FDA WARNING_LETTER - Aqua, Keith A. M.D. - March 17, 2014

The FDA issued a Warning Letter to Keith A. Aqua, M.D., following an inspection from February 3 to March 17, 2014, regarding his conduct of clinical investigations for the investigational drug (b)(4) under Protocols (b)(4) and (b)(4). The inspection, part of the Bioresearch Monitoring Program, found that Dr. Aqua failed to ensure the investigation was conducted according to the investigational plan, violating 21 CFR 312.60.

Specifically, site staff, not subjects, recorded pain-intensity scores for 23 subjects across both protocols, despite the primary efficacy endpoint relying on self-recorded scores. Dr. Aqua's response stated staff were instructed by the CRO to record scores and cited difficulty for subjects to self-record post-operatively. While corrective actions were noted, the FDA deemed the response inadequate due to a lack of detailed implementation plans.

Additionally, Dr. Aqua failed to obtain required local laboratory results (ALT, AST, total bilirubin, creatinine, BUN) at screening or study termination for 8 of 13 subjects in Protocol (b)(4) and 2 of 3 subjects in Protocol (b)(4). Dr. Aqua's response cited difficulties in obtaining tests. His proposed corrective actions, including personal review of lab results, were also deemed inadequate due to insufficient detail.

The FDA requires Dr. Aqua to address these deficiencies and establish procedures for