FDA Research

For FDA-regulated research involving investigational drugs and biologics investigators are required to abide by the following:

For investigator-initiated research involving investigational drugs, follow:

  1. FDA requirements in 21 CFR Part 312, Subpart B for obtaining Investigational New Drug (IND) clearance/approval; and
  2. Review Worksheet: Drugs (HRP-306) for information concerning legal and regulatory requirements that apply to the use of investigational test articles.

For FDA-regulated research involving investigational devices:

Click here for a quick reference guide to device determinations.

  • Mobile Health Apps: If you’re developing a health app for mobile devices and want to know which federal laws apply, check out the Federal Trade Commission’s interactive tool here.
  • General responsibilities of investigators:
  • An investigator is responsible for ensuring that an investigation is conducted according to the signed agreement, the investigational plan and applicable FDA regulations, for protecting the rights, safety, and welfare of subjects under the investigator’s care, and for the control of devices under investigation. An investigator also is responsible for ensuring that informed consent is obtained in accordance with 21 CFR §50.
  • Specific responsibilities of investigators
  • Maintain the following accurate, complete, and current records relating to the investigator’s participation in an investigation
    1. FDA Inspections
    2. Prepare and submit complete, accurate, and timely reports:
      • For investigator-initiated research involving investigational devices, follow FDA requirements in 21 CFR Part 812, Sub-part B for obtaining Investigational Device Exemption (IDE) approval; and
      • Follow Worksheet: Devices (HRP-307) for information concerning legal and regulatory requirements that apply to the use of investigational test articles

For more information about conducting FDA regulated research, and additional requirements for Clinical Trials (ICH-GCP) please refer to the Investigator’s Manual (HRP-103).

 

Brief Overview

This guidance is intended to assist investigators in meeting the various FDA requirements when investigating medical devices in clinical research and in some treatment situations.

Federal regulation 21 CFR 812 explains the requirements for clinical investigations of medical devices. Investigators or sponsors must obtain an Investigational Device Exemption (IDE) from the FDA before beginning a clinical investigation of a medical device. In addition, an IRB must approve investigations of medical devices in humans.

A medical device is considered investigational if either condition applies:

  • The device is not approved for marketing in the United States or
  • The device is approved for marketing but is being clinically evaluated for a new indication.

When is an IDE required?

  • Studies involving unapproved devices that are considered to be significant risk: An IDE is required to perform clinical research using an unapproved device that poses a significant risk to subjects. Typically these studies are conducted to collect safety and effectiveness data used to support Premarket Approval (PMA) applications submitted to the FDA. (See definitions below.)
  • Studies involving an approved device being tested for a new indication: IDE regulations apply to significant risk studies testing an FDA-approved device for a new indication.
Example: Significant risk (SR) studies involve implantable devices such as cardiac pacemakers, orthopedic implants, and stents. SR studies can also involve products not introduced into the body, such as computer software used for prenatal risk evaluation. Each of these studies would require an IDE. For more information, see FDA guidance on Significant and Non-Significant Risk Medical Devices.
Example: A legally marketed coronary stent would be considered an investigational device and would require an IDE if used as part of a study to collect safety and effectiveness data for treating occlusions of other vascular sites.

When is an IDE not required?

  • Studies involving approved devices used within their approved labeling. Devices used within their approved labeling are exempt from IDE regulations.
  • Studies involving devices that are considered to be non-significant risk (NSR): An IDE is not needed for research when the sponsor provides a brief explanation explaining why the device is NSR and the IRB agrees with the sponsor’s explanation.
The following guidance includes examples of significant-risk devices and NSR devices: Significant and Non-significant Risk Medical Devices.
  • IDE-Exempt Studies: FDA regulations provide for exemptions from the requirement for an IND. Two common investigations of medical devices that are exempt from the requirement for an IDE include:
    • Investigations conducted with legally marketed devices used according to labeling.
    • Studies using in Studies using in vitro diagnostic devices labeled “for research purposes only” may be IDE-Exempt as per regulations if the testing:
      • Is noninvasive;
      • Does not require invasive sampling procedures that presents significant risk;
      • Does not introduce energy into a subject; and
      • Is not used as a diagnostic procedure without confirmation by another medically established diagnostic product of procedure

Process for obtaining an IDE

  • Pre-IDE Process: Investigators considering submitting an IDE application to the FDA should communicate with the reviewing division of the Office of Device Evaluation (ODE) prior to the submission of an IDE application. See the FDA IDE Approval Process website for details.
  • The IDE Submission: The IDE submission to the FDA and the IRB application should be initiated at the same time. The FDA has 30 days to review the IDE application. Likewise, the IRB typically reviews an application within a 30-day window, but it may take longer to secure approval. Subjects may not be recruited or enrolled before FDA and IRB approval.

Expanded Access of Unapproved Medical Devices (Treatment Use)

The FDA allows individuals not enrolled in clinical trials to obtain expanded access to investigational devices through the methods described below, under the following circumstances:

  • Patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor or treat the disease or condition;
  • Potential patient benefit justifies the potential risks of the treatment use and those potential risks are not unreasonable in the context of the disease or condition to be treated; and
  • Providing the investigational device for the requested use will not interfere with clinical investigations that could support marketing approval of the expanded access use or otherwise compromise the potential development of the expanded access use.

