Lauren R. Klein, MD, M.S. – FDA Warning Letter, Apr 23, 2019

This FDA Warning Letter, dated October 19, 2021, addresses Dr. Klein regarding objectionable conditions observed during an FDA inspection from April 9 to April 23, 2019. The inspection, part of the Bioresearch Monitoring Program, reviewed Dr. Klein's conduct as a sponsor-investigator for two clinical investigations: Protocol HSR 17-4345 (olanzapine, haloperidol, ziprasidone, midazolam) and Protocol HSR 18-4521 (olanzapine, midazolam), both for acute undifferentiated agitation.

The primary violation cited is the failure to submit Investigational New Drug (IND) applications for these clinical investigations, as required by 21 CFR 312.20 and 312.40(a). Dr. Klein's argument that the drugs were not research interventions and were part of standard of care was rejected. The FDA determined that the protocols pre-specified drug administration, limiting physician judgment, thus constituting clinical investigations.

Furthermore, the FDA found that the investigations did not qualify for the IND exemption under 21 CFR 312.2(b)(1), specifically failing criterion 3 (21 CFR 312.2(b)(1)(iii)). The studies significantly increased risks by not excluding subjects with drug-drug interactions or liver/kidney dysfunction, issues previously