Investigational Device Exemption (IDE) Resources

Overview 

The following information is provided to guide sponsor-investigators (SI) through the Investigational Device Exemption (IDE) process. The information below is provided only as guidance. Specific questions and inquiries regarding IDE Applications should be addressed to the FDA.

An Investigational Device Exemption (IDE) allows the investigational device to be used in a clinical study to collect safety and effectiveness data. Clinical studies are most often conducted to support a Food and Drug Administration (FDA) Premarket Application (PMA). Only a small percentage of 510(k)s require clinical data to support the application. Investigational use of a device also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.

The federal regulations for IDEs are found at 21 CFR 812.

IDE Process Flowchart 

All clinical investigations of medical devices require IRB review and approval.

IDE Regulatory Requirements 

FDA 21 CFR 812 is the US federal regulation that covers IDEs. This regulation details procedures for the conduct of clinical studies with medical devices including applications, responsibilities of sponsors and investigators, labeling, records, and reports.

Investigational devices covered under the IDE regulation are subject to different levels of regulations depending upon the level of risk (i.e., significant risk (SR) and non-significant risk (NSR) device studies).

  • Studies with significant risk (SR) devices must follow all IDE regulations under 21 CFR 812, must have an FDA-approved IDE application, and an IRB approval before the start of the investigation.
  • Studies with non-significant risk (NSR) devices only need to follow abbreviated IDE regulations under 21 CFR 812.2 (b) and require only IRB approval before the start of the investigation. 
  • Studies with devices can also be exempt from the IDE regulations under 21 CFR 812.2(c).

When is an IDE Application Required? 

A sponsor or sponsor-investigator is required to submit an IDE application to the FDA if:

  • The sponsor or sponsor-investigator intends to use a significant risk device in an investigation;
  • The sponsor or sponsor-investigator intends to conduct an investigation that involves an exception from informed consent under 21 CFR 50.24; or
  • FDA notifies the sponsor that an IDE application is required for an investigation.

The following steps summarize the IDE determination process:

Step 1. Is the device subject to IDE regulations?

If the ultimate goal of the device under investigation is to diagnose, cure, treat, mitigate, or prevent disease, then once any human subjects or human specimens are used, regardless of the phase of the study or the amount of data being collected, IDE regulations apply, unless the study is exempted from IDE regulations based on 21 CFR 812.2(c).

Using human subjects (or human specimens) determines the transition to IDE and starts the process of determining the risks to the human subjects. It may be determined that devices or assays are exempt from the IDE regulation, but because of variations in devices and their uses, this determination may only be appropriately made on a case-by-case basis.

Step 2. Is the device Exempt from IDE regulations?

The following categories of devices are exempt from IDE regulations:

  • devices in commercial distribution before 5/28/76
  • devices determined by FDA to be 'substantially equivalent' to a device in commercial distribution before 5/28/76
  • diagnostic devices that:
    • are noninvasive,
    • do not require an invasive sampling procedure that presents significant risk,
    • do not introduce energy into a subject, and
    • are not used as a diagnostic procedure without the confirmation of another medically established diagnostic product or procedure
  • devices used for consumer preference testing or for any test that is not intended to determine safety or effectiveness and does not expose subjects to risk
  • devices exclusively used for veterinary indications
  • devices to be shipped exclusively for research on laboratory animals
  • custom devices unless these are used to assess safety or effectiveness for commercial distribution

Studies exempt from the requirements of IDE regulations are not exempt from the requirements for IRB review and approval. Even though the majority of low-risk devices and in vitro diagnostics (IVDs) are exempt, when a device or assay is used to determine eligibility for a clinical study, or used for a novel indication, and the results are not confirmed with another medically established diagnostic product or procedure, IDE regulations apply.

Device studies that are exempt from IDE requirements still require IRB approval. With your submission materials in eIRB, include the Appendix for Devices to document the specific exemption category that applies to the device.

Step 3. Does the non-exempt device pose a significant risk (SR) or non-significant risk (NSR) to human subjects?

It is the responsibility of the sponsor or sponsor-investigator to make the initial risk assessment, and depending on the outcome, either the FDA makes the final significant risk (SR) or the IRB makes the final non-significant risk (NSR) determination.

The criteria outlined in (21 CFR 812.3 (m)) are used to make the SR determination, based on whether or not the device:

  • Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
  • Is for use in supporting or sustaining human life and represents a potential for serious risk to the health, safety, or welfare of a subject;
  • Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or
  • Otherwise presents a potential for serious risk to a subject.

If the device meets the definition above, it is considered significant risk (SR). If the device does NOT meet the definition above, it is considered non-significant risk (NSR).

An NSR device is considered to have an approved IDE application, therefore no application needs to be filed with the FDA. Please refer to our guidance on Abbreviated IDE Requirements for more information about NSR device requirements.

However, if an IRB determines the study is significant risk, the sponsor or sponsor-investigator must notify the FDA in writing. The study may not begin until the FDA approves the study or provides an NSR determination.

Pre-IDE Process

Sponsors of an SR study are encouraged to review the Contact FDA – Device Guidance to obtain further guidance prior to the submission of an IDE application to the FDA. This will be especially beneficial to new sponsors who have not previously had contact with the agency and for sponsors proposing to study new technologies or new uses for existing technologies. The FDA’s Pre-IDE Program is primarily designed to benefit the IDE sponsor.  By allowing the sponsor to obtain early FDA input on selected (by the sponsor) sections of the IDE application, the FDA hopes that the initiation of clinical trials will be facilitated. This communication may take the form of telephone conference calls, videoconferences, or face-to-face discussions.

