Quality Risk Management to Address Product Impurities
Recently, recalls of angiotensin receptor antagonists, particularly valsartan, and warning alerts about N-nitrosodimethylamine (NDMA) impurities in drug substances such as ranitidine and metformin have demonstrated the urgent need for manufacturers and regulators to control impurities throughout the product life cycle to ensure patient safety.1, 2, 3, 4, 5 In this article, all plausible pathways related to the formation of NDMA impurities in pharmaceutical products and a possible control strategy using quality risk management (QRM) as a tool are discussed.
- 1. US Food and Drug Administration. “Recalls of Angiotensin II Receptor Blockers (ARBs) Including Valsartan, Losartan and Irbesartan.” Updated 3 February 2020. https://www.fda.gov/drugs/drug-safety-and-availability/recalls-angiotensin-ii-receptor-blockers-arbs-including-valsartan-losartan-and-irbesartan
- 2. US Food and Drug Administration. “Statement Alerting Patients and Health Care Professionals of NDMA Found in Samples of Ranitidine.” 13 September 2019. https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine
- 3. US Food and Drug Administration. “FDA Updates and Press Announcements on NDMA in Zantac (Ranitidine).” 16 April 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine
- 4. US Food and Drug Administration. “FDA Updates and Press Announcements on NDMA in Metformin.” 13 July 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-metformin
- 5. US Food and Drug Administration. “Questions and Answers: NDMA Impurities in Ranitidine (Commonly Known as Zantac).” 1 April 2020. https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-ndma-impurities-ranitidine-commonly-known-zantac