Q&A Nitrosamine SAR working group (23 companies and universities)

[Naiffer_Host]

#OpenQ&A
This PPT was presented by Kevin P. Cross, PhD (Instem PLC) @kpcross and David J. Ponting, Ph.D. (Lhasa Limited) @David at QSAR 2021 and describes Lhasa and Instem’s collaborative efforts in the area of N -nitrosamine assessment, including the nitrosamine SAR working group - currently comprising of 23 companies and universities.

QSAR2021 Cross Nitrosamines SAR FINAL.pdf (790.9 KB)

[DAB]

Hi Naiffer @Naiffer_Host ,
Thanks for sharing. This is a very important Topic that requires more attention & understanding.

[Naiffer_Host]

@DAB I will be on the lookout for today’s webinar recording by @David and @MichaelBurns on exactly this topic.
Michael walked us through a fantastic compile knowledge surrounding the formation of the N-nitroso moiety.

[DAB]

@Naiffer_Host
Thanks, the entire session is worth a revisit.
Thanks to all the Presenters for putting together such an excellent broadcast, it was perhaps the first session which provided Insights into Drug Product RA by GSK and Libbs, lots of knowledge sharing

[MichaelBurns]

Thanks @Naiffer_Host and @DAB. I’m pleased you found the presentations useful. I believe the talks are now available online. The slides can be found here, and i believe recordings will also be made available shortly.

https://www.lhasalimited.org/events/2021-webinar-lhasa-limited-nitrosamine-impurity-workshop/9161

[Yosukemino]

Hi, @MichaelBurns. It was a very fantastic workshop. And I made a new thread to discuss further. Recordings have already been uploaded, so I will watch them repeatedly later.

2021 Webinar | Lhasa Limited Nitrosamine Impurity Workshop

I share the materials and recording of Nitrosamine Impurity Workshop by Lhasa. It is one of the most impressive and informative workshop, I think. If you have missed it, please confirm it. https://www.lhasalimited.org/events/2021-webinar-lhasa-limited-nitrosamine-impurity-workshop/9161 And please share what you are interested in.

And I also introduce you another thread. Your knowledge is definitely helpful for other participants, I think. Chemistry of formulation may be different from just chemical reactions, however I would like you to post your thoughts.

Adding trapping agents capable of scavenging adventitious nitrosating agents?

At recent FDA’s Generic Drug Science and Research Initiative Public Workshop, our very own @ASrinivasan introduced the concept of ‘Blocking Nitrosamines formation in Drug Products’ Preliminary review of Drug Substances approved by FDA and listed in USP showed that: ~95 Drugs which are secondary amines ~65 Drugs with dimethylamino groups (alerts for NDMA formation) ~135 Drugs which are tertiary amines In order to avoid formation of nitrosamines in drugs, amines and/or nitrites/nitrosating …

[kpcross]

The latest from the Nitrosamine SAR workgroup is a Tox Forum Symposium on nitrosamines on August 2, 2021. Here is the symposium description.nitrosamine_toxforum_session_summer_2021_FINAL.pdf (143.2 KB) And there are the slides from my presentation. Tox Forum 2021 Cross Nitrosamines SAR no audio.pdf (849.0 KB)
I have also recorded this presentation if people are interested I can make it available.

[Naiffer_Host]

@kpcross We will welcome the opportunity to re-watch the presentation that you kindly upload slides from. Let mw know if I can assist you with sharing the recording. Thx

Do you know if we can access @jbercu slides? We have been discussing in the community details from " Use of less-than-lifetime (LTL) durational limits for nitrosamines: Case study of N-Nitrosodiethylamine (NDEA)" Redirecting

[Naiffer_Host]

From @MonazBmysorewala

@MonazBmysorewala

Hi, All, Hope everything well at your end! Wanted to share my recent experience to qualify Nitrosamine Impurity in Major Antidepressant Drug. It was new nitrosamine impurity not similar to 7 identified listed nitrosamine impurities mentioned in USFDA guidance. Hence, initially, I looked for data, however, no information in public domain was located. Based on visual inspection, it appeared to similar to NDMA. Therefore, I suggested that as per SAR characterization, if we are able to prove that it is similar to NDMA, then TD50 of NDMA can be extrapolated to derive AI for impurity in question. If we are still not able to prove then, it needs to restrict at 18 ng/ day or conduct Ames as well as in vivo Gene Mutation assay. Thanking you in anticipation.

[kpcross]

You will have to contact Joel Bercu for his slides.

[DAB]

Thank you Kevin @kpcross .
Appreciate if you could share the recording with the community.

[kpcross]

If you desire to listen to me narrate my Tox Forum slides you can do so with this link:

[DAB]

Thanks Kevin @kpcross, Appreciate your prompt repsonse.