Stakeholders say they want lower regulatory hurdles for cell and gene therapy (CGT) products, including streamlined pathways. Some researchers said updates to the US Food and Drug Administration’s (FDA) platform technology designation and designated advanced manufacturing technology programs hold the most potential to bring promising CGTs to patients.
On 5 June, FDA held a roundtable meeting with stakeholders from academia and advocacy organizations to talk about potential barriers to developing CGT products. FDA Commissioner Marty Makary began the meeting by saying the agency wants to listen to and learn from stakeholders on how to reduce barriers and cut waste while challenging established norms. (RELATED: This Week: Health officials want to cut red tape for CGTs, FDA’s budget advances, and more, Regulatory Focus 6 June 2025)
“We are asking ourselves, can certain materials be submitted in advance, so approvals are quicker,” said Makary. “Can we use post-approval monitoring and the assurance of post-approval monitoring in the actual decision-making process?”
Vinay Prasad, director of the Center for Biologics Evaluation and Research (CBER), echoed Makary’s eagerness to find new ways to accelerate products to market.
“FDA will consider surrogate endpoints and overall survival,” he said. “We will rapidly make therapies available at the first sign of biomedical success or action, but we will also follow up on quality of life to ensure we’re accomplishing what we think we’re accomplishing.”
Furthermore, he said the agency is interested in leveraging randomized clinical trials (RCT), parachute trials, and real-world data (RWD).
Terence Flotte, dean of the University of Pennsylvania and president of American Society of Gene and Cell Therapy (ASGCT) said that among CBER’s work the platform technology designation program for drug development may have the greatest potential to advance CGT development by allowing a single technology to be used across multiple disease applications with substantially less preclinical work prior to human use.
“What would be really transformative would be if in the future designated platform technologies could also be made available to centers treating commercially pre-available rare diseases in which this could have a dramatic impact,” said Flotte. “Similarly, the FDA designated advanced manufacturing technology program for cell therapy could further streamline the regulatory processes and de-risk investments in novel manufacturing methods so that we don’t get locked into old technology.”
Flotte asked for more flexibility in FDA’s accelerated approval programs and when considering innovative trial designs. He also encouraged applying more weight to real-world evidence and said the agency’s rare disease pediatric review voucher program provides incentives for life-saving innovation that otherwise may not be commercially viable.
David Liu, a Harvard professor and the director of the Merkin Institute for Transformative Technologies in Healthcare, proposed several steps that the US should take to build a national infrastructure for interventional genetics. He urged development of rapid diagnosis and therapeutic development centers to identify and optimize gene editing agents and their delivery vehicles; small scale chemistry, manufacturing and controls (CMC) capabilities to allow fast turn-around; development of cell, rodent, non-human primate or virtual toxicology platforms; streamlined regulatory pathways for “n of few” clinical trials; and public-private platforms that allow for sharing clinical outcomes.“Many of these elements exist already today and are ready for pilot integration within one to two years,” said Liu.
Several attendees raised concerns about the lack of incentives to develop CGT products for children and rare diseases. Catherine Bollard, a pediatrics professor at George Washington University and chief research officer and director at the Center for Cancer and Immunology Research at Children’s National in Washington, DC; was one of them.
“Many of us [in academia] are left in this [investigational new drug] IND limbo or what we call the valley of death,” she said.
Crystal Mackall, founding director of Stanford University’s Center for Cancer Cell Therapy, said that despite scientific successes, the field of CGT is struggling to deliver the treatments to all patients.
“Even in the adult space, we only have market penetration of about 20%, but in pediatrics, we have essentially a complete market failure,” she said.
Mackall said that pediatric drugs aren’t getting to market because of high cost of development and regulatory risk. She said that non-profit research organizations are looking for ways to reduce regulatory risk.
“We all know that we have to uphold the quality standards, but we still have to make it somehow commercially viable or at least sustainable to get these drugs to market,” said Mackall.
Mackall said she hopes FDA and industry stakeholders can align on evidentiary standards, trial designs and endpoint requirements for earliest possible approvals. She also hoped the agency will endorse good manufacturing practice (GMP) standards that are appropriate for small batch or small market manufacturers and work on how to maximize the flexibility of platform designations. She noted that platform designations have been used for [Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)] with success and they should figure out if it can be used for viral-based gene therapies.
