FDA WARNING_LETTER - Binh Bui-Nguyen, MD - September 19, 2014

The FDA issued a Warning Letter to Dr. Binh Bui Nguyen following an inspection from September 17-19, 2014, regarding clinical investigations of the investigational drug (b)(4) for Protocol (b)(4) and Protocol (b)(4). The inspection, part of the Bioresearch Monitoring Program, found that Dr. Bui failed to adhere to statutory requirements and FDA regulations, specifically 21 CFR 312.60, by not ensuring the investigation was conducted according to the investigational plan.

Key violations include: 1. **Failure to perform required laboratory tests:** Subjects in both protocols missed scheduled hematologic laboratory tests, which are crucial safety assessments for monitoring (b)(4)-related adverse events like neutropenia. For Protocol (b)(4), subjects missed urine dipstick tests and 24-hour urine collections, which monitor for renal disorders, and TSH collections. Dr. Bui's response attributing this to subject noncompliance was deemed inadequate due to insufficient detail and documentation of corrective actions. 2. **Failure to adhere to treatment modification rules:** For Protocol (b)(4), a subject experienced creatinine clearance below the threshold requiring treatment interruption, but this action was not taken, leading to worsening renal function. Dr. Bui's explanation that the renal insufficiency was tumor-related and "non-threatening" was rejected as the cause does not negate the protocol's treatment modification rules.