AAM GRx + Biosims 2023 -Event

My USP colleagues are at AAM’s ‘Regulatory Science and Policy Conference for Generics + Biosimilars professionals’ hosting a General session on USP’s efforts to support industry (Nitrosamines Exchange included!)

A special session, ‘What can Industry and FDA do to tackle Nitrosamines impurities’ will have representatives from Amneal, Apotex, Lupin, and FDA OCP, OPQ, OLDP, ORS

It will be interesting to hear firsthand several representatives from the FDA after the August Nitrosamine policy revision. I will bring you some of the highlights and questions asked to the panel discussion!


Certainly, it will undoubtedly be another significant opportunity for discussion and learning in light of the most recent events.


Signs of Progress on the Nitrosamine Front

I found an interesting article on the webpage of Contract Pharma. I guess there were lots of fruitful discussions in it.

  • Bioequivalency after formulation change

Both speakers noted that in vitro studies and PBPK modeling studies have the potential to demonstrate bioequivalence (BE), as do other novel approaches that do not require in vivo BE data and that FDA is open to considering all options.

  • challenges that were not adequately addressed with the NDSRI guidance

The main points were allowing the use of a less-than-lifetime approach for some drugs, the low analytical thresholds needed for low maximum daily dose drugs, the lack of information and feedback on filing strategies to approach FDA with alternative limits, as well as the challenge of the extended timelines for companies with a broad portfolio of products.

  • sign of progress (in FDA letter)

There were also signs of progress mentioned in a recent FDA letter sent to an applicant with an NDSRI deficiency where the FDA agreed that in the interest of public health that they would classify the response amendment to be MINOR to allow for a shortened review in this or any subsequent review cycle. This is fantastic news and the first sign of progress on pending applications since the NDSRI guidance was published.

Finally, collaboration and cooperation were key themes throughout the conference and are important in the visualization and realization of shared goals, I agree with the author.


Some reflections from Dr Aloka @ASrinivasan about the workshop as well as her presentation

taken from her LinkedIn post:

The AAM’s GRX and Biosims Conference just got over yesterday. It is always a wonderful opportunity to meet friends from FDA and Industry and listen to their opinions and also catch up. The agenda was wonderful, most of the sessions gave valuable insight into the current issues in generic and biosimilar industry. I especially loved the session on Q1/Q2 for parenterals and other dosage forms and also the one on Complex Generics. The presentations were kept to a minimum and the discussion was based on the questions from the audience where very eye opening. In contrast the nitrosamine session had numerous presenters and the Q&A were somehow not related to anything we were actually seeing the dashboard. Attendees left a bit disappointed. They were hoping to hear from FDA and their industry partners regarding how some hurdles are being overcome. There were unadressed questions on CBE 30 vs PAS for these changes related to nitrosamines, which was upvoted, which we wish was addressed. Attendees also wanted to know what they could do if the AMES Test was negative to derisk their nitrosamine, other than a transgenic rhodent assay. These are critical questions as they amount to stopping distribution vs keeping the distribution going for some critical products. Again, critical product for a company may not essentially mean somthing that is in shortage, but something that keeps them afloat and helps sustenance. Regarding my part, I presented in the Expo of what I think is going to still be an issue. CPCA while a good interim solution, is not all encompassing as impact of several functional groups are not addressed and ~30% NDSRIs have a limit of 26.5 ng/day based on the hypothetical calculations. Read across studies to find a if there is a suitable surrogate, should always be tried so that, if your product fails the limits based on CPCA, you have a fall back and you also give the regulators a chance to see if the product can be salvaged. I am providing a link to the power point presentation from which my poster was adopted, below, so that people can clearly read it.

Poster-Presentation-from-GRX_Biosims2023.pdf (1.0 MB)


Thanks Naiffer, we all praised your efforts as one of the best initiatives of USP :smiley:

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Thank you for posting @ASrinivasan’s comment and presentation, @Naiffer_Host. I perfectly agree with her. Pharmaceutical companies are now struggling and overcoming nitrosamines contamination issues takes longer. CPCA is helpful in many cases but not almighty. Read across can be applied to only limited nitrosamines. The scientific progress so far is eye-opening, but it’s not enough in certain cases. We want to know further mitigation like the LTL approach, Mw correction of AIs, and other in vivo tests. We also want to know how to prioritize the product for proceeding with risk assessment until or over the deadline. In conclusion, we need further discussion.

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