Coalition comments Regarding the FDA Draft Guidance Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions


As members of the Patient, Consumer, and Public Health Coalition, we appreciate the opportunity to comment on the Food and Drug Administration (FDA) Proposed Guidance on Clinical Data in 510(k) Applications.

The Coalition includes nonprofit organizations representing millions of patients, consumers, researchers, and doctors united to ensure that medical treatments are safe and effective.  The coalition does not have paid staff and does not accept funding from any outside sources, so we have no conflicts of interest.  Since many members of our coalition organizations have been harmed by medical devices cleared through the 510(k) pathway, several of the organizations have submitted their own comments to the docket.

The guidance makes it clear that it is “not intended to propose any changes to applicable statutory and regulatory standards, such as how FDA evaluates SE [substantial equivalence], or the applicable requirements, including 510(k) content requirements and the requirement for valid scientific evidence.” Although the guidance “is intended to describe scenarios when clinical data may be necessary” it is “not intended to supersede applicable regulatory requirements of special controls that outline clinical data requirements for certain device types.”  In other words, the goal is to clarify not change current regulatory requirements.  Nevertheless, it is our expectation that the guidance will improve the quality as well as transparency involving the 510(k) pathway, since there are so many concerns about the definition of “substantial equivalence” and so much public information regarding patients who have been harmed by products cleared through the 510(k) pathway.

We agree with the FDA that when a company considers whether data collected on a comparable device may address questions of safety and effectiveness of the new device, “an adequate justification regarding the applicability of such data should be provided demonstrating why such data would be representative of the new device.”

FDA states that after the agency determines that the intended use of the new device is the same as the predicate device, and that the differences in technological characteristics do not raise different questions of safety and effectiveness, clinical data may be used to determine if the new device is “as safe and effective” as a predicate device. We agree that clinical data may be needed in such circumstance and that clinical data may also be needed at other stages of the 510(k) review process, such as “to determine that new or modified indications for use fall within the same intended use as a predicate device.”  It is our view that clinical data are often needed but not required by the FDA and therefore not provided to the FDA or publicly available to healthcare professionals or patients.  This lack of information makes it impossible for patients and their providers to make well-informed decisions.

In this guidance the FDA defines clinical data as including but not being limited to traditional clinical trials as well as “pre- and post-market clinical investigation(s) or other studies reported in the scientific literature of a comparable device; published and/or unpublished reports on clinical experience of either the device in question or a comparable device; and other sources of clinical experience such as registries, adverse event databases, and  medical records (e.g., electronic health records, claims).”  We question the use of data on comparable devices, since it is impossible to know how comparable another device is until it is studied.  Nevertheless, in the interest of transparency and accountability, we strongly urge the FDA to evaluate the use of each of these types of clinical data (pre-market clinical trials, registries, published reports of the new device, etc.) in 2022 and 2023 and compare those statistics to the use of these individual types of clinical data after the guidance is finalized.

We strongly agree that the FDA should recommend clinical data to determine substantial equivalence (SE) under circumstances such as those below; in fact, the FDA should require such evidence:

  1. There are differences between the indications for use of the new device and the predicate device.
  2. There are differences between technological characteristics of the new device and the predicate device.
  3. SE between the new device and the predicate device cannot be determined by non-clinical testing (analytical, bench, and/or animal).
  4. A newly identified or increased risk for the predicate device suggests clinical data may be needed for the new device.

We also agree with the FDA that the following differences could necessitate clinical trials, and should do so more often than is currently the case:

  • Differences in the patient population
  • Differences in the disease
  • Differences in the anatomical site, structure, or pathology
  • General to specific considerations
  • Expansion of the new device’s currently-cleared indications for use
  • Unknown or different benefit-risk profile for the proposed indications for use

The FDA provided reasonable examples in the scenarios that the guidance described as examples of the above.  It is especially important that scientifically valid clinical data be provided when differences in the intended patient population, in the disease, or in the anatomical site change the risk profile or the benefit-to-risk profile.

The FDA provided other important examples of changes that may require clinical evidence, as shown in the bullets below.  We urge the FDA to always require new clinical evidence (preferably clinical trials) for these types of changes.  Moreover, we are concerned that the changes that the FDA considers “significant” need to be expanded, since “significant” is a subjective term.  How does the FDA plan to define “significant change”? When there is any question of whether a change meets the threshold of “significant,” the best way to resolve that question is using scientific evidence of whether the change meets statistical significance in specified outcomes when the products are compared.

  • Significant change in materials
  • Significant change in device design
  • Significant change in energy source
  • Significant change in other device features

We especially support FDA’s emphasis on the importance of requiring new clinical research when there is new evidence of changes in safety or effectiveness of a predicate, as described in “Scenario #4. Too often, manufacturers choose predicate devices after those devices, or predicates to those predicates, have been recalled or have exhibited new or increased risks based on published reports or adverse event reporting.  We especially urge that the FDA make it clear that no device that has been subject to a Class I recall should serve as a predicate, unless the recall was because of changes in instructions or labeling, since research shows that devices cleared on the basis of a Class I recalled predicate are more likely to also be subject to a Class I recall.[1] If the predicate is recalled or reported to have exhibited new or increased risks based on published reports or adverse event reporting after the substantially equivalent device has already been cleared for market, we agree with the FDA’s example of requiring “a class-wide postmarket surveillance study order under section 522 of the FD&C Act for currently marketed devices for this device type” and requiring “that clinical data be included in 510(k) submissions for new devices seeking marketing clearance for this device type to ensure an adequate safety profile prior to marketing.”

We also agree with Example 4-C, that when there is a report that a device could lead to significant patient injury and the device is lacking clear evidence of safety and effectiveness, the manufacturer should voluntarily recall the device.  However, we question whether submitting a new 510(k) is adequate to address the issue, even if it includes clinical performance data.  Instead, requiring a PMA is the best way to ensure patient safety.

In conclusion, we appreciate the FDA’s efforts to make their expectations more clear to industry regarding when clinical trials or other clinical data should be submitted as part of the 510(k) pathway.  However, we strongly urge that the guidance place more emphasis on the most scientifically credible types of clinical data since those are best to ensure patients’ health and safety; that the agency  provide more explicit information about when clinical data are needed to better safeguard patients’ health, what type of clinical data are needed, and the definitions of significant changes and significant differences that are used to consider companies’ 510(k) submissions claim that their new device is substantially equivalent to a predicate or predicates.


Breast Implant Safety Alliance

Medical Device Problems

Mothers Against Medical Error

National Center for Health Research

Our Bodies Ourselves

The TMJ Association

Woody Matters

[1] Kadakia, K.T., Dhruva, S.S., Caraballo, C., Ross, J.S., Krumholz, H.M. (2023). Use of Recalled Devices in New Device Authorizations Under the US Food and Drug Administration’s 510(k) Pathway and Risk of Subsequent Recalls. JAMA. 329(2):136–143. doi:10.1001/jama.2022.23279

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