Commercial scale is not far-off for advanced therapy medicinal product (ATMP) facilities.
Cell and gene therapy research has made massive strides recently: the number of products going to clinical trials has skyrocketed, and 17 total products approved by the FDA. Most importantly, patients can’t wait any longer.
The ATMP industry needs to be ready to go big with production. But that comes with challenges—primarily that this fledgling market is heading into the unknown. A model for ATMP production at large-scale does not exist. The labor model and process—which is largely open and manual—is difficult to scale. And most likely the technologies or equipment that will make ATMP production feasible at commercial scale haven’t been invented yet.
However, all this uncertainty is not an excuse to delay planning for increasing your production scale. Despite the unknowns, there are plenty of decisions and plans you can build into your current operations and processes to prepare for the future. And it’s best to start during the preclinical testing phase when you’re still flexible.
The challenges of commercial-scale ATMP production
The crux of the problem is that in the clinical phase, where many ATMP companies are today, the goal is investigation and discovery. You want and need flexibility, so the process is open and operator driven. But those enabling factors at small scale will limit you as you scale out.
If the process stays operator-driven, it will require a facility that can accommodate a significant increase in personnel—and that doesn’t just apply to the labs/manufacturing spaces; it’s the breakrooms, meeting spaces, parking lots, etc. The facility footprint and the cost grow exponentially.
Additionally, if the process stays open, it further increases your cost while limiting your functionality and productivity. You’re looking at multiple clean rooms with transitional airlocking space and QC labs, which are costly to construct and maintain. And the process of moving products through the spaces becomes cumbersome.
Ideally, you overcome many of these challenges by shifting from an open, operator-centric process to closed and automated. Of course, where that’s not possible, pre-planning can smooth the path for you down the road. If you have ingenuity, time (because you started planning early) and these five considerations, you will be prepared to successfully scale up your ATMP production when that eventuality comes.
5 considerations to plan for a commercial scale ATMP facility
A solid plan today for your ATMP manufacturing needs in the future will help you achieve a resilient, flexible and future-proof CGMP biomanufacturing facility that helps save lives.
Plan early, with the end in mind, or you could face a costly retrofit later.
1. Evaluate all decisions from a “closed, commercial-scale” mindset
Even if you can’t yet see how your process will become closed and commercial scale, assume it’s coming. The technologies that automate and isolate ATMP production are a matter of when, not if, so make decisions that allow you to implement them in the future. This applies to both the granular and higher-level considerations. If you’re purchasing new flasks for R&D activities, look for ones with a correlative designed to work in a closed system. Alternatively, purpose-built isolator technology will reduce the need for massive clean rooms, transitional airlocks and unidirectional flow systems. This opens space in your facility—what will you use it for?
2. Look for new tech now and opportunities to integrate automation into your ATMP facility
While you’re planning for future automation and closed processes, keep an eye on what technology is currently available or what’s coming soon. Your process is still malleable at this point, so now is the perfect time to find opportunities to incorporate technology and work toward a fully automated system in the future. Think outside of your production here, too. QC testing and warehousing are two prime candidates for automation. It can ease bottlenecks, reduce head-count and increase efficiency.
3. Determine if there are parts of your process that can never be closed
Discovering that a part of your process can never be closed is immensely useful when done early. While your process is still flexible, you can plan around those open elements.
4. Adopt systems that integrate vertically
You can expand your pipeline without expanding your ATMP facility footprint. Especially if you have relatively modest biosafety level (BSL) requirements, you can design your facility with a large ballroom operating area and vertically integrated workstations. Each workstation can be equipped with everything needed for a closed process. Not only does this save time and the risk of contamination, but by stacking these stations, you also save valuable space in your facility. This allows you to increase production without spreading out.
5. Forecast requirements for segregated personnel, materials and waste flows and full-room fumigation at commercial scale
Finally, if you can’t vertically integrate with closure and automation, you can plan for what you will need when your scale increases. This means evaluating your segregated personnel, materials and waste flows, as well as functionality for full-room fumigation. And while segregation of personnel, materials and water may be required, room fumigation is not, so it becomes a business decision that will need to be incorporated into your plans early. Examine these factors down to the quality of the construction and the door seals. When included in the initial design, these details can make a difference in the transition to commercial scale.
All these factors contribute to developing “a commercial state of mind,” or being open to possibility rather than a fear of uncertainty. Because that’s what commercial-scale ATMP production is: an opportunity to innovate and provide more treatments to more patients. Embrace the unknown, pursue technological innovation and design your ATMP facility to be agile and efficient, while leaving room for the future.