The investigational device exemption (IDE) is the framework that allows an unapproved device to be used in a clinical investigation in the United States. It is set out in 21 CFR Part 812, published on 18 January 1980 (45 FR 3751), with informed consent rules in Part 50 (30 May 1980) and institutional review board (IRB) rules in Part 56 (27 January 1981). The current 812.1(a), amended at 90 FR 55979 on 4 December 2025, keeps the design and development requirements of 21 CFR 820.10(c), and through it ISO 13485 clause 7.3, in force for IDE devices where applicable.
Before the first US subject is enrolled, the sponsor must know which of three study categories applies: significant risk, nonsignificant risk or exempt. This article explains each category, the role of the IRB and informed consent, sponsor and investigator duties, and what the IDE application contains.
What an IDE does
Part 812 applies to clinical investigations of devices to determine safety and effectiveness (812.2(a)). An approved IDE exempts the device from requirements that would otherwise prevent it from being shipped for investigation, including registration, listing and premarket notification, performance standards and premarket approval. It does not exempt the device from all quality requirements. Under 812.1(a), good manufacturing practice requirements do not apply, except for the requirements in § 820.10(c), if applicable.
FDA's IDE page summarises what an IDE study requires:
an investigational plan approved by an IRB, and by FDA if the study involves a significant risk device;
informed consent from all patients;
labelling stating that the device is for investigational use only;
monitoring of the study; and
required records and reports.
An IDE allows a controlled investigation. It does not authorise commercial distribution of the device.
Significant risk, nonsignificant risk or exempt
Under 812.3(m), a significant risk (SR) device is an investigational device that presents a potential for serious risk to the health, safety or welfare of a subject and:
is intended as an implant;
is purported or represented to be for use supporting or sustaining human life;
is for a use of substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise preventing impairment of human health; or
otherwise presents a potential for serious risk to the health, safety or welfare of a subject.
A nonsignificant risk (NSR) device is one that does not meet this definition. FDA's January 2006 information sheet, Significant Risk and Nonsignificant Risk Medical Device Studies, explains who decides: the sponsor makes the initial risk determination, the IRB reviews it, and FDA is the final arbiter. The determination is based on the proposed use of the device in the investigation, not on the device alone. Among FDA's SR examples is a change to a commercially available pacemaker, such as new leads, a battery pack or software.
| Significant risk | Nonsignificant risk | Exempt | |
|---|---|---|---|
| FDA approval | IDE application to FDA required (812.20) | No IDE application; the study is considered to have an approved IDE once the IRB approves it | No IDE needed |
| IRB review | Required | Required, including review of the NSR determination | Still required |
| Part 50 informed consent | Required | Required | Not addressed by 812.2(c) |
| Reports to FDA | Full Part 812 reports | Abbreviated reports under 812.2(b) | Part 812 does not apply, except 812.119 |
Sources: 21 CFR 812.2 and 812.20; FDA information sheet (January 2006).
Abbreviated requirements for NSR studies
Under 812.2(b)(1)(i) to (vii), an investigation of a device that is not a significant risk device, and not a banned device, is considered to have an approved IDE if the sponsor:
labels the device in accordance with 812.5;
obtains IRB approval after giving the IRB a brief explanation of why the device is not a significant risk device, and maintains that approval;
ensures informed consent is obtained under Part 50;
complies with the monitoring requirements of 812.46;
maintains the records in 812.140(b)(4) and (5) and makes the reports in 812.150(b)(1) to (3) and (5) to (10);
ensures investigators maintain the records in 812.140(a)(3)(i) and make the reports in 812.150(a)(1), (2), (5) and (7); and
complies with the prohibitions in 812.7, including on promotion and commercialisation.
In our view, an NSR study is not a study without oversight. The IRB acts in FDA's place, and the abbreviated requirements still apply. FDA's information sheet adds that sponsors and IRBs do not have to report IRB approval of an NSR study to FDA.
Exempt investigations
Under 812.2(c), Part 812, with the exception of 812.119, does not apply to seven types of investigation. They include certain devices in commercial distribution before 28 May 1976 or found substantially equivalent to them, when used in accordance with their labelling; consumer preference testing; veterinary devices; devices for laboratory animal research; and custom devices.
For software, the most relevant is 812.2(c)(3), diagnostic devices. The exemption applies if the sponsor complies with 809.10(c) and the testing:
is noninvasive;
does not require an invasive sampling procedure that presents significant risk;
does not by design or intention introduce energy into a subject; and
is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
An exemption from Part 812 is not an exemption from ethics review. FDA's information sheet states that the IRB must still review the study in accordance with the IRB regulations.
