Holub, Richard, MD – FDA Warning Letter, Oct 18, 2007

On September 4-October 18, 2007, the FDA inspected Dr. Richard Holub's conduct of three clinical investigations for Alzheimer's disease drugs. The inspection revealed non-adherence to statutory requirements and FDA regulations, specifically 21 CFR 312.60, 312.62(a), 312.62(c), 312.62(b), and 21 CFR Part 50.

Key violations include: 1. **Failure to personally conduct or supervise the investigation (21 CFR 312.60):** Inadequate supervision led to protocol violations, insufficient drug accountability, improper informed consent, missing records, and inaccurate case histories. 2. **Failure to ensure investigation conducted per signed investigator statement and investigational plan (21 CFR 312.60):** This included non-sequential subject numbering, unperformed protocol-required tests (MRI/CT, MMSE, Modified Hachinski, physical exams, lab assessments), incorrect subject number assignments, enrollment of an excluded subject (taking Aleve), and unlisted study coordinators on Form FDA 1572 who performed significant study activities. 3. **Failure to maintain adequate and accurate drug disposition records (21 CFR 312.62(a)):** Subjects received incorrect study medication kits. 4. **Failure to obtain informed consent