Digitization is a priority area for many cell and gene therapy firms but few have fully embraced the approach, according to Ori Biotech chief data officer Kevin Gordon, who says, “You see companies actively seeking to embrace digital (paperless) across multiple parts of their manufacturing process and only a few have truly gone paperless at this stage.”

In addition to Ori—which partnered with digital tech specialist Vineti in May—Gordon cites Lyell and Tmunity as rare examples of cell and gene therapy firms that have gone digital and fully eliminated paper records from their manufacturing operations.

“Tmunity’s paperless capabilities spanned both vector and T-cell manufacturing and proved massive increases in control and transparency into the manufacturing process,” says Gordon.

This view is shared by Jason Ramseth, chief product officer at cell and gene therapy software firm TrakCel.

“Digitization is not new to biopharma manufacturing, but much of that focus has been on simply taking people-oriented processes and controls and converting paper into electronic documents,” Ramseth explains.

The reason few firms have gone digital is partly to do with how the cell and gene therapy sector evolved, according to Gordon, who notes that the paper batch record has been regarded as the “source of truth” since the start of specialized therapies.

It also reflects the cell and gene therapy sector’s reliance on processing systems developed for the production of protein therapeutics.

“The equipment being used to manufacture these products is rarely designed or capable of directly connecting to a digital environment,” Gordon continues. “Many are not able to be networked and those that are have yet to embrace modern advanced digital manufacturing standards.”

Ramseth also cites the sector’s origins in the traditional drug industry as an issue.

“Given the regulatory environment and influence that big pharma has had on our industry, there is a logical and understandable tendency to revert to traditional and low-risk legacy processes and systems,” he tells GEN.

Solutions

The key to overcoming these challenges is to make a solid plan for going paperless, ideally with a demonstration phase, according to Gordon.

“It takes a solid proof-of-concept showing that a digital record will provide a more accurate source of truth,” he says. “A great example we have seen is a Certificate of Analysis (CofA) report out of LIMS. When you run it out of a digital system both QA and Regulatory teams have output they can consistently trust.”

The next stage is to choose digital technologies for process development, ideally those with commercial-scale equivalents.

“It becomes critical for biopharma companies to look at their process and equipment that may have worked in process development and how those tools would work at commercial scale.  They need to be planning for success early and pick devices and equipment that will allow them to work in a digitally integrated world right from the start,” points out Gordon.

“By adding a few key pieces into the heart of the manufacturing process you begin to break open the ‘black-box’ of manufacturing. Transparency into what is happening within a unit operation in real-time is eye-opening. Once manufacturing teams can see what is happening in a process step and they know that information is immutable, they trust it and can start to look for more opportunities across the enterprise.”

Connectivity

The final—and perhaps most important factor—needed to increase use of digital manufacturing in cell and gene therapy production is demonstrating that the technology is trustworthy.

Gordon says it is critical that devices in the heart of the manufacturing process can see and speak with the internet.

“By connecting to the outside world and relying less on local data centers, integration becomes easier, updates come more easily, and thinking about this process end-to-end becomes a viable option,” he explains.

Fortunately, Gordon says, new technology is not needed as every other major industry has adopted these tenants, even in highly regulated industries like the banking sector.

“What is needed is either a maturing or replacement of the equipment needed to run the unit operations with digitally native pieces. As this progresses, the regulators and QA/QC teams will be able to see that with more real-time information they can have more control, higher visibility, and a much deeper level of comfort that what the final records say for each process match what happened,” continues Gordon.

For Ramseth, collaboration is also important to the adoption of digital manufacturing.

“There is no doubt that we are scratching the surface in terms of the impact that digitization and automation can make on our biopharma industry and best practice sharing, standardization, and industry consortiums/working groups are a good way to incubate and accelerate this thinking,” he tells GEN.