Blog #5 - Michael O'Donnell

Name of Guidance: Guidance for Industry - Formal Dispute Resolution: Appeals above the division level

Status of Guidance: Final

Release Date: February 2000

Link to Guidance: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm077137.pdf

Target Audience: Healthcare industry professionals and study drug sponsors

Laws and Regulations Referenced:
• 21 CFR 10.3
• 21 CFR 10.75
• 21 CFR 312.48
• 21 CFR 314.103
• 21 CFR 312.48
• 21 CFR 312.48
• 21 U.S.C. 360bbb-1
• 63 FR 63978
• 64 FR 13591
• Prescription Drug User Fee Act (PDUFA)
• Federal Food, Drug, and Cosmetic Act (“The Act”)
• Section 351 of the Public Health Service Act (PHS)

Summary:
This guidance provides direction on what type of procedural action should be taken for resolving any disputes between healthcare industry professionals and the Food and Drug Administration (FDA) that cannot be resolved at the division level.

The procedures for study drug sponsors appealing their disputes to the appropriate Office or Center level are explained. Numerous sections of the U.S. Code of Federal Regulations (CFR) and several acts are referenced to support the position on how these procedures should be followed by the sponsor. One of the acts that influenced these procedures is the Prescription Drug User Fee Act (PDUFA). PDUFA is discussed in detail in the context of its role in dispute resolution at the Center or Office level, which is above the division level. Appeals to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) would constitute a Center level appeal. If the dispute cannot be resolved at the Center level, it must continue through the chain of command until a resolution is reached. In extreme cases of unresolved disputes, the appeal may be escalated to the FDA Commissioner for a final ruling on the dispute. The type of dispute appealed may be scientific or procedural in nature.

The guidance places an emphasis on the importance of timely dispute resolution because of the magnitude of the scientific or commercial implications of an appeal. The procedural recommendations of the guidance are intended for appeals involving either PDUFA or non-PDUFA drugs. A generic drug is considered to be a non-PDUFA drug.

Discussed are the PDUFA-recommended timeframes for settling disputes between study drug sponsors and the FDA. The way that PDUFA goals for these timeframes are evaluated is to target a percentage of acted upon appeals for each year. “Acted upon,” here means that all associated requests for information, meetings, presentations, and granting or denying the appeal has been fully completed. The recommendations for percent of acted upon appeals from a 1997 PDUFA-related letter is specifically presented in the guidance as follows:

Year 1999: 70% acted upon within 30 calendar days
Year 2000: 80% acted upon within 30 calendar days
Year 2001 and each subsequent year: 90% acted upon within 30 calendar days

During the resolution process, the sponsor has the right to request a scientific review from an advisory committee, if necessary. Also explained is that a written request must be submitted to CDER or CBER as appropriate, but only after all efforts to resolve the dispute at lower levels have been exhausted.

Non-generic drug disputes have to be submitted to the Formal Dispute Resolution Project Manager (DRPM) of CDEER. Generic drug disputes have to be submitted to the Director of the Office of Generic Drugs. CDER disputes should be sent to one of these two offices as appropriate. CBER-related disputes have to be sent to the DRPM specific to CBER.

The guidance provides a detailed overview of exactly what must be included in the supporting information that is sent with the dispute. There should be a cover sheet, application number, product name, description of dispute, original agency decision, list of necessary supported documents, statement explaining what transpired at previous level of attempted resolution, and sponsor contact information.

According to the guidance, the FDA will notify the sponsor with a written response or via telephone with the resolution of the dispute within 30 days. If more time is needed, the FDA still needs to contact the sponsor within the 30 day window to explain why they need more time to process the appeal. If an advisory committee is approved to be involved in the decision, it could take longer because the advisory committee has to be organized to evaluate the appeal, and there might be a waiting period for the next available meeting to discuss the issue.

After reaching a decision, the advisory committee notifies the FDA of their decision on the issue, and then the FDA has 30 days from that point to in turn notify the sponsor of the FDA decision. The FDA decision will not necessarily be the same as the advisory committee, but the advisory committee’s decision could still provide valuable additional information supporting or rejecting the sponsor’s position on the disputed issue.

Rationale:
This guidance aims to speed up the FDA’s dispute resolution practices for scientific and procedural issues that develop during the course of a study drug product’s development and review processes.

Resulting Recommendations:
There is a need to have as quick a turnaround on the appeals process as possible so that the study drug sponsor can proceed with the next appropriate scientific or commercial action needed, and not lose time while waiting for decisions on appeals. If the procedures recommended in this guidance are followed by study drug sponsors that need to escalate dispute resolution, the sponsors will benefit from improved timeframes.

Impact:
Scientific and procedural disputes are resolved more quickly. CDER and CBER employees at the supervisory level have a defined process to advise sponsors of if the issue is beyond their level of resolution capabilities. Study drug sponsors reviewing this guidance know what is expected from them in the process, and what they can expect from the FDA in terms of time to resolution, when a dispute is raised beyond the Division level.