EMA Nitrosamine Guidance – Deadline March 31, 2021
In September 2019, the EMA began a review under Article 5(3) of Regulation (EC) No 726/2004 to guide marketing authorization holders (MAHs) on avoiding the presence of nitrosamine impurities in human medicines. As part of this review, the CHMP has requested MAHs to review their medications for the possible presence of nitrosamines and test all products at risk. In August 2020, the EMA published an updated version of the Q&A for MAHs and extended the scope of products with new deadlines to meet related to the risk evaluations. By March 31, 2021, for chemical medicines and July 1, 2021, for biological drugs, MAHs need to conduct a risk evaluation to identify active substances and finished products at risk of N-nitrosamine formation or (cross-)contamination and report the assessment.
MAHs should ensure that they and the manufacturing authorization holder have access to all relevant information from the API manufacturers about the potential formation of nitrosamine impurities and the potential for cross-contamination.
The call for review consists of the following three steps:
- Step 1: MAHs to perform a risk evaluation to identify if APIs and/or FPs could be at risk of the presence of N-nitrosamine under the principles outlined in Q&A 7 of the Q&A for the implementation article 5(3):
March 31, 2021, for human medicines containing chemically synthesized APIs; − to be conducted before July 1, 2021, for human medicines containing biological active substances.
- Step 2: If a risk is identified, MAHs to proceed with confirmatory testing to confirm or refute the presence of N-nitrosamines, accordance with the principles outlined in Q&As 8 and 9 of the Q&A for the implementation of Article 5(3). MAHs should report the outcomes as soon as possible.
- Step 3: If the presence of N-nitrosamine(s) is confirmed, MAHs should implement effective risk-mitigating measures through the submission of variations:
− to be undertaken before September 26, 2022, for human medicines containing chemically synthesized APIs;
− to be conducted before July 1 2023, for human medicines containing biological active substances.
MAHs are required to respond to the RAs on the outcome of step 1 and step 2 by utilizing agreed published templates provided on the EMA/ CMDh websites.
How we can help
Our regulatory and scientific experts at Dr. Reddy’s were amongst the forerunners in addressing the issue right from the beginning. We provide our customers with a full assessment for all our sartan APIs, which confirm the absence of NDMAs and analytical testing that already comply with the new acceptance limits. In addition to sartan APIs, we’ve performed a complete Step-1 nitrosamine assessment for around 270 chemically synthesized APIs.
- Call us: +91 40 49002253