NDSRI

In addition to concerns about the small molecule alkyl nitrosamines, including N-nitrosodimethylamine (NDMA), there are also concerns about the formation of Nitrosamine Drug Substance Related Impurities (NDSRI) in pharmaceutical products. Nitrosamine drug substance related impurities have been detected in multiple drug products resulting in withdrawals. NDRSI formation occurs due to the presence of susceptible structural properties, such as a vulnerable amine, that allow for the formation of a nitroso group under certain chemical conditions, including the presence of nitrites from excipients.

The contamination of pharmaceuticals with N-nitrosamines can occur through various mechanisms. These mechanisms include the use of contaminated raw materials, drug substance synthesis, and product manufacturing processes.

To avoid additional batch release testing in quality control (QC), analytical methods used to detect nitrosamines—including NDSRIs—must demonstrate the absence of impurities at a limit derived from the acceptable intake (AI) and the maximum daily dose (MDD) of the active pharmaceutical ingredient (API).

In this webinar Naiffer Romero from the US Pharmacopeia and Marian Twohig, Ph.D., from Waters Corporation will discuss the challenges and analytical approaches to control NDSRIs.

Key learning objectives

• Gain an understanding of the current analytical challenges associated with detecting and controlling nitrosamine drug substance-related impurities.
• Explore a compliance-ready, integrated quantitative workflow for acquiring, processing, reviewing, and reporting genotoxic impurity levels relative to APIs and regulatory thresholds.

Who should attend

• Pharmaceutical scientists involved in the detection and control of nitrosamines impurities

Presenter: Naiffer Romero (Principal Scientist, Scientific Affairs US Pharmacopeia)

Naiffer has more than 20 years of pharmaceutical industry experience. In his 13+ years tenure with USP, he has served several roles: Lead scientist in the dosage form performance laboratory, reference standard development team, Manager in charge of LATAM Compendial engagement and education, responsible for stakeholders and national regulatory bodies engagement. Naiffer is also a certified USP Education instructor. Most recently, Naiffer joined USP's Scientific Affairs performance cell, where he leads scientific outreach and engagement for LATAM & U.S. on key national health priority topics. His combined pharmaceutical expertise includes Analytical Development, salt and polymorph selection, Development of dissolution methods, IVIVC modeling, and impurity analytical strategy. Naiffer also serves as a member of USP's Nitrosamine Steering Committee and community host to 'Nitrosamine Exchange,' a knowledge community in All-things Nitrosamine. Naiffer also liaises technical discussion on pharmacopeial collaboration, including international meetings of World Pharmacopeias (part of WHO).

Presenter: Marian Twohig, Ph.D. (Consultant Scientist, Waters Corporation)

Marian has over 20 years of experience supporting quantitative and qualitative applications in the pharmaceutical, food and environmental and materials science industries. She works as a Consultant Scientist for Waters Corporation where she has previously held several Senior Scientist positions. Currently, the focus of Marian’s work is in the development of quantitative analytical methods to meet the needs of the pharmaceutical industry. She is particularly interested in chromatographic separations and the application of combining low- and high-resolution mass spectral data with other chemical information for identification of unknown chemical entities. Marian holds a Ph.D. in Analytical Chemistry from Munster Technological University, Cork, Ireland

Moderator: Isabelle Vu Trieu (Pharmaceutical Market Development Manager, Americas, Waters Corporation)

Isabelle is a business development professional dedicated to delivering benefits to analytical scientists in the life sciences industry. With over 20 years of experience in providing chromatography and mass spectrometry solutions, Isabelle is particularly interested in helping pharmaceutical scientists achieve the data quality and integrity needed to drive decisions for drug quality, safety and efficacy. Isabelle joined Waters in 2009 and currently manages the development of the pharmaceutical market in the Americas. She holds Masters’ degrees in Chemistry from Columbia University and the University Claude Bernard in Lyon, France as well as a Chemical Engineering degree from Ecole Supérieure de Chimie Physique Electronique in Lyon, France.