Carl June, an immunotherapy professor at the University of Pennsylvania and a researcher whose work helped bring the CAR-T drug Kymriah (tisagenlecleucel) to market, said he is concerned at the direction CGT therapies have taken since the drug was approved.
“Despite our early leadership, much of the innovation in this field is now happening off-shore, outside FDA jurisdiction,” said June. “If we do not modernize our regulatory approach, we risk losing our leadership and undermining the long-term viability of our biopharma industry.”
“In my view, the FDA need not regulate early-stage trials of autologous gene-modified cell therapies,” he added.
June proposed a two-tier model similar to what China has where first in human exploratory trials proceed under institutional review board (IRB) approval and full regulatory review is only required once a therapy shows promise and is ready for larger multi-site trial. He noted that in China, investigator-initiated studies begin without upfront authorization from the national regulatory bodies, and only if a product proves promising do they move to the standard approval process that mirrors the FDA’s regulatory pathways.
June said that while promising new strategies for CGTs are often first developed in the US, they get tested clinically in China due to regulatory hurdles. He also noted that more than 100 CAR-T cell trials for autoimmune disease have begun in Germany with local IRB approval over the past two years because they couldn’t be conducted in the US.
“Why are researchers increasingly taking trials overseas? Simply put, the US process has become too slow, costly and inflexible while other countries make it easier to innovate,” said June. “This is a problem, and it urgently needs a solution.”
Donald Kohn, a pharmacology professor at the University of California, Los Angeles, echoed many of the concerns and said that the most significant barrier to CGT development was not scientific or clinical, but financial, because of the current CMC regulatory expectations.
Jeff Allen, CEO Friends of Cancer Research (FoCR), said that chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an important treatment for patients with cancer and possibly other diseases as well, but it has faced significant regulatory hurdles.
“The progress in CAR-T therapy has been predominantly for the treatment of hematological malignancies but recent data is showing that this could change and if we could get the correct policies in place this could be far more commonplace,” he said.
Allen listed several areas that could use improvement, including thinking of new ways ensure the most promising therapies are advanced in clinical development. He said currently there are limitations in pre-clinical models and in evaluating the potential constructs and novel approaches for efficient screening, and prioritization of gene editing candidates.
Allens said regulations and manufacturing requirements can create hurdles to sustainable development of CGTs and limit commercial interest. He said they should consider new pathways, especially for cancers and other populations. “A new structured approach is needed to balance regulatory oversight with operational feasibility alongside patient need,” he added.
Finally, he urged the use of real-world evidence. In particular he said leveraging data from current clinical practice can be an important tool to monitor long-term outcomes.
While many of the speakers focused on addressing potential regulatory hurdles to getting CGTs to market, Sean Morrison, director of Children’s Research Institute at the University of Texas Southwestern medical Center and member of International Society for Stem Cell Research, warned that there are bad actors who want to sell snake oil to rip off desperate patients by capitalizing on promising research.
“These companies never do clinical trial, they have no plans to do clinical trials, they’re operating illegally but it’s estimated there are 2,000 like this in the United States,” said Morrison who also serves on FDA’s Cellular, Tissue and Gene Therapies Advisory Committee. “They commonly claim to cure diverse medical conditions with one size fits all therapies, even for conditions where there is no plausible scientific rationale or stem cell therapy.”
As an example, he spoke about hundreds of companies who claim to use umbilical stem cells or placental cells to treat Parkinson’s disease, Alzheimer’s disease, orthopedic diseases, and neuropathies despite a lack of scientific rationale for such treatments.
“Americans really need the FDA to protect them from those people,” said Morrison. “Buyer beware is not an effective strategy when it comes to experimental medical therapies because even most physicians don’t have the expertise to evaluate which experimental therapies have merit and which ones don’t.”
“What we’ve learned is that companies that ignore FDA regulations also ignore good manufacturing practices,” he added.
Morrison warned that people have become septic due to such products. He said the challenge is accelerating the development of real therapies, sound scientific rationales, clinical evidence of safety and efficacy, without deregulating to the point where FDA opens the doors for bad actors to sell snake oil. He warned that it would undermine confidence in the agency, and it would undermine confidence in the CGT field in general.
