FDA Regulated Research
- Purpose and Applicability
- Identifying FDA Regulated Activities
- Additional Requirements for Investigational Drugs, Biologics, Botanicals, and Supplements
- Additional Requirements for Investigational Devices
- IRB Review Procedures
- FDA Definitions
- Related Materials
- Regulatory References
- Version Table
Purpose and Applicability
This guidance provides researchers, the Human Subjects Division (HSD), and the UW Institutional Review Boards (IRBs) with an overview of the human subjects requirements for research that is regulated by the Food and Drug Administration (FDA) and for studies that involve the use of an investigational drug or device.
There are many additional sponsor, investigator, and sponsor-investigator responsibilities outside of IRB responsibilities which are described in guidance issued by the FDA.
Details about the following FDA regulated activities can be found elsewhere:
Drugs are regulated by the Center for Drug Evaluation and Research (CDER), a division within the FDA. The CDER grants Investigational New Drugs (INDs) for both emergency and non-emergency use.
Devices are regulated by the Center for Devices and Radiological Health (CDRH), a division within the FDA. The CDRH grants Investigational Device Exemptions (IDEs) and Humanitarian Device Exemptions (HDEs) and grants Humanitarian Use Device status to devices.
Researchers who have the role of both sponsor and investigator have additional FDA-specified responsibilities which the UW expects them to fulfill.
Identifying FDA Regulated Activities
HSD staff make the determination about the applicability of specific FDA regulations based on interpretation of FDA regulations and the information provided in the IRB application by the researcher. The HSD staff procedures for making these determinations are outlined in the SOP FDA Regulated Research.
- FDA opinion is the ultimate authority on this issue and will overrule an HSD staff determination.
- For Department of Defense (DoD) regulated research, HSD defers to the DoD’s broader interpretation of what is FDA regulated. Review the HSD guidance on Department of Defense research for details.
The FDA regulations include general requirements for IRB approval of clinical investigations involving human subjects as well as additional requirements for studies involving investigational drugs and devices.
- General Requirements. The worksheet, Human Subjects Research Determination provides guidance on whether an activity is a clinical investigation involving human subjects.
- Screening tests and procedures unless they are performed solely for determining study eligibility.
- Interviews and questionnaires administered to subjects unless they involve the use of the test article, a human subject, and the data will be submitted to (or held for inspection by) the FDA.
- Investigational Drugs. Review the section of this guidance on Additional Requirements for Investigational Drugs and the worksheet, FDA Drugs and the IND Requirement.
- Investigational Devices. Review the section of this guidance on Additional Requirements for Investigational Devices and the worksheet, FDA Devices and the IDE Requirement.
These activities are not considered by the FDA to be part of the clinical investigation. Although these activities may be associated with FDA regulated studies, the FDA regulations do not apply:
Additional Requirements for Investigational Drugs, Biologics, Botanicals, and Supplements
The FDA requires sponsors/sponsor-investigators to obtain an Investigational New Drug (IND) approval from the FDA before conducting research on a new drug, or on a new use of an already approved drug unless the drug qualifies for an IND exemption.
What is an IND exemption? The FDA identifies particular categories of drug research that do not require an IND approval and that are not subject to the FDA drug regulations (21 CFR 312). These IND exemptions are described in the worksheet, FDA Drugs and the IND Requirement and the FDA provides guidance at this webpage.
Who makes the determination? The sponsor/sponsor-investigator is responsible for determining whether their planned use of an investigational drug is IND exempt and reporting that information in their Zipline IRB application and in the supplement, Drugs, Biologicals, Botanicals, Supplements. The IRB reviewer considers that determination and requests additional information if needed. If the use of the drug qualifies as IND exempt, it may qualify for expedited review if it meets the requirements described in the worksheet, Expedited Review.
Obtaining an IND from the FDA
When to apply for an IND. If the use of the investigational drug does not qualify as IND exempt, the sponsor/sponsor-investigator must apply to the FDA for IND approval. When it is known that an IND is required, the FDA application should be submitted before or at the same time as the IRB application to reduce delays in beginning the study. Review time for initial submission of an IND is 30 days from the date the FDA receives the application.
How to apply for an IND. The FDA provides guidance about the application process at this webpage.
