On January 19, 2011, FDA announced 25 actions that it intends to implement or begin implementing this year with regard to the 510(k) process (and associated action dates)—as well as 7 controversial proposals it has decided not to implement now, but intends to further consider. See FDA, 510(k) and Science Report Recommendations: Summary and Overview of Comments and Next Steps (510(k) Actions Report).i The actions announced are less sweeping than the 55 recommendations for the 510(k) process made by the agency’s internal 510(k) Working Group and Science Task Force and released in August 2010.ii FDA received public comments on those recommendations and states that its actions are in most respects consistent with the comments received.iii
The 25 actions FDA intends to adopt and related timelines are appended at the end of this Alert.iv These actions fall into three broad categories: guidance development, internal/administrative actions, and programmatic/regulatory initiatives. FDA states that the actions are intended to “support innovation, keep jobs here at home, and bring important, safe, and effective technologies to patients quickly.”v These goals were emphasized in a Wall Street Journal op-ed by President Barack Obama.vi In a January 19 press call, CDRH Director Jeff Shuren explained that the actions are also intended to enhance the consistency, predictability, and transparency of the Center’s 510(k) practices.
While certain actions have the potential to meet FDA’s stated goals, it remains to be seen whether, as executed, these actions will produce more consistency and clarity for industry, or greater burden and complexity. Additionally, some changes (e.g., guidance on 510(k)s for modifications, proposed rule on submission of labeling as part of annual listing requirements, device-specific changes described below) may be likely to result in increased regulatory scrutiny and expectations. Highlights of FDA’s planned actions follow.
De Novo Classification: FDA has committed to provide guidance streamlining the de novo pathway for low-risk devices that lack an appropriate predicate. During the 510(k) press call, Director Shuren emphasized that this effort is one of the chief ways in which FDA is seeking to promote the prompt availability of innovative devices. He mentioned that the guidance may reflect actions such as simplifying the content of 510(k)s that must be submitted (and denied) as a prerequisite to de novo classification, as well as doing away with the time-consuming guidance development process for establishing special controls where applicable to a de novo device. (Draft guidance to be developed by September 30, 2011)
510(k) Modifications: Regarding changes to devices with an existing 510(k) clearance, FDA reports that it will clarify the types of changes for which a new 510(k) submission would or would not be expected, as well as changes eligible for a Special 510(k). (Draft guidance to be developed by June 15, 2011). Considering publicly reported concerns about underreporting in this regard, it will be important to see whether FDA’s draft guidance clarifies longstanding expectations or creates new ones.
510(k) Paradigm, including clinical data, “intended use,” multiple and split predicates: The agency plans to provide guidance on several critical topics, including, among others, when clinical data should accompany a 510(k); the appropriate use of multiple predicates (which FDA says it “strongly supports”vii); criteria for identifying “different questions of safety and effectiveness” as well as technological changes generally raising these questions; and characteristics that should be included in the concept of a device’s “intended use.” (Draft guidance to be developed by September 30, 2011)
With regard to multiple predicates, FDA also intends to complete (by October 31, 2011) an analysis of an apparent association between devices whose 510(k)s cited more than five predicates and a heightened rate of adverse event reports. Any determined connection would likely affect the agency’s guidance on use of multiple predicates.
