Remember the days when the biggest concern that both consumers and the pharmaceutical industry had was about potential contamination of medications by nitrosamines? Just a few weeks ago, rumors were flying around fast and furiously among patient groups on social media, firms were issuing recalls of numerous medications, and regulators were involved in issuing policies for manufacturers to assess their manufacturing processes in order to evaluate for the risk of nitrosamine formation during manufacturing. Even though our focus has shifted onto COVID-19, soon enough hopefully, we will be back to some semblance of order, and regulators will inevitably shift their focus from detection kits and hand sanitizer production back to nitrosamines.

By means of background, nitrosamines are a class of chemical compounds that are formed when secondary amines, amides, carbamates, or derivatives of urea react with nitrite or other nitrogenous agents (like oxides of nitrogen), under a range of different pHs. The ubiquity of these functional groups within both API, excipients, starting materials, reagents, and intermediates is concerning. The nitrosamines that regulators are the most concerned about are N-Nitrosodimethylamine (NDMA), N-Nitrosodiethylamine (NDEA), and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). These compounds have been shown to be carcinogenic in toxicological testing.

FDA and other international agencies have found traces of these compounds in the following classes of drug: angiotensin II receptor blockers (ARBs), commonly known as the “sartans”, ranitidine, and metformin. However, the chemical reaction that creates nitrosamines is likely occurring in other compounds with similar structures during their manufacture that have similar conditions during synthesis. In other words, the nitrosamines that have been detected to date may be the tip of the iceberg, and there could easily be more products contaminated with nitrosamines that have not yet been detected. The question is, as a firm with multiple marketed products, what is the best way to address this? Obviously, a complete retrospective analysis of all drugs approved by FDA to date for the potential of nitrosamine formation during synthesis a herculean task. However, it is imperative that all firms understand the possible sources of nitrosamine formation in their manufacturing processes and take proactive measures to reduce the possibility.

At Lachman Consultants, we have the expertise to help you evaluate your manufacturing processes and assess your risk, according to criteria established by multiple regulatory authorities (FDA, EMA, MHRA, TGA). Why not take advantage of this obligatory downtime, and take the time to do a risk-based evaluation of your manufacturing processes now, while we have the time? If you are interested in having Lachman Consultants do a risk-based evaluation of your manufacturing processes, please contact us at