Dr. Peter Marks, PhD, the director of the FDA's Center for Biologics Evaluation and Research, commented on current manufacturing and regulatory barriers to CGT products during a virtual keynote address on Wednesday at the Cell & Gene Meeting on the Mesa (MOTM).

Despite a "bright future" for CGT and a "robust" global pipeline, Marks told the audience that there are some challenges that need to be addressed including disparate requirements among different countries -- from preclinical tests to manufacturing -- that make it difficult for patients in certain areas of the world to have access to therapies, particularly for those with rare diseases.

"Our goal is to try to help streamline the creation of important products for patients," Marks said. "We have to find a way to commercial viability if we're going to succeed, and we have to figure out what's going to get us there."

Marks referenced the Bespoke Gene Therapy Consortium, part of the National Institutes of Health's Accelerating Medicines Partnership program managed by the Foundation for the National Institutes of Health (FNIH), which aims to optimize and streamline the gene therapy development process to help fill the unmet medical needs of patients with rare diseases. The program is developing such a "cookbook" for these products, according to Marks.

Such a standardized "playbook" would make it more commercially viable for manufacturers to produce small batches of therapies, Marks said, noting that many of these therapies only treat 20 to 40 individuals per year and may not have commercial viability for many sponsors.

However, Marks said a playbook has the potential to make it more feasible to manufacture these products and called for making gene therapies for small populations more widely available internationally.

"What may be a tiny population in the U.S. becomes a reasonable size population when you go globally," Marks said. "The difference between 30 patients and 100 patients may make the difference between not commercial viability and commercial viability."

Global regulatory convergence

Marks made the case at MOTM for global regulatory convergence, particularly for rare disease patients whose numbers in any one geography may be very small. The FDA biologics chief opined that commercial viability roughly equates to 100 to 200 gene therapy treatments per year.

"One country may not have this [threshold] but we could potentially think about ways we could get there by finding ways in which we could facilitate gene therapy introduction into multiple high-income countries at a given time, and then potentially adoption into lower- and middle-income countries," Marks said.

According to Marks, patients from lower-income and middle-income countries stand to benefit most from gene therapies because the current standard of care "is not good" for these disorders due to a lack of access -- with many dying in childhood or having "very challenging" lives.

Gene therapies for these individuals could be potentially transformative but "that would rely on providing a regulatory framework that would need to be somewhat harmonized -- and perhaps we need to have something like pre-qualification and equivalent for gene therapies for the regulators," Marks said.

"This concept of global regulatory convergence might make it possible, at least starting in the rare disease space, to get these therapies to more people," Marks said, adding that international regulatory collaboration will also be necessary to deal with "bad actors" in the gene therapy field who can "create problems throughout the ecosystem."

In addition to his keynote address, Marks virtually participated in a panel at the MOTM on the opportunities for global regulatory convergence in CGT with representatives from the European Medicines Agency and Japanese Pharmaceuticals and Medical Devices Agency. The regulators discussed potential areas of international cooperation in terms of common standards and what steps are anticipated to improve equitable access to critical CGT products.

Marks noted that areas of global regulatory convergence and standardization might include clinical study requirements, environmental assessments, as well as manufacturing information requirements.

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