In the Federal Register of May 8, 2013, FDA announced a public meeting titled “510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device.” The notice states that the focus of the meeting will be “FDA's interpretation of its regulations concerning when a modification made to a 510(k)-cleared device requires a new 510(k) submission.” The meeting is to be held on June 13, 2013, from 9am to 5pm. The registration deadline is May 30, 2013.
As discussed in our previous blog post, in July 2011 FDA issued a guidance document intended to update the 1997 guidance of the same name as the meeting. The guidance was met with strong resistance from industry, insisting that the interpretations applied in the guidance would result in the requirement to submit a new 510(k) for numerous device modifications. In response to the feedback from industry, Congress, in enacting the Food and Drug Administration Safety and Innovation Act ("FDASIA") in July 2012, required FDA to withdraw the guidance and prohibited FDA from implementing a new guidance until it submits a report to Congress describing when a new 510(k) should submitted. The report must include FDA’s interpretation of several key phrases in 21 C.F.R. 807.81(a)(3), the regulation governing submission of a new 510(k) for a modification to an existing product. In addition, the report must include “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.” The public meeting is intended to solicit stakeholder feedback on these issues. On a related note, FDA recently issued a draft guidance on when modifications must be reported to FDA, which also received substantial negative feedback from industry (see our previous post here). Perhaps issues discussed at the 510(k) meeting will shed light on those concerns as well.
In the notice, FDA provides a number of specific policy options on which it is seeking feedback, but notes that “implementation of some of these options may require regulatory changes beyond a guidance document.” These options appear to be new ideas that have not previously been presented by FDA, and ones that industry would likely agree require changes beyond a guidance document. In some cases, the changes may require statutory, rather than merely regulatory, changes.
The notice sets forth five policy options, and also asks for ideas of additional policy proposals and examples of device changes that industry believes should not trigger the requirement for a new 510(k). Under each of the five policy options, FDA poses questions on which it is seeking comment prior to the public meeting and will be discussed at the meeting.
The five policy options and examples of the questions for feedback include:
A. Risk Management
FDA says it is primarily concerned with identifying a way to incorporate risk management to ensure “appropriate and consistent modification decisions by industry and FDA staff.” Such decisions are those “that allow for both medical device innovation and effective FDA oversight of device changes.” FDA recognizes the importance of ensuring a process to ensure consistent results, since decisions will be made by a variety of different manufacturers and FDA reviewers. To address these concerns, FDA seeks input on the following:
- How can FDA tie risk management to the decision that a change or modification to a device could significantly affect the safety or effectiveness of the device?
- Given the variability in risk management processes and guides, 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?
- How can FDA assure that a company’s risk management process is comprehensive and appropriately implemented?
B. Reliance on Design Control Activities
The notice expresses FDA’s desire for effective oversight of the design control process, including the opportunity to review design control activities. FDA states that “improper application of these activities may lead to incomplete or inaccurate evaluations of design changes and the marketing of unsafe or ineffective devices.” In considering how FDA can affect oversight of design controls, FDA seeks input on the following:
- Since FDA does not typically review design control information prior to clearance, how can FDA ensure that design control activities will limit the potential for marketing modified devices that may be unsafe or ineffective?
- Manufacturers comply with design control requirements in a variety of different manners. How can FDA ensure consistency in use of design controls to ensure that only safe and effective modified devices are marketed?
C. Critical Specifications
FDA states in the notice that critical specifications could be one way that FDA could link use of design activities to 510(k) modification decisions. This would involve industry and FDA identifying “essential” or “critical” specifications and agreeing on limits and testing protocols for those specifications. So long as the modified device remains within those limits, no new 510(k) would be required. FDA indicates that it would like to discuss the feasibility of this approach with industry, and how it might be implemented. It also states that this approach would not apply to changes to intended use or labeling, “as those aspects of a device are not associated with specifications.”
Based on information provided in the notice, it appears that this approach may be quite burdensome for manufacturers and reviewers. FDA states that, in an initial 510(k) submission, manufacturers would have to identify the following information: a list of potential changes that might be made; critical specifications for each change, i.e., those specifications “that are essential to safe and effective use of the device (e.g., tensile strength)”; bounds for those specifications within which a modified device must remain; and the verification and validation test protocols that will be used to examine the specifications pre- and post-modification. Providing this information would require a significant amount of work by sponsors, and raise new issues for FDA reviewers.
Given the above, FDA is seeking input on the following questions:
- How could critical specifications be incorporated into the review process? For example, if FDA and the sponsor cannot agree on the critical specifications, but FDA is otherwise prepared to proceed with a substantial equivalence decision, how should that be handled?
- How could critical specification agreements be documented?
- Should use of critical specifications be limited to certain types of changes? If so, which ones?
- Are there certain specifications that could be deemed critical for all devices? If so, which ones?
- Could critical specifications be implemented as an optional paradigm, meaning that manufacturers could elect to use it where convenient, and if not elected, the change would remain subject to the 510(k) modifications decision-making paradigm?
D. Risk-Based Stratification of Medical devices for 510(k) Modifications Purposes
Under this framework, FDA would expect 510(k)s for modifications of higher risk devices that meet the standard in 21 C.F.R. § 807.81(a)(3), whereas for lower risk devices, not all modifications would require a 510(k) even if they meet the regulatory standard. Certain modifications, such as a change in intended use, would always require a 510(k), regardless of the level of risk of the device. FDA has the following questions about this approach:
- How should FDA designate higher or lower risk devices? Are higher risk devices only those designated as life sustaining, life supporting, or implants?
- Should FDA require some other measure, such as periodic reports, in lieu of 510(k) submissions for lower risk devices?
- How should FDA determine which modifications to lower risk devices require 510(k) submissions and which do not?
E. Periodic Reporting
FDA is seeking feedback on the submission of periodic reports for modifications to 510(k)-cleared devices that did not require a new 510(k) submission. FDA acknowledges that this would “be similar to annual reporting of device changes for approved class III devices.” It also states that FDA would review these changes to “ensure that decisions were made appropriately.”
FDA would like feedback regarding:
- How often FDA should require periodic reports?
- Should FDA require periodic reports for all 510(k) devices or only certain devices? If only certain devices, which ones?
- What information should be included in a periodic report?
This seems like an option that probably would not appeal to industry as crafted, as it would be imposing an additional obligation not currently required by the regulations. Moreover, it would almost certainly lead to second-guessing “no-file” decisions. If FDA and industry can work to clearly delineate when a new 510(k) is required for a modified device, there should be no need for FDA to review information about modifications that do not fit that paradigm.
Given the negative industry response to the July 2011 draft guidance, industry should take advantage of this opportunity to work with FDA to design a modifications paradigm that will meet the regulatory requirements without imposing burdens unnecessary to assure the development and marketing of safe and effective medical devices and enable further product improvements.
The issue of 510(k) modifications is both recurring and important. This public meeting will not be the final word. Still, it provides an important forum for responding to some novel ideas that have been broached by FDA.