Appealing Premarket Disputes in the Device Center: Reform Is Needed

By Jeffrey K. Shapiro –

A medical device manufacturer in most cases is legally required to obtain 510(k) clearance or premarket application (“PMA”) approval from the Food and Drug Administration’s (“FDA”) prior to commercial distribution.  Premarket reviews are conducted under the auspices of the Office of Device Evaluation (ODE) or the Office of In Vitro Diagnostics (“OIVD”) in the Center for Devices and Radiological Health (“CDRH”).  Unfortunately, disputes between sponsors and FDA sometimes arise during the review process.  A dispute may concern which review process is appropriate, i.e., whether a 510(k) clearance or PMA approval is required.  Or, it may be a disagreement over the type or quantity of supporting bench, preclinical or clinical data that should be required, or whether the data are adequate to support clearance or approval.  There also may be disputes in other areas – for example, the appropriate labeling for a device.  Typically, these disputes will culminate in an unfavorable decision at the ODE or OIVD Division level, such as a “not substantially equivalent” decision on a 510(k) submission or denial of a PMA application.

At present, the time required to appeal an adverse decision is uncertain, and it can easily take six to 12 months, or more.  This delay in market entry burdens applicants with higher than expected costs and retards the introduction of new technology and competitive products.  The public health would benefit if disputes between sponsors and FDA could be resolved in a more predictable and commercially reasonable time frame.

In the discussion below, I will briefly describe the available appeal processes, the problems with them, and potential strategies for a successful appeal.  I will also propose that CDRH establish an Office of Appeals for Premarket Submissions ("OAPS") in the Office of the Center Director to bring greater predictability, consistency and timeliness to the resolution of premarket disputes between sponsors and ODE reviewers.

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A disappointed applicant has a range of appeal procedures theoretically available to obtain reconsideration of FDA actions and decisions.  Although not all options are available in all cases, and not all are immediately available after an initial denial, the potential procedural options include:  filing a petition for administrative reconsideration, 21 C.F.R. § 10.33, filing a citizen petition, 21 C.F.R. § 10.30, filing a petition for a stay of administrative action, 21 C.F.R. § 10.35, requesting a formal evidentiary hearing, 21 C.F.R. Part 12, requesting a public hearing before a public board of inquiry, 21 C.F.R. Part 13, requesting a public hearing before a public advisory committee, 21 C.F.R. Part 14, requesting a public hearing before the FDA commissioner, 21 C.F.R. Part 15, requesting a regulatory hearing, 21 C.F.R. Part 16, and requesting review of a scientific controversy by the Medical Devices Dispute Resolution Panel (“MDDRP”), 21 C.F.R. § 10.75(b)(2). 

For present purposes, it is not worth recounting the detailed requirements for these nine procedures.  (For good summaries of the first eight procedures listed, and an assessment of their advantages and disadvantages, see CDRH’s guidance document, Medical Device Appeals and Complaints: Guidance on Dispute Resolution (1998).  For a discussion of the MDDRP, see Resolving Scientific Disputes Concerning The Regulation Of Medical Devices, A Guide To Use Of The Medical Devices Dispute Resolution Panel; Final Guidance for Industry and FDA (2001).)  Suffice it to say that an applicant seeking to invoke one of these appeal options must have deep pockets, plenty of time to wait, and a willingness to accept varying degrees of public exposure and/or public participation.  Not surprisingly, most of the time these procedures are not commercially feasible.  The proof that they are impractical is that they are invoked rarely or never.

Typically, there is only one procedure that is commercially viable – a request for internal supervisory review.  The boundaries of this process are set forth in a short regulation, 21 C.F.R. § 10.75.  Section 10.75(a) describes when an internal supervisory review may be requested:

(a) A decision of an FDA employee, other than the Commissioner, on a matter, is subject to review by the employee's supervisor under the following circumstances:

(1) At the request of the employee.
(2) On the initiative of the supervisor.
(3) At the request of an interested person outside the agency.
(4) As required by delegations of authority.

The reference to “the request of an interested person outside the agency” is the authority that allows a disappointed applicant to request a supervisory review.