Notably, FDA’s 510(k) Actions Report states that the agency “do[es] not intend to implement the [510(k) Working Group’s] recommendation to eliminate the use of ‘split predicates.’”viii FDA explains that this simply means the agency will no longer use the term “split predicate” (because it perceives industry confusion regarding the meaning of this term); the agency’s report makes clear that it believes use of a “true split predicate” (i.e., a situation where a submitter attempts to “demonstrat[e] that a new device has the same intended use as one predicate while comparing the new device’s technological characteristics with a second predicate that has a different intended use”ix) would be “inconsistent with the 510(k) standard.”x
Appeals: FDA intends to clarify the process for appealing CDRH decisions, including 510(k) rescission decisions (Draft guidance to be developed by October 31, 2011)
Improve internal expertise and knowledge sharing: FDA’s plans in this area include (1) establishing a Center Science Council to, among other things, help “continuously assess the quality, consistency and effectiveness of the 510(k) program” and “periodically audit 510(k) review decisions to assess adequacy, accuracy and consistency”; (2) training CDRH staff and industry on key 510(k) concepts such as “intended use,” when a 510(k) raises “different questions of safety and effectiveness,” the review of devices citing multiple predicates, applying “least burdensome” principles, and the appropriate use of consensus standards; and (3) developing and leveraging the expertise of a network of outside scientific experts. Additionally, through its Center Science Council, FDA will establish an internal team of clinical trial experts to provide support and advice to CDRH staff and investigational device exemption (IDE) applicants on the design of clinical trials; however, it is not yet clear to what extent the Center Science Council will be involved in disputes about the need for clinical data to support certain 510(k) submissions or the adequacy of the clinical data that are collected. (Actions include posting Center Science Council Charter to FDA website by March 31, 2011; posting initial results of 510(k) audit to FDA website by June 15, 2011; developing and implementing training on 510(k) core competencies by August 31, 2011; and posting an SOP for use of external experts by September 15, 2011.)
Streamline guidance and regulation development: FDA intends to provide greater clarity, predictability, and efficiency in these processes. (SOPs to be posted to FDA’s website by July 31, 2011)
Expedite Industry Notification of Regulatory Changes: The agency intends to adopt a standard practice of issuing “Notice to Industry” Letters to inform stakeholders when regulatory expectations (a potential example could be data expectations) change on the basis of new scientific information. FDA has noted industry’s concerns that the use of these letters in lieu of guidance would “eliminat[e] the opportunity for public comment” and industry suggestions that an SOP be established to “clearly define the parameters for when and about what topics the Center would issue such letters.”xi (SOP to be posted to FDA website by June 15, 2011)
Initiate rulemakings: FDA will develop regulations to address the submission of device labeling as part of the requirement for manufacturers to submit updated device listing information annually. FDA “believe[s] that periodically submitting updated labeling to CDRH would help the Center stay abreast of new information in product labeling and that periodically auditing the submitted labeling would aid the Center in assuring the quality and accuracy of device labeling.”xii In addition, FDA will promulgate new rules to (1) implement a Unique Device Identification (UDI) system, which FDA expects to facilitate identification of device-specific problems, and (2) improve documentation of 510(k) transfers of ownership (UDI proposed rule to be published by June 30, 2011; device labeling and 510(k) transfer proposed rules to be published by December 31, 2011)
Hold public meetings regarding making publicly available sensitive device information: FDA’s internal 510(k) Working Group and Science Task Force recommended that CDRH develop publicly available databases that would include various information about cleared devices (e.g., labeling, device photographs or schematics). While this information could potentially facilitate preparation of 510(k)s, public comments expressed significant concerns about confidential or proprietary information being included in the database. FDA has committed to hold a public meeting on April 7-8, 2011, to further discuss this proposal.
Changes to be Implemented on a Case-by-Case/Device-Specific Basis
FDA has decided to move forward with certain controversial recommendations made by its internal 510(k) Working Group, although in more limited form; the agency states it will implement the following “on a case-by-case basis through device-specific guidance.”xiii FDA has not, however, identified the specific devices that would be subject to these requirements or identified time frames for implementation; additionally, in some cases, the actions contemplated may be beyond what FDA can appropriately effectuate through guidance. Given their potential significance, these areas remain important for industry to monitor and assess as FDA moves towards implementation.
