Research with Drugs and Medical Devices (FDA Regulated)
Certain categories of research involve either methodologies that might require additional considerations or for which there are federally mandated determinations that IRBs are required to make and document. These categories of research include, but are not limited to:
- Clinical investigations involving drugs or biologics
- Clinical investigations involving medical devices
- Gene therapy research
- Prospective research in emergency settings
- Expanded access of an investigational drugs or devices, including single patient treatment use and compassionate use requests
- Emergency use of an investigational article or product
- Humanitarian use devices
Research Involving Drugs or Biologics
All research involving use of FDA regulated drugs or biologics require submission of an Investigational New Drug Application to the FDA unless the research meets the criteria for exemption from the requirements as outlined below or the research involves the use of a drug other than the use of a marketed drug in the course of medical practice.
Please note that the UM IRB has the right to decline review of all protocols for which there is a lack of subject matter expertise on the Committee or for which the Committee is not properly constituted. The UM IRB will only review protocols involving drugs or biologics if the IRB Chair, in consultation with the IRB Director, feels it is within the expertise of current IRB members.
For sponsored research, applications for research on the use of a drug, unless that research is exempt from the IND regulations, must be accompanied by documentation from the FDA that includes a valid IND number. The IND number must either match the number on the sponsor protocol with the same title as the proposed research or be listed on communication from the sponsor specific to the proposed research, or on communication with the FDA. The research must not begin until a valid IND is in effect. This includes recruiting, obtaining consent, and screening participants for a specific study that is subject to an IND.
A study may qualify for IND exemption if it meets one of the FDA exemptions from the requirement to have an IND:
- Exemption 1: A clinical investigation of a drug product that is lawfully marketed in the United States if all the following apply:
- The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug;
- If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;
- The investigation does not involve a route of administration or dosage level or 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;
- The investigation is conducted in compliance with the requirements of 21 CFR 312.7.
- Exemption 2: A clinical investigation involving an in vitro diagnostic biological product if all the following apply:
- The diagnostic involves one or more of the following: blood grouping serum, reagent blood cells, and anti-human globulin;
- The diagnostic test is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure; and
- The diagnostic test is shipped in compliance with 21 CFR 312.160.
- Exemption 3: A drug intended solely for test in vitro or in laboratory research animals if shipped in accordance with 21 CFR 312.160.
- Exemption 4: A clinical investigation involving use of a placebo if the investigation does not otherwise require submission of an IND
When an exemption determination is needed, this assessment will be based on the information provided by the investigator and/or the sponsor. It is the responsibility of the investigator and/or sponsor to provide accurate information. Exemption determinations may be made by the IRB or may be determined by the FDA.
Research Involving Medical Devices
Research with medical devices falls into four categories:
- Investigations of significant risk devices
- Investigations of non-significant risk devices
- Investigations exempted from the IDE regulations
- Research involving medical devices for the collection of data but where the medical device is not under investigation to evaluate the safety and effectiveness of the device
When a device risk determination is needed, the convened IRB will determine whether the study presents a significant risk or a non-significant risk of harm to study participants. This assessment will be based on the information provided by the investigator and/or the sponsor. It is the responsibility of the investigator and/or sponsor to provide accurate information.
The IRB’s risk determination will be documented in the IRB meeting minutes. If an investigator submits a Non-Significant Risk research protocol that is determined by the IRB to be a Significant Risk study, the investigator and the Sponsor, if necessary, will be notified in writing. The UM IRB will not review Significant Risk Device investigations at this time.
Non-significant Risk Device Investigations
When research involves use of a medical device and the investigators/sponsor indicates that the device may qualify as non-significant risk, the IRB either confirms (1) that appropriate documentation is provided from the FDA to classify the device as non-significant risk or (2) the device does not qualify as a significant risk device, according to the following regulatory criteria outlined below. A significant risk device is an investigational device that presents a potential for serious risk to the health, safety, or welfare of a participant AND:
- Is intended as an implant; or
- Is purported or represented to be for a use in supporting or sustaining human life; or
- Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health; or
- Otherwise presents a potential for serious risk to the health, safety, or welfare of a participant.