IND and IRB approval. The IRB review may begin prior to FDA approval, but the IRB application cannot be fully approved until the IRB receives documentation that the FDA received the application and has issued an IND. This documentation (email, letter) must: (1) be from the sponsor, FDA, a multi-site coordinating center, or a Contract Research Organization (CRO); (2) refer to the specific research study by title; and (3) provide the IND number assigned by the FDA. The IND number must also be entered into the Zipline SmartForm for drugs. Per the FDA, the investigation may proceed once the sponsor has been notified by the FDA that the investigation may proceed or 30 days after the FDA receives the application so long as the IND is not placed on Clinical Hold.
Additional Requirements for Investigational Devices
The FDA requires sponsors/sponsor-investigators to obtain an Investigational Device Exemption (IDE) approval from the FDA before conducting research on a new device, or on a new use of an already-approved device unless the device qualifies for an IDE exemption or as an abbreviated IDE. The FDA provides a helpful summary presentation about IDEs on this webpage.
What is an IDE exemption? The FDA identified particular types of devices that do not require an IDE approval and that are not subject to the FDA device regulations (21 CFR 812). These IDE exemptions are described in the worksheet, FDA Devices and the IDE Requirement.
Who makes the determination? The sponsor/sponsor-investigator is responsible for determining whether their planned use of an investigational device is IDE exempt and reporting that information in their Zipline IRB application and in the supplement, Devices. The IRB reviewer considers that determination and requests additional information if needed. If the use of the device qualifies as IDE exempt, it may qualify for expedited review if it meets the requirements described in the worksheet, Expedited Review.
What is an abbreviated IDE? When particular criteria are met, the study can be considered to have an FDA approved IDE without having applied for one. This is called an abbreviated IDE and in these cases no interaction with, or documentation from the FDA is required. The requirements for an abbreviated IDE are described in the worksheet, FDA Devices and the IDE Requirement.
Who makes the determination? The sponsor/sponsor-investigator is responsible for determining whether their planned use of an investigational device qualifies for an abbreviated IDE and reporting that information in their Zipline IRB application and in the supplement, Devices. However, the FDA requires concurrence from the convened IRB that the use of the device qualifies.
Significant risk versus nonsignificant risk device. One criterion for an abbreviated IDE is that the use qualifies as nonsignificant risk. Guidelines for making that determination are in the worksheet, FDA Devices and the IDE Requirement.
- If the sponsor/sponsor-investigator determines that the device is significant risk, then it does not qualify for an abbreviated IDE and an IDE application must be submitted to the FDA. The IRB does not need to make a risk determination. The FDA will review the application and will issue either an IDE or a determination letter stating that the use is nonsignificant risk. The IRB must accept the FDA’s determination.
- If the sponsor/sponsor-investigator determines that the device is nonsignificant risk the convened IRB must make a concurrent determination. If the IRB concurs, there is no need for the FDA to weigh in. If the IRB disagrees with the sponsor’s nonsignificant risk determination, the sponsor/sponsor-investigator must either ask the FDA for a risk determination or apply to the FDA for an IDE.
Obtaining an IDE from the FDA
- When to apply for an IDE. If the use of the investigational device does not qualify as IDE exempt or as an abbreviated IDE, the sponsor/sponsor-investigator must apply to the FDA for IDE approval. When it is known that an IDE is required, the FDA application should be submitted before or at the same time as the IRB application to reduce delays in beginning the study.
- How to apply for an IDE. The FDA provides guidance about the application process at this webpage.
- IDE and IRB approval. The IRB review may begin prior to FDA approval, but the application cannot be fully approved until the IRB receives documentation that the FDA received the application and has issued an IDE. This documentation (email, letter) must: (1) be from the sponsor, FDA, a multi-site coordinating center, or a Contract Research Organization (CRO); (2) refer to the specific research study by title; and (3) provide the IDE number assigned by the FDA after its review of the IDE application. The IDE number must also be entered into the Zipline SmartForm for devices. Per the FDA, the investigation may begin 30 days after the FDA receives the IDE application unless FDA notifies the sponsor that the investigation may not begin.
FDA Device Tracking Requirements
The FDA requires that device manufacturers track certain devices. The requirement is communicated to the manufacturers with an IDE determination or as part of the device market approval. Tracking facilitates notification and recall should a device present a serious risk to health that requires prompt attention. A device registry typically satisfies the requirements of a tracking program.
The tracking requirement is permanent. It ends only when the manufacturer has evidence to confirm that: (1) the FDA has lifted the tracking requirement; (2) a device has been returned, destroyed, or explanted; or (3) the patient/subject has died.
Tracking is typically required:
- If the failure of the device would be reasonably likely to cause serious adverse health consequences.
- If the device is: (a) intended to be implanted in the human body for more than one year; or (b) a life-sustaining or life-supporting device used outside a device user facility.
IRB Review Procedures
What to submit for an FDA regulated study
- IRB Protocol application form
What to submit for an investigational drug study.
- Drug supplement
- Investigator brochure and/or package insert
- IND confirmation email or letter (when an IND is required)
- Add IND number to Drugs web form in Zipline (when an IND is required)
What to submit for an investigational device study.
- Device supplement
- Additional information about the device (if available: device manual or similar documentation; package insert; photo, drawing, etc.)
- IDE confirmation email or letter (when an IDE is required)
- Add IDE number to Devices web form in Zipline (when an IDE is required)
Consent considerations for FDA regulated studies.
Required elements of consent.The FDA required elements of consent can be found in the worksheet, Consent Requirements and Waivers. Additional guidance about how to describe procedures, risks, and costs of participation related to investigational drugs and devices can be found in the Separate Key Information consent template.
Reporting requirements. Certain IRB determinations and findings about FDA regulated research must be reported to the FDA. These include: suspension or termination of IRB approval; unanticipated problems; serious or continuing noncompliance. More information about reporting requirements can be found on this webpage, Guide to Reporting New Information and in the SOP RNI Reporting by Researchers.
Biologic, also known as a biological product, means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), appliable to the prevention, treatment, or cure of a disease or condition of human beings.
Botanical means a finished, labeled product that contains vegetable matter, which may include plant materials, algae, macroscopic fungi, or combinations of these. Depending in part on its intended use, a botanical product may be a food, drug, medical device, or cosmetic.
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 Food and Drug Administration under section 505(i) or 529(g) of the act, or need not meet the requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be later submitted to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit. The term does not include experiments that must meet the provisions of part 58, regarding nonclinical laboratory studies. The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part.
Custom device means a device that is not being used to determine safety or effectiveness for commercial distribution, but which has all the other characteristics of a device, as defined by the FDA. Data are not collected on its use for submission to the FDA. Custom devices are not subject to FDA regulations. The concept of custom device should not be used to circumvent the FDA regulations. Use of custom devices may still require IRB review, however, if the use meets the Health and Human Services definition of human subjects research. Required characteristics of a custom device: (1) necessarily deviates from devices generally available or from an applicable performance standard or premarket approval requirement in order to comply with the order of an individual physician or dentist; (2) is not generally available to or used by other physicians or dentists; (3) is not generally available in finished form for purchase or for dispensing upon prescription; (4) is not offered for commercial distribution through labeling or advertising; and (5) is intended for use by an individual patient named in the order of a physician or dentist and is to be made in a specific form for that patient or is intended to meet the special needs of the physician or dentist in the course of professional practice.
Examples: Hydrocephalic shunts made of some other material than silicone because the patient is allergic to silicone; thoracic aortic aneurysm grafter ordered individually for each patient.
Device means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: (1) recognized by an official pharmacopoeia or formulary, or any supplement to them; (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease; or (3) intended to affect the structure or any function of the body, and which does not achieve its primary intended purposes through chemical action within or on the body and which is not dependent upon being metabolized for the achievement of its primary intended purposes. The term device does not include software functions excluded pursuant to section 520(0).
Examples: artificial heart valve; bandaid; bedpan; diagnostic test for HIV/AIDS; enema kit; thermometer; insulin pump; mobile app for sending post-operative photos to a physician; pregnancy test; software programs for x-ray machines
Drug means: (1) a substance recognized by an official United States pharmacopoeia or formulary, or any supplement to any of them; (2) a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease; (3) a substance (other than food) intended to affect the structure or any function of the body; and (4) a substance intended for use as a component of a medicine but not a device or a component, part, or accessory of a device. Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical versus biological process).
Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.
Investigational Device Exemption (IDE)
An IDE application is the document submitted to the FDA for permission to conduct a clinical study using a significant risk device that is new or not approved for a given use. When the FDA receives an IDE application, it assigns an IDE number to the specific use of the device.
