Analytical challenges and the effective management of nitrosamines: The evolving landscape of NDSRI analysis

Nitrosamine Drug Substance Related Impurities (NDSRIs) remain a topic of significant concern to the pharmaceutical industry, with multiple batch recalls in 2022 and beyond across different drug classes, including beta blockers and ACE inhibitors, to name but a few. Secondary amine-containing APIs have the potential for nitrosation in the presence of nitrite and acidic conditions, posing an inherent risk of NDSRI formation during pharmaceutical manufacture and storage. Such NDSRIs pose a significant challenge due to the lack of specific carcinogenicity data. Without this data, it is challenging to determine when, where, or indeed if there is a need to develop an associated analytical method. While the advent of the Carcinogenicity Potency Categorization Assessment (CPCA) has provided a systematic way to define an Acceptable Intake (AI), the challenges of analyzing NDSRIs at part per billion levels remain extremely difficult.

In this part online seminar, part panel discussion, we will present and discuss nitrite in excipients, nitrite and NDSRI analysis methods and challenges, NDSRI risk assessment, and a comprehensive and industry-accessible NDSRI database. The discussion will examine the challenges of NDSRI analysis, including matrix effects and the risk of false positive results arising during sample preparation.
 

Presenter: Andrew Teasdale (Senior Principal Scientist, AstraZeneca)

Andrew Teasdale BSc (Hons), PhD has 30 years’ experience in the pharmaceutical industry as an analytical chemist and within quality assurance and regulatory roles. In his current role he chairs AstraZeneca’s Impurity Advisory Group. Dr Teasdale has published a number of papers relating to mutagenic impurities, extractables and leachables, elemental impurities and other impurity related matters. Andrew has also represented EFPIA in ICH Q3C, Q3D and Q3E Expert working groups. He has also advanced several key scientific advancements in the control of impurities, as the inventor of the purge factor concept and the instigator of the development of Elemental Impurities database for excipients. In addition to over 50 scientific papers, he has also written 3 books.

Presenter: Giorgio Blom (Associate Principal Scientist, AstraZeneca)

Giorgio Blom is an Associate Principal Scientist in Trace Analysis at AstraZeneca in the UK, working in Pharmaceutical Technology and Development. He leads AstraZeneca's global Trace Analysis Expert Working Group. His work encompasses the development of novel methods to enable accurate and reliable quantitation of nitrosamines and their precursors to low parts per billion levels in drug substance, drug product, and excipients, with a focus on automation and QBD principles. As part of his role, Giorgio works with various industry groups to define best-practice procedures for trace analysis within the pharmaceutical industry and influence future practices. Giorgio obtained his degree in Chemistry with a major in Forensic Science from Avans University in the Netherlands and obtained his PhD in the field of Forensic Taphonomy.

Presenter: Grace Kocks (Senior Global Alliances Manager, Lhasa Limited)

Grace joined Lhasa in 2013 as a Scientist, after achieving her BSc in Biomedical Science at the University of Leeds. Now as Senior Global Alliances Manager, she works closely with regulatory authorities, whilst bridging the gap between Lhasa and their members to enhance overall engagement. In 2020 she became a committee member of The Industrial Genotoxicology Group (IGG), which seeks to organise annual meetings covering topics relevant to genotoxicity in industry.

Grace has continued to build on Lhasa’s strong reputation for facilitating data sharing amongst industry members and is proud to co-chair two industry data sharing consortiums. Vitic Nitrites is the most recent of these initiatives. Established in 2020, the initiative focuses on data collection of nitrites levels in excipients to support compiling nitrosamine risk assessments. Grace collaborates with industry to increase the knowledge and data available, continuously advocating for: ‘shared knowledge is shared progress’.

Presenter: Joerg Schlingemann (Principal Expert QC Systems, Merck Healthcare KGaA)

Joerg is a director and principal expert for quality control systems within Merck KGaA’s/EMD Serono’s healthcare quality unit. He studied molecular biology in Uppsala and Heidelberg, where he completed a doctorate degree at the German Cancer Research Center in 2005.

Joerg Schlingemann has 14 years of experience in the pharmaceutical industry from various roles within quality control and quality assurance. Since late 2019, Joerg has been leading EMD Serono’s analytical activities for N-nitrosamines, based on which he has authored or co-authored several scientific publications dealing with analytical challenges, NDMA in metformin, nitrite in excipients and the prevalence of NDSRIs. Joerg is an advocate of scientific collaboration, data sharing and expressive visualization of data.

Presenter: Sebastian Hickert (Senior Manager, Merck KGaA)

Sebastian leads the team for liquid chromatography within Merck´s central R&D analytics department. He earned a PhD in food chemistry from the university of Münster. Sebastians team uses various chromatography techniques such as HPLC and ion chromatography hyphenated to conductivity-, UV- and MS detection for nitrite determination in APIs, excipients and other pharmaceutical materials. Within the last years, he has contributed several scientific publications and presentations concerning nitrite analytics. Sebastian joined Merck in 2017 as senior scientist before moving on to managerial positions in 2018.

Presenter: Jon Bardsley (Market Development Manager, Pharma & Biopharma, Thermo Fisher Scientific)

Jon Bardsley has over a decade of experience of small-molecule pharmaceutical DMPK and regulated bioanalytical studies within with large Pharmaceutical environments. His passion for development of robust and accurate analytical methods for high-throughput studies has seen him also gain experience in contract research organizations. Jon sits on the ReidBioAnalyticalcommittee of the Chromatography Society and is a subject matter expert in the bioanalysis community. Following a period as Senior Applications Specialist for Chromatography, Jon now holds the position of Vertical Marketing Specialist for Pharma & BioPharma within Thermo Fisher Scientific, with a view to bringing relevant technologies together to help solve customer challenges.