Substantial equivalence (SE) is the FDA's standard of review for the 510(k). The new device must have the same intended use as a legally marketed comparison device (predicate device) and, if its technology differs, must not raise different questions of safety and effectiveness.
Definition and legal basis
Substantial equivalence (SE) is the standard by which the US authority FDA assesses a 510(k) premarket notification. The manufacturer compares its new device with an already legally marketed device, the predicate device (German: Vergleichsprodukt). Unlike with the PMA, it does not have to independently demonstrate the safety and effectiveness of its device. By its own account, the FDA relies in the 510(k) context in part on its earlier finding regarding the predicate.
The statutory basis is Section 513(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act, the US federal law on foods, drugs, and cosmetics), codified in the US Code as 21 U.S.C. 360c(i). Under it, a device is substantially equivalent to a predicate if it has the same intended use and the FDA finds that it either has the same technological characteristics or, if the characteristics differ, is as safe and effective as a legally marketed device and does not raise different questions of safety and effectiveness. A significant change in materials, design, energy source, or other characteristics counts as a differing technological characteristic. The regulation 21 CFR 807.100(b) adopts these criteria. For differing characteristics, the FDA can require clinical or scientific data if it considers them necessary.
The FDA explains the procedure in the guidance “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]” of July 28, 2014. FDA guidances are not binding.
The predicate device
According to 21 CFR 807.92(a)(3), a legally marketed device is one of the following: a device that was marketed before May 28, 1976, a device that was reclassified from class III to class II or I (see FDA device classification), or a device that was found substantially equivalent in the 510(k) process. The guidance usually calls this device the “predicate device” or “predicate.” For devices marketed before 1976, this applies only insofar as no PMA is required for them. A device that was removed from the market on the FDA's initiative or that a court found to be “misbranded” or “adulterated” does not qualify as a predicate.
For the choice of the predicate, the guidance names several rules:
- One predicate is sufficient. The FDA recommends naming a single one. If several are named, the manufacturer should designate a primary predicate, that is, the one with the most similar indications for use and technological characteristics.
- Several predicates are only an option if they support the same intended use. A “split predicate,” where the intended use is measured against one device and the technology against another device with a different intended use, is not compatible with the 510(k) standard.
- Reference devices are further legally marketed devices that can support scientific methods or reference values. They are expressly not a predicate.
- The manufacturer names the predicate in the 510(k) summary, which the regulation describes in 21 CFR 807.92. If it modifies its own device that has already been cleared, it can use that device as the predicate.
FDA review steps
The guidance organizes the review into decision points of a flowchart. The FDA proceeds in sequence:
- Decision point 1: Is the predicate legally marketed? If not, the device is not substantially equivalent (NSE).
- Decision point 2: Do both devices have the same intended use? To this end, the FDA checks whether the entire labeling is consistent with the statements on use. If not, NSE follows.
- Decision point 3: Do the devices have the same technological characteristics? If yes, the device is substantially equivalent (SE).
- Decision point 4: Do the differing characteristics raise different questions of safety and effectiveness? If yes, NSE follows.
- Decision points 5a and 5b: Are the proposed scientific methods for evaluating the differences acceptable, and do the performance data demonstrate equivalence? Only with two “yes” answers is the device substantially equivalent.
According to the guidance, a “different question” is a question that is raised by the technological characteristics of the new device, did not apply to the predicate, and constitutes a significant safety or effectiveness problem.
Intended use and indications for use
For substantial equivalence, the intended use must be the same. The guidance understands this as the general purpose or function of the device, which includes the indications for use. According to 21 CFR 814.20(b)(3)(i), these describe the disease or condition that the device diagnoses, treats, prevents, cures, or mitigates, including the patient population. The FDA determines the intended use on the basis of the proposed labeling (see Intended use).
Not every change in the indications for use means a new intended use. According to the guidance, this is only the case if the change raises different questions of safety and effectiveness and rules out a meaningful comparison with the predicate. According to the guidance, particular attention is required for, among other things, a different patient population, such as adults versus children, or a different clinical setting, such as hospital versus home use.
Possible outcomes and missing predicate
Under 21 CFR 807.100(a), the FDA can classify a device by order as substantially equivalent or as not substantially equivalent, request additional information, withhold the decision until a disclosure statement under Part 54 is provided, or notify that no premarket notification is required. Until the applicant receives an order on substantial equivalence, it may not market the device.
The guidance distinguishes two kinds of NSE decisions. If there is no predicate, there is a new intended use, or the differing characteristics raise different questions, the device is automatically class III by operation of law. It then needs a PMA or, if it is suitable, a De Novo request. If, on the other hand, only the submitted evidence is insufficient, a new 510(k) with different or additional data remains possible. If there is no predicate with the same intended use, the manufacturer can, according to the guidance, submit a De Novo request, either after an NSE decision or directly. For the direct route, the guidance recommends clarifying in advance via the Pre-Submission whether a valid predicate exists.
Selecting the predicate: 2023 draft
In September 2023, the FDA published a draft of the guidance “Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission.” According to our research, no final version has been published (as of October 2026). The draft bears the notation “Not for Implementation” and is therefore only an indication of the FDA's direction.
