Research Knowledge Base
Review of FDA-Regulated Research Policy
Summary: This document describes the policy the UW-Madison Health Sciences IRBs follow for conducting reviews of applications that fall under US Food and Drug Administration (FDA) regulations.
Adopted by: HS IRBs Policy Committee
Adoption date: October 5, 2015
1. The Health Sciences IRBs apply the following definitions for the review of FDA-regulated research.
1.1. Biologic means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative thereof, applicable to the prevention, treatment or cure of a disease or condition of human beings.
1.2. Clinical investigation means any experiment that involves a test article and one or more human subjects, and that either must meet the requirements for prior submission to the FDA under section 505(i) or 520(g) of the Federal Food, Drug and Cosmetic Act (FD&C Act), or need not meet the requirements for prior submission to the FDA under these sections of the Act, but the results of which are intended to be later submitted to, or held for inspection by, the FDA as part of an application for a research or marketing permit.
1.2.1. Clinical investigation does not include experiments that must meet the provisions of 21 CFR 58, regarding nonclinical laboratory studies.
184.108.40.206. Nonclinical laboratory study means in vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety.
1.2.2. The terms clinical investigation, investigation, clinical research, research, clinical study, and study are deemed to be synonymous under FDA regulations.
1.3. Device means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is:
1.3.1. Recognized in the official National Formulary, or the United States Pharmacopoeia;
1.3.2. Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease; or
1.3.3. Intended to affect the structure of any function of the body and which does not achieve its primary purposes through chemical action and which is not dependent upon being metabolized.
1.3.4. This definition includes in vitro diagnostic devices.
1.4. Drug means
1.4.1. Articles recognized in the official Unites States Pharmacopoeia, official Homeopathic Pharmacopoeia, or official National Formulary;
1.4.2. Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease; or
1.4.3. Articles intended to affect the structure or any function of the body.
1.5. Human subject means an individual who is or becomes a participant in research, either as a recipient of a test article or control. A subject may be either a healthy human or a patient. Decedents are not human subjects.
1.6. Off-Label means the use of an approved drug, an approved or cleared device, or a licensed biologic for an indication not in the approved labeling.
1.7. Significant risk device means a device that presents a potential for serious risk to health, safety or welfare of subject and:
1.7.1. Is intended as an implant;
1.7.2. Is purported or represented to be for a use in supporting or sustaining human life;
1.7.3. Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health; or
1.7.4. Otherwise presents a potential for serious risk to health, safety, or welfare of subject.
220.127.116.11. A device that does not meet the above criteria for a significant risk device is a Non-significant Risk Device.
1.8. Test article means any drug (including a biological product for human use), medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the FD&C Act.
2. Research with Test Articles Generally
2.1. The FDA regulates clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration, including foods, dietary supplements that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products.
2.2. UW-Madison applies FDA regulations to clinical investigations that involve one or more test articles.
2.3. Examples of FDA-regulated research include, but are not limited to:
2.3.1. Research testing the safety and/or efficacy of unapproved or unlicensed drugs, biologics or medical devices.
2.3.2. Research testing the safety and/or efficacy of off-label use of approved drugs, approved or cleared medical devices, or licensed biologics.
2.3.3. Research comparing the safety and/or efficacy of approved drugs, approved or cleared medical devices, or licensed biologics regardless of whether the test articles are used within their FDA-approved or cleared indications.
2.3.4. Research testing or evaluating software and hardware used in support of diagnostic or therapeutic devices or radioactive materials (e.g., tracers).
2.3.5. Research testing the safety and effectiveness of an In Vitro Diagnostic (IVD) device using tissue specimens.
3. Research with Drugs
3.1. A clinical investigation with a drug may begin only after the IRB has approved the study and one of the following conditions have been met:
3.1.1. The IRB receives documentation that the research will be conducted under an applicable Investigational New Drug Application (IND);
3.1.2. The IRB determines that use of the drug in the investigation does not require an IND because the drug is lawfully marketed in the US and all of the following are true:
18.104.22.168. The investigation is not intended to be reported to 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;
22.214.171.124. 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;
126.96.36.199. 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;
188.8.131.52. The investigation is conducted in compliance with the requirements for institutional review set forth in 21 CFR 56 and with the requirements for informed consent set forth in 21 CFR 50; and
184.108.40.206. The investigation is conducted in compliance with the requirements of 21 CFR 312.8 (related to promotion and charging for investigational drugs).
3.1.3. The IRB formally determines that satisfactory justification has been provided by the investigator as to why an IND is otherwise not required.
3.2. Applications for research on the use of a drug, unless that research is exempt from the IND regulations as described in 3.1.2 or 3.1.3 above, must be accompanied by documentation from the FDA that includes a valid IND number.
3.2.1. 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.
3.3. A clinical investigation involving the use of a placebo is exempt from the requirements for obtaining an IND if the investigation does not otherwise require submission of an IND.
3.4. Clinical investigations that are exempt from IND regulations still require IRB review and approval.
3.5. Approved drugs used in studies that are provided as part of standard of care and are not the subject of the investigation (e.g., supportive care to mitigate side effects of study treatment) are generally not considered to be test articles.
