FDA WARNING_LETTER - Jon B. Cole, MD - April 26, 2019

This Warning Letter, Ref: 21-HFD-45-04-01, dated October 19, 2021, addresses objectionable conditions observed during an FDA inspection of Dr. Cole's clinical site from April 10 to April 26, 2019. The inspection, part of FDA’s Bioresearch Monitoring Program, reviewed Dr. Cole's conduct as a sponsor-investigator for two clinical investigations: Protocol HSR 14-3841 ("Ketamine vs. Haloperidol for Severe Agitation") and Protocol HSR 17-4306 ("Ketamine vs. Midazolam for Severe Agitation").

The primary violation identified was 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. Cole argued the drugs were treatments, not research interventions, and that the studies met IND exemption criteria under 21 CFR 312.2(b)(1).

The FDA refuted these arguments, stating the protocols pre-specified drug interventions, limited EMT-P clinical judgment, and involved the removal of alternative treatments, thus constituting clinical investigations. Furthermore, the studies did not meet the IND exemption criteria, specifically 21 CFR 312.2(b)(1)(iii), because