The draft recommends choosing, from the valid predicates, one that has no unmitigated use-related or design-related safety issues. To this end, it advises searching the MAUDE, Medical Device Reporting, and MedSun databases in advance for reported injuries, deaths, and malfunctions (see MAUDE database). It also recommends a predicate without a design-related recall.
Relation to human factors
The FDA guidance “Content of Human Factors Information in Medical Device Marketing Submissions,” final since May 29, 2026, also applies to 510(k) submissions and supplements the FDA human factors guidance. It clarifies that for the 510(k), substantial equivalence is the decision standard and human factors information forms only one component of the overall assessment. Substantial equivalence therefore does not by itself determine which human factors information must be submitted. That is governed by the guidance.
The predicate appears in several places there:
- Known use problems: A section of the HFE/UE report (HFE/UE report) summarizes known use problems of earlier models or similar devices, expressly including those of predicates. The guidance recommends stating that none are known if that is the case (see Known usability problems).
- Changes to the user interface: For a modified device whose predicate is the manufacturer's own cleared device, the guidance asks whether the user interface, users, uses, use environments, training, or labeling change. Without such changes, the lowest of the three human factors categories is sufficient. If a manufacturer extends the indication to pediatric patients, the guidance counts this as a new user group.
- Comparison with the predicate: In the category 2 examples, manufacturers compare indications, use environment, users, and labeling with the predicate. For a low-complexity user interface and similar devices that have long been on the market, they justify why they do not submit human factors validation data. The guidance emphasizes that such examples are not exhaustive and depend on the case.
- Limits of equivalence: The FDA can also require validation data when they were not customary for the device type so far, for example in the case of a significant difference from similar legally marketed devices. Named are a new technological characteristic, new indications for use, a changed use environment, or new user groups.
For practice, it follows that the differences from the predicate should be captured early, not only technically but also from the perspective of use. The starting point is the use-related risk analysis (URRA). Whether hazard-related use scenarios in the sense of IEC 62366-1, called critical tasks by the FDA, are affected determines the further scope.
Substantial equivalence is the FDA's decision standard for the 510(k) under Section 513(i) FD&C Act and 21 CFR 807.100. The new device must have the same intended use as a legally marketed predicate device and must either have the same technological characteristics or, despite differences, raise no different questions of safety and effectiveness.
The FDA reviews in five decision points: predicate, intended use, technological characteristics, different questions of safety and effectiveness, and methods and performance data. If there is no predicate, De Novo or PMA come into question.
For human factors, the 2026 FDA guidance mentions the predicate, among other things, in connection with known use problems. Whether validation data are needed depends on risk, complexity, and changes, not on substantial equivalence alone.
Frequently asked questions (FAQ)
What is a predicate device?
A predicate device is the legally marketed device to which a new device is compared in the 510(k). Under 21 CFR 807.92, it was on the market before May 28, 1976, was reclassified from class III to II or I, or was itself found substantially equivalent in the 510(k) process. One predicate is sufficient; several make sense only for the same intended use.
What does substantial equivalence mean, and what does it not mean?
Under Section 513(i) FD&C Act, it means the same intended use and either the same technological characteristics or differences that raise no different questions of safety and effectiveness. It does not mean that the devices are identical. Differing technology is possible as long as the device is as safe and effective as a legally marketed device.
What happens if there is no suitable predicate?
Then a device is not substantially equivalent and is class III by operation of law. It needs a PMA or, if it is suitable, a De Novo request. The FDA guidance recommends clarifying the question of a valid predicate in advance in a Pre-Submission.
Do I have to submit human factors data for a 510(k)?
That follows from the FDA guidance on the content of human factors information, not from substantial equivalence. What matters are the use-related risk analysis, whether critical tasks exist, the complexity of the user interface, and changes compared with an existing device. The manufacturer assigns the submission to one of three categories. Depending on the category, a justification is sufficient or a full report with validation data is needed.
Should I consider known use problems of the predicate?
In categories 2 and 3, the guidance recommends a section on known use problems of earlier models and similar devices, expressly including those of predicates. The 2023 draft also advises searching reporting databases such as MAUDE before choosing the predicate. This draft, however, is not binding.
Are you planning a 510(k) and want to set up the human factors work to fit your predicate? We support you with planning, execution, and documentation.
More about our usability engineeringSources
- FDA Guidance: Content of Human Factors Information in Medical Device Marketing Submissions
- FDA Guidance: Applying Human Factors and Usability Engineering to Medical Devices
- IEC 62366-1:2015+AMD1:2020, Medical devices, Part 1: Application of usability engineering to medical devices
- 21 CFR 807.100, FDA action on a premarket notification
- 21 CFR 807.92, Content and format of a 510(k) summary
- Federal Food, Drug, and Cosmetic Act, Section 513 (21 U.S.C. 360c), Classification of devices intended for human use
- FDA Guidance: The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]
- FDA Draft Guidance: Best Practices for Selecting a Predicate Device to Support a Premarket Notification [510(k)] Submission