NEWS

New Office and New Leader Aim To Streamline FDA Cancer Drug Review Process

Renee Twombly

By late this summer, the U.S. Food and Drug Administration is expected to put both a new face and a new place on its review of cancer drugs.

By August, the first phase of the FDA's new campus at White Oaks, Md., will be open, and one building will house the new Office of Oncology Drug Products (ODP). At the helm will be Richard Pazdur, M.D., head of the FDA's Division of Oncology Drug Products, who was named to head the new office on April 22.



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Richard Pazdur

 
The new office represents a major change in the way that the FDA has historically reviewed cancer drug applications—a move toward centralization. The FDA says that substantial changes to its organizational structure will provide a stronger and more consistent approach to the review process for drugs and most therapeutic biologics used to diagnose, treat, and prevent cancer. It will work to speed up review of the drugs and to make sure they are safer, agency leaders said.

"Our goal with this new office is to have improved efficiency, coordination of oncology efforts across the agency, and better outreach to stakeholders groups such as the National Cancer Institute and patient and professional groups," said John Jenkins, M.D., director of the Office of New Drugs and the Center for Drug Evaluation and Research. Jenkins oversees the "super office," as it is now becoming known, that will include the ODP as well as four other suboffices.



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John Jenkins

 
The review of new cancer drug applications had been spread among several different centers within the agency, mainly the Center for Biologics Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDER)—a split that some observers say led to philosophical inconsistencies in the drug review process, with reviewers at the different centers and divisions applying their own criteria and expertise, which may not have been strictly related to cancer, to the same drug application. The result was a complicated review of new cancer therapies.

Cancer patient advocates who have strongly pushed for the reorganization say, for example, that prostate cancer drugs have been primarily reviewed by urology experts instead of experts in prostate cancer, and, similarly, hormonal treatments for breast cancer were reviewed by endocrinologists.

"We can't have people who are not trained in oncology making decisions on a disease that requires training and judgment on clinical protocols," said Ellen Sigal, Ph.D., who is the founder of the Friends of Cancer Research. "We will never progress with chemoprevention and early detection and diagnostics unless oncology is consolidated and overseen by people who have the training to make these very complex decisions."

Jenkins points out that the creation of ODP is just one aspect of a general reorganization at the FDA, which, in the future, will streamline drug review processes across different diseases. In cancer, "bringing reviewers together in the same center gives us the critical mass to achieve some of the goals we have laid out for the oncology office," he said. "I think it is a real opportunity to advance the area of oncology drug development."

Change Amid Controversy

Word of transformations in the agency came in the summer of 2002—the very time that Congress was probing alleged FDA failures in its review of Erbitux (cetuximab), a targeted therapy on the agency's Fast Track program. Congressional investigators found serious flaws in research by ImClone Systems Inc., the sponsor of the application, and FDA officials also testified they had also found major deficiencies in the way ImClone conducted its clinical trials. A congressional subcommittee criticized the CBER for not informing ImClone of those deficiencies earlier in the review process and focused on the different ways that the biologics and pharmaceutical sides of FDA operate.

Within weeks, then deputy commissioner Lester Crawford, D.V.M., Ph.D., announced that the FDA would combine both biologics and drug reviews into one center. Jenkins pointed out that the move was not congressionally mandated but instead came "more from a desire to put like reviews together, avoid redundancy, have a critical mass of expertise so you are not dividing your experts between two different groups."

The move was cheered by patient advocates, the drug development industry, and oncology societies—but only as a first step in a process to establish a centralized oncology office at the FDA. By most accounts, that effort was spearheaded by patient advocates who have long felt that a single destination for oncology applications at the FDA would lead to faster review and approval of new therapies.

"I don't know that there were bad reviews of cancer drugs by the FDA or that applications weren't being reviewed well. Our argument was that it would make more sense if applications were reviewed by people who knew how the drugs were to be used and who would, in fact, use them," said Ellen Stovall, president of the National Coalition for Cancer Survivorship.



