Health Canada Nitrosamine Guidance -Effective Sep 2022

This week Health Canada published their ‘Guidance on Nitrosamine Impurities in Medications’, this follows up on their Q&A document and revisions originally issued on November 26, 2019.

  • Timelines for 3-Step approach:
    Risk Assessment by March 2021
    Confirmatory Testing by October 2022
    Changes to Markey Authorization by October 2023

  • Factors to consider when defining priorities:
    The maximum daily dose of the drug product
    Route of administration 
    Duration of use
    Indication and consideration of special populations
    Toxicological profile of the API
    The presence of structural elements in the API or conditions in the manufacturing and packaging processes for the API or drug product, which are conducive to nitrosamine formation
    Reference: NDMA impurity in valsartan and other pharmaceutical products:
    Analytical methods for the determination of N-nitrosamines|attachment
    (3.0 MB)

  • Responsibility of manufacturers
    MAHs should complete robust risk evaluations using a holistic approach. A detailed assessment of all stages of the product’s life cycle should be done and would include the following:
    -An appropriate level of documented root cause analysis 
    -Evaluation of manufacturing controls and conditions for the APIs, nonmedicinal ingredients (excipients) and drug product
    -The potential interactions with the container closure system and
    -The potential of increased risks over the retest period for the API or the shelf life of the drug product

  • Statements or declarations by manufacturers and suppliers in lieu of completing risk assessments
    Statements and declarations provided by manufacturers and/or suppliers are not a substitute for an overall robust risk assessment by the MAH. While the knowledge and expertise offered by manufacturers is valuable and is encouraged to support the risk assessment process, manufacturer/supplier statements or declarations do not replace a documented risk assessment by the MAH.

Health Canda Guidance: