FDA rules for clinical studies of medical devices

Clinical investigations of devices to determine safety and effectiveness are governed by 21 CFR part 812, which applies to all such investigations except the categories exempted in § 812.2(c).¹ Whether the study may begin without a submission to FDA depends on whether it uses a significant risk device: a sponsor must submit an investigational device exemption (IDE) application if it intends to use a significant risk device, if the investigation involves an exception from informed consent under § 50.24 or if FDA notifies the sponsor that an application is required.¹ Every investigation within part 812 also runs under the human subject protection rules in part 20 CFR part 50 and the institutional review board rules in part 56.²³

When part 812 applies

Part 812 applies to all clinical investigations of devices to determine safety and effectiveness, subject to the exemptions in § 812.2(c).¹ An investigation is defined in § 812.3(h) as a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.¹ The first exempted category in § 812.2(c)(1) covers a device other than a transitional device that was in commercial distribution immediately before 28 May 1976, when used or investigated in accordance with the labeling indications in effect at that time.¹ Further exempted categories follow in that paragraph.

Parts 50 and 56 reach further than part 812. Both define a clinical investigation to include an experiment involving a test article and human subjects whose results are intended to be submitted later to FDA, or held for its inspection, as part of an application for a research or marketing permit.²³ An IDE application under part 812 is itself listed as an application for a research or marketing permit.² Under § 56.103(b), FDA may decline to consider data from a clinical investigation that was not approved by and subject to continuing review by an IRB meeting part 56.³

An approved IDE exempts the device from misbranding under section 502 of the act, from registration, listing and premarket notification under section 510, from performance standards, premarket approval and banned device regulations, and from good manufacturing practice requirements under section 520(f) except for the requirements in § 820.10(c), if applicable.¹ That carve-out for § 820.10(c) was added by the amendment published at 90 FR 55979 on 4 December 2025.¹

Significant risk and non-significant risk investigations

An investigation of a device other than a significant risk device is considered to have an approved IDE application, provided the device is not a banned device and the sponsor meets the conditions in § 812.2(b)(1).¹ Those conditions are:

• labelling the device in accordance with § 812.5,
• obtaining and maintaining IRB approval after presenting the reviewing IRB with a brief explanation of why the device is not a significant risk device,
• ensuring that each investigator obtains informed consent from each subject in accordance with part 50,
• complying with § 812.46 on monitoring,
• maintaining the records required by § 812.140(b)(4) and (5) and making the reports required by § 812.150(b)(1) through (3) and (5) through (10),
• ensuring that participating investigators maintain the records required by § 812.140(a)(3)(i) and make the reports required by § 812.150(a)(1), (2), (5) and (7).
• complying with the prohibitions in § 812.7.

The IRB carries the risk determination in the first instance. Under § 812.66, an IRB may determine that an investigation presented to it under § 812.2(b)(1)(ii) involves a significant risk device. In that case the IRB must notify the investigator and, where appropriate, the sponsor.¹ The sponsor may then begin only as provided in § 812.30(a).¹ This differs from the European regime. A non-significant risk device study in the United States proceeds on IRB approval alone, with no application to the national authority.

The IDE application and FDA action

The application is a signed Application for an Investigational Device Exemption, submitted with accompanying materials in electronic format to an address in § 812.19.¹ It contains, in order, the name and address of the sponsor and a complete report of prior investigations of the device with a summary of the investigational plan or the complete plan.¹ FDA may require the complete plan and the complete report where no IRB has reviewed them, where FDA has found an IRB’s review inadequate or on request.¹ A study involving an exception from informed consent under § 50.24 requires a separate IDE, prior written authorisation from FDA and prominent identification on the cover sheet.¹ FDA provides a written determination on such an application 30 days after receipt or earlier.¹

The investigational plan under § 812.25 contains the following, in order:

• the purpose, including the name and intended use of the device and the objectives and duration of the investigation,
• a written protocol with an analysis demonstrating that the investigation is scientifically sound,
• a risk analysis covering increased risks, their minimisation, a justification and a description of the patient population,
• a description of each important component, property and principle of operation of the device,
• the sponsor’s written monitoring procedures and the name and address of any monitor,
• copies of all labelling and of all consent forms and informational materials,
• a list of all IRBs asked to review the investigation and a certification of any action taken,
• the name and address of each other institution at which part of the investigation may be conducted,
• a description of any additional records and reports.

