Hi, I would like to gather your thoughts about something!
With the recent discussion at the HESI/FDA workshop, I came to realize that understanding the safety assessment of Nitrosamine Impurities is so critical beyond just defining a limit. A comprehensive knowledge of mutagenicity processes to de-risking a particular structure is essential to the risk assessment.
I also recognize that not every organization has at their disposal a team of toxicologists to do that expert assessment; in many instances, the responsibility falls in a small group of R&D/QC folks that got put together to perform the ‘risk assessment’ or their consultant (if applies).
We need to recognize that this knowledge will not come in the form of a recipe from the regulatory agency, a guideline document, or pharmacopeial chapter/monograph, or supplier documentation. Everybody has to go through the same learning curve to build an understanding and maturity of their product to answer the question: Is my pharmaceutical product at risk of Nitrosamines?
I need your help answering these questions:
Do we need basic education training on the toxicology of Nitrosamines for non-toxicologies?
Is there any organization that offers such training already?
Is there an organization that we could tap to develop or plan such training?
Would you be willing to participate in such training?
We might be into something essential for the entire community.
Thanks for recognizing and highlighting the importance of Toxicology for Nitrosamines risk assessment in this Global forum.
If you allow me (as a Regulatory Toxicologist) I just wanted to add few more thoughts:
Yes, you are correct “safety assessment of Nitrosamine Impurities is so critical beyond just defining a limit”. AI is just a tool or resultant of assessment.
In addition to mutagenicity, we may need to have additional facets that can confidently de-risk the structure. Hope you are aware in recent FDA/HESI workshop- FDA emphasized we need clear data…data…data…to take a call.
You are again correct stating “We need to recognize that this knowledge will not come in the form of a recipe from the regulatory agency, a guideline document, or pharmacopeia chapter/monograph, or supplier documentation”- The reason is could be a famous saying we have in our domain “Toxicological risk assessment is both an art and science”
To Answer your questions:
Do we need basic education training on the toxicology of Nitrosamines for non-toxicologist?
Ans- It would be good to have basic education training on the toxicology , that allows rationale to know how to identify hazard and risk. At the same time it would be great to have basic fundamentals on analytical and chemistry for toxicologists too!
** * Is there any organization that offers such training already?
Ans- Just to suggest few- TERA -in USA and Toxgurukul- in India. There are still more. May be other can add!
*** * Is there an organization that we could tap to develop or plan such training?
Ans- Above both suggested can help in organizing such trainings. If you need any help, I will be happy to connect you to them.
Would you be willing to participate in such training?
Ans- I would love to participate and contribute in whatever way I could do always for our community.
Last but not least- I strongly believe, It is not only toxicology, a good knowledge on chemistry, analysis, and formulation, etc (Now computational knowledge also…), all together required for an expert assessment!
So, we need all set of experts together to address this issue!
I would like to see training provided for those who are new"er" to doing this work. You are correct that not every company may have a seasoned toxicologist.
Your point about needing a significant understanding of the chemistry and analytical methodologies in addition to focused areas within toxicology is very much on target. I do fear that more than an introduction to toxicology is really required, however.
In fact, FDA has a training course, though not for nitrosamines, but called “Toxicology for non-Toxicologists” which talks about NOAEL, TD50 etc. I think a workshop would be great. I heard novice questioins in the June 15 conference, where it was being assumed that Ames Assay will give an idea of AI or the 28 day mice study can establish the AI of NDSRIs. I am a chemist but lived in the company of toxicologists for a long time, but would still attend such a course. Go Naiffer!
As another toxicologist, I would welcome a training for non-toxicologists. One of the challenges even for a toxicologist is that the nitrosamine space is very murky. There is a difference between what the science supports, and what makes a regulator comfortable. We are trying to build that bridge through scientific meetings such as HESI. But it is slow moving for sure. The science continues to advance, especially for Nitrosamines in both toxicology and chemistry. So we can provide the “state of the science”, but know the regulatory environment is still a haze.
I think science related to nitrosamines is too complex. And the toxicology for nitrosamines is also too complicated. Nevertheless, lots of people from different fields are involved with nitrosamine issues. They don’t all have to understand nitrosamines’ toxicology, but the toxicological approach is sometimes essential to solving this problem. We should learn more. We will welcome @Naiffer_Host’s suggestion!!
@Yosukemino, your statement succinctly captures the essence of the context: “They don’t all have to understand nitrosamines’ toxicology, but the toxicological approach is sometimes essential to solving this problem.”
@Naiffer_Host , certainly! I completely agree that it’s important to acknowledge that the knowledge we seek won’t be handed to us in the form of a simple recipe or guideline. Building a solid understanding of the potential risks of Nitrosamines and their impact on pharmaceutical products requires a learning curve that everyone must go through.
It may be worth considering collaborations with relevant regulatory bodies or pharmaceutical industry consortia. These organizations often have a vested interest in promoting product safety and may be open to developing or planning training initiatives on Nitrosamines.
I believe that, considering the diverse individuals actively engaged in this community, it is worth contemplating, as a humble suggestion, the establishment of a collaborative working group. However, it is important to approach this endeavor without the intention of rigidly formulating a prescriptive “recipe” or “checklist.”
I too agree that the toxicology training is required, as this is not only carrier oriented requirement but also to know the impact on individual kind of medicines we use now and then.
Please share if anybody has HESI/FDA sessions summary.
I absolutely agree. I had this discussion already 2-3 years ago concerning extractables/leachables topic. Training in some sense is required - back and forth
I can only propose what we (analytical/organic chemists in our company) tried to do to overcome this lack of knowledge.
We do not have an in-house toxicologist but an excellent external partner whom we asked to introduce us into the field of toxicology over several sessions. A very intense but efficient training.
Additionaly we discussed various approach with him on how to deal we toxicologically relevant risks during emerging during E&L or nitrosamine risk evaluation on specific projects.
I suppose if you have toxicologists or toxicology departements at your company just ask them to spend couple of hours over several weeks to tranfer some knowledge to you. It will require some time but it is worth the effort