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 [ Ссылка ], 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.

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