Nitrosamine Impurities Testing and Analysis
Nitrosamine impurities became a focus for the pharmaceutical industry in July 2018 after a recall was announced for Sartans due to the presence of the carcinogenic impurity, N-nitrosodimethylamine (NDMA).
An increase in observations of nitrosamine contamination in various finished products, drug substances and drug product batches has led regulatory bodies to mandate the screening of these impurities on a global scale.
Active pharmaceutical ingredients (APIs) and drug products (containing chemically synthesized APIs) may be at risk of containing nitrosamines. Eurofins BioPharma Product Testing Toronto Inc can assist you with identifying nitrosamine impurities in drug products and APIs.
Step 1: Risk Assessment
- Evaluation of medicinal products containing chemically synthesized APIs, where our expertise in regulatory affairs can assist with the risk assessment.
A risk assessment of the manufacturing process helps drug manufacturers identify potential sources of nitrosamine formation to implement proper controls. Market Authorization Holders (MAHs) of affected medications are responsible for conducting this risk assessment.
Step 2: Confirmatory Testing of API and FP
- Our GMP labs use validated and sensitive methods specific to your products.
Confirmatory Testing is required if a risk is identified from the risk assessment. Our lab in Toronto offers confirmatory testing of nitrosamines by LCMS/MS to determine trace impurity levels of nitrosamine contamination. Analytical method qualification, method development, and method validation is available for determination in specific product matrices per GMP requirements.
Our laboratories specialize in method development and validation for highly sensitive and specific methods to help face the challenges of low detection levels of nitrosamine impurities, difficult and complex matrices and identification of unknown impurities during the pharmaceutical method development process.
Step 3: Changes to the Marketing Authorization
- For MAHs to introduce any required changes, such as an amendment of the manufacturing process or changes to product specifications.
Health Canada's deadline for confirmatory testing is on October 1, 2022.
Health Canada has listed the following affected medications for potential nitrosamines contamination:
- Sartans or Angiotensin II Receptor Blockers (ARBs) valsartan, candesartan, irbesartan, losartan and olmesartan
- Metformin
- Nizatidine (brand name Axid)
- Pioglitazone
- Ranitidine
- Rifampin
- Priftin (rifapentine)
- Rifadin IV (rifampin)
- Varenicline
- Orphenadrine
- Amitriptyline
Common nitrosamine targets:
- NDMA (N-nitrosodimethylamine)
- NDEA (N-nitrosodiethylamine)
- NEIPA (N-nitrosoethylisopropyleneamine)
- NDIPA (N-nitrosodiisopropylamine)
- NDBA (N-nitrosodibutylamine)
- NMBA (N-nitroso-N-methyl-4-aminobutyric acid)
- MNP (1-methyl-4-nitrosopiperazine)
- NMPA (N-nitrosomethylphenylamine)
(Capabilities for other nitrosamine impurities may be available upon discussion.)