Pre-Conference Session

27 October 2020

Nitrosamine Impurities - GMP and Regulatory requirements


During this pre-Conference Session you will hear an update on how to deal with Nitrosamine Impurities from a GMP perspective and how to handle cases of Nitrosamine contamination in terms of filing changes/variations. You will get to know

  • Which “lessons learned” future risk mitigation strategies can be based on
  • How a comprehensive supply chain quality oversight should look like
  • What has to be considered regarding the CEP procedure in case of Nitrosamine Impurities

This year is a special year and will be remembered for a long time. The Covid-19 pandemic is shaping our professional environment as well as our private lives. But life goes on and we need and want to educate ourselves.

Therefore we offer this year’s pre-conference session of the 23rd APIC/CEFIC Global GMP & Regulatory API Conference as a Live Online Conference. All lectures will be held consecutively and can be attended by all participants live online.

This pre-conference session ideally complements the following 23rd APIC/CEFIC Global GMP & Regulatory API Conference.

APIC has published a guidance on Nitrosamines Risk Assessment complemented by a template, which provides practical assistance on how to report on the risk of potential presence of nitrosamine impurities.



In June 2018 EU authorities were notified that a Chinese API manufacturer has detected the presence of N-nitrosodimethylamine, NDMA, in batches of Valsartan. NDMA is known to be genotoxic and carcinogenic and is classified as a Class 2A carcinogen to humans. After a referral under Article 31 of Directive 2001/83/EC the CHMP assessed the impact of the presence of this impurity on the benefit-risk balance of valsartan-containing drug products and issued a recommendation whether the concerning marketing authorisations can still be maintained or should be suspended.

Meanwhile, different Nitrosamines (NDMA, NDEA and others) were detected in almost every drug product which contains a sartan derivative as an API. Marketing Authorisation Holders have been requested to evaluate the risk of the presence of Nitrosamine impurities in human medicinal products containing chemically synthesised APIs.


Target Audience

This pre-conference session 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 as well as people working in the regulatory affairs area are addressed.



Nitrosamine Impurities – Lessons Learned

  • Initial cause of Valsartan contamination and other causes
  • Article 31 and its implications
  • Where do we go from here?

How to evaluate Risks associated with Nitrosamine Impurities

  • Key factors of a systematic risk based approach
  • Challenges of assessing the risks of
    - Drug Products
    - APIs and Excipients
    - Packaging Materials
    - Implication of ICH M7

Nitrosamine Impurities and Supply Chain Quality Oversight

  • How to deal with the challenge of complex supply chains
  • What the QP has to consider
  • Communication – which parties and key persons have to be involved?

Nitrosamine Impurities and the Impact on the Ph. Eur.

  • Revisions of monographs and preparation of general texts

Nitrosamine Impurities and the CEP procedure – an update

  • Actions taken on CEP applications
  • GMP inspections
  • Work to be done by CEP holders

Nitrosamine Impurities – handling Changes/Variations in a global Environment

  • Variations/Changes as consequences to mitigate the risks
  • Filing a variation/change
  • Is a global approach workable?



Hélène Bruguera, EDQM, France

Ms Bruguera joined the European Directorate for the Quality of Medicines (EDQM) in 2000, as a scientific officer with the Certification Division. She is currently the Head of Division, dealing with the management of the evaluation of CEP applications as well as the EDQM inspection program for API manufacturers. She is a member of the IGDRP ASMF Working Group and a member of the EU team in the ICH Q11 IWG.

Marieke van Dalen, Aspen Oss B.V., The Netherlands

Ms Dalen is the global regulatory specialist in the regulatory group dedicated to API’s, with almost 30 years of experience in the regulatory field. She is a board member of APIC, the European API Industry organization, and she participates in the Japan task force, Emerging markets task force and the Quality metrics task force. She frequently represents APIC in meetings and conferences organized by EMA, EDQM, ICH etc.

Dr Andrew Teasdale, Astra Zeneca, United Kingdom

Dr Teasdale is an analytical chemist and held several positions within quality assurance and regulatory roles. He has led a number of industry expert groups within Pharmaceutical Research and Manufacturers of America (PhRMA), European Federation of Pharmaceutical Industries and Associations (EFPIA), Product Quality Research Institute (PQRI) and the Extractables and Leachables safety Information exchange (ELSIE).  He is also currently the chairman of the Joint Pharmaceutical Analytical Group (JPAG) in the UK.

Dr Ulrich Kissel, European QP Association, KisselPharmaConsulting, Germany

Dr Kissel is Qualified Person and Member of the Board of Directors of the European Qualified Person Association (EQPA). He works as a GMP consultant and contract QP to the Pharmaceutical Industry. Previous to his current role he held leadership positions in Quality and Supply Chain and served for many years as QP for Roche.