Formal Dispute Resolution:Sponsor Appeals Above theDivision LevelGuidance for Industry and ReviewStaff Any sponsor appeal of a scientificand/or medical matter proceeds to the next management level in the center chain of commandabove the level at which the decision being appealed was made. However, regardless of theregulatory mechanism cited by a sponsor, if a sponsor challenges specific administrative and/orprocedural decisions that arise during the course of an FDR, CDER and CBER intend to reviewthese interim decisions as part of the review of the pending substantive scientific and/or medicaldispute, and not as a separate review.
In the Prescription Drug User Fee Act of 1992 (PDUFA) and subsequent reauthorizations,9CDER and CBER agreed to specific performance goals for activities associated with thedevelopment and review of human drug applications, as defined in 21 U.S.C. 379g. Theseperformance goals contain specific time frames for resolving disputes affecting an IND, NDA, orBLA. For disputes involving human drug applications covered by PDUFA, the PDUFA goal isto respond to an appeal of a dispute above the original signatory authority within 30 calendar days of the center’s receipt of the written appeal (see section V.A.1., Timelines for ReviewingFormal Dispute Resolution Requests for Human Drug Applications Covered by PDUFA,BsUFA, or GDUFA).
What Is an Appropriate Matter for a Formal Dispute Resolution Request?
CDER and CBER consider a regulatory action taken by the FDA that relates to a sponsor’sapplication for a user fee product and has scientific and/or medical significance to be a matterthat could be appropriately handled through FDR. The following are a few examples ofregulatory actions that would be appropriate for a request for FDR: Complete response (CR) IND clinical hold (partial or full) Request for breakthrough therapy designation denied Request for proprietary name review denied Refuse to receive for an ANDA
Can a Sponsor Request a Meeting as Part of an FDRR?
After a sponsor has decided to submit an FDRR, as part of the appeal, it can request a meeting with the deciding official for the appeal (e.g., a Type A meeting for human drug applications covered by PDUFA, a BPD Type 1 meeting for human drug applications covered by BsUFA, or a meeting for a human drug application covered by GDUFA).14 This meeting is an opportunityfor the sponsor to discuss the appeal issue(s) with the deciding official for the appeal.
Can a Sponsor Request an Advisory Committee Meeting as Part of FDR? As part of an original appeal or at any point in the FDR process, a sponsor can request that ascientific dispute be reviewed by an appropriate advisory committee. Because it can take asignificant amount of time to schedule an advisory committee meeting, if a sponsor believes thatreview by an advisory committee is the most appropriate venue for resolution of a scientificcontroversy, such a sponsor request should be made as early in the dispute resolution process asfeasible.
How to Request Formal Dispute ResolutionThe sponsor should submit an FDRR to the sponsor’s application as described below. Beforesubmitting a request, it is strongly encouraged that the sponsor contacts CDER or CBER andprovides advance notice of the sponsor’s intent to submit an FDRR to ensure prompt handling ofthe appeal. Contact information for each Center is provided below.
Requests for CDERRequests for FDR with CDER should be submitted to the sponsor’s application. The requestshould be submitted as an amendment to the appropriate application file (IND, NDA, BLA, orANDA) and a copy should be submitted to the CDER Formal Dispute Resolution ProjectManager (FDRPM). The contact information can be found on the CDER Formal DisputeResolution web page.15 CDER encourages sponsors to contact the FDRPM before submitting arequest for FDR.
FDA ACTIONThe FDRPM or CBER Ombudsman functions as the administrative contact for all issues relatedto FDRRs. The FDRPM or CBER Ombudsman is responsible for communicating andexplaining all regulatory processes related to FDR to the sponsor. The FDRPM or CBEROmbudsman will conduct a preliminary review of the sponsor’s FDRR to evaluate whether theappeal satisfies the procedural criteria (as described in section IV., Procedures for Submitting aRequest for Formal Dispute Resolution) so that the FDRR can be accepted. If the sponsor’sFDRR is accepted, the FDRPM or CBER Ombudsman will forward the appeal to the appropriateCDER or CBER management level, as established under the center chain of command. TheFDRPM or CBER Ombudsman will also send an acknowledgment letter to the sponsoridentifying the deciding official, the due date for response to the FDRR, and the date of anymeeting (if applicable). If an FDRR is not accepted, the FDRPM or CBER Ombudsman willsend a letter to the sponsor on behalf of the deciding official identifying the reasons why therequest was not accepted and outlining a possible path forward for acceptance of the sponsor’sFDRR. Additionally, if a request for FDR is inappropriately submitted to CDER or CBER, thenthe FDRPM or CBER Ombudsman will re-direct the request to the appropriate entity within theFDA.
