CDER Explains its 4 Expedited Review Programs
CDER deputy director for science operations Richard Moscicki says that FDA’s breakthrough therapy designation for new drugs often is misinterpreted by the media or consumers to mean that the drug has already been conclusively shown to be a major game-changing advance. “What I’d like the public to understand,” Moscicki says in a CDER Conversation, “is that FDA tags drug candidates early in the development process with the ‘breakthrough’ designation because they have the potential to be true breakthroughs in the long run. Drugs that receive the breakthrough designation have given a signal during testing that encourages CDER to invest a major effort and make sure that they are evaluated as efficiently as possible.”
Moscicki says the agency looks for early patient data that says that the drug is likely to provide a substantial improvement over what is currently available to treat a serious disease or condition. “There are different ways that a company can show a substantial improvement,” he writes. “For instance, they can do a head-to-head comparison of their new drug to the current standard of care in an early clinical trial… In some situations, we will consider early patient data where there isn’t a direct comparison in the clinical study, but we have other information, such as a solid understanding of the natural progression of the disease.”
Companies that receive a breakthrough therapy designation receive enhanced communication and input from CDER, Moscicki says. Senior management becomes directly involved in the drug’s development to help guide and shape further clinical studies and to make sure that the drug is being developed and reviewed as efficiently as possible.
Moscicki says the program has been popular since its 2012 start and positive feedback has been received from industry. By 3/31, he says, CDER had received 342 requests from companies and had granted 111 breakthrough designations. The Center is now reviewing the program to truly assess its effectiveness, and reports that 41 applications for breakthrough designated drugs have reached marketing approval. “These numbers indicate that the program is working in terms of expediting development and review,” he writes. “But we want to make sure that we have the bar set at the right place in terms of judging what constitutes a ‘substantial improvement.’”
The conversation with Moscicki also looks at the Center’s three other expedited review programs — accelerated approval, priority review, and fast track. “All of these programs are aimed at serious diseases,” he says, “many without adequate treatment options. Expedited review pathways are for life-threatening diseases like cancer, not toenail fungus.”
Accelerated approval, he says, allows use of a surrogate endpoint in the main clinical trial that would be used to approve the product. For priority review, clinical trials have been completed and FDA has seen a significant improvement in safety, effectiveness, or both. Under priority review, the review time is reduced from 10 months to six months. Fast track designation is designed for drug candidates intended to treat a serious condition that demonstrated in non-clinical studies the potential to address an unmet medical need.
Moscicki says there is nothing in any of the expedited review programs that lowers the agency’s standards. “Even though we have some flexibility in how we review drugs that are a part of these expedited pathways,” he says, “our standards for safety and effectiveness remain unchanged. All new drug candidates, whether they receive an expedited designation or not, still have to prove safety and effectiveness.”
He also stresses that an expedited designation does not guarantee that a drug will be approved. “What it means is that we’re going to give the drug candidate special attention and work with the company to develop, test, and evaluate the drug’s safety and effectiveness as efficiently as we can,” he declares.