IRBs and informed consent
If an IRB decides that a study proposed as NSR is in fact SR, it must notify the investigator and, where appropriate, the sponsor (812.66). The sponsor may then not begin the investigation except as provided in 812.30(a), meaning after FDA's 30-day period or approval.
An NSR determination does not by itself allow expedited IRB review. According to FDA's information sheet, a study must be NSR and present no more than minimal risk to the subject to qualify under 21 CFR 56.110.
Informed consent follows Part 50, Subpart B. A study that relies on the exception from informed consent for emergency research under 50.24 needs a separate IDE, and FDA provides a written determination within 30 days of receiving it (812.20(a)(4)).
Sponsor and investigator responsibilities
Sponsors are responsible for selecting qualified investigators, providing them with the information they need, ensuring proper monitoring, ensuring IRB review and approval are obtained, and informing FDA and the IRBs of significant new information (812.40). Investigators are responsible for conducting the investigation in accordance with the signed agreement, the investigational plan and applicable regulations, for protecting subjects, and for controlling the devices under investigation (812.100).
The IDE application and the 30-day clock
For an SR study, the application contents are set out in 812.20(b):
| Item | Content |
|---|---|
| (b)(1) | Name and address of the sponsor |
| (b)(2) | Report of prior investigations and an accurate summary of the investigational plan, or the complete plan |
| (b)(3) | Methods, facilities and controls used for manufacturing, processing, packing, storage and installation |
| (b)(4) | Example of the investigator agreement and list of investigators who have signed |
| (b)(5) | Certification that all investigators have signed or will sign the agreement |
| (b)(6) | Names and addresses of the IRBs, and certification of IRB action |
| (b)(7) | Names and addresses of other institutions involved |
| (b)(8) | Amount charged for the device, if sold, and why the sale is not commercialisation |
| (b)(9) | Claim for categorical exclusion or an environmental assessment |
| (b)(10) | Copies of all labelling |
| (b)(11) | Informed consent forms and other information provided to subjects |
| (b)(12) | Any other relevant information FDA requests |
Source: 21 CFR 812.20(b).
Under 812.30(a), an investigation may begin 30 days after FDA receives the application, unless FDA notifies the sponsor that it may not begin, or earlier if FDA approves it by order. IRB approval is also required before the study starts (812.42). FDA may approve the investigation as proposed, approve it with modifications or disapprove it, and a sponsor can request a regulatory hearing under Part 16 (812.30(c)).
In the EU, device clinical investigations follow the MDR instead, including Article 62, Article 70 and Annex XV.
A hypothetical example
Hypothetical example: a Dutch company plans a US study of its AI decision-support software.
It first assesses the proposed use against the four limbs of 812.3(m), and any diagnostic exemption against each condition in 812.2(c)(3). The key questions are whether clinicians will act on the output during the study, and whether the diagnosis is confirmed by another, medically established method. The company documents the rationale and gives it to the IRB.
The outcome determines the start:
SR: IDE application to FDA, then the 30-day period or approval, plus IRB approval.
NSR: IRB approval based on the company's explanation, with the abbreviated requirements.
Exempt: no IDE, but IRB review is still needed.
The same software can fall into a different category if the protocol changes how clinicians use its output. Our article on SaMD technical documentation covers how to keep the design evidence for the investigational version in order.
Conclusion
The IDE category is decided by the proposed use in the study, not by the device alone, and the rationale deserves the same care as the protocol. An NSR study still runs under IRB oversight and the abbreviated requirements. And because 812.1(a) keeps 820.10(c) in force for IDE devices, design controls start before the main clinical study, not after it.
Our article on medical device regulatory strategy for the EU and US covers where a US study fits in the wider plan. If you need help with the study category or the IDE application, our regulatory strategy team can help, or contact MedQAIR.
Frequently asked questions
Does every device study need an IDE application to FDA?
No. Only significant risk studies need an IDE application to FDA. NSR studies are considered to have an approved IDE once the IRB approves them and the abbreviated requirements are met, and exempt studies under 812.2(c) need no IDE.
Who decides whether a study is SR or NSR?
The sponsor makes the initial determination, the IRB reviews it, and FDA is the final arbiter.
Can an NSR study start without contacting FDA?
Yes, once the IRB has approved it. FDA's information sheet states that IRB approval of an NSR study does not have to be reported to FDA.
Does software need an IDE?
It depends on the proposed use in the study. Software can be SR, NSR or exempt; FDA lists a software change to a pacemaker as an SR example.
What happens after the 30 days?
Under 812.30(a), an SR investigation may begin 30 days after FDA receives the application unless FDA notifies the sponsor otherwise, provided IRB approval is also in place.
