ANVISA starts nitrosamine monitoring program
Brazil counts now on the Medicines Nitrosamine Monitoring Special Program, developed by ANVISA to deepen investigation on impurities presence of Nitrosamine in active pharmaceutical ingredients (APIs) and medicines. The focus of such program are medicines of the category known as Sartans, generally used for high blood pressure control.
The program, which might get started in September, will be coordinated by the Agency and developed in two phases, with the collaboration of the National Institute of Quality Control (INCQS/Fiocruz).
Although considered chemical compounds usually found in water, vegetables and other food, in 2018 the N-nitrosamines or nitrosamines were detected in medicines, as result of changes in APIs manufacturing, bringing a global alert about its probable carcinogenic potential for humans.
Therefore, the nitrosamine monitoring program is one more ANVISA’s step towards protecting public health and to ensure quality, efficacy and safe of medicines for human use.
In the first phase of the program, companies interested in participating of the monitoring will be able to voluntarily send samples of medicines and APIs Losartan and Valsartan to the INCQS, which will perform laboratory analysis to identification and quantification of nitrosamines. Such interested companies must fulfill a form with product data, prior to sending it to INCQS.
In the second phase, samples of such products and also of others will be analyzed by ANVISA and by other entities of local (states and municipalities) health surveillance, pursuant to the provided on Law 6.437/1977. The chronogram of analysis of the program estimate investigation of a total of nine active principles up to June 2021.
Origen of nitrosamines
The N-nitrosamines or nitrosamines are compounds usually found in water, smoked food and grilled, dairy and vegetables. Its known that exposition to those compounds within the safe limits represents low risk to health grievances. However, beyond the acceptable levels and for prolonged periods, exposing to nitrosamines may increase the risk of cancer incidence.
In case of medicines, in July 2018, the German Regulatory Agency (Federal Institute for Drugs and Medical Devices – BfArM) and the European Medicines Agency – EMA withdrew the marketing of generics of Valsartan drug when was discovered that changes in manufacturing process of the API Valsartan took to origination of impurity N-nitrosodimethylamine (NDMA) in batches that were produced by a Chinese company.
In the following weeks, it was identified that the API of other manufacturers also had the same impurity. The NDMA is highly toxic, specially to the liver, and recognized as carcinogenic by studies performed in animals, being classified by the International Agency of Cancer Research as probably carcinogenic for humans.
Since those moment, it was observed the occurrence of reports about other APIs, of other therapeutic types, that also are known or suspected pioneers of contain NDMA and other nitrosamines potentially carcinogenic as well.
In Brazil, ANVISA withdrew approximately 200 batches of medicines of Sartanas type. Besides, the Agency suspended the manufacturing, import, supply, marketing and use of APIs with suspect of contamination. In total, were made 14 suspensions of three ingredients.
Check the news on this theme: Approved regulation on nitrosamines
Considering the importance of this theme, ANVISA published, in May 2019, the Resolution of Board Directors (RDC) 283, which established the necessity of the productive sector to investigate, control and eliminate nitrosamines potentially carcinogenic in angiotensin II antagonists receptor, which have vasodilator function in the organism.
Therefore, the special monitoring program started now is a complement to the actions that have been already adopted by the Agency. It is important highlight that the voluntary participation of the interested in the first phase of the program aim to stimulate the adherence of the productive sector to adopt collaborative measures to face the problem.
The design of the program was presented in a meeting with the productive sector, hold on September 16th, 2020.
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