Control of Nitrosamine Impurities in Human Drugs
Understanding FDA's Final Guidance for Industry, USP Chapter <1469> and an In-Depth Discussion of Sample Preparation Issues, Methodology and Acceptance Criteria
Live, Interactive Training Webinar
Date: Wednesday July 12, 2023
Time: 10:30 am - 12:30 pm ET (New York Time)
Instructor: Anthony Destefano Ph.D. Biography>>>
Registration Form ►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.
Webinar outline and time breakdown:
Time*
10:15 AM Log-In Period
10:30 AM Introduction
Live Lecture Part 1
11:30 AM 10 Minute Break
Live Lecture Part 2
12:30 PMLive Questions & Discussion
*Please note all times are Eastern Time (New York Time)
This live training webinar includes the following for each registered attendee:
- A copy of the presentation slides
- A certificate of training for attendee training records
Who should attend:
The following individuals or disciplines will benefit from attending this Webinar:
- Quality Assurance Personnel
- Quality Control Personnel
- Regulatory Compliance Managers
- Analytical Chemists
- Laboratory Management
- Chemical Manufacturing and Control (CMC) Personnel
Instructor: Anthony J. DeStefano Ph.D.
Consultant - Former USP Sr. Vice President of General Chapters and Healthcare Quality Standards
Tony DeStefano began his career at Procter & Gamble in mass spectrometry. After P&G acquired Norwich Eaton Pharmaceuticals, he managed Physical Measurement and Method Development Sections for several years, after which he established Norwich’s first Bioanalytical Section. In 2002, he returned to Cincinnati to manage the bioanalysis programs for multiple clinical studies. He has spoken and written extensively in the areas of regulated bioanalysis and analytical and bioanalytical validation and outsourcing. In 2008 he joined the US Pharmacopeia as its Vice President of General Chapters. At USP, he led initiatives to maintain, update and redesign its General Chapters. He was promoted to Senior Vice President and had responsibility for the Health Care Quality Standards, Excipients, Dietary Supplements and Food Ingredients groups. He was a USP representative to the ICH Q3D Expert Working Group on metal impurities and the Pharmacopoeial Discussion Group (PDG). The purpose of the PDG, with representatives from the European Pharmacopoeia, the Japanese Pharmacopoeia, the U.S. Pharmacopeia and the World Health Organization as an observer, is to harmonize pharmacopeial standards (excipient monographs and selected general chapters, including elemental impurities) in three major regions of the world. While at USP, he lead the effort to replace USP Heavy Metals <231> with the new general chapters <232> and <233>. He has spoken extensively regarding these chapters both domestically and internationally. He was a co-developer of the initial USP training course on elemental impurities and served as the trainer for the first session. He is currently a consultant through YourEncore and Nuventra, and personally, consulting on analytical, bioanalytical, compendial and quality-related issues. He is a member of the American Chemical Society (ACS), Chair of the Board of the Product Quality Research Institute (PQRI), and a past president of the American Association of Pharmaceutical Scientists (AAPS) Full Bio >>>