Sponsored content brought to you by

For cell and gene therapy developers racing toward the clinic, manufacturing decisions made early can have consequences years later. One of the biggest traps is assuming processes can be standardized across products, says Pratima Cherukuri, general manager and senior vice president of plasmid DNA at Bionova Scientific.

“It’s not building with Lego blocks,” Cherukuri says. Unlike monoclonal antibodies, cell and gene therapies involve highly complex biological systems, meaning a manufacturing process that works for one product may not translate neatly to another.

That complexity makes it important to think about commercial manufacturing long before commercialization is imminent. In fact, Cherukuri says developers should begin considering it while planning clinical supply. Waiting until later to change a process can cost millions of dollars and introduce significant delays.

Early questions should include the potential patient population, anticipated dose, and whether the process can scale to meet future demand. A process developed for Phase I might produce enough material for a small trial, but that does not mean the same equipment or approach can support Phase III or commercial production.

Cherukuri believes that process development should focus on reaching the target manufacturing scale as efficiently as possible. Adding intermediate development stages without a clear technical rationale can increase complexity, require additional process optimization, and extend both timelines and overall program costs. “Things like that need to be considered early on,” she says.

Analytics and partnerships

Analytics deserve the same attention. “Your process is as good as your analytics,” is a principle that every experienced cell and gene therapy developer has come to appreciate, Cherukuri says. If analytical methods are not sufficiently robust, developers might struggle to determine whether a manufacturing failure reflects the process itself or the way the product is being measured.

The programs that move most smoothly, therefore, have a clear understanding of their process, analytical methods, and eventual scale. Ideally, sponsors also arrive at their first CDMO (contract development and manufacturing organization) conversations with an understanding of all of these features of developing and producing a product.

Not every emerging biotech will have those answers. For first-time developers, the CDMO might need to play a larger role in defining a practical development path that accounts for both scientific needs and available funding.

That requires a genuine partnership. “It can’t be, ‘Well, this is the program. I give it to you. Make it work,’” Cherukuri says. Nor should a CDMO operate as a “black box” that takes custody of a program and only reappears when the product is ready, or even worse, when it has failed specifications.

Instead, both sides need transparency around risks, timelines, and goals. Early engagement can also be structured around stages, allowing developers to test and refine a process at smaller scales before committing to larger-scale development and GMP manufacturing.

Managing the market

The changing plasmid DNA market makes that flexibility particularly important. Demand from traditional cell and gene therapy programs has moderated, while mRNA development has taken a larger share of the market. Those programs can require smaller quantities of plasmid DNA but place greater emphasis on quality because plasmid DNA sits closer to the final mRNA product.

Looking ahead, Cherukuri expects pressure across cell and gene therapy manufacturing to focus on reducing cost of goods and accelerating timelines. For plasmid production, new approaches could also reshape manufacturing. Bionova, for example, is exploring cell-free plasmid production alongside technologies designed to reduce endotoxin and residual impurities.

For emerging biotechs, however, Cherukuri’s advice comes back to the beginning: design the right plasmid for the target biology and engage manufacturing expertise early. “It can be a stepwise partnering,” she says. “You don’t have to sign a full development-to-GMP program.”

The important thing is to start planning before early manufacturing decisions become expensive commercial problems.

To learn more, visit www.bionovascientific.com.