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.
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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:
https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/medications-guidance.html