- Notification of Device Modifications: On a case-by-case basis, FDA would require manufacturers to provide regular, periodic updates of device modifications. FDA’s 510(k) Actions Report “recognize[s] that might not be necessary to assure that new 510(k)s are submitted when appropriate for modifications to cleared devices.”xiv According to the report, “Generally, the circumstances under which it would be most helpful to receive periodic reports of modifications are when a change is made to a higher-risk device for which the impact on safety or effectiveness is unclear; specifically, it is unclear whether or not CDRH should require the submission of a 510(k). In these cases, CDRH would want to be notified periodically that such a change was made in lieu of submitting a 510(k).”xv
- Report All Known Safety and Effectiveness Information: Case-by-case, FDA would require 510(k) submitters to include in their submissions “a brief description of safety and effectiveness information specific to the device to be reviewed that is already known to the submitter.” xvi (Emphasis in original) FDA believes the 510(k) Working Group’s original recommendation that the agency consider new regulations extending this requirement to all 510(k) submitters and all safety and effectiveness information “known to or that should be reasonably known to” each submitter “may be too broad in scope and overly burdensome.”xvii The report does not, however, clarify what the legal basis would be for requiring selected submitters to provide all known information and, in particular, information not related to a determination of substantial equivalence.
- Provide Manufacturing Information and/or Submit to Pre-Clearance Inspections: FDA intends to develop device-specific guidance detailing when manufacturing information would be requested in 510(k) submissions. In response to industry comments, FDA notes its “agree[ment] that manufacturing process information should be provided only for a subset of higher-risk devices for which the receipt and review of such information could prevent potential safety or quality problems.”xviii Similarly, FDA intends to provide guidance detailing the device-specific circumstances when it believes it should exercise existing statutory authority to conduct manufacturing inspections in connection with the review of a 510(k).
- Adopt Use of an “Assurance Case” Framework for 510(k) Submissions. FDA intends to institute a pilot program to study the use of an “assurance case” framework for infusion pumps. This approach would require 510(k) sponsors to structure their submissions in a manner that more stringently demonstrates the validity of predicate comparisons. Despite industry comments that this approach could substantially hinder the already-burdened review process and/or should be limited to certain higher-risk devices, FDA has stated its belief that the use of assurance cases can improve the review of 510(k)s and aid industry in identifying and addressing potential 510(k) weaknesses pre-submission. The agency advises that it “will make any assessment of the pilot program available to the public upon the program’s completion and seek public input before deciding whether or not to apply an assurance case approach to other device types and, if so, which ones.”xix
Proposals for Which Decision-Making Has Been Deferred
Not least among FDA’s announcements are its decisions not to act (pending an opportunity for input by the Institute of Medicine (IOM)) on certain potentially significant and/or detrimental recommendations of the agency’s internal 510(k) Working Group and Science Task Force. These proposals generated significant controversy in public comments received by FDA,xx and the agency announced on January 19 that it will await possible IOM input before deciding whether or to what extent to implement the recommendations. (During the media call accompanying the announcement of FDA’s planned actions, CDRH Director Shuren clarified that there is no requirement that the IOM comment on all or any of these proposals, but FDA will consider relevant IOM comments, if any. The IOM is expected to issue its own report on FDA’s 510(k) process in summer 2011; the agency has not specified any timeline for further action following that report.)
