Cell therapy manufacturing is the process by which a cell therapy medicinal product is created. This includes the process to isolate, modify, grow, formulate, quality test and store cells for clinical and commercial use.
Your manufacturing approach is not like classic biotech. You can’t leverage the economies of scaling up; because of your small batch sizes (sometimes as small as one patient, in the case of autologous therapies), you can only scale out.
That means duplicating your cell therapy manufacturing process, along with every inefficiency lurking within it. A highly classified background, an idle piece of equipment, a labor-intensive cleaning regimen—these challenges may not seem prohibitive in the lab, but they can mean the difference between success and failure at commercial scale. This is especially true as the marketplace around you grows more crowded and competitive; last year alone, the number of cell, gene, and tissue-based developers in the world grew by almost 20%.
But focusing on the most efficient manufacturing approach won’t solve everything, either. You need to consider other factors as well, such as your tolerance for risk, your capital spending goals, and your expectations for future growth. Identifying and tailoring an approach that balances all of these considerations is the key to meeting your manufacturing goals.
The four cell therapy manufacturing approaches are dedicated rooms, chasing workstations, segregated unit operations and an emerging option called process-in-a-box systems.
In this approach, a single cleanroom is dedicated to one product batch for its entire lifecycle. Each room features a Grade B background with open processing done in biosafety cabinets. Operators follow the rigorous gowning, cleaning, and environmental monitoring protocols necessary to support such highly classified spaces.
This approach may suit your operation if:
Challenges to consider:
This ballroom approach features workstation types that are each designed for a single step in the process. Based on the length of each step and the number of batches necessary to meet their throughput goals, manufacturers can calculate how many they need of each workstation type.
This approach frees manufacturers to optimize the occupation schedule of shared equipment, particularly for processes that take several days to move from initial steps to final form/finish. For example, once operators move a batch from manipulation equipment (such as a cell separator or electroporator) to growth promoting equipment, they can prep and redeploy the manipulation equipment for another incoming batch; it doesn’t need to sit idle, waiting for the return of its dedicated batch.
Of course, this level of optimization and process intensification is favorable purely from an efficiency perspective. However, manufacturers must weigh the risks of relying on shared equipment.
This approach may suit your operation if:
Challenges to consider:
How one cell therapy pioneer uses large-scale isolators to manage contamination risks and improve their flexibility and cost control.
Cellectis, a biopharma pioneer with a pipeline of gene-edited allogeneic CAR T-cell immunotherapies in development, recently launched a new clinical and commercial production facility.
The cell therapy manufacturing strategy behind their new facility is based on two guiding elements:
1. Small batch sizes: Each batch produced in the new facility targets just three or four patients.
2. Low-risk tolerance: Cellectis prioritized risk management as a top driver for this capital project. Its goal was to eliminate the possibility of cross-contamination while designing as much process flexibility and efficiency into their facility as possible.
How they put this strategy into action:
To understand the teams’ approach, consider taking the “chasing workstations” manufacturing philosophy and fitting it inside a large-scale isolator. In this way, the isolator replaces the highly classified cleanroom environment; product batches move from one open process workstation to the next inside the isolator’s sterile environment, which unlocks all the efficiencies of “chasing workstations” while eliminating almost any risk of environmental contamination.
This strategy resulted in a facility that features two such large-scale isolators, each in its own suite (with room for expansion). The facility was designed with ample flexibility to accommodate operations that can’t take place inside the isolator (such as process steps that rely on large equipment). In those cases, operators can remove the batch, perform any necessary manipulations inside a closed system, then return the batch to the isolator.
Why this approach suits Cellectis:
Challenges we considered:
This approach combines elements of the first two layouts. Product batches move between higher- and lower-classified spaces as the process unfolds. Open process steps are contained to dedicated suites with a Grade B background, while operations that leverage closed processing equipment take place in a more cost effective, lower-classified ballroom-style space.
This approach may suit your operation if:
Challenges to consider:
An end-to-end, single-point, automated process-in-a-box platform will resolve most of the challenges explored above and radically change cell therapy manufacturing.
The idea is to take the concept of a product-dedicated suite and apply it to a fully closed piece of equipment. That all-in-one piece of equipment removes the risk of the cleanroom and opens the door to a leaner labor model, greater quality control, and virtually no risk of contamination.
From a facility perspective, this concept is game-changing. Rather than building, validating, and maintaining whole cleanrooms, it’s possible that manufacturers could contain their process-in-a-box system inside small-scale, fit-for-purpose environmental chambers. This would open the door to a whole different kind of manufacturing space—one that features densely stacked, fully closed systems inside a warehouse or a hospital wing, with no need for the traditional cleanroom.
This approach may suit your operation if:
Challenges to consider:
No two manufacturing strategies are the same. Each unique approach requires significant time and expertise to get right. But from a high-level perspective, a few generalizations emerge that may help you begin to consider your own unique approach:
Every cell therapy manufacturer balances risk, efficiency, and cost control differently, but those who will succeed as commercial-scale manufacturers share one common value: they strive to make their facilities work as hard as possible by designing flexibility into every square foot.
Whether you pursue a network of product-dedicated cleanrooms run by a large workforce or a warehouse densely stacked with automated cell processing systems, the best approach is a versatile one that will help you to stay ahead of changes in your portfolio, your process, and the technology that’s available to you. By designing a facility that’s ready for future flexibility, you will be better positioned to continuously optimize your footprint, control your operating costs, and deliver a new generation of therapies to the patients who need them, rapidly and reliably.
Reach out to discuss your project, and how we can help tailor your unique manufacturing approach.
How the ATMP and cell and gene therapy industries can prepare to scale manufacturing operations safely, sustainably, and strategically.
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