Article | February 29, 2024

Examining The 2024 Regulatory Landscape Of Cell And Gene Therapy

Source: Cell & Gene

By Life Science Connect Editorial Staff

GettyImages-1808017268_450_300

A recent episode of Cell and Gene Live provided a platform for regulatory experts to delve into the complexities of cell and gene therapy regulation and what changes the industry can expect in 2024. Moderated by Erin Harris, chief editor of Cell and Gene, the Cell and Gene Live 2024 Regulatory Outlook featured discussions with Dr. Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), and Dr. Nicole Verdun, super office director at CBER, and focused on key challenges, advancements, and regulatory strategies for navigating the evolving landscape of advanced therapies.

Verdun opened by shedding light on the establishment of the Office of Therapeutic Products, emphasizing its pivotal role in addressing unmet needs in rare diseases. She highlighted the office's focus on enhancing operational efficiencies and fostering collaboration with external stakeholders to expedite the approval of innovative therapies. “We are working quite a lot on getting advice to sponsors in a timely fashion,” she explained. The office is doing this, she said, by “increasing communication and making sure that that communication that we're giving is consistent and is helpful to really spearhead getting a lot of these therapies to market where there's a significant unmet need.”

Lessons From Approvals

Marks underscored key learnings from recent gene therapy approvals, emphasizing the significance of manufacturing, accelerated approval endpoints, and global regulatory communication. However, he insisted that the one area where more development is truly needed is in manufacturing process development. “We still have not made the quantum leap forward that we need to in our ability to manufacture cell and gene therapies to help reduce the cost and improve accessibility. And that's something that I think you'll see us continue to try to work on with the community,” he said.

He also emphasized the importance of leveraging accelerated approval endpoints and enhancing communication with sponsors and regulatory counterparts to streamline the approval process. For example, he said CBER is piloting programs to actively communicate with biotech firms in order to accelerate the time to approval. “So, all of those things, I think, will hopefully combine if we can make some headway on making this an exceptional year for forward movement in gene therapies,” he added.

Overcoming CMC Challenges

The speakers addressed challenges in chemistry, manufacturing, and controls (CMC) for advancing cell and gene therapies and their impact on regulatory approval. Verdun emphasized the significance of ensuring comparability during late-stage product development and transitioning to commercial manufacturing. Verdun stated, “This really is something where, again, communication is key and partnering with the agency is key. How we evaluate the patient data really depends on the individual trial and what was changed. And we have an evaluation of those changes and the impact on the endpoints and impact on the product specifically around CMC and clinical and what we're changing there. And so, I really think this is more of an individual conversation that we're willing to have, but it really does vary based on the individual circumstances.”

She went on to emphasize the need for robust potency assays and standardized manufacturing processes to ensure consistency and quality across cell and gene therapy products. “We're now in a place where we don't have assays in place or other pieces to truly get to comparability,” Verdun explained. “I would encourage sponsors to think through some of these potential challenges early on and plan for that as much as you can so that we aren't in a space where we're trying to make sure that the clinical data that was collected on one form of the product is applicable to what we're wanting to do in the commercial setting.”  

Verdun highlighted the importance of transparent communication and collaboration between sponsors and regulatory authorities to navigate CMC-related complexities effectively. “Communication is key because the more we can talk about the individual circumstances, we can get to some resolution here,” she said.

Pathways For Pediatric Treatment

Harris brought up an audience question about how to accelerate development of pediatric products for rare diseases that affect both adults and children. Verdun emphasized the significant potential of gene therapy in diseases where early intervention can mitigate morbidity and organ damage. “It really is prudent to try and get these gene therapies to patients earlier in their life,” she said. “We are very open to accelerating development in the pediatric space.”

However, she acknowledged the importance of not rushing pediatric products to clinical trials, let alone to market. “We have to make sure that things are safe and that we have enough in the preclinical setting to give us some assurance that we are ready to give things to pediatric patients,” she added.

Marks chimed in to underscore the FDA's openness to studying gene therapies in pediatric patients and addressing disease-specific considerations. He stressed the importance of disease context in determining the appropriate patient population for clinical trials while also acknowledging the FDA's role in facilitating dialogue with developers regarding the adoption of new analytical methods. At the same time, he encouraged developers to engage with the agency early and consistently throughout the validation process of new methods, ensuring alignment and acceptance of these advancements.

Integration Of AI And Machine Learning

Marks and Verdun presented the use of AI and machine learning in cell and gene therapies as inevitable due to their ability to enhance analytic tools, safety surveillance, and pharmacovigilance. From a regulator standpoint, Marks stated, "Sponsors deserve human review of their applications, but we will use the tools of AI. And I think during 2024, we'll be spending time not just at our center but across FDA, trying to further refine our strategy for dealing with AI because it's moving so rapidly.”

The Cell and Gene Live 2024 Regulatory Outlook provided valuable insights into the evolving regulatory landscape of cell and gene therapy. With a focus on collaboration, innovation, and patient access, the discussions underscored the importance of ongoing dialogue between regulators, industry stakeholders, and the scientific community to accelerate the development and approval of transformative therapies. As the field continues to advance, proactive engagement and strategic partnerships will be key to unlocking the full potential of cell and gene therapies for patients worldwide.