US regulators are preparing to revisit a now-withdrawn draft guidance on the clearance of medical devices through the 510(k) premarket notification pathway, and are looking for industry's help in formulating a new guidance document meant to eventually take its place.
In 2011, FDA released a new guidance document, 510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device, meant to bring an update its 510(k) process, which had largely remained static since 1997-a long time even by regulatory standards.
But if the changes were meant to allay industry concerns, they wound up having the opposite effect. Numerous industry analysts noted that the 2011 guidance would significantly increase the number of required 510(k) applications, potentially creating a backlog of applications and further slowing the device regulatory process.
"The only thing that appears certain is that CDRH believes many more modifications necessitate a new 510(k) than had been the case," explained FDA Law Blog's Jennifer Newberger in a July 2011 post. "There are no changes where 510(k)s that were needed are no longer required, but there are many changes for which companies would have used a letter to file that would now need a 510(k).
Industry's unrelenting criticism of the 2011 guidance eventually found its way before Congress, which at the time was considering reforms to FDA under the terms of the FDA Safety and Innovation Act (FDASIA).Legislators, already focused in on the medical device process due to other alleged problems, were receptive to that criticism, and in July 2012 voted to order FDA to withdraw the guidance under Section 510(n)(2)(B) of the law.
The agency was further ordered to entirely disregard the 2011 guidance document (which, it should be noted, is not so much agency policy as a notice of its interpretation of its prior rulemaking) and not issue any other 510(k) guidance until it has briefed Congress in a report on its intent to issue new guidance. The 1997 guidance remains in effect until that time.
Looking for Help with a New Report…and Guidance
That report is due to Congress within 18 months of the passage of FDASIA, which occurred in July 2012, and now FDA is advertising its intent to involve industry in the process of reforming that guidance.
"The report must address the interpretation of several phrases in 21 CFR 807.81(a)(3) (the regulation governing submission of 510(k)s for changed or modified devices), possible processes for industry to use to determine whether a new 510(k) is required, and how to leverage existing quality system requirements to reduce premarket burden, facilitate continual device improvement, and provide reasonable assurance of safety and effectiveness of modified devices," FDA explained.
But how do you best solicit feedback from industry? In addition to the usual method-the docket of the Federal Register-FDA said it plans to hold a public meeting regarding proposed changes, at least some of which it believes may require additional rulemaking beyond the issuance of a guidance document.
One of the most prominent topics identified by FDA is the use of "risk management" in the regulatory decision process for devices that might require a 510(k) submission. At present, such devices are subject to one of three possible risk classifications: Class III, for high risk devices; Class II, for moderate-risk devices; and Class I, for low-risk devices.
The larger problem, to read FDA's explanation, is really one of consistency between all classification decisions. How do you ensure that two wildly different devices that have the exact same risk profile end up under the same device classification?
"FDA would like to solicit specific, detailed, and practicable proposals that incorporate risk management into this decision process in a way that ensures appropriate and consistent modification decisions by industry and FDA staff," it writes. "Appropriate decisions in this context are those that allow for both medical device innovation and effective FDA oversight of device changes."
FDA further observed that "Inconsistent decisions will make policy unclear and unpredictable for those making future decisions," thereby harming the ecosystem for medical devices.
With those thoughts in mind, FDA said it has a huge number of questions it is wishing to address at its upcoming meeting on 13 June 2013:
- How can risk management be tied to a decision on whether a modification requires a new 510(k)?
- More specifically, how can FDA tie risk management to the decision that a change or modification in a device is one that could significantly affect the safety or effectiveness of the device?
- How can a single risk management process be chosen that leads to consistent and appropriate decisions on whether a 510(k) is required for a device modification?
- How can the inherent subjectivity of risk management be controlled to ensure consistent and appropriate decisions on whether a 510(k) is required for a device modification?
- How can FDA obtain assurance that a company's risk management process is comprehensive and appropriately implemented?
- How can FDA ensure that design control activities will limit the potential for marketing of device modifications that may be unsafe or ineffective?
- How can FDA ensure consistency in use of design controls to ensure that only safe and effective modified devices are marketed?
- Industry members have proposed the use of critical specifications, a new concept, to make decisions on whether a 510(k) is required for a device modification easier. Is this approach feasible?
- How could critical specifications be incorporated into FDA's review process?
- How should situations where agreement cannot be reached within review timeframes be handled?
- How could situations where FDA is ready to proceed with a substantial equivalence decision, but critical specifications have not been agreed upon, be handled?
- How could critical specifications agreements be documented? Should they be summarized in 510(k) Summaries or substantial equivalence letters?
- Should use of critical specifications be limited to certain types of changes? If so, which ones?
- Are there particular specifications that could be deemed critical for all devices? If so, which ones?
- Could critical specifications be implemented as an optional paradigm?
- How should FDA delineate higher versus lower risk devices? For example, would higher risk devices include only those designated as life-sustaining, life-supporting, or implants?
- Should FDA require some other measure, such as periodic reports, for modified lower risk devices in lieu of 510(k) submissions?
- How should FDA delineate which lower risk device modifications require 510(k)s and which do not?
- How often should FDA require periodic reports, e.g., annually, biannually, etc.?
- Should FDA require periodic reports for all 510(k) devices or only certain devices? If not all devices, then which ones?
- What information should be included in a periodic report?
FDA Meeting: 510(k) Device Modifications; Deciding When to Submit a 510(k) for a Change to an Existing Device