Recording Online Training: Nitrosamine Impurities Update - Im Auftrag der ECA Academy

Recording Online Training: Nitrosamine Impurities Update - Im Auftrag der ECA Academy


ECA-Member*: EUR 890,--
Regular Fee*: EUR 990,--
EU/GMP Inspectorates*: EUR 495,--
APIC Member Discount*: EUR 950,--

Alle Preise zzgl. MwSt.

* auch unkompliziert per Kreditkarte bezahlbar American Express Visa Mastercard

Rückfragen unter:
Tel.: 06221 / 84 44 0 E-Mail:


Dr Mark Harrison, Astra Zeneca, United Kingdom
Dr Corina Nachtsheim, Quality Assessor, Germany
Dr Ulrich Rose, EDQM, France
Dr Andrew Teasdale, Astra Zeneca, United Kingdom


It is the aim of this Live Online Training to provide the latest information on requirements Marketing Authorisation Holders have to meet with respect to Nitrosamine Impurities. Important points to be considered by Quality Assurance and Quality Control departments from manufacturers of APIs and finished products will also be discussed. You will get to know
  •  what regulatory authorities want to see regarding assessment of risks
  •  which European Pharmacopoeia monographs of sartans
  •  how to conduct a significant and comprehensive risk assessment
  •  which quality and safety aspects have to be taken into account for a risk assessment
  •  how to choose a suitable analytical method for determination of Nitrosamines


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 a genotoxic and carcinogenic agent in animals and is classified as a Class 2A carcinogen to humans. After a referral under Article 31 of Directive 2001/83/EC triggered by the European Commission the CHMP assessed the impact of the presence of this impurity on the benefit-risk balance of sartan-containing drug products and issued a recommendation whether the concerning marketing authorisations can still be maintained or should be suspended.
Building on this Article 31 referral EMA together with the EU Network and international partners was continuing the review to identify whether there are any consequences for medicinal products apart from the class of sartans. As a result of this the CHMP issued a document entitled “Nitrosamine impurities in human medicinal products” as part of the procedure under Article 5(3) of Regulation EC (No) 726/2004.. This assessment report contains comprehensive recommendations on how to detect and mitigate the risk of Nitrosamine Impurities in human medicinal products containing chemically synthesised APIs as well as biological medicinal products.

In a subsequent assignment the CHMP was requested by the European Commission to assess the impact of the outcome of the Article 5(3) assessment on Nitrosamines regarding angiotensin-II-receptor antagonists (sartans) which resulted in a final assessment report with respect to Candesartan, Irbesartan, Losartan, Olmesartan and Valsartan. This assessment report contains changes to the current conditions to the Marketing Authorisations for sartans such as limits for Nitrosamine Impurities to be implemented for the finished products and deadlines to be met.

As a consequence the five European Pharmacopoeia monographs on sartans with a tetrazole ring, namely Valsartan, Losartan Potassium, Irbesartan, Candesartan ciletexil and Olmesartan medoxomil have been revised to align them with the above mentioned final assessment report. The implementation date of these monographs is 1 April 2021.


This Training 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. On this event regulatory requirements will be discussed and hence it is applicable to people working in the regulatory affairs area.

Technical Details

To participate in an on demand training course or webinar, you do not need any software. The recordings are made available via a streaming server. In general, the recording is provided in MP4 format, which any PC (Microsoft Windows, Apple IOS) or tablet can easily display.

Timing and Duration:

When you register for the on demand Training course or webinar you can decide at what date you want to follow the training course online. For a 1-day training course you will have 2 days in which the stream is available (for 2-day training course 3 days and for a 3-day training course 4 days). Within in this timeframe you can start & stop the stream according to your needs.

In time before the scheduled date (your desired date) you will receive an e-mail from us with a link for direct participation as well as your log-in data.

Training Course Documentation and Certificate:

The presentations will be made available as PDF files via download shortly before the online training course. After the event, you will automatically receive your certificate of participation.


Latest European Pharmacopoeia Activities on Control of Nitrosamine Impurities
  • General principles of control DNA reactive (genotoxic) impurities in the European Pharmacopoeia
  • Update on revisions of monographs on Sartans – Nitrosamine impurities
  • Update on revisions of general monographs
Assessment and Communication of Risks – what Regulatory Authorities want to see. An Update
  • Regulatory Basis
  • Requirements for Nitrosamines
  • Limits and Deadlines
  • Scenarios for implementation
  • Sartans and Non-Sartans
Management of Nitrosamines – Key Quality and Safety Challenges
  • How are Nitrosamines formed and under what conditions
    • Synthetically – API manufacture
    • Within the drug product + other routes
    • How to place risks into context
  • Analysis of Nitrosamines
    • Sensitivity challenges
    • Interference / false positives
  • Safety of Nitrosamines – are all of concern?
    • Factors that impact potency
    • Can Less than lifetime approaches be taken?
    • How to assess – utility of the Ames test – factors for consideration
Nitrosamine Impurities – How to Conduct an Actual Risk Assessment
  • Development of a systematic risk based approach
  • Key factors and the development of a decision tree
    • API
    • Drug Product
Analytical Methods for Determination of Nitrosamines used for Confirmatory Testing
  • Current status of methodology
  • Analytical challenges
  • Sensitivity
  • Specificity – risk of false positives

Recording from 10 June 2021

Duration of Recording: 4h 19min


Aufzeichnungen Online Seminare/Webinare nach Thema