FDA WARNING_LETTER - Robert J. Hayashi, M.D./Washington University School of Medicine, Department of Pediatrics - July 08, 2022

This Warning Letter, Ref.: 23-HFD-45-03-02, dated March 14, 2023, addresses objectionable conditions observed during an FDA inspection of Dr. Hayashi's clinical site between June 23, 2022, and July 8, 2022. The inspection, part of FDA’s Bioresearch Monitoring Program, evaluated the conduct of clinical investigations and protection of human subjects, specifically focusing on Protocols (b)(4) and (b)(4).

The FDA found that Dr. Hayashi failed to ensure the investigation was conducted according to the investigational plan, violating 21 CFR 312.60.

Specific violations include: 1. **Protocol (b)(4) Deviation:** A 5-year-old pediatric subject (b)(6) randomized to the (b)(4) was administered 12 mg of (b)(4) on Day 1 of the final two cycles of maintenance therapy (Cycles 5 and 6), contrary to the protocol requirement to omit this treatment. This led to unnecessary invasive procedures (lumbar punctures, general/local anesthesia) and increased risk of neurotoxicity and infection. 2. **Protocol (b)(4) Deviation:** Subject (b)(6), the only enrolled subject, received a 3-day course of (b)(4) despite not meeting the required (b