Investigational New Drug (IND)
An IND application is the document submitted to the FDA for permission to conduct a clinical study using a drug or biologic that is new or not approved for a given dosage, formulation, or indication. When the FDA receives an IND application, it assigns an IND number to the specific use of the item.
Investigator means an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject) or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.
Sponsor means a person or other entity that initiates a clinical investigation, but that does not actually conduct the investigation, i.e., the test article is administered or dispensed to, or used involving, a subject under the immediate direction of another individual. A person other than an individual (e.g., a corporation or agency) that uses one or more if its own employees to conduct an investigation that it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators.
Sponsor-investigator means an individual who both initiates and also conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, e.g., it does not include a corporation or agency. The obligations of a sponsor-investigator under this part include both those of a sponsor and those of an investigator.
A supplement is a product (other than tobacco) that is:
- Intended to supplement the diet, and that bears or contains one or more of the following dietary ingredients: (a) a vitamin; (b) a mineral; (c) an herb or other botanical; (d) an amino acid; (e) a dietary substance for use my man to supplement the diet by increasing the total dietary intake; or (f) a concentrate, metabolite, constituent, extract, or other combination of these ingredients;
- Not represented for us as a conventional food or sole item of a meal of the diet; and
- Is labeled as a dietary supplement.
SOP FDA Regulated Research [HSD staff access only]
SOP RNI Reporting by Researchers
SUPPLEMENT Drugs, Biologics, Botanicals, Supplements
WEBPAGE Consent Guidance
WEBPAGE Department of Defense Guidance
WEBPAGE Expanded Access Guidance
WEBPAGE Guide to Reporting New Information
WEBPAGE Humanitarian Use Device Guidance
WEBPAGE Single Patient Emergency or Compassionate Use
WORKSHEET Consent Requirements and Waivers
WORKSHEET Expedited Review
WORKSHEET FDA Devices and the IDE Requirement
WORKSHEET FDA Drugs and the IND Requirement
WORKSHEET Human Subjects Research Determination
- 21 CFR 50, 56, 312, 812
- FDA Guidance, Custom Device Exemption, September 2014
- FDA Guidance video, IDE Basics, December 2014
- FDA Guidance, How to Determine if Your Product is a Medical Device, September 2022
- FDA Guidance, Frequently Asked Questions About Medical Devices, January 2006
- FDA Guidance, Significant Risk and Nonsignificant Risk Device Studies, January 2006
- FDA Guidance, IND Applications for Clinical Investigations: Overview, date retrieved 07.28.2023
- FDA Guidance, Investigational New Drug Applications (INDs) – Determining Whether Human Subjects Research Studies Can Be Conducted Without an IND, September 2013
- FDA, Guidance for IRBs, Clinical Investigators and Sponsors: IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed, August 2013
- FDA Guidance, Medical Devices; Custom Devices; Technical Amendment, published 10.12.2016
- FDA, “Part 11, Electronic Records: Electronic Signatures – Scope and Application Guidance”, August 2003
- FDA, “Procedures for Handling Inquiries Regarding the Need for an Investigational Device Exemptions Application For Research Involving Medical Devices”, October 26, 2001 (IDE Guidance Memorandum #D01-01)
FDA/OHRP Guidance, “Use of Electronic Informed Consent: Questions and Answers”, December 2016
Citation showing that the FDA’s definition of “human subject” is limited to living individuals (except with respect to the use of devices): FDA Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception from Informed Consent Requirements for Emergency Research, March 2011, Question #114.
Open the accordion below for version changes to this guidance.
|Version Number||Posted Date||Implementation Date||Change Notes|
|2.0||08.31.2023||08.31.2023||Significant revision to FDA suite of materials; transfer relevant content from GUIDANCE Applicability of FDA Regulations and SOP FDA Regulated Research to this new web guidance; SOP FDA revised to describe staff- and IRB-focused procedures|
|1.3||12.28.2021||12.28.2021||Add note that HSD defers to DoD opinion about applicability of FDA regulations|
|1.2||08.25.2017||08.25.2017||Updated per new FDA guidance regarding waiver of consent for minimal risk FDA regulated studies|
|1.0||04.15.2015||04.15.2015||Newly implemented guidance|
Keywords: Device; Drug; FDA