Last verified: August 16, 2026, against the electronic Code of Federal Regulations (eCFR), Title 21, Part 812 (ecfr.gov/current/title-21/chapter-I/subchapter-H/part-812), and cross-referenced against Cornell Law School’s Legal Information Institute text of 21 CFR 812.3 and 812.20. This is a regulatory-orientation guide, not legal or regulatory advice — confirm any specific determination with your IRB and, where relevant, with FDA’s Center for Devices and Radiological Health (CDRH) or a qualified regulatory affairs professional.
The determination in one table
| Question | Significant Risk (SR) | Nonsignificant Risk (NSR) |
|---|---|---|
| Governing definition | 21 CFR 812.3(m) | Any device study that does not meet the 812.3(m) SR criteria |
| FDA submission required? | Yes — full IDE application under 21 CFR 812.20, reviewed by CDRH | No separate FDA application in the typical case — handled under the abbreviated IDE requirements at 21 CFR 812.2(b) |
| Who may begin the study | Only after FDA approves the IDE (by order) or 30 days pass after FDA’s receipt of the application without an FDA hold, for non-banned devices | Once the IRB approves the study as NSR and informed consent/labeling requirements are met |
| IRB’s role | Reviews the investigational plan; FDA is the SR/NSR gatekeeper of record for the formal application | Makes the initial SR/NSR determination itself, and if it concludes NSR, that determination controls unless FDA later disagrees |
| Ongoing obligations | Investigational plan changes generally require an FDA supplement (21 CFR 812.35) before implementation, plus annual progress reports and adverse-device-effect reporting | IRB continuing review, device labeling per 812.5, and informed consent — no FDA supplement process |
What 21 CFR 812 is, and where the SR/NSR determination fits
21 CFR Part 812, titled “Investigational Device Exemptions,” is the FDA regulation that lets a sponsor legally ship and use an unapproved medical device in a clinical study before that device has been cleared through the 510(k) pathway or approved through a premarket approval (PMA) application. Without an IDE exemption, shipping an unapproved device across state lines for a study would otherwise violate the Federal Food, Drug, and Cosmetic Act’s premarket-clearance requirements. Part 812 is the device-study analog to 21 CFR Part 312, the Investigational New Drug regulation that performs the equivalent function for drugs and biologics — see IND vs. IDE for how the two pathways compare at a structural level.
The single most consequential decision inside Part 812 is the significant risk (SR) / nonsignificant risk (NSR) determination, because it decides which of two entirely different regulatory tracks a device study follows: a full FDA-reviewed IDE application, or the lighter, IRB-managed “abbreviated IDE requirements.” Everything else in this guide follows from that one classification.
The SR criteria under 21 CFR 812.3(m)
A device study is a significant risk (SR) investigation if the device presents a potential for serious risk to the health, safety, or welfare of a subject, and:
- it is intended as an implant; or
- it is purported or represented to be for a use in supporting or sustaining human life; or
- it is substantially important in diagnosing, curing, mitigating, or treating disease, or otherwise prevents impairment of human health; or
- it otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
A study is a nonsignificant risk (NSR) investigation if it does not meet any of those four SR criteria. There is no separate regulatory definition of NSR beyond this negative test — an NSR device study is, by definition, any device study that is not SR.
What the determination is not: it is not a judgment about whether the device is likely to work, and it is not the same question as whether the device itself is inherently dangerous outside a study context. A device with a benign everyday use can still be SR in a particular protocol if the study’s specific use exposes subjects to serious risk (for example, an implant study, or a use that substitutes for an FDA-cleared diagnostic in a way that could mislead treatment decisions). The determination is protocol-specific, not device-specific in the abstract.
Who makes the determination, and what happens on disagreement
In practice, the sponsor makes an initial SR/NSR assessment and presents it, with supporting rationale, to the reviewing IRB. The IRB then makes its own independent determination — it is not simply required to accept the sponsor’s classification. If the IRB agrees the study is NSR, the study can generally proceed under the abbreviated IDE requirements without any FDA submission, provided the sponsor also maintains the other 812.2(b) conditions described below.
If the IRB determines the study is SR, or if the sponsor disagrees with an IRB’s NSR finding, the sponsor must either submit a full IDE application to FDA or resolve the disagreement before proceeding. FDA itself retains final authority: even where an IRB has approved a study as NSR, FDA can subsequently determine the study is actually SR (for instance, on inspection or during review of a related submission). When that happens, the sponsor must submit an IDE application, and any subjects already enrolled generally cannot continue in the study until FDA approves the application or notifies the sponsor that continuation is permitted — a materially different position than a drug study that simply proceeds while an IND amendment is pending. Sponsors who are uncertain whether a device meets the SR criteria may ask FDA directly for a risk-determination opinion before finalizing the protocol, which is the lower-risk path when the classification is genuinely close.
Full IDE application (SR studies)
An SR device study requires a complete IDE application submitted to CDRH under 21 CFR 812.20(b), containing, in order: sponsor information; a complete report of prior investigations of the device (nonclinical/bench, animal, and any earlier clinical data) plus the investigational plan or an accurate summary of it; manufacturing information sufficient to assess device quality under good manufacturing practice; an example investigator agreement plus a list of investigators who have already signed one; the names, addresses, and chairpersons of every reviewing IRB, plus certification of IRB action; a list of any other institutions where the study will be conducted; a sales-justification statement if the device will be sold during the study; an environmental-impact categorical-exclusion claim or assessment; copies of device labeling; copies of the informed consent materials; and any other information FDA requests. See IDE Application for the full mechanics of this submission and FDA’s review process.
