Nitrosamines risk assessment: why?
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- Опубліковано 16 тра 2020
- This is the first video of a series which will summarize how the risk assessment for nitrosamines in drug products should be done.
Since 2018, many batches of drug products have been recalled from the market due to the presence of impurities called nitrosamines, which were above the permitted limits.
But what are nitrosamines?
Their chemical structure consists of a bond between an amine and a nitroso group. Hence, they can generally be formed from the reaction between secondary or tertiary amines and a nitrosating agent.
But what is the problem caused by the exposure of the population to nitrosamines?
They are a class of compounds which can generally react with the DNA, potentially causing mutations which increase our chance of developing cancer.
However, it is important to mention that:
1. The drugs which have been recalled are not our only source of exposure to nitrosamines. There are nitrosamines in the food we eat, the water we drink, and even in the air we breathe. Drugs which contain such impurities only add a little to a basal exposure which we all already have.
2. The risk of cancer in the world population is estimated to be around 33%
3. The available data indicate that our exposure to nitrosamines through these sources increases our risk of cancer in at least 0.001 to 0.01%.
4. The acceptable limit for nitrosamines in drug products corresponds to levels even lower than our exposure through the other sources, representing a negligible increase in the risk of cancer (less than 0.001%).
5. In some cases, the recalls were because significant levels of nitrosamines had been found. However in many cases, levels only slightly above the limit were found.
But if in many cases the risk was so low, why was is necessary to recall the drugs from the market?
What happens is, regulatory agencies do not allow for the drugs on the market to present any additional risk, if this can be avoided. Even if it is lower than the risk offered by the food and other sources to which we are exposed everyday.
This is the reason why in September 2019, the regulatory agency of Europe, EMA, determined that the pharmaceutical companies must evaluate all their synthetic drug products for the risk of formation and contamination by nitrosamines.
And how should this evaluation be done?
Watch the next video to find out.
References:
EMA. EMA/217823/2019 Assessment report. v. 31, n. February, p. 1-41, 2019.
FDA Questions and Answers: NDMA impurities in ranitidine (commonly known as Zantac), available at www.fda.gov/drugs/drug-safety..., acessed on May 17, 2020.
ICH M7 (R1). Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, 2017.
LITEPLO, R. G.; MEEK, M. E.; WINDLE, W. WHO Concise International Chemical Assessment Document 38: N-nitrosodimethylamine. IPCS Concise International Chemical Assessment Documents, n. 38, 2002.
SNODIN, D. J.; ELDER, D. P. Short commentary on NDMA (N-nitrosodimethylamine) contamination of valsartan products. Regulatory Toxicology and Pharmacology, v. 103, n. April, p. 325-329, 2019.
Great video! Thank you for making this information accessible to the general public.
Bruna Claas - Create & Communicate Thank you dear 🥰
These are outstanding videos - very clear and concise, full of great information. Thank you so much!
Thank you dear!! I'm happy to know you find them useful :)
Your presentation skills are well appreciated. An informative video with great contents!
Thanks dear! :)
Good video.
It is easy to understand!! As nitrosamines are cohort of concern under ICH M7, contamination of them should be avoided strictly. I'm looking forward to the next videos.
I'm glad you like the videos!! :)
Excelente vídeo!!!!
Renata Debiagi Obrigada!! 😊
Gr8 video. Simple and very clear language.
Appreciate your presentation skills .
Thank you! :)
Nice one.
Go4Growth Media thank you!!
Hai Fernanda your videos are very useful. Please do a video on possibility of nitrosamines from activated carbon and atmospheric oxygen and nitrogen.
Hi Raja! I'm happy to know this is useful :)
E-250: sodium nitrite contributes to the formation of nitrosamines by digestion of preserved meat , however it can be hindered by consuming vitamin-C to prevent the formation of nitrosamines due to the antioxidant effect.
Which type of drug occur nitrosomine impurity ??
Great video, congratulations on your presentation skills! Can you please let me know the reference where you found the following information " 3. The available data indicate that our exposure to nitrosamines through these sources increases our risk of cancer in at least 0.001 to 0.01%."? Thank you :)
Hi Inês! These values arise from the exposure to NDMA that we have from these sources, and the references are provided in 1:34 of this video - EMA 2019 and WHO 2002, as well as Snodin 2019 (the complete reference is in the description box). These references mention that our exposure to NDMA through these sources is in the range of 0.1 to 1 ug/day.
Since for NDMA, 0.096 ug/day represents a negligible increase in the risk of cancer (1:100,000 or 0.001%), we can estimate that an exposure of 0.1 and 1 ug/day corresponds to a risk of 0.001% and 0.01%, respectively.
And we say “at least”, because in this calculation we consider only NDMA data, while we are also exposed daily to many other nitrosamines, although exposure data may not be available.
My doctor (and no one else for that matter) doesn't want to address my concern about the valsartan contamination. The FDA has chosen to downplay it.
I found out today that Rifampin (for Latent Tuberculosis) is one of these drugs with higher levels of nitrosamines found. I am taking Rifampin right now. The FDA chose not to recall this drug. What is my risk? Am I in danger by continuing this drug? My doctor did not thinks so.
Hello Luke!
I cannot tell you exactly what is your risk, since this would depend on the actual amounts of nitrosamines you have been exposed to. Maybe the company responsible for manufacturing this drug has this information, you may want to check with them.
However, considering that FDA chose not the recall this drug, this decision was probably based on a risk-benefit evaluation. I would recommend to listen to your doctor and not stop the treatment unless he tells you to, since the risk of stopping the treatment could be higher than continuing.
From where I can get more information about nitrosamine impurities?
I have included some references in the video description, but there is a lot of information at EMA's website; at Lhasa's website you can find some free webinars and even here on UA-cam. See some of the links below:
EMA's website: www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities
Lhasa's website: www.lhasalimited.org/
Webinars on UA-cam: ua-cam.com/video/QlFYfsZlPXY/v-deo.html
Dear sir any risk during handling of ndma impurities during sample preparation plz give me reply as soon as possible.
Hi dear, for more information on safety and handling I recommend accessing the ECHA website: echa.europa.eu/et/substance-information/-/substanceinfo/100.000.500
Mmmmmm😮
Sartan products banned
Nothing but promo by the bacon and hotdogs industry. Trying to change public perception of a dangerous chemical.