Merck & Company – FDA EIR, Jan 20, 2021

An FDA surveillance inspection of Merck & Company's Rahway, NJ facility was conducted from January 11 to January 20, 2021, under the Sponsors, Contract Research Organizations, and Monitors Compliance Program Guidance Manual (CPGM) 7348.810. The inspection focused on clinical trial activities related to IND 132120 [MK-6482]. The primary observation cited on a Form FDA-483, referencing 21 CFR 312.50, was a failure to ensure proper study monitoring, specifically the untimely submission of monitoring follow-up letters to clinical sites. For example, Site 011 had 11 out of 22 letters submitted late, and Site 040 had 9 out of 21 submitted late, exceeding the stipulated timeframe in the Clinical Monitoring Plan. Additionally, management discussions highlighted two significant concerns. First, the protocol deviation management plan lacked approval signatures and change control documentation, raising questions about its formal implementation and oversight. Second, there was inadequate evidence of monitors retraining clinical site personnel to address recurring protocol deviations, such as a high percentage of "Out of Window" visits at Site 011, indicating a lack of vigilance in preventing repeated non-compliance. Merck management, represented by Ms. Deborah Driscoll and Mr. Andrew Lee, committed to investigating the observations, providing a written response to the FDA-483 within 15 business days, ensuring future protocol deviation plans have proper controls, and improving monitor retraining to address and prevent repeated deviations effectively. They also pledged to include a study impact analysis of protocol deviations in the clinical study report.