FDA's working group on CBER/CDER consolidation will meet for the first time the week of Sept. 16.

The group is to be chaired by Senior Associate Commissioner Murray Lumpkin, MD, and is expected to include Center for Drug Evaluation & Research Director Janet Woodcock, MD, and Center for Biologics Evaluation & Research Director Kathryn Zoon, PhD.

Lumpkin previously served as director of CDER's review management division under Woodcock and is widely viewed by industry to have played a key role in improving the review process at CDER.

Other representatives of the working group may come from the Office of the Chief Counsel, the Office of Regulatory Affairs, and the Office of Management Systems.

Meetings of this "internal" group will not be open to the public, FDA indicated.

The working group will "develop by January an implementation action plan and timeline for the consolidation" which will address "issues related to the product and process logistics of the consolidation," FDA said Sept. 6. On that schedule, the plan could be developed in time for work on the agency's FY 2004 budget during the spring of 2003.

The consolidated CBER/CDER center will take charge of all biologics reviews with the exception of vaccines, blood products and gene and tissue therapies.

"This consolidation will allow CBER to concentrate its scientific expertise and effort in the crucial areas of vaccines and blood safety. These are top priority items critical to our national defense and public health," FDA said. "Moreover, CBER will be able to concentrate its expertise on such cutting edge biologic scientific areas as gene therapy and tissue transplantation."

The consolidation comes after years of lobbying by the biotechnology industry to bring biologics reviews more in line with drug reviews, particularly in the manufacturing area. The move also follows Congressional pressure on FDA to adopt more consistent review standards between the drug and biologics centers in the wake of the ImClone Erbitux investigation.

The Biotechnology Industry Organization welcomed the announcement, saying it is "pleased with the Bush Administration's efforts to bring life-saving drugs to patients faster alongside greater consistency in the drug development and review process."

BIO lobbied for better CBER communication with sponsors and more consistent review procedures during the PDUFA III legislative debate (¹ Also see "BIO Wants More Binding FDA/Sponsor Meetings As Part Of PDUFA III" - Pink Sheet, 25 February, 2002., p. 5).

In contrast with CBER, CDER's practice of more regular, open communication with sponsors was generally viewed as the preferable approach by members of the House Energy & Commerce/Oversight Subcommittee at a hearing on the Erbitux review (² Also see "Erbitux Hearing Puts Focus On Pre-Approval Promotion, FDA Communication" - Pink Sheet, 17 June, 2002., p. 5).

CBER's unanticipated rejection of ImClone's "fast track" BLA for the colorectal cancer agent and an early sell-off of stock by ImClone's CEO has led to charges of insider trading.

The committee has been keeping the pressure on CBER to reform; Woodcock and Zoon met with Energy & Commerce staff Aug. 27 to discuss the steps being taken to standardize the review procedures and practices across the centers (³ Also see "CBER/CDER Merger Is One Topic Of Erbitux Discussions In House Cmte." - Pink Sheet, 2 September, 2002., p. 9).

In a nod toward another of BIO's concerns, FDA's consolidation announcement says that "current FDA policy on generic biologics will not be affected by this decision."

BIO noted: "It is our understanding that therapeutic biologics will continue to be regulated under the Public Health Service Act," which does not set up a system for handling generic BLAs.

The shift of a majority of biologics reviews to CDER, however, could be a step toward generic biologics. CDER may provide a more favorable climate for the creation of a generic biologics program than CBER.

Zoon has been supportive of BIO's opposition to generics; meanwhile, at CDER, guidances are in the works on reviewing "interchangeable" insulin and human growth hormone, two drug products with complexity similar to most biologics (⁴ Also see "Generic Somatropin NDAs Would Require Human Immunogenicity Tests – FDA" - Pink Sheet, 22 April, 2002., p. 14).

CDER is expected to handle biologics manufacturing reviews under the consolidated plan, although it remains unclear whether the agency will use CDER or CBER personnel and resources for the job.

Good Manufacturing Practices-related application delays have become common for biologic products. CBER Review Management Associate Director Robert Yetter recently noted that as of the beginning of 2002, six of 12 pending BLAs were being delayed because of manufacturing problems ("⁵ Also see "Manufacturing Issues Delay Half Of Pending BLAs, CBER’s Yetter Says" - Pink Sheet, 3 June, 2002. p. 6).

Some CBER reviewers and staff are expected to join the combined CDER team to provide the necessary scientific expertise for biologics reviews. Specific staff announcements have not been made, but it is expected that CBER will lose about 70% of its staff to CDER.

The question remains whether a biologics division will be created within CDER or biologics reviews will be distributed among the center's existing review divisions, which are divided by therapeutic area.

There are indications that many products will simply be transferred to CDER review divisions. For example, the oncology division is expected to receive the BLAs for Erbitux; AstraZeneca's Iressa , which is coming up for advisory committee review; Genentech's Tarceva and Avastin , both still in Phase III; and possibly cancer vaccines.

One major known effect of the consolidation will be a dramatic decrease in CBER user fee dollars. The funding that would have gone to CBER for review of therapeutic biologics will now be directed to CDER instead.

BIO noted the potential impact of the funding decrease, saying that it is "essential that FDA ensure the necessary resources and expertise are brought to bear on the biologics under the purview of" the new, smaller CBER.

Submissions for new products to both CBER and CDER have been declining in recent years, while user fees have increased to over $500,000 per full application. Hence, the consolidation can also be seen as a way to use staff more efficiently.

The consolidation may allow for a fairly smooth transition in terms of the review of efficacy data, the standards for which have been fairly similar at CDER and CBER. Safety data reviews, however, may be more complicated; CBER reviewers may have expertise in biologics safety issues that their CDER counterparts do not.

The CDER assumption of biologic reviews is not expected to require Congressional authority or new legislative or regulatory language. The HHS Secretary may simply delegate authority for the approval of biologics to the CDER director.

This is not the first time FDA has consolidated duties of the biologics and drug centers. The Bureau of Biologics merged with the then-Bureau of Drugs in 1982 to form the Center for Drugs and Biologics.

In that consolidation, biologics personnel were brought in to address complaints about lengthy reviews in the Bureau of Drugs. Then-Bureau of Biologics Director Harry Meyer, MD, was given directorship of the new Center for Drugs and Biologics.

Like the more recent consolidation, the formation of the combined drug and biologics center was achieved about one-and-a-half years into a new Republican administration.

However, unlike the prior consolidation, FDA does not have a permanent commissioner leading the reorganization: Arthur Hayes, MD, was appointed FDA commissioner four months into the Reagan Administration, while FDA still awaits a permanent head. Lester Crawford, PhD, was appointed deputy commissioner in March and has since been serving as agency chief (⁶ [A#00640090001], p. 3).

The combined center lasted until 1987 when the structure was deemed to be too unwieldy and the rise of AIDS demanded the allocation of more resources by the drug review center.

One difference between that experiment and the currently proposed consolidation is that the drug center is only absorbing a portion of CBER's duties.

Woodcock will be on familiar ground with the review of biologics. Woodcock headed the Office of Therapeutics at CBER before coming to CDER. However, Woodcock will have to juggle her prominent role in FDA's new GMP initiative with her expanded duties in CDER.

CBER/CDER Consolidation Working Group Set To Meet Week Of Sept. 16

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