FDA will emphasize official written action letters in its internal policy on communication with sponsors drafted in response to the Congressional investigation of the Erbitux review, Acting Commissioner Crawford said Oct. 10.

"We believe...that the result of an NDA review should be committed in writing. There should be a letter that exchanges hands because there are many different interpretations of what was said and who said what," Crawford told the House Energy & Commerce/ Oversight Subcommittee follow-up hearing on ImClone's application for Erbitux (cetuximab).

Crawford noted that FDA is in the process of developing a policy that outlines appropriate communication between sponsors and FDA, which "is a result of this committee's interest."

Office of New Drugs Director John Jenkins, MD, sent a draft of the policy in a July 23 memo to each of FDA's office and division directors (¹ Also see "FDA Developing Reviewer Communications Policy; Draft Expected This Year" - Pink Sheet, 23 September, 2002., p. 5). Jenkins attended the hearing, but was not called to testify (² Also see "Erbitux Hearing May Feature FDA Reviewer Communication Policies" - Pink Sheet, 7 October, 2002., p. 26).

In the draft, FDA states that "CBER and CDER believe that the integrity and the transparency of the review process are best served by issuance of an official written regulatory action following an appropriate review of the application."

"The official written regulatory action, signed by the designated signatory authority, provides an official record of the Agency's decision following review of the marketing application."

Crawford highlighted the communications policy as one of three steps the agency is taking in response to the Erbitux investigation, along with the proposed CBER reorganization and plans to "systematize" communications with the Securities & Exchange Commission (see ³ Also see "FDA/SEC Communication Will Be “Systematized” In Response To Erbitux" - Pink Sheet, 14 October, 2002.).

The agency expects to put the draft out for public comment "by the end of the year," Crawford said.

Subcommittee members generally responded favorably to the proposed policy during the hearing.

The purpose of the communications policy "will be not only to systematize and bring some consistency between what the different centers say to the industry that are sponsoring these products, but also from reviewer to reviewer what is said," Crawford explained. "Consistency among reviewers...is one of the great management challenges at FDA."

Rep. Cliff Stearns (R-Fla.) applauded the effort to draft the policy, saying, "every reviewer is different, you know. Different reviewers could have this idea; this reviewer could have this idea. So we need a consistent policy where we would say this is what should be done."

Chairman Jim Greenwood (R-Penn.) asked Crawford to elaborate on FDA's willingness to meet with sponsors as needed to discuss issues with applications.

"Do you think it should be the policy that the sponsor wants a face-to-face meeting, that that ought to be the sponsor's right, or is that not simply at the subjective decision of a particular reviewer as to when those meetings should occur?" Greenwood asked.

"It seems to me that companies ought to be able to make written inquiries in regards to the status of their applications and receive written responses all along," he added.

Crawford agreed with Greenwood that "sponsors do have the right to have meetings with FDA." He noted that the reauthorized Prescription Drug User Fee Act allows for increased meetings between sponsors and the agency (⁴ Also see "PDUFA III Authorizes FDA To Alert MDs To Failed Phase IV Commitments" - Pink Sheet, 27 May, 2002., p. 3).

However, Crawford added, "there has to be some order in the process." There "was a time when I was first at FDA in the 1970s when sponsors...could just fall in off the street and come by and see you. Those meetings were better described as lobbying meetings than scientific interchange meetings. It's come a long way since then."

Meetings "have to be scheduled correctly. You have to make sure that you have the right people at the meeting both from the company's side" and FDA, Crawford added. However, "meeting with reviewers is a right that the companies have and should expect."

"That sounds like the right policy to me," Greenwood added.

The policy notes that final regulatory decisions can only be made by the "signatory authority."

"In communicating deficiencies identified during the review and comments on draft labeling, CBER and CDER review divisions should make clear to the sponsor the preliminary nature of the communications and the fact that a decision regarding the official regulatory action for the application has not yet been made," the memo states.

As Crawford explained during the hearing, "the final decision on whether or not they are going to file rests with the division director, so theoretically the division director can overturn a decision made earlier."

As a result, "we have to have a focal point for transmitting information."

Crawford noted during the hearing in response to questions from Greenwood that Oncology Division Director Richard Pazdur, MD, would have final "signatory authority" over all oncology applications following the pending CBER/CDER reorganization.

However, Crawford added, it is not yet settled whether or when the Erbitux review will be transferred from CBER to CDER.

"My decision" to transition the Erbitux BLA "has not been fully reached. Those [applications] that are under review at the present time I would want to make sure they did not leave the unit, that being those doing the review. I think it is important to note that the entire unit would transfer in one center to the Center for Drug Evaluation & Research," Crawford said.

The draft communications policy strikes a fine balance on another issue raised by Greenwood during the Erbitux hearings: whether FDA should "tip-off" sponsors that an adverse regulatory decision is coming.

During the first Erbitux hearing in June, Pazdur noted that it has been his division's practice to alert sponsors ahead of a negative action in order to give them the opportunity to withdraw the application.

Greenwood applauded that approach, suggesting that it would have prevented the "precipitous" reaction to the Erbitux refuse-to-file decision on Wall Street and among patients (⁵ Also see "Erbitux Hearing Puts Focus On Pre-Approval Promotion, FDA Communication" - Pink Sheet, 17 June, 2002., p. 5). Greenwood repeated that sentiment Oct. 10.

In keeping with the emphasis on formal, written communication, the memo encourages CBER and CDER to issue official regulatory action letters instead of suggesting that sponsors withdraw an application.

"CBER or CDER officials should not request or suggest to a sponsor that the sponsor withdraw a pending marketing application except in the most unusual circumstances (e.g., the marketing application was submitted to the wrong center)."

"While a sponsor may voluntarily withdraw a marketing application at any time after it is submitted for review, CBER and CDER believe that it is generally preferable that applications not be withdrawn by the sponsor and that an official written regulatory action be issued documenting the agency's review of the application," the draft policy states.

"In cases where a sponsor voluntarily withdraws a marketing application in advance of an 'adverse' regulatory action (e.g. RTF, non-approval), CBER and CDER will acknowledge the sponsor's withdrawal of the application in writing."

"The withdrawal acknowledgement letter will generally include the deficiencies identified by the review division at the time the application was withdrawn."

The policy does stress the importance of communicating deficiencies clearly, and advising a sponsor when the problem appears serious enough to prompt a refuse to file or other adverse decision. However, a communication like that "should only occur with concurrence from the review division director."

Although the draft is not considered final FDA policy, it is understood to have been forwarded to the CDER review divisions with instructions that it be considered the policy of the Office of New Drugs.

FDA Emphasizing Written Communication With Sponsors On Pending NDAs

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