Free webinar – Nitrosamine Impurities: Risk Based Approach & Testing. Steps Towards Fulfiling EMA & FDA Nitrosamine Advice



Eurofins BioPharma Product Testing Italy and Li-Med invite you to participate at our free webinar on nitrosamines analysis. This webinar will provide insights on technical best practises and analytical strategies for assuring your pharmaceutical product’s safety. During this Live Webinar the relevant aspects of risk mitigation with respect to potential nitrosamine contamination in drug substances and drug products will be discussed. You will hear what you need to know about the required risk assessments for medicinal products containing chemically synthesized APIs. Thanks to our long-standing experience in the industry, our experts have been developing various methods and successful approaches for the determination of nitrosamine residues in different matrices through sophisticated mass spectrometry technologies both with full GMP approach and with a screening approach.   You will get advice from Eurofins BioPharma Product Testing Italy experts on the most advanced analytical methods applicable to overcome the challenges of low detection levels, difficult matrices and identification of unknowns in the course of pharmaceutical impurities analysis.

In 2018, the presence of the nitrosamine N-nitrosodimethylamine (NDMA), a potential carcinogen, in certain sartan active pharmaceutical ingredients (APIs) resulted in several regulatory warnings. Both the EMA European Medicines Agency) and FDA announced the recall of medicines which contained the active ingredient valsartan.

Further FDA and EMA have expanded their scope of investigation to evaluate other active pharmaceutical ingredients (APIs) that contain nitrosamine impurities. Concerns over the presence of this class of genotoxins has since widened to include other medicines, such as Ranitidine.

In September 2019, EMA published a press release where pharmaceutical companies were advised on steps to be taken to avoid nitrosamines in human medicines. Further document (EMA/511347/2019) was addressed to Marketing Authorisation Holders (MAHs). The guidance states that all pharmaceutical manufacturers should conduct a risk assessment and proactively test their products to protect patients and ensure that effective measures are taken to prevent the presence of nitrosamine impurities in human medicines. Risk assessment should be performed by 31st March 2021 for chemical medicines and 1st July 2021 for biological medicines. Marketing authorization holders should by 26th September 2022 for chemical medicines, and 1st July 2023 for biological medicines perform further confirmatory testing on the products identified to be at risk of N-nitrosamine formation or (cross-)contamination. Mitigation measures where risks are identified should be applied starting with the highest risk products.

Also, the FDA have taken steps in providing specific analytical testing methods for NDMA in ranitidine drug substance and drug product. FDA issued a guidance on Sept. 2020 on Control of nitrosamine impurities in human drugs. Manufacturers should conclude a risk assessment of approved or marketed products within 6 months of publication of this guidance to ensure the safety of drug supply in the US. To ensure the safety of the U.S. drug supply, confirmatory testing of drug products and submission of required changes in drug applications should be concluded within 3 years of the date of publication of this guidance.

Method development and validation of suitable analytical procedures have become imperative to determine levels of nitrosamine impurities. Ultra-low levels of these impurities must be quantified in diverse and complex matrices. The developed methods then need to be validated to conform to GMP requirements


Nitrosamine Impurities and the Sartan Cases – Background

  •  Initial cause of Valsartan contamination
  •  Other causes and their implications

Regulatory requirements: EMA & FDA

Root causes for Nitrosamine Impurities – How to Assess the Risks

  •  Development of a systematic risk based approach
  •  Key factors and the development of a decision tree


– Drug Products

Assessment and Communication of Risks

Confirmatory Testing: Analytical Methods for Determination of Nitrosamines

  •  Current status of methodology-

– GC-MS or HPLC-MS equipment?

  •  Analytical challenges

– Sensitivity

– Specificity – risk of false positives


This webinar is of interest to all personnel involved in risk assessments of drug substances and drug products regarding potential Nitrosamine contamination. Scientific staff, Laboratory Managers, Supervisors and Analysts in pharmaceutical quality assurance and quality control departments are addressed. During this event regulatory requirements will be discussed, and hence the event also is applicable to people working in the regulatory affairs area.


Valentina Paschetta  & DavideTartaglione

Valentina Paschetta

Head of the R&D, validation and study chemical laboratory at Eurofins BioPharma Product Testing Italy

Davide Tartaglione

Senior Consultant Pharma Division at Eurofins BioPharma Product Testing Italy

Official Language: English


** Israel Time Zone




Start Time

4:00 pm

October 20, 2020

Finish Time

5:00 pm

October 20, 2020


On-Line Meeting

Event Participants