The US Food and Drug Administration (FDA) has released two long-awaited guidance documents regarding the appeals process to be used by medical device manufacturers that have received a rejection by the agency.
FDA has been working to revamp its appeals process for several years now. Starting in late 2011, the Center for Devices and Radiological Health-the center that reviews most medical device applications-released the draft of its CDRH Appeals Process guidance, which said it aimed to provide clarity for those in industry who wanted to appeal an adverse decision, such as the denial of a premarket approval (PMA) or 510(k) premarket notification application.
The guidance document is intended to replace two earlier guidance documents:
- Medical Device Appeals and Complaints: Guidance for Dispute Resolution (February 1998)
- 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 (July 2001)
But since that draft document's release, FDA has been largely silent on its progress, leaving industry to wonder when it would come out, and in what form.
Industry Comment on Draft Guidance
At least three entities made comments on the guidance: medical device manufacturer Cook Medical, and industry associations AdvaMed and the Medical Imaging & Technology Alliance (MITA).
Their comments to the agency reflected several concerns about the draft guidance as written. MITA, for example, wrote that it was concerned about the active role that CDRH envisioned its ombudsman playing in the appeals process. "We are concerned that decisions involving the CDRH Ombudsman are not always consistent and transparent," MITA wrote. "Much as other parts of the draft guidance require the Agency to document its decision-making in the appeals process, actions within the discretion of the Center Ombudsman should also be supported by sound and transparent reasoning."
Another part of the guidance calls for FDA to focus on the information that was available at the time of review, and not to accept any major new information. MITA said that while it understands the intent of that section-to avoid having companies submit incomplete applications and then try to appeal with the full information-they said the presence of the information during an appeal should not be an automatic disqualifier.
"This is especially the case when the Agency believes that this information would resolve the appeal efficiently or promote sound decision-making on the underlying issues at hand," MITA argued.
Advamed also registered its desire to see additional clarity in the final guidance, writing that more specific timeframes for various activities would be greatly appreciated, as would the potential to convene an advisory panel to adjudicate an appeal.
Advamed wrote that it also believes that an appeal should be able to be filed prior to speaking with the Ombudsman, as these discussions are "not necessarily useful or productive." Cook Medical's comments mirror this point as well, adding that it is "rarely productive to engage in discussions with agency representatives after a decision" is issued. "Requiring such discussions would do nothing more than discourage and delay resolution of appeals," Cook added.
Since those comments were submitted more than a year ago, there has been little to indicate when the final guidance would be released. Then, in April 2013, FDA Law Blog, an industry-focused legal blog maintained by the law firm Hyman, Phelps & McNamara, reported that FDA would soon release the final guidance, citing "knowledgeable officials at CDRH."
The problem, they explained, was that the FDA Safety and Innovation Act (FDASIA) of 2012 had instituted additional requirements within Section 517A that FDA needed to meet before the guidance could be finalized. That section, FDA explains, required the agency to have specific processes and timelines for appeals of "significant decisions" regarding 510(k)s, PMAs and investigational device exemptions (IDEs). Left undetermined by FDASIA was the meaning of the term "significant decision" and how that would affect the process.
Now FDA is out with its final guidance, as well as an accompanying question and answer guide regarding how industry should understand the guidance Section 517A of FDASIA.
The basics of the guidance are relatively similar to the draft guidance. FDA said it expects sponsors to have exhausted all other appeal options (starting the next consecutive level above the current review division) within CDRH before a petition or appeal is filed with the FDA commissioner under 21 CFR 10.75.
In general, that hierarchy will go from branch, to division, to office, to CDRH to commissioner, FDA explained. FDA may "telescope" this review if it believes it is appropriate to do so by conversing with an official involved in a higher chain of command. This is also useful in cases where a device's approval decision could be a threat to public health, the guidance explains.
"However, nothing in this guidance should be construed as constraining the ability of a stakeholder to exercise options for appeal or petition at any time that is permissible under applicable statutory and regulatory provisions," FDA conceded.
Industry Comments Accepted
To MITA's point regarding new information being introduced into the process, FDA conceded the point that a CDRH official "may, at his or her discretion, allow the introduction of new information in the interest of expediting a decision or reaching an agreement between the stakeholder and the Center."
The guidance also now contains more specific timelines for many activities, including a maximum 30 day window for appeals of a "significant decision," and a 60-day timeframe in which FDA must make a decision regarding the appeal. Such documents should be clearly marked as an "appeal," FDA said. Teleconferences may also be requested, and CDRH must decide whether to permit such a teleconference within 30 days of the request.
Per AdvaMed's request, FDA said it will also not permit companies to request an external review authority, such as an advisory panel, to review an application. "A decision to convene an Advisory Panel to consider a section 10.75 request for review is at the discretion of the review authority," FDA"s guidance says. Due to the time and cost of these panels, they will likely only be used in "unusual circumstances generally involving highly complex scientific and clinical matters," FDA explained.
However, external subject matter experts may also be brought on as dispute consultants of sorts, allowing FDA and the company to utilize an "efficient means to obtain an external opinion." FDA will be the final arbiter on which SMEs are acceptable for use.
Definitions under 517A of FDASIA
FDA's accompanying guidance on 517A "significant decisions" explains that FDA has defined the term to mean the following:
- finding a 510(k) to be not substantially equivalent (NSE)
- finding a PMA or Humanitarian Device Exemption Application to either be not approvable or approvable with conditions
- finding an IDE application to be disapproved
- failure to reach an agreement regarding a protocol under Section 520(g)(7)
An approval decision or any of the previous that is not satisfactory may also be appealed as a "significant decision," FDA said.
Also important to sponsors is FDASIA's requirement that FDA provide, upon request, a "substantive summary of the scientific and regulatory rationale for any significant decision regarding such submission, including documentation of significant controversies or differences of opinion and the resolution thereof."
FDA said it takes the term "substantive summary" to include the following elements:
- an explanation of the rationale for the regulatory decision
- documentation of significant controversies or differences of opinion, i.e., ones the resolution of which had a direct bearing on the regulatory decision
- references to published literature and consensus standards upon which the decision-maker relied
FDA's guidance may be found here (FR) and its 517(A) guidance here (FR).