Experts suggest the FDA’s Advanced Manufacturing Technologies designation could be a lifeline for improving production processes for approved cell and gene therapies.
The brief history of the cell and gene therapy sector has shown regulatory approval is not the finish line. Rather, companies that win approval face a new challenge: reliably and profitably making products at scale. With struggles to turn clinical advances into commercial successes suggesting many companies lack an answer, the FDA’s Advanced Manufacturing Technologies (AMT) designation, finalized at the end of last year, has emerged as a potential lifeline for beleaguered biotechs.
Inefficient production that was manageable during development can buckle under the pressures of commercial supply, explained Anna McMahon, director of regulatory affairs at Cellares. “Demand often rises after approval while new [manufacturing] sites are added. If manufacturing and QC release depend on manual handling and paper records, supply can lag, treatment slots can slip and the waitlist will get longer.”.
Cellares, along with Cellino and Oribiotech, have created platforms designed to address some of the challenges and secured the FDA’s first AMT awards. Assessing the opportunities open to such businesses, regulatory expert Don Fink of Dark Horse Consulting told BioSpace that CGT makers “battling supply issues in terms of product capability and capacity” of approved therapies could adopt new manufacturing approaches to improve their commercial viability—and an AMT designation could help get such a change approved.
A Pattern of Commercial Failures
Eight of the 28 cell and gene therapies approved by the European Medicines Agency are unavailable because they were not commercially viable, McMahon said. The challenges date back to the first gene therapy approved in the EU, a $1 million–plus treatment for familial lipoprotein lipase deficiency that uniQure pulled from the market after five years in response to “extremely limited” use.
While Europe-specific payment challenges are a factor, cell and gene therapies in the U.S. face similar problems.
A prime example is Massachusetts-based bluebird bio, which was sold this year for just under $50 million after failing to build a profitable business on the approved therapies Lyfgenia, Zynteglo and Skysona. Before going private, Bluebird reported challenges with the production process for Zynteglo and Skysona, leading it to wind down that method and pursue alternatives.
Bluebird, which has rebranded as Genetix Biotherapeutics, told investors the need to secure FDA approval for changes to manufacturing methods could delay the transition to alternative manufacturing processes.
Looking back further into the field’s history, California-based Dendreon filed for bankruptcy in 2014 after struggling to reduce the cost of making its cell-based cancer therapy, the first FDA-approved cancer “vaccine.”
Dendreon and Genetix are not alone in their struggles. Fink noted that some companies reach the market with “hands-on, less automated” production processes. While they may have effective automation for some parts of the process, he explained, overall there are inefficiencies that constrain output, add to staffing and space requirements and otherwise increase the cost and time of production.
Making Post-Approval Pivots
Fink said making changes to a manufacturing process post-approval is a “more reliable” approach than trying to move to a new platform during development because a company has an approved drug to use in comparability tests. If the company can show products made using the new and old processes are comparable, it may be able to win FDA approval for the new production method.
McMahon said that besides comparability, regulators focus on “the control strategy and change management that preserves patient access.” Because AMT designations offer opportunities to interact with the FDA, McMahon sees the status as beneficial for companies that want to make post-approval changes to manufacturing processes.
“It provides a venue to align the plan, acceptance criteria and documentation expectations upfront so studies continue without disruption,” McMahon said. “As identical sites come online, the same validated methods and electronic records are repeated across regions, which supports consistent filings, efficient inspections and stable supply.”
McMahon cautioned, however, that “switching to a different manufacturing process post-approval is a significant investment.” The costs informed McMahon’s recommendation that companies considering post-approval changes “ensure that the new platform is sustainable and a long-term solution.” McMahon also advised companies to check that potential manufacturing partners have “done their due diligence to ensure that product reviewers and inspectors have a good knowledge of the new technology and their facility.”
One year into the program, companies with AMT designations have yet to demonstrate that the status can facilitate post-approval changes. Meanwhile, the pool of potential customers with approved therapies continues to grow. In July, the industry body Alliance for Regenerative Medicine listed 15 cell, gene and tissue therapies that had already been greenlit by the FDA in 2025 or could be submitted to the agency for approval before year’s end.