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Ellen Stovall

 
"We wanted to see all oncology expertise in one office and under one experienced leader, so that they can work from a common platform and a common set of policies and experiences," said Richard Schilsky, M.D., a professor of hematology/oncology at the University of Chicago who represented the American Society of Clinical Oncology (ASCO) in the effort to reorganize the FDA's cancer mission.



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Richard Schilsky

 
Not only were a "partition of effort" and a "philosophy of entrenchment" problems, Schilsky said, but also he is concerned that the fallout from safety problems seen with COX-2 inhibitors might affect the way all new drugs are handled. And in cancer, such caution could be a problem, he said. "In the cancer area in particular there is a continuing need to strike an appropriate balance between risk and benefit because these drugs may have significant toxicities."

"The community was united on this, and we pushed them," said Sigal. And she was deeply surprised that the FDA did not push back. "I started off 2 years ago as a skeptic of the FDA and thought nothing would happen. But they were extremely collaborative—not confrontational at all—working with us to do everything they could to get input from the community."

In July 2002, the FDA announced it would create ODP, to be housed in the CDER, and that this new office will be a consolidation of three existing areas within CDER—those responsible for the review of drugs and therapeutic biologics, as well agents used in medical imaging.

To support this oncology office and coordinate work performed throughout the FDA centers, FDA also created a cross-cutting "Oncology Program" within the oncology office to facilitate expert consultation across the agency and provide a forum to discuss and develop regulatory policy and standards.

In October 2004, the FDA announced that it was seeking a new director for the office, a process that included participation by Sigal, Schilsky, and others, including William Hait, M.D., Ph.D., the director of the Cancer Institute of New Jersey who was representing the American Association for Cancer Research (AACR).

"The way modern translational research is done has more to do with molecular targets and pathways than the size and shape of the molecule," Hait said. "And with these development processes fragmented, consistency in the evaluation and approval process often wasn't there, so it becomes frustrating to the pharmaceutical industry and biotechnology industry who became less and less sure about the pathway to get these drugs approved."

Hait said the new office, run by an effective leader, will offer "a more transparent, easier-to-understand system to navigate."

In the Hot Seat

But no one expects the job of new ODP director to be easy. The office will be large—up to 140 employees. "There is a lot of development work going on in the oncology area," Jenkins said. "The director will be involved in overseeing three very busy clinical divisions, tending a lot of meetings with sponsors, and reviewing a lot of applications and making decisions about what drugs should be approved and what drugs are not ready for approval. It is going to be a big job."

And advocates say that centralization of the oncology office will not be complete until review of vaccines and gene therapy products is also transferred from CBER, a move that Crawford has declined to make to date, saying that there are sufficient differences in the review of vaccines and cell and gene therapies that they should remain in the center for biologics.

They also say that improvements need to be made in use of the Oncology Drug Advisory Committee and in the process that grants accelerated approval, among other issues. Another big issue that may loom before the director is the "drumbeat" for expanded access to unproven therapies for patients in desperate need, said Stovall, a movement she does not agree with. The issue has been spearheaded by the Abigail Alliance, which has been publicly lobbying the FDA to implement a faster system for providing investigational drugs to cancer patients.

Jenkins lists improvement in outreach to professional groups, governmental institutes, and advocates as a top goal, as well as continuing work on "guidance" documents that define the FDA's "best thinking" on development of drugs to treat the differing types of cancer. "If an industry develops a drug for colon cancer, for example, we would have a guidance that lays out what types of studies researchers need to undertake and what types of endpoints they should be looking at in the trial. The same would be true for lung and breast cancer and others," he said. "There are broad principles that apply across all oncology indications, and then we have specifics, such as the endpoints and how much data are needed for approval."

Jenkins adds that having a new oncology office and new director "is a real step forward," but is quick to say that "I think we would characterize this as building on prior success, not trying to fix something that was broken."



             
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