If the above criteria above are not met, the device may be designated as non-significant risk. No application is required to be submitted to the FDA. If the IRB cannot determine the risk of the device, the IRB may defer the determination to the FDA.
When research is conducted to determine the safety or effectiveness of the non-significant risk device the following abbreviated IDE requirements must be ensured by the designated Sponsor (or the Principal Investigator, if there is no sponsor):
- The device is not a banned device.
- The sponsor labels the device in accordance with 21 CFR 812.5.
- The sponsor obtains approval of the investigation after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device and maintains such approval.
- The sponsor ensures that each investigator participating in an investigation of the device obtains from each participant enter investigator’s care, consent under 21 CFR 50 and document it, unless documentation is waived.
- The sponsor complies with the requirements of 21 CFR 812.46 with respect to monitoring investigations;
- The sponsor maintains the records required under 21 CFR 812.150 (b) (1) through (3) and (5) through (10);
- The sponsor ensures that participating investigators maintain the records required by 21 CFR 812.140 (a) (3) (i) and make the reports required under 812.150 (a) (1), (2), (5), and (7); and
- The sponsor complies with the prohibitions in 21 CFR 812.7 against promotion and other practices.
Investigations Exempted from IDE regulations
Clinical investigations that are exempt from IDE regulations still require IRB review and approval. An investigation of a medical device in human subjects research that is exempt from the IDE regulations must fall into one of the following categories and will be determined along with the review and approval of a submission:
- A device legally marketed in the US that is used or investigated in accordance with the indications in the FDA-approved labeling.
- A device, other than a transitional device, in commercial distribution immediately before May 28, 1976, when used or investigated in accordance with the indications in labeling in effect at that time.
- A device, other than a transitional device, introduced into commercial distribution on or after May 28, 1976, that FDA has determined to be substantially equivalent to a device in commercial distribution immediately before May 28, 1976, and that is used or investigated in accordance with the indications in the labeling FDA reviewed under subpart E of part 807 in determining substantial equivalence.
- A diagnostic device (that is, an in vitro diagnostic device) if the testing:
- Is noninvasive
- Does not require an invasive sampling procedure that presents significant risk,
- Does not by design or intention introduce energy into a participant, and
- Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
- A device undergoing consumer preference testing, testing of a modification, or testing of a combination of two or more devices in commercial distribution, if the testing is not for the purpose of determining safety or effectiveness and does not put participants at risk.
- A custom device as defined in 21 CFR 812.3(b), unless the device is being used to determine safety or effectiveness for commercial distribution.
When an exemption determination is needed, this assessment will be based on the information provided by the investigator and/or the sponsor. It is the responsibility of the investigator and/or sponsor to provide accurate information. Exemption determinations may be made by the IRB or may be determined by the FDA.
Research Involving Medical Devices for the Collection of Data
Expedited review category 4 allows for the “collection of data through noninvasive procedures” and specifically notes: “Where medical devices are employed, they must be cleared/approved for marketing.” Studies intended to evaluate the safety and effectiveness of the medical device do not qualify under this category of review. The use of marketed medical devices for the collection of data on research studies may be part of a research protocol undergoing expedited or convened review. This type of use is generally considered not to be FDA regulated as it does not meet the definition of a clinical investigation intended to evaluate the safety and effectiveness of the medical device. In essence, the device is not the participant of the investigation.
Gene Therapy Research
Gene therapy research may require special considerations. If the project involves gene transfer (administration of recombinant vectors) to human participants for other than clinical purpose, review by the NIH Recombinant DNA Advisory Committee (RAC) may be required. The FDA must review any such study prior to final IRB approval. In addition, the protocol will require review by the University of Montana Institutional Biosafety Committee.
Other Types of FDA-Regulated Research
The UM IRB will not review the following types of research at this time:
- Prospective research in emergency settings
- Expanded access of an investigational drugs or devices, including single patient treatment use and compassionate use requests
- Emergency use of an investigational article or product
- Humanitarian use devices