March 31, 2021 is the deadline for Marketing Authorization Holders (MAH) to conduct the initial risk evaluation and report results for all human pharmaceutical products and active substances at risk for the presence of nitrosamines.
Laboratory testing for the presence and identification of nitrosamine beyond established limits in any pharmaceutical product is the critical first step of a risk assessment strategy. This supports drug manufacturers identify contributing factors and level of risk of nitrosamines by performing gap assessments and if required, changes to the manufacturing and control processes.
To determine presence of nitrosamines, we have developed, validated, and qualified analytical methods using LC MS/MS to perform trace-level risk assessments of pharmaceutical products including:
- finished drug products (including Generic and over-the-counter (OTC) products),
- raw materials, and
- chemically synthesized APIs
MAHs are required to report results to Health Canada or, if in the US or Europe, to their respective regulatory authority. Assessments are not required to submitted, however be kept on file for future inspections. If nitrosamines are identified during laboratory testing, the product will then be subject to confirmatory testing to be completed by September 26, 2022.
The European Medicines Agency (EMA) first became aware of nitrosamines, a known carcinogen, in medicines in mid-2018 when it was first detected in sartan, an API used in blood pressure medications. Warnings and recalls have since expanded to include angiotensin II receptor blockers (ARBs), nizatidine, and ranitidine.
As there are many products in the marketplace, prioritization for evaluation and confirmatory testing is being placed to the highest risk products. Prioritization factors include and not limited to daily dose requirements for patients and length of treatment.
Investigative and enforcement activities are expected to continue as a coordinated effort between Canada, US, and Europe to identify and control the presence of Nitrosamine impurities in products at risk of N-nitrosamine formation, contamination, or cross-contamination. For example, as recently as February 11th, the EMA issued a requirement to test for the presence of nitrosamines in some batches of rifampicin-containing medicines as a precautionary measure.
Contact us if you require support with initial and confirmatory nitrosamines testing for existing and new products. A listing of our methods for nitrosamines testing can be found here.
Canadian Analytical Laboratories is a Health Canada and FDA registered facility. We provide pharmaceutical manufacturers with cost-effective quality control testing, method development and regulatory compliance support for Rx, OTC, Precursor Class A controlled substances delivered with expertise and fast turnaround times.