FDA pledges to support cell and gene therapy manufacturing innovation

Manufacturers aiming to follow Yescarta and Kymriah to market can count on FDA support after the agency said it will help cell and gene therapy firms adopt better production methods.

A US Food and Drug Administration (FDA) spokesman told Bioprocess Insider the agency’s emerging technology team has been tasked with working with cell and gene therapy firms to “identify innovative approaches for efficient product manufacturing.”

The move is part of a wider FDA effort to support modernization of drug manufacturing methods outlined by then agency commissioner Scott Gottlieb in February.

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Continuous support

The FDA emerging technology team was set up to help firms implement innovative systems that improve drug quality. It works with developers to help address potential regulatory or scientific issues prior to the submission.

To date, most requests for help have come from solid dose drug firms looking to implement continuous manufacturing alongside existing batch processes.

The most notable project involved Janssen and Rutgers University, which sought input on plans to start making the HIV drug Prezista (darunavir) using continuous processes. The change was approved by the FDA in 2016.

But the emerging technology team is also ready to work with biopharma. The spokesman told us: “The ETT within FDA supports the adoption of innovative technology to modernize pharmaceutical development, which includes support for continuous manufacturing for biological products under BLAs regulated by CDER.”

He added that the support offered to biopharma will include assistance with continuous processes, explaining “the FDA supports implementation of continuous manufacturing technologies for biologics.

“In fact, continuous mode, or perfusion, bioreactor technology has been used in licensed biotech products such as enzymes since the 1990s.”

Biopharma interest in continuous manufacturing is growing says Doug Hausner, associate director industrial liaison at Rutgers University’s Engineering Research Center for Structured Particulate Organic Systems (ERC-CSOPS).

He told us: “The FDA has started to fund biopharmaceutical continuous manufacturing projects including one here at Rutgers that was funded at the end of last year.”

“I have also seen presentations on a number of BioCM systems that are setup within R&D in companies like Pfizer presented at IFPAC Cortona 2018” Hausner continued.

Regulatory innovation

The involvement of the emerging technology team is also part of a wider programme of support for the cell and gene therapy sector.

In January the FDA confirmed it was working on a raft of guidance documents on the subject, with topics ranging from clinical development through to manufacturing.

The FDA declined to share specific details – the spokesman told us the agency “cannot comment on additional guidance under development at this time.” Instead it provided an overview of the subjects being addressed.

“We are looking closely at steps that can potentially foster innovationntroduce advances in manufacturing and enforcement that can promote efficiencies that may help to address the challenges that arise in the development of safe and effective cell and gene therapy products.

“Challenges include complexities associated with manufacturing these products in a safe, reliable, and cost-effective way, and in a manner that allows for the efficient use of these products in the clinic,” he added.

The agency also acknowledged technology development is an iterative process that will involve both manufacturing expertise and awareness of market trends.

“We still have much to learn about how these products work, how to administer them safely, and whether they will continue to work properly in the body without causing adverse side effects over long periods of time” the spokesman said.

“In contrast to traditional drug development, when it comes to cell and gene therapies some of the more challenging questions relate to product manufacturing and quality, safety –  or questions about the durability of response” he said.