Section 10.75(b)(1) explains how the review will proceed:

(b)(1) The review will be made by consultation between the employee and the supervisor or by review of the administrative file on the matter, or both. The review will ordinarily follow the established agency channels of supervision or review for that matter.

As noted, the supervisor may consult the employee and/or review the administrative file.  The brevity of this provision allows FDA flexibility in the procedures to be followed.  For example, although the foregoing provision does not mention any role for the “interested person,” in practice interested persons are typically granted a meeting with the supervisor, if requested.  In some cases, but not always, the employee (or employees) responsible for the decision are also present at the meeting.  The downside of a flexible procedure is that some applicants may not know how best to proceed, since the regulation does not provide much instruction.  Indeed, the handling of these reviews tends to be fairly ad hoc.  In these situations, the CDRH Ombudsman can be a helpful resource in explaining the process and/or participating as an observer.

Section 10.75(c) specifies when a Center Director or the Office of the Commissioner will personally review an appeal:

(c) An interested person outside the agency may request internal agency review of a decision through the established agency channels of supervision or review. Personal review of these matters by center directors or the office of the Commissioner will occur for any of the following purposes:

(1) To resolve an issue that cannot be resolved at lower levels within the agency (e.g., between two parts of a center or other component of the agency, between two centers or other components of the agency, or between the agency and an interested person outside the agency).
(2) To review policy matters requiring the attention of center or agency management.
(3) In unusual situations requiring an immediate review in the public interest.
(4) As required by delegations of authority.

Finally, section 10.75(d) provides that a supervisory review is confined to information already in the administrative record:

(d) Internal agency review of a decision must be based on the information in the administrative file. If an interested person presents new information not in the file, the matter will be returned to the appropriate lower level in the agency for reevaluation based on the new information.

This requirement means that an applicant needs to think carefully about whether the administrative file contains the information upon which the appeal will be based.  If not, steps need to be taken to be sure that such information is in the administrative file (with an opportunity for the initial decision makers to consider it) prior to an appeal.

Typically, a supervisory review should be requested in writing, with an explanation why the original decision is erroneous.  The request should briefly describe the review process and then clearly explain the erroneous decision.  Applicants often damage their chances by an overly complex and detailed account of the proceedings below.  The impression of complexity may actually lead supervisory management to defer to the judgment of the reviewers.  Management also has limited time to digest the facts; keeping it simple is therefore more likely to speed the process and make the case more persuasive.

It is also a mistake to cast aspersions on the reviewers, suggesting that they are biased or simply out to “get” the company, or that they are incompetent.  Rather, it is more persuasive to focus the presentation on the facts, and to avoid questioning the good faith, competence or motives of the reviewers.  Remember:  the official reviewing the appeal is the supervisor of the reviewers, and is already working with them daily on a wide variety of matters.  The supervisory official is not likely to be easily persuaded by an assertion that the reviewers are either evil or incompetent.  Unfortunately, many appeals are presented in just this fashion.  In a supervisory review, it is far more persuasive to present the dispute as an honest difference of opinion, but one in which the reviewers made the wrong decision.

In some cases, the issue may have a legal or regulatory aspect to it.  FDA is legally required to treat like products alike.  The most common legal issue that can arise is an allegation that this requirement is not being followed, and the applicant’s product is being sent down a more difficult regulatory pathway than similar products or is subject to more burdensome data requirements.  This type of dispute may be a candidate for review by the Office of Chief Counsel (“OCC”) rather than a supervisory appeal.  There is not a specific procedure required for OCC review.  The applicant writes to the OCC, explains the issue and perhaps requests a meeting to present the case.  If the OCC agrees on the merits, they may intervene with the reviewing division at OIVD or ODE.

If the aid of the OCC is sought, it is critical that the dispute be cast in legal terms.  The OCC provides legal advice, and will not overrule a scientific decision.  Furthermore, the issue must be ripe for OCC review.  Typically, the OCC will not intervene until there is an actual decision to review.  For example, if there were a dispute over an additional information (“AI”) request during a 510(k) review, the OCC would be unlikely to intervene.  Rather, the applicant would typically need to take the process through to at least a “not substantially equivalent” decision before seeking help from the OCC.
 
