The following categories of studies require full review by the RDRC. Each protocol is reviewed prior to a Committee meeting by at least three Committee members: one physician, a radiation dosimetry reviewer, and a radiochemistry/radiopharmacy reviewer (see RDRC Application Checklist; Appendix D). Protocols subject to the requirements of 21 CFR 361.1 that involve administration of radioactive drugs to research subjects under 18 years of age are also reviewed by one or more ad hoc pediatric consultants to the Committee, who report their assessment of the protocol in writing.
1. FDA-approved radiopharmaceutical being investigated for a new indication or used for research purposes under conditions that differ from those specified in approved labeling (package insert), e.g., different route of administration, different dosage range, altered method of compounding, etc., under conditions that do not require submission of an Investigational New Drug application (IND) to the FDA (as defined by 21 CFR 312.2)
2. Radiopharmaceutical covered by an IND application with a sponsor outside Washington University with external manufacturing by a commercial sponsor.
3. Radiopharmaceutical covered by an IND application that is sponsored by a Washington University investigator.
4. Radiopharmaceutical covered by an IND application with an external sponsor, where manufacturing of the radiopharmaceutical is to be performed at Washington University.
5. Radioactive drugs used for basic physiological or pathophysiological investigations under the conditions specified at 21 CFR 361.1. Such drugs are defined as “generally recognized as safe and effective” (GRASE) and thus exempt from the new drug provisions of the Food, Drug, and Cosmetic Act. This is the specific category of drugs that the RDRC is chartered to approve by the FDA.
The full RDRC also reviews, approves and maintains institutional Drug Master Files (DMFs) for the radioactive drugs produced in the Washington University Cyclotron Facility and used under the authority of 21 CFR 361.1. Each DMF includes, in one place, the required information concerning the chemistry, manufacturing and controls information for the radioactive drug, as well as documentation of the “no clinically detectable pharmacological effect” level and the radiation dosimetry for the radioactive drug. RDRC applications can incorporate any necessary information in a DMF by reference to the DMF.
For applications that will undergo full-committee review by the RDRC, the more detailed form, “Application For Use of Radioactive Drugs In Investigations Involving Human Subjects”, must be used. Additional documents that need to be submitted along with the application form are specified on these forms.