Building A Fit-For-Purpose, Strategic Cell & Gene Production Facility

By Life Science Connect Editorial Staff

Choosing to build a manufacturing facility as a small or mid-size biopharmaceutical company hinges on a highly individualized evaluation of an organization’s resources and needs. For many, the benefits of pursuing an in-house facility – complete control over production, coupled with long-term cost savings – make it an attractive option. By employing flexible and sustainable design strategies and best practices, combined with contingency planning based on current market conditions and exit strategies, companies can make building their own facilities a reality.

In a recent Cell & Gene Live event, Cell & Gene chief editor Erin Harris spoke with experts from two such companies, who shared their experiences with establishing state-of-the-art manufacturing facilities in a competitive and shifting market. Speakers for the event included:

• Will Junker, head of vector manufacturing quality, Kite Pharma
• Mitch Lower, senior vice president of technical operations, Kriya Therapeutics

In 2021, Kriya completed renovations on a 51,000 square foot facility in Research Triangle Park, North Carolina, focused on cGMP production for its pipeline of gene therapies. Kite Pharma, which has commercialized both Yescarta and Tecartus, has likewise established cell therapy manufacturing sites in California, Maryland, and Europe. Together, the pair explored the challenges that accompany this pursuit, which requires a thorough understanding of the demands of cGMP production, compliance, and regulatory considerations, among other variables.

Location, Location, Location: Choosing Where (And How) to Build

When it comes to deciding how to approach in-house capabilities and infrastructure, the first consideration for any cell and gene therapy company is patient access. For Kite, this meant having the partnerships in place to locate centralized facilities and be able to transport samples and finished therapeutics between the more than 500 oncology centers it works with. “The supply chain part between the hospital and the facility is always the top consideration,” Junker said. “Do we have access to an airport? How long will cells that we harvest from a patient be in the air before they reach our facility, and how long will they be in the air after the cryo-preservation, after manufacturing processes, until they go back to that treatment center and reach the patient?”

Ultimately, Kite elected to locate its facilities near airports in order to maximize this patient access. Ensuring this access can also influence the type of build an organization pursues. According to Junker, taking a “prefabricated pod approach” to building can offer organizations more flexibility to change or expand a space to accommodate different therapeutics or processes. This approach is even more flexible if employed in combination with a new build. “If you decide to have a brand-new building, Greenfield – we did that as well – and configure it internally with whatever suite configuration you want or you need,” he explained. That option is going to take a little bit longer, but it gives you a higher degree of fit-for-use if you want than working with prefabricated pods, due to the fact that you have control over the space.”

The necessary clean room classification for an asset’s manufacturing process likewise has a significant impact on facility design: everything from floors to surfaces to ceilings is influenced by ISO classifications. These considerations should be balanced by those pertaining to the needs of personnel,, as the elements ranging from the flow of a facility to its aesthetics can influence operators’ efficiency and effectiveness. “For us, it was important to have daylight available and for it to be as pleasant an environment as possible for our operators,” adds Junker. In order to achieve a qualified environment, organizations must balance a facility from an air handling perspective and evaluate a containment strategy holistically rather than looking at GMP classification in general. “Your rooms are all very small, so this is a lot of air handling capacity that you need to provide for that. Again, every room, every suite has their own air handler and complete air supply segregated from every other suite,” he explained. “Those are really considerations that drive your construction schedule in a much different way than when you go and have a bioreactor hall and a purification suite for a recombinant product.”

The Right People: Who (And When) To Hire

Considerations surrounding where to build a facility go hand in hand with staffing it. According to Lower, one of Kriya’s first hires, establishing the company culture early is key to informing subsequent growth. “We spent quite a bit of time thinking through what kind of phenotype of employee we needed to support that culture, and then we leveraged our networks to sort of target individuals we felt had that phenotype and could really step into the culture that we created,” Lower said. For early startups, this often means starting with additions who can wear multiple hats, as many of the business and technical processes are either underdeveloped or nonexistent. “It meant bringing in people who can step from whatever the fire of the day was into the next one.”

Lower noted that there is no longstanding experience surrounding these therapies in the industry yet, making it important to secure access to personnel or a partner with related commercial experience early on in your planning. “Much of [the cell and gene space] is academic still and people are sprinting these assets forward, not really thinking about the industrialization side of this,” he explained. To encourage a more long-range view of its business, Kriya made efforts to secure both those with a strong biologics operations background and those with significant gene therapy expertise. “So people with really broad experiences across different modalities, different phases, even different scales.”

Even with all of these variables in place, organizations should be ready to encounter challenges that force them to reevaluate or revamp their approaches. “We course-corrected maybe a year or two ago, really focusing on the manufacturability of our product,” Lower said. “There's not a lot of experience in looking at a research grade material and saying, can I manufacture that at scale? So we have now built a team earlier to provide manufacturability assessments before programs leave research, and that really set us up for success down the road.”

Conclusion

Ultimately, the small-scale, in-suite processes that typify advanced therapy modalities require operators that possess significant expertise, which can drive costs and result in scarcity, depending on where a facility is located. Supply chain accessibility is another factor that can be highly influenced by location. Other considerations, such as whether a facility is a new build or renovation, a Greenfield or Brownfield development, can also impact this assessment. Building a facility the right way has the potential to help accelerate manufacturing, affording companies greater control over processes and timelines. “[When we started], there was very little innovation in the industry, and so if you think about trying to really drive down cost of goods, which was part of our mission and the timeline by which we were trying to do it, there really was probably not an external channel that would've achieved that,” Lower said.

Understanding how things will look under the payer model is likewise crucial. For autologous therapies like the ones produced by Kite, the overhead costs and demand forecasting needed to operate effectively necessitated establishing an early understanding of how and where insurers will pay, as well as how an organization can work with hospitals and providers to get a clearer picture of demand. “With more patients, you drive the cost down a little bit, but you still need to operate your facility,” Junker said. “You need to have your operators, your personnel available, your staff available, and you need to manage all this. You need to have the full breadth of a biopharmaceutical operation to support all the way from R&D through the tech ops part as well as commercial – everything. Everybody is part of that overhead.”