As noted earlier, if a scientific and/or medical dispute concerns a human drug applicationcovered by PDUFA, BsUFA, or GDUFA, the deciding official should complete his or her reviewand provide an interim response or a decision on the appeal to the sponsor within 30 calendardays from receipt of an FDRR that has been accepted. The deciding official should respond tothe sponsor within the 30-day window in writing or by telephone (i.e., 30-day response). If theresponse is by telephone, the deciding official should follow up with a written confirmationwithin 14 calendar days of the verbal response.
If the sponsor requests a meeting as part of its appeal, CDER or CBER should treat the meetingrequest as a Type A meeting under PDUFA, a BPD Type 1 meeting under BsUFA, or a meetingunder GDUFA. If the meeting is granted, the deciding official should provide an interimresponse or a decision on the FDRR to the sponsor within 30 calendar days of the meeting date.This time period allows the deciding official to consider the discussion at the meeting in his orher decision making process.
There may be instances when, to reach a decision, the deciding official needs additionalclarifying information or input from other persons knowledgeable about the specific matter indispute, or about the issue or area more generally. In such situations, the deciding official shouldissue an interim response to the sponsor identifying the additional information or input needed.If the product is a human drug application covered by PDUFA, BsUFA, or GDUFA, suchinterim responses should be made within 30 calendar days of receipt of the appeal.
In instances when the deciding official needs clarifying information from the sponsor,17 a request for this information should be sent within 30 calendar days from receipt of the appeal. The deciding official should provide an interim response or a decision on the appeal within 30 calendar days from receipt of the clarifying information submitted to the sponsor’s application.
In instances when the deciding official decides a meeting with the sponsor is needed before a response can be issued, a meeting request should be sent within 30 calendar days from receipt of the sponsor’s FDRR. CDER or CBER should schedule any meetings as quickly as the sponsor and the FDA are able to agree on a mutually acceptable date and time. After the meeting is held, the deciding official should provide an interim response or a decision on the appeal to the sponsor within 30 calendar days from the meeting date.
In instances when the deciding official needs to discuss an FDRR with one or more members of an advisory committee or internal or external experts, CDER or CBER should inform the sponsor that the deciding official is seeking this additional input within 30 calendar days from receipt of the sponsor’s FDRR. CDER or CBER should schedule such discussions with the members of an advisory committee or internal or external experts as quickly as possible. After this discussion takes place, the deciding official should provide an interim response or a decision on the appeal to the sponsor within 30 calendar days from the date of the discussion.
In instances when the deciding official decides to seek input from an advisory committee, CDER or CBER should inform the sponsor of this request within 30 calendar days from receipt of the sponsor’s FDRR. The deciding official should provide an interim response or a decision on the appeal to the sponsor within 30 calendar days after the date of the advisory committee meeting.
If the deciding official is unable to complete the review and provide either an interim response or a decision on the FDRR to the sponsor within 30 calendar days, CDER or CBER should notify the sponsor, explain the reasons for the delay, and provide the anticipated time frame for completing the review. In these cases, the PDUFA, BsUFA, or GDUFA goal for the appeal response would not be met.
REPEAT APPEALS If a sponsor’s FDRR is denied at one management level, the sponsor can appeal the same matter to the next higher management level in the center chain of command. A new FDRR should be submitted for each appeal to the next management level and should follow the process and timelines provided in this guidance. If the sponsor has exhausted the center’s management levels and remains unsatisfied with CDER’s or CBER’s decision, the sponsor may request review of the matter by the Commissioner of Food and Drugs (Commissioner) under 21 CFR 10.75(c). Requests for review by the Commissioner should be submitted to the FDA’s Ombudsman, with a copy provided to the center that denied the appeal, as described in section IV.A., How to Request Formal Dispute Resolution. Review of such matters by the Commissioner is discretionary
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