Nitrosamines Identification for Pharmaceuticals

• Boasts over 15 years of experience in the analysis and study of nitrosamines across various sectors.
• Employs more than 25 specialists dedicated exclusively to the study of nitrosamines, with specific and advanced expertise in this field.
• Developed over 70 methods for the analysis of NDSRIs (Nitrosamine drug substance-related impurities).

• Houses more than 6 different analytical techniques including MS/MS and HRMS coupled with GC and LC systems, essential for detecting even the smallest traces of nitrosamines in products.
• Equipped with 7 LC/MS-MS dedicated exclusively to nitrosamine testing.
• Conducts over 15,000 tests of nitrosamines in drug products and APIs

• The laboratory is located in a modern facility housing 3 different departments, each dedicated to specific research and analysis areas.
• The work environment is designed to promote multidisciplinary collaboration among different specialized teams, ensuring an integrated and comprehensive approach to the nitrosamines analysis.

Background
Scientist with more than 20 years of industrial and academic experience in different fields of food/pharma safety.

Role
Managing a team of more than 20 people dedicated to R&D on Analytical Chemistry (particularly focused, interested and expert in mass spectrometry), he is currently the Mérieux NutriSciences Chemistry Research Director – Project Manager. He actively participates in funded scientific projects, in scientific congress with presentations, posters and, as far as possible, writes articles published in scientific journals in different areas of application of his work.

Background
Scientist with more than 15 years of experience in different fields and in particular with 13 years of experience in the GMP Facility.

Role
Manager at the GMP Validation Team involved in the validation of methods according to ICH or other international guidelines in compliance with cGMP/euGMP or GLP standard.

Nitrosamines are classified as probable human carcinogens, which means that long-term exposure above certain levels may increase the risk of cancer. They are present in some foods and drinking water supplies, and where they have been found in medicines the risk of developing cancer has been low but under authorities evaluation and control.

On September 26^th, 2019 the CMDh (Heads of Medicines Agencies) published the notice “Information on nitrosamines for marketing authorisation holders” asking to all Marketing Authorization Holders (MAHs) of human medicinal products containing chemically synthesised active pharmaceutical ingredients to evaluate the risk of the presence of nitrosamine impurities in their products. Now at the end of 2023, these 3 years of study and research have unveiled a much more challenging issue caused by the formation of complex nitrosamines (NDSRIs) that require high levels of expertise and technology to be detected in order to ensure product safety.

STEP 1 – RISK EVALUATION. MAHs should perform risk evaluation of their medicinal products containing chemically synthesised and biological APIs using quality risk management principles, as per ICH Q9 guideline and principles described in ICH M7 guideline related to toxicology assessment and control strategy. Prioritization of products is prescribed and risk evaluation of high risk / high priority products should be done immediately (e.g. higher daily exposure and chronic use). Risk evaluation documents should be made available upon request.

STEP 2 – CONFIRMATORY TESTING. Confirmatory tests should be carried out using validated and sensitive methods. MAHs should inform the competent authorities immediately if tests confirm the presence of a nitrosamine impurity irrespective of the amount detected.

STEP 3 – CHANGES TO THE MARKETING AUTHORISATION. MAHs should apply for a variation in a timely manner to introduce any required changes, such as amendment of the manufacturing process or changes to product specifications.