The supervisory review process is usually the best and most realistic choice for an appeal.  At present, however, the process has a number of shortcomings.  First, there are no deadlines for FDA to review an appeal, hold a meeting, or make a decision.  Typically, an appeal needs to be squeezed into upper management’s busy schedule.  Matters that are “on the clock” such as a 510(k) decision or a PMA application milestone generally will take precedence.  Thus, appeals can languish for months until a meeting is held, and then sit for more months before a decision is made.   My own experience is that a supervisory review process can easily take more than six months to be completed, frustrating the applicant who remains in limbo.  There is no way for the public to know what the average time is for supervisory reviews, because no performance metrics are ever published. 

Second, there is an inherent conflict of interest in the supervisory review.  The supervisor must work with the review team daily on a wide range of matters.  The supervisor cannot afford to alienate them, and will presumptively have confidence in them.  Furthermore, they can have communications about the appeal with the review team that the applicant will not know about.  While most supervisors (in my experience) are careful to conduct a review fairly and impartially, the organizational and psychological dynamics add to the difficulty of successfully overturning an erroneous decision.

A desirable reform would be to create an Office of Appeals for Premarket Submissions (“OAPS”).  The OAPS would be located organizationally in the CDRH Director’s Office, reporting to the CDRH Ombudsman.  (This proposal could be extended to include the other Centers, in which case the OAPS should be located in the Commissioner’s Office.)  The Ombudsman would have overall responsibility for the operation of the OAPS.  The OAPS would have a dedicated staff with multidisciplinary scientific and medical expertise regarding medical devices.  Ideally, the staff would come from review division and would therefore have varied experience in conducting premarket reviews.  The staff should also have access to a dedicated OCC counsel as needed.

Crucially, the OAPS would operate under published written procedures with established milestones and timelines.  Initially, it might be necessary to offer OAPS review as a voluntary pilot project, since section 10.75(a)(3) currently offers “interested persons” a right to invoke supervisory review.  Ultimately, however, if the OAPS were successful, it might be appropriate to amend section 10.75 to incorporate review by the OAPS.  There is no reason that statutory changes should be required, since the creation of the OAPS would simply be a different way to handle supervisory reviews already established by regulation, not statute.  Ideally, all appeals would be routed to the OAPS, with appeal from the OAPS to the CDRH Director’s Office or to the Commissioner.  This approach would free up the Directors of OIVD and ODE from having to spend time and resources on appeals from the divisions, and would eliminate the conflict of interest inherent in this type of supervisory review.

There would be other benefits.  First, the OAPS could regularize the review process, creating publicly known milestones and timelines.  This would be consistent with the current “transparency” initiatives underway at FDA.  Right now, the supervisory review process is largely ad hoc, and is a mystery to many applicants.  Second, the OAPS would eventually have an experienced team focused on processing appeals.  This development would lend itself to consistency and efficiency in handling appeals.  It might even be possible to develop a database with information about dispute resolution patterns.  Such information would allow for published appeal metrics, including a data based insight into the performance of the review divisions.  For example, if a particular reviewing group develops a record of generating unusually high (or low) numbers of appeals and/or reversals, that would be valuable for FDA management to know.  Finally, the OAPS would be a single office that could be held accountable for timely and fair dispute resolution.  Right now, no one at FDA is specifically and publicly accountable for ensuring either timeliness or fairness in dispute resolution (although the CDRH Ombudsman can help impose accountability internally to a certain extent).

In conclusion, FDA offers many procedural avenues for dispute resolution.  None of them is satisfactory, however, and reform is needed.  Some day, it would be a good idea for Congress to sweep out all of the underbrush and establish by statute a few, practical and well delineated appeal procedures.  In the meantime, a more expeditious approach would be to revise internal supervisory review to have the bulk of such appeals handled by a specialized office, the OAPS.  This reform would greatly benefit the public health by bringing fairness, consistency, and, above all, timeliness to the appeals process.