Under 21 CFR 812.30, FDA notifies the sponsor in writing of the application’s receipt date, then approves it as proposed, approves it with modifications, or disapproves it. For non-banned devices, the study may begin once either FDA affirmatively approves the IDE by order, or 30 days pass after FDA’s receipt of the application without FDA notifying the sponsor of a hold — a default-permission structure that parallels, but is a legally separate mechanism from, the 30-day IND review clock under 21 CFR Part 312. Once a study is underway, most changes to the investigational plan require an FDA supplement under 21 CFR 812.35 before they can be implemented, and sponsors must file annual progress reports and report unanticipated adverse device effects.
Abbreviated IDE requirements (NSR studies)
Under 21 CFR 812.2(b), an NSR device study is exempt from most of Part 812’s procedural requirements — including the full IDE application — provided the sponsor:
- labels the device for investigational use only, in accordance with 21 CFR 812.5;
- obtains and documents IRB approval of the investigation, after presenting the IRB with an NSR rationale;
- ensures investigators obtain informed consent from each subject under 21 CFR Part 50;
- complies with the monitoring requirements of 21 CFR 812.46;
- maintains required records and makes required reports, including reporting to the IRB (and, for certain unanticipated adverse device effects, to FDA); and
- does not promote or commercialize the device as if it were approved for the use under study.
This is what “abbreviated IDE” refers to: the exemption from the formal FDA application and prospective FDA approval step, not an exemption from IRB oversight, informed consent, or safety monitoring, all of which still apply in full.
Devices excluded from Part 812 entirely
A small set of device categories fall outside Part 812 altogether under 21 CFR 812.2(c), and therefore require neither a full IDE application nor an NSR determination: devices in commercial distribution before May 28, 1976 (or later devices FDA found substantially equivalent to a pre-1976 device) used according to their existing labeling; certain noninvasive diagnostic devices; devices used solely for consumer-preference testing unrelated to safety or effectiveness; devices intended solely for veterinary use or laboratory-animal research; and custom devices, unless they are being used to determine safety or effectiveness for future commercial distribution. Confirming a device actually falls into one of these categories — rather than assuming it does — is a determination worth documenting alongside the SR/NSR analysis, since the exclusion criteria are narrower than they first appear (a device merely predating 1976 does not qualify if its labeled use has changed).
Why this determination matters for study timelines
The SR/NSR classification is frequently the single largest driver of how long it takes to get a device study open. An NSR determination that the IRB accepts can allow enrollment to begin as soon as IRB and consent requirements are satisfied — no FDA review cycle at all. An SR determination adds, at minimum, the 30-day FDA review window, and in practice often longer if FDA requests modifications. Because sponsors and IRBs sometimes reach different conclusions on genuinely borderline devices — particularly novel diagnostics and software-driven devices whose “substantially important in diagnosing” status under 812.3(m) is not always obvious on first read — building in time for this determination, and for a possible FDA risk-determination request, before finalizing a study start date is standard practice in clinical research administration.
Frequently asked questions
Is the SR/NSR determination the same as an IRB risk-level categorization for human-subjects protection generally (like minimal risk under the Common Rule)?
No. The Common Rule’s “minimal risk” standard (45 CFR 46) is a separate framework used across all human-subjects research, including for expedited-review eligibility. The SR/NSR determination under 21 CFR 812.3(m) is specific to device studies and specific to whether a full IDE application is required; a study can be non-minimal-risk under the Common Rule while still being NSR under Part 812, or vice versa, since the two frameworks ask different questions for different purposes.
Can a sponsor start an NSR study without any FDA contact at all?
Generally yes, once the IRB has approved the study as NSR and the other 812.2(b) conditions are met — that is the point of the abbreviated pathway. FDA retains authority to later determine a study is actually SR, which is why documenting the NSR rationale presented to the IRB matters even though no FDA submission is required up front.
What happens to subjects already enrolled if FDA later determines a study the IRB approved as NSR is actually SR?
The sponsor must submit an IDE application, and enrollment of new subjects, and often continuation of subjects already enrolled, generally cannot proceed until FDA approves the application or otherwise notifies the sponsor that the study may continue — confirm the specific posture of any affected study directly with FDA/CDRH rather than assuming continuation is permitted by default.
Does the abbreviated IDE pathway mean informed consent isn’t required?
No. Informed consent under 21 CFR Part 50 is required for both SR and NSR device studies. The abbreviated pathway removes the formal FDA application and prospective approval step for NSR studies — it does not remove informed consent, IRB oversight, monitoring, or reporting obligations.
Related CASRAI pages
- IDE Application (Investigational Device Exemption Application) — the full mechanics of the formal IDE submission for SR studies.
- Investigational Device — the underlying definition and scope of what counts as an investigational device under 21 CFR 812.3(g).
- IND vs. IDE — how the device pathway compares structurally to the drug/biologic IND pathway under 21 CFR Part 312.
- Category A vs. Category B IDE Studies: Medicare Coverage — a related but distinct classification (Medicare coverage category, governed by NCD 310.1) that applies specifically to SR device studies seeking Medicare reimbursement for routine care costs.