Specifically, FDA is delaying decisions on the following controversial recommendations pending possible IOM consideration:
- Establish device Class IIb. Under this proposal, FDA would issue guidance creating a “Class IIb” classification for devices for which clinical data, manufacturing data, and/or postmarket data would generally be needed to support clearance. While we do not yet know whether FDA will ultimately accept or reject this proposal, FDA’s 510(k) Actions Report advises that, “The intent of this recommendation was not to expand the types of devices subject to clinical data requirements, but rather to place a greater onus on CDRH to identify in advance those devices for which clinical data would be required. However…[FDA] understand[s] that implementing this recommendation may have unintended consequences.”xxi
- Seek statutory authority to expand regulation of off-label use. FDA’s 510(k) Working Group recommended that FDA seek expanded statutory authority to consider off-label use when determining a device’s intended use in the clearance process. FDA’s 510(k) Actions Report states that this recommendation “was intended to be limited to the rare circumstance where a manufacturer seeks clearance for one use but actually intends to market the device for a different use in order to avoid having to provide data regarding the true intended use,” rather than to “force industry to provide data on potential off-label uses even if the device under consideration was never intended to be used for such purposes.”xxii FDA further acknowledges “the challenges of drafting new legislative authority narrowly tailored to the limited circumstances” it intended to address and thus “understand[s] it may not be feasible to implement this recommendation without inadvertently restricting the practice of medicine.”xxiii
- Consolidate the terms “indication for use” and “intended use”. Under this proposal, the agency would combine these terms and use only the term “intended use.” The proposal raised the possibility that changes in indications for use could increasingly be considered to be changes in intended use necessitating additional 510(k) clearance. FDA’s 510(k) Actions Report clarifies that, “The intent of this recommendation was to reduce current confusion over the terms “intended use” and “indications for use”; not to reduce the instances in which a new indication for use would still represent the same intended use. However,…we understand that implementing this recommendation may not achieve our intended goal.”xxiv
- Define conditions disallowing device use as predicate. The 510(k) Working Group recommended that FDA consider developing guidance to describe when a device should no longer be permitted to be used as a predicate because of safety or effectiveness concerns. Public comments opposed this recommendation on grounds that any FDA guidance may exceed statutory criteria governing the types of predicates that are inappropriate for determining substantial equivalence; that disallowing the use of certain predicates would unnecessarily constrain the availability of the 510(k) pathway for otherwise eligible devices; and that such an approach would present challenges with respect to marketed products that had relied on disallowed predicates in their 510(k) submissions. In light of these comments, FDA’s 510(k) Actions Report acknowledges that “implementing this recommendation may have unintended consequences.”xxv
- Issue a regulation defining FDA’s authority to rescind a 510(k). FDA has decided to await possible IOM input on this proposal in light of significant public concerns about the agency’s authority and the unnecessary and duplicative nature of rescission given FDA’s ability to recall or take other enforcement actions against unsafe or ineffective devices. However, the agency’s 510(k) Actions Report makes clear that, notwithstanding this, FDA believes that it “ha[s] the authority to rescind a 510(k) under appropriate circumstances.”xxvi In the January 19th press call, CDRH Director Shuren emphasized that, even pending any IOM recommendation regarding this proposal, FDA will not refrain from taking action to rescind 510(k) clearances if the agency believes such action is warranted. Dr. Shuren noted that, as referenced above, one action item FDA is proceeding to implement is guidance addressing the appeals process for 510(k) rescission decisions
- Seek greater authority to require postmarket surveillance as a condition of clearance. In deferring decisionmaking on this proposal, FDA has taken note of varying concerns raised in public comments, including questions about the need for such expanded authority in light of FDA’s existing authorities in this area, and anticipated deleterious effects on industry, physicians, and innovation.
- Require manufacturers to keep one unit of a device available in the clearance process. Here, FDA noted the challenges raised by industry, given that many firms do not manufacture and/or would be significantly burdened to manufacture, store, install, or calibrate a device or prototype prior to clearance.
Thoughts for Industry
In sum, the actions FDA has announced for implementation with respect to the 510(k) process are not as drastic as the agency’s internal working group recommendations; however, industry should carefully review FDA’s outputs as target action dates arrive to better evaluate their impact. Additionally, certain of the most controversial proposed 510(k) changes, though in abeyance for now, are still open for future decision, and FDA has not identified a specific time frame for their resolution. Further, FDA has indicated that it will move forward to implement some controversial recommendations on a case-by-case basis with respect to specific devices but has not provided key details (e.g., what types of devices will be affected and when). Accordingly, industry should continue to closely monitor FDA’s actions in the 510(k) area and identify opportunities to provide input on these actions, including commenting on draft guidances and proposed rules and/or, where appropriate, seeking to be heard through the legislative process associated with reauthorizing the Medical Device User Fee and Modernization Act of 2002 (MDUFMA).