Is FDA Mimicking MDR? Clinical Data Recommendations for 510(k) Submissions

WHOA.  Did you see this? On September 7, 2023, FDA issued a new guidance document entitled Recommendations for the Use of Clinical Data in Premarket Notification [510(k)] Submissions. This is one of three 510(k) guidance documents that FDA issued on the same day that radically change how the medical device industry can seek clearance of its Class II medical devices in the U.S. These new guidance documents should give pause to medical device manufacturers who thought they knew what to expect from FDA when making their substantial equivalence claims. The changes are part of FDA’s 510(k) plan to modernize the 510(k) program as part of the CDRH Safety Action Plan.  The idea is to provide greater clarity around what may be required for 510(k) submissions. However, the language in this particular guidance appears to give FDA rather broad authority to request clinical data based on their interpretation of whether the sponsor has successfully demonstrated substantial equivalence.  Let’s look more closely.

Historically, FDA has not required clinical data to support the safety and effectiveness of Class II medical devices for which there is a suitable predicate and for which the sponsor is able to establish substantial equivalence. Though it has always had the authority to request clinical data, this has typically not been a requirement. Not having to generate pre-market clinical evidence is a critical component to the 510(k) process as it facilitates introduction of new medical devices that are not considered to be high risk in an efficient manner to address patient needs. It also creates competition in the device industry, which is a healthy component of a functional economy. Over the years, there have been criticisms of the 510(k) program, particularly when something goes wrong with a particular device. However, the general consensus based on decades of performance data indicates that the devices cleared under the 510(k) program are overwhelmingly safe and effective for patients. In addition, FDA can require additional special controls and post-market surveillance studies (under Section 522) in the case where a new device is substantially equivalent, but may raise some new questions of safety or effectiveness. 

Though the release of this new guidance is consistent with FDA’s modernization plans, the language of the guidance gives pause. Further, within the context of global regulatory requirements, I can’t help but wonder whether FDA isn’t eyeing the EU MDR regulations that required medical device manufacturers to identify clinical data to support their MDR CE mark. Under EU MDR sufficient clinical data had to be generated for devices that are typically considered Class II in the U.S. With all that data lying around, why wouldn’t FDA want to get a closer look at it? I’ve personally experienced requests from FDA for clinical data rivaling what is typically found in a national joint registry in other countries. While this was in the post-market setting, the sense is that FDA wants more clinical data. This guidance would indicate they are finding ways to make it more likely to be a requirement for market clearance. 

While the new guidance clearly sticks to the standard requirements for 510(k) devices stating that “clinical data would not be necessary to demonstrate [substantial equivalence] to a predicate device and requiring clinical data would be inconsistent with the least burdensome provisions of the FD&C Act”, the guidance further states, rather vaguely, that “for certain devices subject to 510(k) requirements, obtaining clinical data may be necessary to demonstrate that a new device is [substantially equivalent] to a predicate device.” (emphasis added). 

The guidance goes on to state that FDA may request “clinical performance data” if the Agency determines that non-clinical, animal, or other bench studies are not sufficient to support safety and effectiveness. In addition, clinical data may be requested if there are differences in indications or technological differences between the new and predicate device. Clinical data may also be necessary when substantial equivalence cannot be determined by non-clinical testing or there are newly identified or increased risks. These broad criteria mean that nearly any 510(k) submission for a new device that is not nearly identical to its predicate could be subject to the requirement that clinical data be provided to obtain clearance. 

While I am a proponent of clinical research and robust post-market clinical evidence of safety and performance, I have concerns about the impact of this new guidance on the ability of sponsors to get Class II devices cleared without the need for pre-market clinical research studies. The language of the guidance is broad enough to give FDA justification for clinical data requirements well beyond what has been expected in the past. Requirements like this will hamper innovation and delay patient access to new devices. Medical device manufacturers should prepare themselves for the possibility that the 510(k) program in the U.S. just got an EU MDR upgrade.