FAQs FDA-Regulated Research

“...articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease…” and “...articles (other than food) intended to affect the structure or any function of the body of man or other animals.” 21 U.S.C. 321(g)(1)

“...any experiment in which a drug is administered or dispensed to, or used involving one or more human subjects...” – “...an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice...”

Clinical investigations may involve testing (collecting safety or effectiveness data) on a drug* including an FDA approved drug; unapproved use of an FDA approved drug; and/or an investigational drug?

A wide range of products (not chemically synthesized) such as virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component...allergic product, protein applicable to the diagnosis, prevention, treatment, or cure of a disease or condition of humans.

Investigational biologics fall under the FDA Investigational New Drug (IND) regulations.

Dietary supplements are regulated as drugs when intended to test their ability to diagnosis, cure, mitigation, treatment, or prevention of disease.

For more details, see the ORI Dietary Supplement Study FAQ. 

Unusual Products That May Be Investigational Test Articles Depending On Use In Research (PDF) 

Check the flow chart on the ReGARDD IND website and FDA's IND Exempt Guidance. If still uncertain, you may seek advice from the FDA Review Division responsible for the relevant therapeutic area of the proposed trial.

FDA IND Responsibilities

IRB policy requires mandatory training for investigators who are also serving as sponsors of an IND. This involves completion of the Good Clinical Practice Course for Clinical Trials Involving Investigational Drugs on CITI. The ReGARDD training below may be substituted for the CITI GCP course upon request, by providing completion documentation to the ORI HSP Training Support Team.

ReGARDD Training Modules on IND Sponsor-Investigator Responsibilities

Complete the study device section and attach the Study Device Form as well as applicable product information or correspondence.

• Application Sample Drug Form (PDF)
• IRB Application Instructions for Drug Investigation

ReGARDD IND Maintenance

ORI Guide for IRB Review of Phase I Drug Trials (PDF)

University of Kentucky Investigational Drug Services - Pharmacy Services (HTML) (Requires linkblue login)

• For non-oncology studies: centralids@uky.edu
• For oncology-related studies: IDSOncology@uky.edu 

Sample Investigational Product Accountability Log (.doc)

If time is sufficient, contact the UK Office of Research Integrity (ORI) at (859) 257-9428 to reach an IRB Chair for confirmation that use meets FDA criteria. Follow the steps in the Emergency Use SOP and use the Checklist for documentation.

• Emergency Use Procedures for Investigational Drugs/Devices
• Emergency Use SOP [C3.0250]
• Emergency Use Checklist (PDF)
• FDA Emergency Use of an Investigational Drug or Biologic
• FDA's Emergency Call Center

The FDA Expanded Access program provides a pathway for investigational treatment outside of clinical trials for life-threatening conditions or serious disease with no comparable or satisfactory therapy options. Expanded Access requires FDA approval, IRB approval, and the company’s agreement to provide the investigational product.

• FDA Expanded Access Website
• ORI Emergency and Early/Expanded Access Program for Drugs and Devices (PDF)
• Individual Patient Expanded Access Applications: Form FDA 3926
• Expanded Access Program Search Navigator
• FDA Expanded Access Instructional Videos
• FDA Expanded Access Requests for Investigational Oncology Products
• FDA Expanded Access Sample Consent Template (PDF)

An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:

• intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
• intended to affect the structure or any function of the body of man or other animals, and which does not achieve primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.

A clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device. 21 CFR 812.3

Complete the study section and attach the Study Device Form as well as applicable product information or correspondence.

• Application Sample Study Device Form (PDF)
• IRB Application Instructions for Device Investigation

App or software used as an accessory to a regulated medical device; or used to transform a mobile platform into a regulated medical device (e.g., control the function of operation of a medical device, used in active patient monitoring to analyze patient-specific medical device data).

See the FDA Policy for examples of software or apps that are not considered medical devices, those that are devices, but FDA will not enforce regulations because they are low-risk, and those that FDA will regulate.  

See the FDA Digital Health Policy Navigator Tool designed to help product developers understand whether a software function is potentially subject to or the focus of the FDA's regulatory oversight as a device, and if so, the considerations that may assist in determining the applicable FDA-specific legal and regulatory requirements and recommendations.

See the FDA Infographic to determine whether Clinical Decision Software is a medical device. 

Check the flow chart on the ReGARDD IDE website. If still uncertain, you may seek regulatory guidance from the FDA Device Advice Website or email FDA DICE.

