMA Sept 26, 2022, for chemical medicines and July 1, 2023, for biologics). In addition, on June 1, 2021, USP published general chapter <1469> - Nitrosamine Impurities, which contains proposed acceptance criteria for quantitative and limits test used in measuring nitrosamine levels in drug substances as well as discusses issues with sample preparation and presents four methods validated to quantify nitrosamine impurities in drug products.

The purpose of this webinar is to review the FDA guidance in detail and present a high-level overview of USP general chapter <1469>.

Learning Benefits:
Introduction – Why a Guidance Now?
Background
Nitrosamine Impurities – Formation, Sources and Root Causes
Risk-based Approach to Limiting Impurities
Recommendations to Drug Substance Manufacturers
Recommendations to Drug Product Manufacturers
Reporting Changes to FDA
USP <1469> – Sample Preparation Issues
USP <1469> – Methodology Summary
USP <1469> – Proposed Acceptance Criteria
Who should attend:
The following individuals or disciplines will benefit from attending this Webinar:

Analytical Chemists
Laboratory Management
Regulatory Compliance Managers
Quality Control and Assurance Personnel
Chemical Manufacturing and Control (CMC) Personnel