Tablets & Capsules

© Copyright Tablets & Capsules 2020 usp.org FDA warning letters cite drug manufacturers for failing to test excipients or verify COAs By John Giannone, Michael Rashed, Peter Claise, and Doug Podolsky This article discusses the recent increase in FDA warning letters citing cGMP violations related to excipients and describes USP's analysis of the excipient-related warning letters issued from 2013 through 2018. It also explains how USP's programs and resources can help drug companies comply with FDA regulations. In 2017 and 2018, the FDA's Center for Drug Evaluation and Research (CDER) issued 38 warning letters to phar- maceutical firms in the US and 12 other countries for fail- ing to test for identity of incoming excipients, failing to verify the information on excipient suppliers' certificates of analysis (COAs) at regular intervals, or both. This com- pares with three warning letters in the four years from 2013 to 2016 that specifically cited excipients or inactive ingredients, according to an analysis by the US Pharma- copeia (USP) of FDA warning letters issued between 2013 and 2018. This increase represents a significant uptick in warning letters that expressly identify excipients or inac- tive ingredients in current good manufacturing practice (cGMP) violations. We note that a majority of the 38 warning letters issued in 2017 and 2018 were sent to firms that manufacture over-the-counter (OTC) medicines. FDA has stated that in the past several years it has been working to inspect all facilities that had not been previously inspected [1]. The agency also noted that this work has contributed to an increase in basic cGMP problems identified in facilities making lower-risk OTC medicines. According to the FDA's Regulatory Procedures Manual, the agency issues warning letters for violations of reg- ulatory significance. The FDA warning letters analyzed by USP are written notifications that the FDA has found manufacturers to have violated cGMP regulations such that their drug products are adulterated within the mean- ing of the Federal Food, Drug, and Cosmetic (FD&C) Act. The letters also inform the companies that they are re- sponsible for correcting the problems cited and informing the FDA of their plans for correction. Warning letters give firms an opportunity to take voluntary and prompt cor- rective action before the agency initiates an enforcement action, if warranted. © Copyright Tablets & Capsules 2020 usp.org 5

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