Gottlieb Boosts New Drug Approvals, Continuous Mfg.
FDA commissioner Scott Gottlieb assured Congress 11/30 that the timely implementation of the 21st Century Cures Act is one of the agency’s highest priorities. During a House Energy and Commerce Committee hearing on the status of the Cures Act almost one year after its enactment, Gottlieb said the law is a “defining element of my own policy planning at FDA.” He promised to soon release a document “that will take full measure of how we’re expanding on the provisions in Cures, to make sure we are continuing to expand on what Congress set out to achieve.”
An area with the greatest promise is oncology, Gottlieb acknowledged. “With the advent of more targeted medicines, we’re sometimes able to observe earlier, and in some cases, outsized benefits,” he said. “These situations are compelling us to explore new ways to facilitate and expedite the development and review of these products. For example, we’re currently examining approaches to better expediting review and approval of these products by leveraging FDA’s existing expedited programs.”
Gottlieb said the agency is moving accelerated approval beyond a drug’s effect on a surrogate endpoint in order to look at promising clinical endpoint measurements in early and small trials. For example, he said, such an approval could be granted for a “targeted drug, introduced in a properly selected group of patients, which has an outsized effect on overall survival in a rare or deadly cancer,” but where that benefit is seen only in a small trial, and where the agency would still need more evidence to fully understand how to best use the drug in clinical practice. “We might want to approve such a product earlier, and require a post-market confirmatory study to validate the finding – similar to an accelerated approval approach,” he explained.
Gottlieb said FDA needs to “better define what’s meant by intermediate endpoints to ensure that product developers with promising drugs take full advantage of this provision and can consider it in a broader range of such settings. As the mechanism of diseases, like cancer, become more clearly defined, and drugs targeting these conditions are more carefully tailored to the underlying biology of disease, we’re going to see more such cases – situations where a new drug offers an outsized survival benefit in a selected population of patients in a smaller, early stage clinical trial. One reason we’d want to consider accelerated approval in these settings is that it would include authority to require confirmatory evidence to support the continued marketing of the drug and an expedited withdrawal mechanism if that evidence fails to confirm the benefit. We intend to further explore the application of these principles in additional policy work that we’re undertaking.”
Asked by committee chair Greg Walden (R-OR) to expand on FDA’s Oncology Center of Excellence (OCE) and its role in the recent approvals of two new CAR-T cell therapies, Gottlieb said OCE was instrumental in reviewing the products and it is likely to become a model across the agency. “We believe that the orientation for the future across the entire agency is to try to consolidate the clinical portion of the review among the agency’s various product Centers,” he said. “We divide medical products into different Centers, but the clinical aspects of the review are the same, even if the product features are different. So trying to consolidate that clinical portion of the review provides a lot of efficiency, rigor and helps quicken the process. So standing up this new oncology Center, we think, is critical to the future of these classes of products.”
Gottlieb was also asked to update the committee on FDA’s efforts to advance continuous manufacturing. He said a $1 million contract with University of Connecticut was awarded to build a manufacturing platform for complex dosage forms, and another $4 million is available for other grants. The criteria FDA looks at to consider a grant are based on programs developing regulatory tools that could serve as the basis for how it is going to evaluate this technology when sponsors bring in applications where they are employing continuous manufacturing.
Continuous manufacturing is important to advance because it will allow more efficient and maybe lower-cost manufacturing, and it could pay a role in reducing drug shortages “because you don’t have as much risk of discontinuities in the manufacturing processes as you would in traditional manufacturing,” Gottlieb told the hearing. “By using continuous manufacturing, you acquire a much smaller and less expensive footprint. So I think the further deployment of this technology is going to lend itself to potentially repatriating some of the manufacturing that has gone offshore... Last point, I think, is this technology will be important to some of the newer, more complex products in development like gene therapies. So we think continuous manufacturing will be adopted outside of small molecule manufacturing and into biologics.”