In April, Scott Gottlieb, MD, stepped down after two years of service as commissioner of the Food and Drug Administration (FDA). Gottlieb was the keynote speaker at this year’s Asembia Specialty Pharmacy Summit in Las Vegas. During his speech, he discussed how the agency wrote “modern rules for new technological paradigms,” in order to create a regulatory framework to help govern drug development and approval opportunities in the future.
Gottlieb discussed those changes and how they will help implement sound regulations and policy moving forward.
On gene therapy:
“We had to rewrite the rules for how we were going to approach these new technologies and really lay the foundation for what the regulatory architecture would look like moving forward. In respect to gene therapy, a lot of the issues are not on the clinical portion of the review. These gene therapy products are so effective, you can often determine clinical effectiveness on a very small series of patients.
“But there are safety issues: how durable will the treatment effect be? Will there be off-target effects? Those issues relate less to the clinical performance that is assessed in any premarket study and more to the product features and the vector itself that is delivering the gene. That is, how the gene gets set and sorted, and any manufacturing issues related to that.
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“It’s exactly inverted from traditional drug development where approximately 80% of the complexity and challenge for the FDA is the clinical portion of the review and 20% is the CMC, or the chemistry, manufacturing, and controls portion of the review. When it comes to these gene therapy paradigms, 80% of the complexity for the agency is the product portion and only 20% is on the clinical portion.
“This lends itself to a whole new paradigm where you can use the framework of accelerated approval to allow these products to come to market more quickly based on small amounts of clinical data, recognizing that you aren’t going to answer all the longer-term questions in any reasonably-sized premarket setting. But, you have much more robust authority to require postmarket follow-up of these products, closely monitoring the patients under that legal framework.”
On cell-based regenerative medicine:
“With cell-based regenerative medicine, we promulgated a policy to establish a right mind about when a cell, taken out of your body and manipulated, could become a drug. That existed in law and regulation, but it never existed in practice if the agency hadn’t drawn a bright line and started to vigorously enforce around that line. We were seeing rapid growth in clinics, all marketing different stem cell products—some with really tragic outcomes. So we put out that guidance and started taking enforcement actions establishing that bright line.
At the same time, we recognized that a lot of innovations happen in small academic medical centers where individual investigators were trying to develop these products. They didn’t have the resources or the sophistication to file individual license applications to become drug developers so, for the first time, we developed a framework, where as long as individual investigators were following the same manufacturing protocols for products, they could pull their clinical data and file a common application in order to get an individual license to each academic institution to market their own products. It was a highly novel approach to how we go about giving biological license applications to sponsors for the first time—and a paradigm we could replicate in other settings.”
On targeted medicine:
“When it came to targeted medicine, we faced the idea that disease was no longer defined by phenotype but by genotype. This was really the holy grail of what came out of mapping the human genome. But the regulatory paradigm didn’t give us readily available tools to take advantage of this. So we started things like basket trials or tissue-agnostic trials where you’d get approval for a drug in multiple tissue types as long as they targeted the same molecular signature of disease. You’d also see master protocols where you could study multiple drugs within the context of the same registration trail or the same patient cohort. These were all designed to try to change the paradigm to allow for more easy and efficient development of targeted medicine.”
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