IND An Investigational New Drug is a drug that has not yet been approved by the FDA for marketing and is available only for use in research to determine safety and effectiveness. All investigational drugs require an FDA IND number, signifying acceptance by the FDA of an IND application for research. The IND may be held by the sponsor (e.g. Pfizer), or by the researcher (the academic sponsor investigator) APPROVED DRUGS—NEW USES When research is proposed that involves use of an FDA-approved drug for a new use, the researcher must determine whether or not an IND is required. The HIC reviews this determination and either concurs or not. The IRB must consider whether the proposed use of the drug in the research puts the subject population at greater risk from the drug than the risk that is known for the FDA-approved population APPROVED DRUGS—NEW USES Examples for consideration: Use of an increased dose Use of a different route of administration Longer duration Use in a vulnerable population Use in a population where there is reason to believe the population has different pharmacodynamic responses than the indicated population IRB DETERMINATION When the IRB has determined that an IND is not required, the IRB minutes must indicate the following: * the condition/disorder to be treated * the variance from current FDA approval (e.g., different indication or population) * determination that the risks associated with its use in the disorder/condition are not anticipated to be significantly increased over known risks. IND AND THE HIC APPLICATION The HIC application requires that a drug, biologic or radiotracer not approved by, but regulated by, the FDA, or a radiotracer regulated by the RDRC, provide the following information: * the IND number assigned by the FDA * the name of the person/entity holding the IND * For radiotracers regulated by the FDA but not approved them, the IND number, OR * Confirmation that the radiotracer is under RDRC/RSC oversight (where an IND number is not required) EXEMPTIONS FROM IND FILING There are 4 exemptions from IND filing. The most common is category 1 The intention of the investigation is NOT to report to the FDA in support of a new indication for use or to be used to support any other significant change in the labeling The drug is lawfully marketed as a prescription drug product, and the intention of the investigation is NOT to support a significant change in the advertising The investigation does NOT involve a route of administration or dosage level or use in populations or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug. The investigation will be conducted in compliance with the requirements for institutional (HIC) review and with the requirements for informed consent of the FDA regulations (21 CFR Part 50 and 21 CFR Part 56). The investigation will be conducted in compliance with the requirements regarding promotion and charging for investigational drugs. IND EXEMPTIONS Other categories: In vitro study of a diagnostic biological product involving blood grouping serum, reagent red blood cells or anti-human globulin, in a test intended to be used in a diagnostic procedure confirming the diagnosis made by another medically established diagnostic procedure or product . Studies where the drug is intended solely for tests in vitro or in laboratory research animals A clinical investigation involving use of a placebo if the investigation doesn’t otherwise require an IND submission IND EXEMPTION AND THE IRB The IRB must review the investigator’s HIC application exemption request and must agree with the exemption. The correspondence to the investigator acknowledges this, and cites the FDA exemption regulation, 21 CFR 312.2(b) INVESTIGATIONAL DEVICES The FDA also has regulations concerning investigational devices (IDE) These regulations mirror those of INDs. There are specified exemptions They require IRB determinations regarding need for an IDE, based on risk They consider risk level: significant or non-significant The determination that a device is non-significant does not mean that the research is minimal risk The HIC application includes specific questions and requirements for IDE determination and also for YNHH review and approval.