Regulators in high-income countries have a responsibility to help health authorities in low- and medium-income countries develop regulatory frameworks for cell and gene therapy products to ensure these treatments are available to all, asserts the US FDA’s biologics center’s director Peter Marks.
The World Health Organization plans to soon issue a white paper proposing a harmonized regulatory framework for cell and gene therapy products, according to Peter Marks, director of the US Food and Drug Administration’s Center for Biologics Evaluation and Research. Such a framework is considered necessary for facilitating access to these products for patients in low- and medium-income countries and to ensure their commercial viability.
Marks discussed the WHO’s plans and described some of the global regulatory challenges in bringing cell and gene therapies to market in at a 30 June webinar sponsored by the Parenteral Drug Association on advanced therapy medicinal products, where he also discussed some of the evolving regulatory requirements for these products in high-, middle- and lower-income countries.
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Marks, a proponent of using regulatory convergence to increase access to novel therapies, asserted that “there is a responsibility for regulators in high-income countries to help regulators in low- and medium-countries develop the framework necessary so that some of these products are brought forward in their countries and are appropriate and are safe.”
As he explained at a cell and gene therapy policy meeting in November, Marks expects that regulatory convergence among high-income countries could help facilitate commercial availability and pave the way for the use of gene therapies in low- and middle-income countries. He further suggested then that low- and middle-income countries adopt something akin to the WHO’s prequalification process for vaccines.
Challenges for regulators
In the high- and middle-income countries, the regulatory frameworks for cell and gene therapies are in a state of flux, Marks said. For cell therapies, there is a lack of alignment of regulations in high-income countries, while for gene therapies, there are more similarities.
At international meetings of regulators, the one thing that everyone can agree on is that “the existing frameworks are not permanent” and that some markets “under-regulate” while others “over-regulate” these products.
Yet in low- and middle-income countries, there is no framework at all. For these countries, it can be “quite challenging” for regulators to devise a framework from scratch. “The issue that comes up is that with low- and middle-income countries, they have no experience with cell and gene therapies. If you have to develop regulations out of nothing, it can be quite challenging. When you think about it, small countries have a regulatory agency that consists of a few dozen people.”
Rather than having these health authorities devise regulations “from scratch,” it would be better to leverage a harmonized regulatory framework that has already been developed by other higher-income countries that have more experience in novel therapies.
WHO white paper proposed
Marks is on the WHO team that is developing the white paper, or “unified regulatory schema,” for regulatory convergence on cell and gene therapies.
He said he hopes the white paper will “bring some order to this area.” The team was “making a lot of progress on this before COVID-19 came along,” and he expects that the WHO will be publishing this paper in the “not too distant future.”
Marks said that some possible areas of regulatory convergence could include preclinical study requirements for toxicology studies, environment assessments, manufacturing information, clinical outcomes and inspectional requirements.
The idea for the white paper emerged from a September 2018 meeting of the International Conference of Drug Regulatory Authorities (ICDRA) in Dublin, Ireland.
ICDRA’s press release from the meeting said that the WHO would develop with member states a “current state of the art document capturing areas where agreement among experienced regulatory authorities exists, noting where harmonization has yet to be achieved, and documenting existing areas of uncertainty; areas covered could include definitions, quality attributes, standards and clinical development pathways.”
ICDRA was established in 1980 to bring together regulatory authorities from WHO member states to strengthen collaboration and develop international consensus on regulatory priorities.
Ensuring commercial viability
Marks said that global regulatory convergence for these products will help ensure that the markets for cell and gene therapies are large enough for commercial viability.
Many gene therapies for ultra-rare diseases target small patient populations enrolling up to 100 patients a year. One country may not have enough patients with a rare disorder to make it commercially viable for a company to launch the product. However, Marks said, “if you market across countries you can get to that commercial viability.”
Sponsors should bring in other regulators
Marks emphasized, as he had at the November cell and gene therapy policy meeting, that sponsors should ask officials with other authorities such as the European Medicines Agency to join some some of their meetings with the US FDA as a way to come together to develop enough national markets for the scale required to make many cell and gene therapies viable.
At the PDA webinar, Marks encouraged sponsors to promote convergence by inviting other regulators to attend their pre-IND Initial Targeted Engagement for Regulatory Advice on CBER Products (INTERACT) meetings with the FDA. This could go a long way toward educating other authorities on how the FDA assesses potential cell and gene therapy products.
CBER announced in June 2018 the implementation of the INTERACT program, which is intended to help accelerate development and approval of novel biologics and other products reviewed by the center.
“We are perfectly happy if a sponsor invites other regulators to listen in on early meetings,” said Marks. “We have no problem with regulators from other countries listening in on these meetings because it could orient them to some very interesting products that they otherwise would not have exposure to.”