It includes lots of helpful information concerned with nitrosamines risk assessment such as STEP1 outcome in EMA, STEP2 challenges and safety challenges. You can find there are lots of residual challenges which include definition of “no risk” is not clear, the rules used in ICH M7 is not always valid and there are serious gaps among guidelines in several authority. In addition that, challenges in confirmatory testing which will come next are also mentioned. To solve these problems, understanding of the science will be the key. I perfectly agree with it. What do you think about it?
I agree Yosuke.
Without understanding the chemistry behind the formation of the impurities it´s more difficult to stablish the urgency and need for control/analysis, and of course to find the best analytical methods for testing.
@Yosukemino Thanks for sharing the paper… waiting on my library to send me a copy. Andy does a fantastic job exposing the industry challenges. I’m really interested in reactions from some of the FDA answers to the industry during the joint meeting last May 4th. I would even dare to say that FDA’s strong stand will have a very important effect on emerging regulations from some agencies. At least that has been my reading from discussion with certain regulatory representatives.
@Frabaneda did you chance to review Christopher, @MichaelBurns, Timothy, and Nathan publication. It’s a wonderful insight into reactions that have the potential to destroy the nitrosamine’s moiety. The Nitrosamine chemistry explored is not just fascinating but also a window to how complex it can be.
I would welcome any comment from our organic & medicinal chemist on this.
Thanks @Yosukemino for sharing.
Understanding the Chemistry of Nitrosamine formation & it’s fate in the process is the key to successful Nitrosamine Risk Assessments that will decide the way forward wrt Testing strategies.
Thank you for the information, is this the only document that contains the results of the Step 1 risk assessment in the EMA?
As for the FDA, are the results of the Step 1 risk assessment available to the public?
@Katahira I’m not aware of any FDA report on the current status of Nitrosamine Metrics. Perhaps a good topic to inquire the agency about. Also remember that different than EMA, FDA did not ask manufacturers to send their risk assessment documentation.
Thank you for your response. I will take the information you provided into consideration. I did not know that the FDA does not require the step1 reports. FDA website stated that "FDA expects risk assessments (step 1) to have been already completed as the recommended completion date was March 31, 2021 ", so they may be not know the Step1 results.
Here, they explain the current situation and prospects related to Nitrosamine Impurities. And there are lots of challenges despite the closed deadline. I perfectly agree with them. The new pragmatic interim limit is needed!!
@AndyTeasdale explained the current challenges for nitrosamine contamination in the pharmaceuticals in the latest version of Regulatory Highlights. Through this article, we can understand what happened in the last four years and what we should do next. It’s excellent!!