FDA finalized a guidance to the industry regarding nitrosamine impurities, “Control of Nitrosamine Impurities in Human Drugs” in Feb 2021. However, the guidance has left the industry with more questions than answers. Post publication of the final guidance, FDA and Industry (AAM, PHARMA, CHPA) had a meeting on May 4, 2021, where the pharmaceutical industry representatives presented on how the FDA’s nitrosamine related decisions have overly impacted the innovators, generics and over the counter pharmaceutical industry alike . Agency has posted their responses to the industry’s questions in FDA website. While the document provides information regarding some of FDA’s current thinking on the nitrosamine impurities, there are several topics which need clarification. One of the major questions is related to nitrosamine drug substance related impurities (NDSRIs). The NDSRIs have their origin in the drug substance itself and thus dicult to control without understanding the source of nitrosating agent in the route of synthesis of the drug substance and the formulation of the finished product. The other question that has been troubling industry is the acceptable levels of NDSRIs in their drug products. Agency, in the May 4th, 2021 meeting has expressed that “read across” may be acceptable in setting limits of NDSRIs. However, with nitrosamine related data being far and few in literature, this may be challenging

Although almost 3 years have elapsed since the contamination incident, the FDA and other international regulatory agencies continue to face many challenges. One is that nitrosamines are formed and widely distributed in the environment—found in fresh vegetables, fruits, smoked and grilled meats and fish; in water; in the air; and formed endogenously. Therefore, eliminating or minimizing nitrosamines in drugs is problematic. Eliminating or minimizing nitrosamines as impurities in drugs begins with quality control. To date, not all root causes have been identified; new root causes continue to emerge. Factors such as stability, excipients, and storage conditions aect nitrosamine formation, hampering mitigation and control eorts.

The third edition of Nitrosamine Impurities forum scheduled on 1st -2nd June 2022, in Hyderabad will have one day conference and one day workshop. The forum aims to discuss on the recent developments related to nitrosamine impurities, the challenges facing by the pharmaceutical industry and work towards possible solutions that may lead to a world with lower levels of nitrosamines. The workshop will span over 5 hours with an open discussion and question and answer session.