The report of prior investigations under § 812.27 must be comprehensive and adequate to justify the proposed investigation. It includes a bibliography of relevant publications, copies of published and unpublished adverse information and a summary of other unpublished information reasonably obtainable by the sponsor.¹ Where nonclinical laboratory studies are provided, the report states whether they complied with the good laboratory practice regulations in part 58.¹ Where United States clinical data are provided, the report states whether each investigation complied with parts 50, 56 and 812.¹

Under § 812.30(a), an investigation of a device other than a banned device may not begin until 30 days after FDA receives the application. If FDA notifies the sponsor that the investigation may not begin, it may start only once FDA approves an IDE by order.¹ Section 812.20(a)(2) states that a sponsor shall not begin an investigation for which FDA’s approval is required until FDA has approved the application.¹ Section 812.42 requires both IRB and FDA approval before any investigation or part of an investigation begins.¹ Grounds for disapproval or withdrawal in § 812.30(b) include noncompliance, untrue statements of material fact, failure to respond to a request for information and a finding that risks are not outweighed by anticipated benefits.¹

Sponsor and investigator responsibilities

Sponsors select qualified investigators, supply them with the investigational plan and the report of prior investigations, ensure proper monitoring, ensure that IRB review and approval are obtained and keep the IRB and FDA informed of significant new information.¹ A signed agreement is obtained from each investigator under § 812.43(c), including the curriculum vitae, relevant experience, a commitment to comply and financial disclosure information sufficient for the certification required by part 54.¹ That financial information is submitted in a marketing application rather than in the IDE.¹

Monitoring duties are set out in § 812.46. A sponsor who discovers noncompliance must promptly secure compliance or discontinue shipments and terminate that investigator’s participation.¹ A sponsor must immediately evaluate any unanticipated adverse device effect. Where the effect presents an unreasonable risk, the sponsor terminates the affected investigations no later than 5 working days after making that determination and no later than 15 working days after first receiving notice of the effect.¹

Investigators are responsible for conducting the investigation according to the signed agreement, the investigational plan and applicable FDA regulations, for protecting subjects and for control of the device.¹ An investigator may assess potential interest before approval, but may not request written informed consent or allow participation before IRB and FDA approval.¹ Investigator reports under § 812.150(a) carry fixed deadlines.¹

• unanticipated adverse device effects to the sponsor and reviewing IRB within 10 working days
• withdrawal of IRB approval within 5 working days
• emergency deviations from the investigational plan within 5 working days
• use of a device without informed consent within 5 working days
• progress reports at least yearly
• a final report within 3 months of termination or completion

IRB review

An IRB reviewing investigations under part 812 must comply with part 56 in all respects, including composition, duties and functions.¹ Each IRB has at least five members with varying backgrounds, at least one whose primary concerns are scientific, at least one whose primary concerns are nonscientific and at least one who is not affiliated with the institution.³ IRBs in the United States that review FDA-regulated clinical investigations must register with the Department of Health and Human Services before reviewing such an investigation and renew every 3 years.³ Approval criteria are listed in § 56.111, and continuing review takes place at intervals appropriate to the degree of risk and at least once per year.³ IRB records are retained for at least 3 years after completion of the research and are open to FDA inspection.³

Informed consent

No investigator may involve a human being as a subject without the legally effective informed consent of the subject or the subject’s legally authorised representative, except as provided in §§ 50.22, 50.23 and 50.24.² The information given must be in language understandable to the subject, and no consent may include exculpatory language waiving legal rights.² The basic elements in § 50.25(a) include a statement that the study involves research, a description of reasonably foreseeable risks, a description of expected benefits and a disclosure of appropriate alternative procedures.² Consent is documented on a written form approved by the IRB and signed and dated by the subject or the representative, with a copy given to the person signing.²

Three exceptions exist. Section 50.22, added by the rule published at 88 FR 88248 on 21 December 2023, allows an IRB to waive or alter consent for a clinical investigation involving no more than minimal risk where the investigation could not practicably be carried out without the waiver.² Section 50.23 covers life-threatening situations, with written certification by the investigator and an independent physician, and documentation to the IRB within 5 working days of use.² Section 50.24 covers emergency research and requires community consultation, public disclosure and an independent data monitoring committee.²

Where children are subjects, subpart D of part 50 applies. An IRB may approve only investigations that satisfy § 50.51, § 50.52 or § 50.53, and must determine that provisions for parental permission and child assent under § 50.55 are adequate.² Investigations that meet none of those three sections may proceed only under § 50.54, which requires a determination by the Commissioner of Food and Drugs after consultation with a panel of experts and opportunity for public comment.²

