FDA “Independent Consultant” Guidance Implements PDUFA III Provision

FDA is ruling out the use of prospective clinical trial investigators as independent consultants for protocol reviews requested by sponsors, the agency indicated in a draft guidance.

Under the Prescription Drug User Fee Act III, sponsors of biotechnology products may request that FDA bring in an independent consultant to participate in the review of clinical trial protocols.

"We suggest that you not recommend consultants who...you intend to ask to be an investigator," the guidance states.

The FDA ¹ draft guidance, "Independent Consultants for Biotechnology Clinical Trial Protocols," outlines when and how sponsors may participate in the program; the document was issued May 7.

The agency will allow companies to submit a list of recommended consultants who would be screened for conflicts of interests.

Sponsors should avoid recommending consultants whom they know to have a financial conflict or who have been involved in the design or planning of the clinical trial, FDA said.

The guidance stresses that the consultant does not need to be mutually agreed upon between the sponsor and FDA.

After considering the list submitted by the sponsor, "we may or may not select the consultant from your list of recommendations," FDA said.

"If we grant the request" to use a consultant, "we will engage an independent consultant, of our choosing."

The independent consultant program fits well with FDA Commissioner McClellan's emphasis on accelerating drug development and eliminating surprises in the review process.

The program was advocated by the Biotechnology Industry Organization during the PDUFA III negotiations, and has been highlighted by BIO as one PDUFA III item it fought to include in the final agreement (² (Also see "PDUFA III Implementation Begins: FDA Working Groups Under Way" - Pink Sheet, 17 Jun, 2002.), p. 3).

The draft guidance closely follows the language included in the FDA/industry PDUFA III agreement (³ (Also see "PDUFA III “Good Review Management Principles” To Stress Early Action" - Pink Sheet, 18 Mar, 2002.), p. 3).

As described in the agreement, only products that have the potential to represent "a significant advance in the treatment, diagnosis or prevention of a disease or condition, or to address an unmet medical need" are eligible for independent consultant review, the guidance states.

Products will only qualify if they are biotechnology derived, "for example, DNA plasmid-proteins, synthetic peptides of fewer than 40 amino acids, monoclonal antibodies for in vivo use, and recombinant DNA-derived products."

FDA expects to grant requests for review by an independent consultant except in situations where "we determine that engaging an expert consultant would not serve a useful purpose (e.g. it is clearly premature)." Products will be allowed only one independent consultant review during development.

To ask that FDA engage a consultant, sponsors should include a written request as part of their submission seeking a formal meeting, including the reasons why the company feels an expert consultant should be engaged.

"These reasons might include preliminary discussions with FDA that resulted in disagreement over the protocol or a novel or unorthodox approach to the clinical trial or its analysis," the guidance says.

When a sponsor requests that FDA engage an independent consultant, this will push back the PDUFA deadlines for meeting with the company on that application, the agency noted.

"We will need time to select and screen the consultant for potential conflicts of interest and the consultant will need sufficient time to review the scientific issues involved," the guidance says. "Therefore, we will extend the performance goals for scheduling and holding the formal meeting an additional 60 days."

FDA will be taking comments on the draft guidance for 90 days.