Healthy Skepticism Library item: 1051

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Publication type: Journal Article

Christensen D.
FDA Reorganization Intended to Streamline Review Process for Biologics
Journal of the National Cancer Institute, 2003 Apr 16; 95:(8):576-577
http://jnci.oxfordjournals.org/cgi/content/extract/95/8/576

Full text:

In a move applauded by many in the biotechnology industry, the U.S. Food and Drug Administration is moving review of therapeutic biologicsdrugs produced from living sources like microorganisms from its Center for Biologics Evaluation and Research (CBER) to the Center for Drug Evaluation and Research (CDER). The change is intended to speed approval of biologics and streamline the review process.

Initially, several divisions from the Office of Therapeutics Research and Review will be moved from CBER to CDER, said Murray M. Lumpkin, M.D. Lumpkin is the principal associate commissioner at FDA and was the co-chairman of the consolidation working group responsible for implementing the move. The funds to be transferred nearly $32.9 million, about 20% of CBER’s budget for fiscal year 2003represent more than 200 full-time positions. The FDA hopes to accomplish this consolidation by June 30, 2003. Ultimately, CDER may be reorganized to better incorporate the various functions of these new divisions, Lumpkin said.

CBER will retain oversight of new vaccines (including therapeutic vaccines), blood safety, tissue manipulation, and gene therapy. The categories of products being transferred to CDER include monoclonal antibodies intended for therapeutic use; cytokines, growth factors, enzymes, and interferons intended for therapeutic use; and proteins intended for therapeutic use that have been extracted from animals or microorganisms, excluding human blood and components. “Our thought process was that as these particular products have become more mature they have integrated themselves into the general medical armamentarium,” Lumpkin said. “In a general sense, they are looked at and used as drugs.” By evaluating these biologics at CDER alongside drugs used to treat similar disorders, there will be more consistency in oversight of clinical trials, he said. In addition, Lumpkin noted that there are economic benefits if FDA avoids duplicating staff expertise between the two centers. The consolidation allows the agency to move toward developing more disease-based or physiology-based review systems, he said.

“By organizing the drug development and review process around the disease being treated, informed by specific product and technology expertise, the agency decision process for these products can be made even more patient-centered and science-based,” Lumpkin said.

Cancer research will benefit from such a system, said Paul A. Bunn, M.D., president of the American Society of Clinical Oncology and director of the University of Colorado Cancer Center in Denver. For example, such a system might help the agency focus on developing appropriate endpoints for cancer clinical trials. Some such discussions are already under way, he said, because in divisions not familiar with cancer and the side effects of cancer drugs, the review and guidelines for clinical trials were sometimes unclear.

“The supposition that there’s ever been an absolute bright line between CBER and CDER was never true,” said Gillian Woollett, D.Phil., vice president of science and regulatory affairs at BIO, a biotechnology industry organization in Washington, D.C. “What we would like to see in the future is adoption of the best practices from each.” CBER, for example, is further ahead on developing secure e-mail systems to accept confidential information electronically, she said, whereas CDER has more expertise in designing clinical trials.

“Regulatory mechanisms historically have been created in order to address particular problems; the first company through [the process] often ends up creating the regulation,” Woollett said.

Uncertainty about how to design studies and what results will be needed to get therapies approved can slow the development and approval of new treatments, she said. “Industry wants a certain level of predictability, and anything that improves that will be good,” she continued. “At this point, it’s not easy for us to say if the reorganization of FDA is good or bad. Given that it has already happened from a policy point of view, we just look forward to working with the agency.” In an attempt to make the transistion smoother, the FDA decided to move CBER’s therapeutic biologics division as a unit, Lumpkin said. By and large, the same people should continue doing the same work, simply under the auspices of a different center, he said.

However, some key personnel have left the FDA. Kathy Zoon, Ph.D., the center’s former director, left the agency in January and moved to the National Cancer Institute. Jay Siegel, M.D., formerly director of the Office of Therapeutics Research and Review, has also left the agency.

“When they announced [the move of review of biologics], my first reaction was, this is wonderful,” said Abbey Meyers, president of the National Organization for Rare Disorders in Danbury, Conn. “However, the move appears to be very disruptive, and because the FDA has lost staff I’m afraid that it might end up slowing the approval of biologics over the next few years.” Despite the rocky start, Meyers said she hopes that the agency will begin approving biologics more quickly because of the reorganization. More than half of drugs used to treat orphan disorders are biologics, she noted.

The cost of biologics has some people, like Meyers, hoping that the FDA will allow generic equivalents. Generic products are allowed under the laws regulating drugs but not under the older laws that regulate biologic products. However, Lumpkin said, biologics will continue to be regulated under the same laws, which means that the move to CDER will not open up the possibility of developing and marketing generic biologics.

Another recent change at the FDA is the creation of the Office of Combination Products (OCP).

The new office is headed by Mark Kramer, who previously directed the combination products program within FDA’s Office of the Ombudsman. “The need [for the office] is predicated on the fact that there are more and more product combinations of drugs and devices, or drugs and biologics, or biologics and devices, and this presents a challenge to the regulatory system,” Kramer said. To date, such products have typically been handled through intercenter agreements. However, he said, there has been a perception that, under the current system, a center not primarily responsible for a product’s review might not put the same priority on timeliness as the lead center.

That in turn could slow the approval process for combination products. OCP’s roles mandated by the Medical Device User Fee and Modernization Act of 2002 include assigning a combination product to one of FDA’s centers based on the products primary mode of action, overseeing coordination between centers, resolving disputes over the timeliness of premarket review of such products, and ensuring consistency of postmarket regulation of such products.

Combination products may be subject entirely to one set of regulations or to a hybrid set of regulations for ensuring quality control or adverse event reporting. “The main emphasis is to avoid double regulation while ensuring appropriate regulation,” Kramer said.

The creation of the OCP “is a helpful step,” said Bunn. Combination products such as radiolabeled antibodies and immunotoxins are being developed and tested for a variety of diseases, including cancer, but there have been questions about how they’d be reviewed and assessed, he said. “What’s really important is that you have rules and guidelines and that they are level across the agency.”

“OCP is a good idea,” agreed Meyers. “It was talked about for a long time before they did it, so they got everybody’s buy-in. Combination products need some special attention and this move should provide that.”