Lauren R. Klein, MD, M.S. — FDA Warning Letter Findings

In the case of a lawfully marketed prescription drug, the investigation is not intended to support a significant change in the advertising for the drug.

The clinical investigations conducted under Protocols HSR 17-4345 and HSR 18-4521 are subject to the IND regulations under 21 CFR 312.2 and do not meet the exemption criteria under 21 CFR 312.2(b)(1). As noted above, FDA regulations require a sponsor to submit an IND before conducting a clinical investigation of a drug in human subjects, unless the clinical investigation qualifies for an IND exemption under 21 CFR 312.2(b). Under 21 CFR 312.2(b)(1), the clinical investigation of a lawfully marketed drug product in the United States is exempt from the IND regulations for a clinical investigation if all of the following exemption criteria are met…

The investigation is conducted in compliance with the requirements of 21 CFR 312.7. Your use of the investigational drugs (olanzapine, haloperidol, ziprasidone, and midazolam) in the clinical investigations conducted under Protocols HSR 17-4345 and HSR 18-4521 did not qualify for the exemption at 21 CFR 312.2(b)(1). For example, these investigations did not satisfy the third exemption criterion above, found at 21 CFR 312.2(b)(1)(iii). That is to say, the investigations…

The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use, and there is no intent to use the investigation to support any other significant change in the labeling of the drug.

The investigation does not involve a route of administration, dosage level, use in a patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.

Protocols HSR 17-435 and HSR 18-4521 were clinical investigations of drugs as defined by 21 CFR 312.3(b). For the purposes of 21 CFR part 312, a clinical investigation is defined as “any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part [312], an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice” [21 CFR 312.3(b)]. The clinical…