For studies that are not exempt, sponsors are responsible for making the initial risk determination (SR or NSR) and presenting it to the Institutional Review Board (IRB). A device is significant-risk (SR), if use in the study presents potential for serious risk to health, safety, or welfare of a subject, particularly if it

• is an implant;
• is used to support or sustain life;
• is used to diagnose, cure, mitigate, or treat disease, or otherwise prevent impairment of human health; or
• otherwise presents a potential for serious risk to health, safety, or welfare of the subject.

21 CFR 812.32

An SR device study requires an IDE be submitted to FDA and full IDE requirements apply.

• FDA SR/NSR Guidance (PDF)

If the IRB does not concur with the sponsor SR/NSR designation, the FDA serves as the final arbiter.  To obtain a written risk determination from FDA submit correspondence labeled “Study Determination” in triplicate to USFDA, CDRH, Document Mail Center – WO66-G609, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002.

• ReGARDD Sample FDA Risk Determination Request

A device is NSR, if use in the study does NOT meet above SR definition as assessed by sponsor-investigator and confirmed by IRB. 

An NSR device study has Abbreviated IDE requirements and is conducted under the purview of the IRB.

If the IRB does not concur with the sponsor SR/NSR designation, the FDA serves as the final arbiter.  To obtain a written risk determination from FDA submit correspondence labeled “Study Determination” in triplicate to USFDA, CDRH, Document Mail Center – WO66-G609, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002.

• ReGARDD Sample FDA Risk Determination Request

FDA IDE Responsibilities for sponsor-investigators of SR Device Studies

IRB policy requires mandatory training for investigators holding IDEs or serving as sponsor-investigator for SR or NSR device trials. This involves completion of the Good Clinical Practice Course for Clinical Trials Involving Investigational Medical Devices on CITI.  The ReGARDD training below may be substituted for the CITI GCP course upon request, by providing completion documentation to the ORI HSP Training Support Team.

ReGARDD Training Modules on IDE Sponsor-Investigator Responsibilities

• ReGARDD IDE Template
• FDA IDE Application Website

See FDA IDE Reports and ReGARDD IDE Maintenance including Supplements, Reports, and Amendments.

See FDA IDE Responsibilities for sponsor-investigators of SR Device Studies

• FDA Responsibilities of Sponsors of Nonsignificant Risk Devices Studies
• FDA Responsibilities of Investigators for Nonsignificant Risk Device Studies

Sample Policy/Procedure Template: Investigational Device Accountability (.doc)

Investigational Device Accountability Log (.doc)

• IRB Summary - Humanitarian Use Devices (PDF)
• Humanitarian Use Device SOP [C3.0200]

If time is sufficient, contact the UK Office of Research Integrity (ORI) main line to reach an IRB Chair for confirmation that use meets FDA criteria. Follow steps in the Emergency Use SOP and use the Checklist for documentation.

• Emergency Use Procedures for Investigational Drugs/Devices
• Emergency Use SOP [C3.0250]
• ORI Emergency Use Checklist (PDF)
• FDA Emergency Use of an Investigational Device
• FDA's Emergency Call Center

The compassionate use provision provides a path to accessing investigational devices where a patient has a life-threatening or serious disease or condition; there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; and potential patient benefit justifies the potential risks of the investigational device. Compassionate use requires FDA approval, IRB approval, and manufacturer agreement to provide the investigational device.

• FDA Expanded Access for Medical Devices including Compassionate Use
• ORI Emergency and Early/Expanded Access Program for Drugs and Devices (PDF)
• Medical Device Clinical Investigations, Compassionate Use, and Treatment IDE SOP [C3.0150]

Consult the FDA Digital Center for Excellence and use the Digital Health Policy Navigator to determine if subject to FDA oversight and applicable FDA legal and regulatory requirements

Consult the FDA website and Graphic, Final FDA Guidance, and/or consult the Digital Center for Excellence with questions.  

• CLINICAL DECISION SUPPORT TOOL: Flowchart for Determining when FDA Regulations apply (PDF)
• FDA Final Clinical Decision Support (CDS) Software Guidance
• Determine if Your Clinical Decision Support (CDS) Software is a Medical Device Infographic

For formal classification of a product, a 513(g) request for information with the applicable Office of Health Technology (OHT). You may also engage FDA or request feedback through the Pre-Submission program.

FDA Guidance Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions

FDA List of Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices

Mobile Health App Interactive Tool for determining which laws and rules may apply – Federal Trade Commission