Labelling, promotion and charging

An investigational device or its immediate package bears the manufacturer’s name and place of business, the quantity of contents where appropriate and the statement “CAUTION—Investigational device. Limited by Federal (or United States) law to investigational use.”¹ The labelling describes all relevant contraindications, hazards, adverse effects, warnings and precautions, and may not represent that the device is safe or effective for the purposes under investigation.¹ Section 812.7 prohibits promoting or test marketing an investigational device before FDA approves it for commercial distribution.¹ Charging subjects or investigators more than the cost of manufacture, research, development and handling is a prohibited commercialisation.¹ A sponsor must promptly terminate an investigation that has unduly prolonged, including where data show that premarket approval of a class III device cannot be justified.¹

Data from investigations outside the United States

FDA accepts information from a clinical investigation conducted outside the United States in support of an IDE or a device marketing application if the investigation is well-designed and well-conducted and the conditions in § 812.28(a) are met.¹ The first condition is a statement that the investigation was conducted in accordance with good clinical practice, defined in that section as a standard covering design, conduct, monitoring, recording and reporting that provides assurance of credible data and protected subjects.¹ Good clinical practice for this purpose includes review and approval by an independent ethics committee before initiation, continuing review and documented freely given informed consent.¹ This route covers submissions under section 515, section 520(m), a 510(k) notification and a De Novo classification request.¹

Questions people also ask

When must a sponsor submit an IDE application to FDA before starting a device study?

Section 812.20(a)(1) requires an application where the sponsor intends to use a significant risk device in an investigation, where the investigation involves an exception from informed consent under § 50.24 or where FDA notifies the sponsor that an application is required.¹ An investigation of a device that is not a significant risk device and is not banned is considered to have an approved IDE if the sponsor meets the seven conditions in § 812.2(b)(1).¹

Who decides whether a device presents significant risk?

The reviewing IRB makes the determination when the investigation is presented to it under § 812.2(b)(1)(ii). If the IRB determines that the investigation involves a significant risk device, § 812.66 requires it to notify the investigator and, where appropriate, the sponsor, and the sponsor may then begin only as provided in § 812.30(a).¹ FDA can also notify a sponsor under § 812.20(a) that an application is required.¹

How long does FDA have to act on an IDE application?

Section 812.30(a) provides that an investigation may not begin until 30 days after FDA receives the application for a device other than a banned device, unless FDA notifies the sponsor that it may not begin, or until FDA approves an IDE by order.¹ For an investigation involving an exception from informed consent under § 50.24, FDA provides a written determination 30 days after receiving the IDE or earlier, and the study may not proceed without prior written authorisation.¹

Can a change to the protocol be made without a supplemental IDE application?

Section 812.35(a)(1) requires approval of a supplemental application, and IRB approval where appropriate, before a change to an investigational plan is implemented.¹ A deviation to protect the life or physical well-being of a subject in an emergency is exempt from prior approval and is reported to FDA within 5 working days.¹ Certain developmental changes and protocol changes may be made with notice to FDA within 5 working days where the criteria in § 812.35(a)(3) are met.¹

Can an investigational device be given to a patient outside the trial?

Section 812.36 provides for treatment use of an investigational device in patients with a serious or immediately life-threatening disease for whom no comparable or satisfactory alternative is available.¹ The criteria include that the device is under investigation in a controlled clinical trial under an approved IDE for the same use or that such trials have been completed.¹ For a serious disease, the device ordinarily becomes available for treatment use after all clinical trials have been completed.¹

How long must IRB and investigator records be kept?

Part 56 requires IRB records to be retained for at least 3 years after completion of the research and to be accessible for FDA inspection and copying.³ Investigator records under § 812.140(a) include all correspondence, records of receipt and disposition of the device, each subject’s case history with consent documentation and the protocol with the dates of and reasons for each deviation.¹

Footnotes

1. 21 CFR Part 812, Investigational Device Exemptions. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-812 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹² ↩¹³ ↩¹⁴ ↩¹⁵ ↩¹⁶ ↩¹⁷ ↩¹⁸ ↩¹⁹ ↩²⁰ ↩²¹ ↩²² ↩²³ ↩²⁴ ↩²⁵ ↩²⁶ ↩²⁷ ↩²⁸ ↩²⁹ ↩³⁰ ↩³¹ ↩³² ↩³³ ↩³⁴ ↩³⁵ ↩³⁶ ↩³⁷ ↩³⁸ ↩³⁹ ↩⁴⁰ ↩⁴¹ ↩⁴² ↩⁴³ ↩⁴⁴ ↩⁴⁵ ↩⁴⁶ ↩⁴⁷ ↩⁴⁸ ↩⁴⁹ ↩⁵⁰ ↩⁵¹ ↩⁵² ↩⁵³

2. 21 CFR Part 50, Protection of Human Subjects. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹²

3. 21 CFR Part 56, Institutional Review Boards. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