Aemps withdraws Ranitidine tablets from 16 pharmaceutical companies for containing N-nitrosodimethylamine, a possible carcinogen for humans

 

On September 13th, the Spanish Agency for Medicines and Health Products (Aemps) ordered the withdrawal of all drugs in tablets (see list) containing Ranitidine, belonging to 16 pharmaceutical companies, from the European and international markets, after having detected that they contained an impurity with possible carcinogen effect.

According to the Aemps, before ‘the potential risk derived from the accumulative effect of this impurity’ they have decided to adopt ‘prevention measures to avoid its presence in medicines’.

Aemps’ Headquarters – Spanish Agency for Medicines and Health Products

 

Ranitidine is used to reduce acid production in the stomach in cases of gastric ulcer or gastroesophageal reflux. The impurity found in the aforementioned medicine is N-Nitrosodimethylamine, a substance that has demonstrated that increases the risk of having lung and other cancer, in animals.

The International Agency for Cancer Research of the World Health Organization rates this impurity as level 2A, ‘probably carcinogenic for humans’, which means that the association between the product and the tumours is not supported by clinical trials but, according to its results on animals, it is likely to have it in humans.

Nevertheless, intravenous Ranitidine medicines remain on the market and are not subject to withdrawal, as they are essential in some therapeutical indications such as the hypersensitivity prevention and reactions related to the infusion with paclitaxel and patisiran.

In 2018, more than a hundred different medicines for high blood pressure, like valsartan, were withdrawal, for containing the same type of impurity. In this case, the impurity was originated as a consequence of a change in the manufacturing process of the API, which changed the final result of the recipe. 

In front of another alarming case in the pharmaceutical industry, after the incident of almost 20 babies affected by hypertrichosis due to intake Omeprazole contaminated with Minoxidil, and after the evaluation, across the whole continent, the European Medicines Agency (EMA) has concluded that the manufacturing processes requirements of some medicines should be hardened. 

According to sources from Farmaindustria, the employer of the sector, ‘Although it is not expected that such impurities are formed during the synthesis of the vast majority of active substances, it cannot be ruled out that in certain synthetic routes, or during the production process under certain conditions, these impurities appear, so they must be controlled and eliminated during the manufacturing process’.

Every day succeed food fraud cases that can go more or less unnoticed, such as the presence of horse meat in pork meat or flour in cocoa powder, among many others. However, cases of drug contamination that may affect our health integrity should not be heard. These type of news should lay the groundwork for all these companies that handle medicines and active ingredients to take much more exhaustive and objective quality control measures. 

In IRIS Technology we all are ‘evangelists’ of the PAT systems (Process Analytical Technologies) since we landed on the Industry 4.0 world. We understand the added value that provides having in-line and real-time quality control systems that nurture the manufacturing process and ensure the quality of the final product. 

The implementation of PAT systems in the production line involves the control of the process by monitoring the target features (what the process is aimed at) not only supervising and adjusting the conditions according to optimum criteria of the traditional recipe. This target features usually require chemical analysis or complex physical properties determination as opposed to only measure simply properties such as temperature, pH or flow rate. A PAT approach is aimed by design to improve the efficiency of the manufacturing process while enabling quality costs savings by moving quality control closer to the production line (in-line, at-line, online) and far away from post-manufacturing quality laboratories.

 

If you wish to know more about our PAT systems, don’t hesitate to contact us: info@iristechnology.com