4. Research with Radioactive Materials
4.1. Human subjects research using a radioactive drug or biological product may be conducted without an IND if it is reviewed and approved by a Radioactive Drug Research Committee (RDRC) which has been approved by the FDA and the following additional conditions are met:
4.1.1. The research constitutes basic science research, and not research that is intended for immediate therapeutic, diagnostic, or similar purposes, or to determine the safety and effectiveness of the radioactive drug or biological product for such purposes (i.e., the research cannot constitute a clinical trial for the product).
220.127.116.11. Under FDA guidelines, basic science research:
18.104.22.168.1. Is intended to obtain basic information on (1) metabolism (including kinetics, distribution, dosimetry, and localization) of a radioactive drug or (2) human physiology, pathophysiology, or biochemistry.
22.214.171.124.2. Is not intended for immediate therapeutic, diagnostic, or similar purposes to the study subject.
126.96.36.199.3. Is not intended to determine the safety and effectiveness of a radioactive drug in humans as a therapeutic, diagnostic, or similar type of medical product.
4.1.2. The dose to be administered must be known not to cause any clinically detectable pharmacological effect in humans.
4.1.3. The total amount of radiation to be administered as part of the study must be the smallest radiation dose practical to perform the study without jeopardizing the benefits of the study, and must be within specified limits.
5. Research with Biologics
5.1. Clinical investigations of biologics are regulated in the same way as clinical investigations for drugs, and require an IND, unless the biologic is part of a combination product that the FDA has assigned for premarket approval to the Center for Devices and Radiological Health. In such cases, the biologic/device combination product would require an Investigational Device Exemption (IDE) prior to research approval by the IRB.
5.2. Licensed biologics used in studies that are provided as part of standard of care and are not the subject of the investigation (e.g., supportive care to mitigate side effects of study treatment) are generally not considered to be test articles.
6. Research with Devices
6.1. A clinical investigation with a medical device may begin only after the IRB has approved the study and one of the following conditions has been met:
6.1.1. The IRB receives documentation that the research will be conducted under an applicable IDE;
6.1.2. The IRB formally determines and documents that the proposed use of any investigational device satisfies the FDA criteria for non-significant risk devices (see Definitions above);
188.8.131.52. Non-significant risk devices are considered to have an approved IDE when the IRB agrees with the sponsor that the device meets the criteria for a non-significant risk device.
184.108.40.206. If the investigator applies to the IRB for a non-significant risk determination for a device study, but the IRB determines that the device is significant risk, the IRB notifies the investigator and the sponsor, if appropriate.
6.1.3. The IRB determines that the device meets regulatory criteria for an exemption from IDE regulations as described in 6.3 below; or
6.1.4. The IRB formally determines that satisfactory justification has been provided by the investigator as to why an IDE is not otherwise required.
6.2. Applications for research on the use of a significant risk medical device must be accompanied by documentation from the FDA that includes a valid IDE number.
6.2.1. The IDE 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.
6.3. Investigations exempted from the IDE regulations.
6.3.1. An investigation of a medical device in human subjects research is exempt from the IDE regulations if it falls into one of the following categories:
220.127.116.11. A device legally marketed in the US that is used or investigated in accordance with the indications in the FDA-approved labeling.
18.104.22.168. A 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 subject, and
- is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
22.214.171.124. 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 subjects at risk.
126.96.36.199. 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.
188.8.131.52. 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.
184.108.40.206. 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.
6.3.2. Clinical investigations that are exempt from IDE regulations still require IRB review and approval.
6.4. Approved or cleared devices used in studies in an incidental way, where the device or the use of the device is not the focus of the research, are generally not considered to be test articles.
7. Research with In Vitro Diagnostic Devices
7.1. The Health Sciences IRBs follow FDA regulations regarding IVDs.
7.1.1. Because the FDA regulations define a subject to include a human on whose specimens an investigational device is used, regardless of whether or not the samples to be used are individually identifiable, an IVD study to support a premarket submission to the FDA is considered a human subject investigation and subject to IRB review.
7.1.2. The Health Sciences IRBs also follow the FDA Guidance for Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable.
- This policy applies to how the Minimal Risk and Health Sciences IRBs apply FDA regulations to human subjects research.
Applicable HRPP Policy
- Control of Test Articles Used in Research Policy
- Clinical Trials Registration & Results Reporting
- Emergency Use of Test Articles and of Humanitarian Use Devices Policy
- Exempt Research
- Humanitarian Use Device Policy
Attachments and Other References
- Guidance on FDA Regulation of Medical Mobile Apps
- Guidance on Requirements by the FDA for the Investigator as a Sponsor
- Investigational Software Guidance
Keywords: FDA, Biologic, Clinical investigation, Device, Drug, Human Subject, Off-Label, Significant risk device, Non-significant Risk Device, Test article, IND, Radioactive Materials, Radioactive Drug Research Committee, RDRC, radioactive, basic science research, biologics, devices, diagnostic device, consumer preference testing, In Vitro Diagnostic Devices, IVDs, IVD