The time is right for the FDA to reorganize in a stepwise, structural, disease-oriented manner to align its regulatory science with major advances in medicine, according to a panel at a Senate briefing on Capitol Hill.
At a meeting sponsored by the advocacy group Friends of Cancer Research (FOCR), speakers discussed the FOCR’s concept of reorganizing FDA into disease-oriented Centers of Excellence. They said this approach to medical product development would provide a more integrated, coordinated, and efficient approach to FDA evaluation and reviews of new drugs, biologics, and diagnostics. They stressed that the concept of FDA reorganization by disease is especially suited to oncology, where advances in genomics have been especially dramatic and treatments are becoming ever more complex and targeted.
“FDA is doing a great job with what they have…the question is, can it be better?” said FOCR Chair and Founder Ellen Sigal, PhD. “My answer is yes.” She pointed out that Congress has not modernized FDA’s organizational structure since the 1970s, an era which predated many of the molecularly targeted drugs now available to oncologists. FOCR is proposing that FDA establish 3-4 pilot areas for Centers of Excellence, with the first focusing on oncology. Other pilots might focus on neurodegenerative, cardiovascular, and infectious diseases.
Currently, FDA is organized into separate centers that regulate drugs, biologics, and devices. This individual “silo” approach does not always work well in today’s era of modern medicine, especially oncology, said speakers. At worst, it could delay the approval process.
For example, the current FDA review system segregates new medical drugs by product into the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER), but this divided approach is not suited to all oncology drugs or to those used in combination, especially immunotherapies. What if one immunotherapy drug is approved in CDER and one in CBER? Should a combination of the two (increasingly used in oncology) be approved in CDER or CBER? The “silo system” is also not suited to drugs that have companion diagnostics, said speakers.
The FDA has made “tweaking” sorts of changes since the 1970s, but it is time to look at major organizational change given “the recognition that things are dramatically different now than they were even 10 years ago,” said Steven K. Galson, MD, MPH, Senior Vice President for Global Regulatory Affairs and Safety at Amgen, Inc., and former Director of CDER at FDA. Galson pointed out that in the past drugs were “mostly made synthetically by chemists,” but now there are many more biologic therapies and increasingly sophisticated medical applications and software.
“Leadership on this issue is very important,” said Mark McClellan, MD, PhD, a former FDA commissioner who is now Director of the Duke-Robert J. Margolis, MD, Center for Health Policy at Duke University. “There are more and more products that don’t fit neatly into one category.” He noted that, during his time at FDA, many more biologics were moved from CBER to CDER, which involved “a fairly significant structural change” undertaken for efficiency. He said it is time to look at “where the biggest bang for the buck” would be with a more integrated structure at FDA. “Here the goal is efficient organization for the benefit of patients,” he said.
“Medicine has evolved tremendously; just the definition of cancer has changed in the last 20 years,” said Otis Brawley, MD, Chief Medical Officer and Vice President of the American Cancer Society Cancer Action Network. “This has happened with the advent of genomics.” Given these advances, he said it makes sense that FDA might benefit from “a slight reorganization.
”Brawley told OT that the idea of FDA disease-oriented centers “clearly needs to be fleshed out,” but he said the future of cancer medicine is moving in a direction that embraces change. In this future, he said, “it’s not the type of cancer but the molecular marker of the cancer that matters.” So the science is moving toward asking this question: “Does the tumor express this molecular marker and does the drug hit this marker?” He cited imatinib (Gleevec) as an example of a drug that treats cancer not by type but by molecular marker, since it is prescribed for leukemia as well as for gastrointestinal stromal tumors.
Brawley, who has served as a member of the FDA’s Oncologic Drugs Advisory Committee (ODAC) emphasized that he thinks the FDA is currently doing a good job, but could benefit from some small changes. “My experience on the ODAC is that the system is actually working very well,” he said.
“We have many reasons to think that this kind of organization could be good for the FDA,” said George D. Demetri, MD, Professor of Medicine at Harvard Medical School and Director of the Center for Sarcoma and Bone Oncology and Senior Vice President for Experimental Therapeutics at Dana-Farber Cancer Center. He added, “I think cancer is a good proof-of-concept place to start.” Demetri said that when he talks to staffers in CDER and then to those in CBER “I do worry that they may be playing with different sets of cards.” He told OT that it might be helpful to think of an FDA reorganization in terms of three intersecting rings (like the intersecting Olympic rings) that overlap and blend seamlessly together. “We certainly don’t want to tear down the house; I think there’s a way to do this constructively,” he said.
The FOCR meeting on FDA disease-oriented Centers of Excellence was held Feb. 24, the day the Senate confirmed Robert M. Califf, MD, as the new FDA commissioner. After his confirmation, FOCR’s Sigal said, “We are at a critical moment in public health and it is paramount to have a strong leader at the helm of the FDA. We are glad to see the Senate confirmed someone who has proven he is uniquely qualified to fill the role, Dr. Robert Califf.”
Professional oncology groups also praised Califf, a cardiologist who most recently served as FDA Deputy Commissioner for Medical Products and Tobacco. Before joining the FDA, he was Professor of Medicine and Vice Chancellor for Clinical and Translational Research at Duke University. Any reorganization at FDA in the near future would fall under Califf’s administration.
“Dr. Califf’s considerable expertise and long experience in clinical and translational medicine makes him well-suited to lead the FDA’s efforts to assure the safety and effectiveness of treatments and medical devices to ensure that the right treatment is delivered to the right person at the right time,” commented Richard L. Schilsky, MD, Chief Medical Officer at the American Society of Clinical Oncology, in a statement.
“While the scientific opportunities that exist today to develop more effective cancer treatments have never been greater, we also recognize that the science is increasingly complex, especially when factoring in the rapidly expanding effectiveness of molecularly targeted therapies and combination therapies,” said Jose Baselga, MD, PhD, President of the American Association for Cancer Research (AACR) and Physician-in-Chief and Chief Medical Officer at Memorial Sloan Kettering Cancer Center, in a statement. “Therefore, this extraordinary time of promise will require an experienced and visionary leader at the FDA to ensure that the necessary regulatory framework is in place to approve innovative therapies that are both safe and effective, and we believe Dr. Califf is the right person for this extremely important position,” Baselga added.
In 2013, then FDA Commissioner Margaret Hamburg, MD, formed a working group within FDA to look at ways of improving operational and program alignment to avoid duplication of effort within the agency. The intent was to see whether FDA’s regulatory science activities would benefit from better management. That working group looked at CDER and CBER as well as FDA’s other components. FDA is a bureaucracy with broad responsibilities (food and feeds, medical devices and radiological health and tobacco, as well as drugs) and as such is unlikely to move quickly on any pilot reorganization. But it also wants its regulatory science to be cutting-edge and to address the increasing complexity of the therapies it evaluates. The President’s Precision Medicine Initiative encourages federal agencies to work toward regulations that align with targeted medicines and diagnostics. And Vice President Joe Biden’s Cancer Moonshot encourages visionary thinking.
“Clearly, FDA has the last word on it,” said Sigal of the disease-oriented Centers of Excellence approach. But, she added, “Some external input on this is really critical.” Still a question mark, she added, is whether the pilot reorganization approach would require Congressional action. The Senate is considering new legislation in this area, said Sigal.