European Medicines Agency’s (EMA) issues guidance to avoid Nitrosamine in human medicines. EMA continue to monitor the presence of nitrosamine impurities in medicines, in co-operation with regulators from outside the European Union (EU), and to work with marketing authorisation holders to find rapid solutions to address any adverse findings. EMA carried out a review Article 5(3) from September 2019 to June 2020, the guidance to marketing authorisation holders, how to avoid the presence of nitrosamine impurities in human medicines. The CHMP has asked marketing authorisation holders to review their medicines for the possible presence of nitrosamines and test all products at risk, as mentioned in theguidance and review their manufacturing processes to identify and, if necessary, mitigate the risk of presence of nitrosamine impurities in three steps. The European medicines regulatory network has agreed to extend the deadline to complete step 1 to 1st October 2020.This follows reports of the challenges encountered in meeting the original deadline of 26 March 2020, and the impact of the severe restrictions in place to combat the COVID-19 pandemic. The European medicines regulatory encourages marketing authorisation holders to submit the outcome of step 1 before 1st October 2020 if they complete the risk evaluation or identify a risk in their products. Marketing authorisation holders should inform the national competent authorities as soon as possible if tests confirm the presence of nitrosamine, irrespective of the amount detected, assess the immediate risk to patients to take appropriate action to avoid or minimise the exposure of patients to nitrosamines. The European medicines regulatory network plans to complete this exercise by 26 September 2022.
At all steps, timelines should be shortened and marketing authorization holders should immediately inform authorities if findings indicate an immediate risk to public health.
Step 1: Conduct a risk evaluation to identify active substances and finished products at risk of N-nitrosamine formation or (cross-) contamination and report by 1 October 2020. If a risk for an active substance is identified, marketing authorization holders to submit the step 1 response template and proceed with step 2 confirmatory testing of the finished product. If no risk identified, marketing authorization holders should conduct a risk evaluation of the finished product and submit the outcome of step 1 only when they reach a final conclusion on the active substance and finished product.
Step 2: Confirmatory testing on the products to be at risk of N-nitrosamine formation or (cross-) contamination.
Step 3: Apply for any necessary changes to the manufacturing process resulting from this review using the established regulatory procedures.
Nitrosamines are chemical compounds classified as probable human carcinogens on the basis of animal studies. However, there is a very low risk that nitrosamine impurities at the levels found could cause cancer in humans. EMA has asked marketing authorization holders to take precautionary measures to mitigate the risk of nitrosamine formation or presence during the manufacture of all medicines containing chemically synthesized active substances.
For detailed information visit, https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities#review-of-sartans-(angiotensin-ii-receptor-antagonists)-section