IMPORTANT NOTE: Medical providers must obtain both FDA and IRB approval for use of an investigational medical device through the expanded access. For more information, see Expanded Access for Medical Devices.

IRB Applications for Investigators of Medical Devices

  • Investigators must check the box on the electronic Initial Review Application indicating that the study involves investigation of a medical device. By doing so, the investigator will be prompted to answer the appropriate questions and provide the information needed for IRB review.
    • For investigations involving a non-significant risk device (NSR), the investigator must include the sponsor’s statement explaining why the investigation poses a NSR along with detailed information about the investigational device (similar to an investigational brochure).
      • If the IRB agrees that the device poses a NSR, an IDE from the FDA will not be required.
      • If the IRB determines that the device poses a significant risk, then the study will continue to be reviewed at the Full Committee level for future submissions.
    • For investigations involving a medical device that is exempt from the requirement for an IDE, the IRB may approve the study without an IDE.
    • For investigations involving a significant risk device, investigators must submit an IDE approval letter from the FDA with the application for initial review and detailed information about the investigational device. If the sponsor has not yet received the approval letter, the IRB will review the study and may approve it with the condition that the study cannot start until the investigator submits a copy of the approval letter to the IRB and the IRB acknowledges receipt.

Investigator Reporting Requirements

Type of Event

Report Recipients

Unanticipated adverse device effect (any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.)

Sponsor: within 10 days of knowledge

IRB: within 5 days of knowledge

Withdrawal of IRB approval

Sponsor: within 5 working days

Progress Report

Sponsor, monitor and IRB no less than annually

Protocol Deviations to protect the life or physical well-being of a subject in an emergency

Sponsor and IRB within 5 working days of deviation

Use of Investigational Device without informed consent

Sponsor and IRB within 5 working days after use

Final report

Sponsor and IRB within 3 months after termination or completion of study

 

Control of Investigational Devices

Investigators conducting studies in which an investigational device will be used must ensure adequate control of the device. Adequate control and handling of investigational devices include all of the following:

  • Ensuring that the investigational device is used only as described in the IRB approved protocol, the signed agreement, the investigational plan and applicable FDA
  • Providing the investigational device only to participants under the investigator’s direct supervision or under the supervision of a sub-investigator responsible to the investigator.
  • Supplying the investigational device to only persons authorized to receive
  • Maintaining accurate, complete, and current records relating to the investigator’s participation in an investigation, including records of receipt, use or disposition of a device that relate to:
    • The type and quantity of the device, dates of its receipt, and the batch number or code mark.
    • The names of all persons who received, used, or disposed of each device.
    • Why and how many units of the device have been returned to the sponsor, repaired, or otherwise disposed of.
  • Returning any unused devices or following the sponsor’s requirements for disposition of unused devices if the investigation is terminated, suspended, discontinued, or completed. See Sample Investigational Device Accountability Log.

Humanitarian Device Exemption (HDE)

An HDE is a type of Pre-Market Approval (PMA) that allows the FDA to grant an exemption from the effectiveness requirements of the PMA regulations. Devices approved an HED are referred to as a Humanitarian Use Devices (HUD). The provisions for obtaining an HDE are:

  • The device is designed to treat or diagnose a disease or condition that affects fewer than 4,000 individuals per year in the U.S.
  • The device is not available otherwise, and there is no comparable device available to treat or diagnose the disease or condition; and
  • The device will not expose patients to unreasonable or significant risk, and the benefits to health from the use outweigh the risks.

Treatment under an HDE is not considered research, but the FDA requires IRB approval prior to use. The IRB looks at the safety of the device and decides what information patients should receive about the safety and effectiveness of the HUD. Physicians who want to use an HUD at UC Davis should submit a standard IRB application and indicate on the electronic Initial Review Application that the device is an HUD.

Drug-Device Combination Products

If an investigator is interested in investigating a combination product, the following links may be useful:

  • The Office of Combination Products (OCP) was created in 2002 to facilitate the review process for combination products by coordinating interactions between reviewing branches.
  • The OCP provides applicable guidance documents for combination products.
  • Some recent combination product approvals include:
    • Drug-eluting coronary stents;
    • Spinal fusion putty; and
    • An influenza vaccine administered via an intranasal delivery device.

Importing Medical Devices

A complete overview of medical device import/export regulations is provided by the CDRH. Clinical investigators should be aware that the FDA does not recognize regulatory approvals from other countries. Therefore, an imported medical device must meet all FDA requirements.

Device Classifications

The level of regulatory controls placed on a medical device is determined by the risk classification. Most research reviewed by the IRB involves significant risk, Class III devices. To help determine device classification, regulatory controls, and exemptions, the Center for Devices and Radiological Health (CDRH) maintains:

  • A searchable classification database containing information about all approved Class I, Class II, and Class III devices.
  • A listing of Class I and Class II devices deemed exempt from Premarket Notification 510(k) regulations.

References