The sponsor should contact the Office of Device Evaluation (ODE) reviewing division directly or may contact the FDA IDE staff for assistance:

IDE Staff
Investigational Device Exemptions Program
Office of Device Evaluation
Center for Devices and Radiological Health
10903 New Hampshire Avenue
WO66-1648
Silver Spring, MD 20993-0002
Telephone 301-796-5640

Please review the latest FDA Guidance for IRBs, Clinical Investigators, and Sponsors for more information.  

IDE Application Guidance

The following are required items for IDE Applications to the FDA:

  • The IDE holder’s name and address
  • A report with all prior investigations of the device and a summary of the investigational plan.
  • A description of methods, facilities, and controls used in the manufacture, processing, packing, storage, and, if applicable, installation of the device.
  • An example of the agreement to be signed by the investigators and a list of the names and addresses of all investigators.
  • A statement certifying that all investigators participating in the study will sign the agreement and that no investigator will take part in the study before signing the agreement.
  • An IRB list with the name, address, and chairperson of each IRB that will review the investigation and a certification of IRB study-related action.
  • If the device will be sold, the amount to be charged for the device and a rationale of how its sale does not amount to commercialization of the device.
  • The IDE Sponsor-Investigator writes the IDE Application.

 The IDE Application submission to the FDA must also include:

  • IDE Cover Letter
  • Investigators Certification of Financial Interest
    • Form FDA 3674 
    • eCopy of submission
      • An electronic copy (eCopy) is an electronic version of your medical device submission created and submitted on a compact disc (CD), digital video disc (DVD), or flash drive. An eCopy is accompanied by a paper copy of the signed cover letter. 
      • Please refer to FDA guidance on eCopy submissions.

Submitting an IDE Application to the FDA

On the outer packaging of the submission (e.g., the FedEx label), identify the contents as "Initial IDE Application," "IDE Supplement," etc. The same identification should appear in the “RE:” section of the cover letter. Keep a copy of the courier receipt. Track the shipment on the courier website for confirmation of delivery. File a PDF copy of the delivery confirmation with the PDF copy of the signed submission.

FDA will reply to the submission with an acknowledgment letter containing:

  • the date of receipt of the IDE application;
  • the IDE number assigned to your application; and
  • the name of the project manager to address in future submissions under the IDE.

An IDE application is considered approved thirty (30) days after it has been received unless FDA informs the sponsor otherwise. An IDE may be approved, approved with conditions, or disapproved. It is advised you obtain written confirmation (email or fax) that the FDA review has been completed and that the study may proceed.

For more detailed information, please review the FDA Application guidance. Review the IDE Application Checklist to ensure it contains all pertinent information.

Maintaining the IDE

IDE sponsors or sponsor-investigators are required under 21 CFR 812.150 to submit the following reports:

  • Unanticipated Adverse Device Effects (UADE): A UADE Report consists of a completed Form FDA 3500A and an analysis of the event in a cover letter, submitted to FDA and all reviewing IRBs and investigators within ten (10) working days after the sponsor first receives notice of the adverse effect.
  • Withdrawal of IRB Approval: Submitted to FDA and all reviewing IRBs and participating investigators within five (5) working days after receipt of notice of the withdrawal of IRB approval of an investigation (or any part of an investigation).
  • Withdrawal of FDA Approval: Submitted to all reviewing IRBs and participating investigators within five (5) working days after receipt of notice of any withdrawal of FDA approval.
  • Current List of Investigators with Addresses: Submitted to FDA every six (6) months.
  • Progress Reports: Submitted to FDA and all reviewing IRBs at regular intervals and at least yearly.
  • Recalls and Device Disposition: Submitted to FDA and all reviewing IRBs within thirty (30) working days after receipt of a request to return, repair, or dispose of any unit of an investigational device. The report must state why the request was made.
  • Final Report: For a significant risk device, the sponsor must submit a final report notifying FDA and all reviewing IRBs within thirty (30) working days of the completion or termination of the investigation. The sponsor must also submit a final report to FDA and all reviewing IRBs and participating investigators within six (6) months after the completion or termination of the investigation.  
  • Use of a Device without Informed Consent: Submitted to FDA within five (5) working days after receipt of notice of such use.
  • SR Device Determination: Submitted to FDA within five (5) working days after determination by an IRB that the device is an SR device and not an NSR device as the sponsor had proposed.
  • Other Reports: Accurate, complete, and current information about any aspect of the investigation upon request from FDA or the reviewing IRB.

Definitions

The following definitions appear in the Investigational Device Exemption regulations 21 CFR 812.3:

FDA is the United States (US) Food and Drug Administration in charge of overseeing Title 21 Federal Regulations.

Indications for use describes the disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the patient population for which the device is intended.

Intended use is the general purpose of the device or its function, including its indications for use.

Investigation is a clinical investigation or research (study/trial) involving one or more subjects to determine the safety or effectiveness of a device.

Investigational device is a device, including a transitional device, that is the object of an investigation.

Investigator is an individual who actually conducts a clinical investigation (i.e., under whose immediate direction the investigational device is administered, dispensed to, or used involving a subject). In the event the investigation is conducted by a team of individuals, "investigator" refers to the responsible leader of the team.

  • Sponsor is a person or other entity that initiates but does not actually conduct the investigation. An entity other than an individual (e.g., a corporation or an agency) which uses one or more of 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. FDA requires that the sponsor of an IDE must be located in the United States (see 21 CFR 812.18).
  • Sponsor-investigator is an individual who both initiates and actually conducts, alone or with others, a clinical investigation (i.e., under whose immediate direction the investigational device is administered, dispensed, or used). For example, a clinical investigator can sponsor his/her own study, in which case they become a sponsor-investigator. The term does not include a corporation or agency. The obligations of a sponsor-investigator include those of an investigator and those of a sponsor.
  • Subject means a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used, or as a control. A subject may be in normal health or may have a medical condition or disease.

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