[description continued] Based on the ICH M7 Questions and Answers, the LTL approach is not applicable when we calculate the limit based on the PDE, although it is applicable when the limit is based on the AI. This is because the PDE calculation already incorporates a factor for time adjustment, which is not true for the AI. Because the AI is based on a lifetime TD50, when the exposure is for less than a lifetime, this needs to be adjusted. This less than lifetime approach that we have described, including the safety factors, has been successfully applied in many different industries to protect from carcinogenic risk. In the scope of ICH M7, it not only allows for more achievable limits to be applied by the industry who needs to control low level impurities, but also gives us a much more realistic estimation of risk. References: Halmes N.C. et al, 2000. Reevaluating cancer risk estimates for short-term exposure scenarios. Toxicological Sciences, 58, 32-42, 2000. Johnson G.E. et al, 2009. Non-linear dose-response of DNA-reactive genotoxins: Recommendations for data analysis. Mutation Research 678, 95-100. US EPA, 2005. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001F. Washington, DC: Risk Assessment Forum. Available at: www.epa.gov/cancerguidelines/ Felter, S.P., et al., 2011. A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens. Crit. Rev. Toxicol. 41, 507-544. International Conference on Harmonisation (ICH), 2017. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. M7(R1). Peto, R., et al., 1991. Dose and time relationships for tumor induction in the liver and esophagus of 4080 inbred rats by chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine. Canc. Res. 51, 6452-6469
If the world had more people like you, it would be a better place. You make a difference, Dr uromi thank you for curing my Herpes Type 2 and introducing your medical products to the worlds
Best information provided, mutagenic impurities, nitrosamine impurities are the concerns in many APIs. All information u covered in your video, again one request, can you plz make video on steps in APIs synthesis. Thanks
@@FernandaWaechter Hi Fernanda, I am so glad to see your reply, my request is please explain, how many steps are involved in API synthesis, what are the things research scientist should keep in mind before API synthesis. Steps like patent search, then raw materials ordering, then process development, validation, then exhibit on plant scale. Can you please arrange it and explain in one video.
[description continued]
Based on the ICH M7 Questions and Answers, the LTL approach is not applicable when we calculate the limit based on the PDE, although it is applicable when the limit is based on the AI.
This is because the PDE calculation already incorporates a factor for time adjustment, which is not true for the AI.
Because the AI is based on a lifetime TD50, when the exposure is for less than a lifetime, this needs to be adjusted.
This less than lifetime approach that we have described, including the safety factors, has been successfully applied in many different industries to protect from carcinogenic risk. In the scope of ICH M7, it not only allows for more achievable limits to be applied by the industry who needs to control low level impurities, but also gives us a much more realistic estimation of risk.
References:
Halmes N.C. et al, 2000. Reevaluating cancer risk estimates for short-term exposure scenarios. Toxicological Sciences, 58, 32-42, 2000.
Johnson G.E. et al, 2009. Non-linear dose-response of DNA-reactive genotoxins: Recommendations for data analysis. Mutation Research 678, 95-100.
US EPA, 2005. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001F. Washington, DC: Risk Assessment Forum. Available at: www.epa.gov/cancerguidelines/
Felter, S.P., et al., 2011. A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens. Crit. Rev. Toxicol. 41, 507-544.
International Conference on Harmonisation (ICH), 2017. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. M7(R1).
Peto, R., et al., 1991. Dose and time relationships for tumor induction in the liver and esophagus of 4080 inbred rats by chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine. Canc. Res. 51, 6452-6469
Thank you for creating these presentations which are easy to understand for non-toxicologist ✌🏻👏🏼
Hi Pragnesh, it's my pleasure! I'm happy to know you like them :)
Love your work! You make these complex subjects so easy to learn
Thanks Joel!! :) and thanks for all your help, I always learn a lot from you
Beautifully clear. Love it! Please create more content! Obrigada!
Thank you dear! :)
Thank you so much...it was much awaited. Curious to see next one.
Perfeito, Fer. Super parabéns!!!!
Obrigada Andressitaa!
Thank you very much..for explaining in simple way
Arrasou Fer!!! Parabéns por mais um vídeo informativo e mto esclarecedor!
Obrigadaa Mariah!! :)
If the world had more people like you, it would be a better place. You make a difference, Dr uromi thank you for curing my Herpes Type 2 and introducing your medical products to the worlds
I love your video！Your video is very helpful to me. looking forward to your new video，Please create more !
Thank you dear! Happy to know it was helpful! :)
Hi ....you are simply amazing
Best information provided, mutagenic impurities, nitrosamine impurities are the concerns in many APIs. All information u covered in your video, again one request, can you plz make video on steps in APIs synthesis. Thanks
Hi Bhushan, I'm glad you like this video! Could you please clarify what you would like to see covered about steps in API synthesis?
@@FernandaWaechter Hi Fernanda, I am so glad to see your reply, my request is please explain, how many steps are involved in API synthesis, what are the things research scientist should keep in mind before API synthesis. Steps like patent search, then raw materials ordering, then process development, validation, then exhibit on plant scale. Can you please arrange it and explain in one video.
👍👍👍👍👍
Dame nostra
Good presentation