Reducing the Manufacturing Costs of Allogeneic Cell Therapies

By Erin Harris, Editor-In-Chief, Cell & Gene
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On the heels of our second Cell & Gene Live event sponsored by Invetech, Can Innovation Drive Down Cell Therapy Manufacturing Costs?, I brought you up to speed on ways to drive down the cost of manufacturing autologous cell therapies as explained in the event. Here, we focus on the strategies that can reduce the manufacturing costs of allogeneic cell therapies.

Our discussion featured Dr. Mark Gilbert, SVP of R&D of Acepodia; Thomas Lequertier, Head of Cell Therapy Manufacturing Unit of Celyad Oncology; and Ludek Sojka, Ph.D. Chief Technology Officer of SOTIO who agree that for allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes must be addressed. For example, cost of goods sold can be significantly reduced via true end-to-end automation enough to minimize the theoretical price gap between autologous and allogeneic cell therapies because labor costs will be reduced. The highly specialized nature of the field requires ongoing workforce education and training that currently hikes up costs. “End-to-end automation is a must, because as of now, we need extensive labor to deliver the therapies,” explains Lequertier. Dr. Gilbert explained the following regarding autologous applications, but the same holds true for allogeneic therapies: “It is not easy to identify and recruit skilled technicians; and that has to change if we want to manage more than a several hundred thousand patients per year.”

Automation for Allo

In addition to labor cost reduction, automation has the potential to pave the way towards commercialization and mass production as it has been the case for many production industries. According to McKinsey & Company, allogeneic CAR T-cell procedures can provide several significant advantages in manufacturing, including reduced cost of goods sold; a simplified supply chain; and avoidance of issues with autologous CAR T-cells in harvesting, product variability, long vein-to-vein time, and T-cell dysfunction. Allogeneic T-cell therapies are moving toward late-stage clinical trials and commercial registration with the promise of having these breakthrough therapies available for market launch.

To strengthen and speed up the development of this commercial allogeneic process platform, Cell & Gene Live panelists corroborated the importance of establishing collaborations with external service providers to develop and integrate advanced technology that will provide solutions for today’s cell therapy manufacturing challenges. Indeed, industry partners in manufacturing automation that transition cell-based therapies to commercial-scale manufacturing also understand the same to be true. “Allogeneic therapeutic products by nature require manufacturing systems that can handle large volumes, increasing the cost of production,” says Anthony Annibale, Global VP, Commercial, at Invetech. “By using a combination of off-the-shelf manufacturing modules and configurable platforms, allogeneic therapeutic developers can minimize tech transfer costs as their manufacturing needs evolve from process development to GMP-scale.”

Optimize Quality Control

To capitalize on the simplified logistics, time to delivery, and reduced cost of off-the-shelf approaches, the industry must optimize quality control to achieve long term stability at high yields and high efficacy. Off-the-shelf therapies enable immediate treatment — unlike CAR-T patient-specific manufacturing — and can enable treatment everywhere from outlying hospitals and clinics to large medical centers. According to the National Center for Biotechnology Information, allogeneic stem cell therapy, for example, offers advantages over the autologous counterpart. The stem cells are derived from young healthy donors, eliminating any co-morbidities associated with disease states. Allogeneic cells grown and kept in stem cell banks are available for immediate delivery. Biopharmaceuticals, such as monoclonal antibodies (mAbs), have benefited from the availability of large-scale bioprocessing technologies and the associated economies of scale. However, this is not currently the case for allogeneic cell therapy manufacturing due to the inherent complexities of manufacturing living cells as the final product.

As allogeneic therapies mature, creating a mature manufacturing industry will be essential. Where suitable, adapting strategies and hardware from bioprocessing and other manufacturing industries will accelerate progress in cell therapy. In some instances, gaps remain that will necessitate new technology development. Achieving faster and cheaper cell therapy manufacturing will also require much closer cross-disciplinary working to realize efficiencies. Making manufacturing more consistent, reproducible, and automated will lower the cost substantially. And, as new pathways to cell therapy manufacturing emerge, technology developers will play a critical role in ensuring integration solutions keep up with clinical developments.

Planning Manufacturing Systems that Grow with Your Cell and Gene Therapies

By Marisa Reinoso, Sr. Product Marketing Manager, Cell Therapy, Invetech

Cell and gene therapies (CGT) have the potential to reduce total disease costs by 18-30%, amounting to an aggregate cost savings of more than $33B over 10 years.[1] If the industry is able to reduce the costs of manufacturing, these savings would increase significantly.

CGT manufacturing requirements evolve from pre-clinical to clinical and commercial development, often significantly escalating costs at each step. There is universal agreement in the industry that closing, integrating, and automating manufacturing operations can drive significant cost reductions. Consequently, for most CGT manufacturers the question is not whether to close and automate, but rather when and how. What does an optimal manufacturing roadmap look like? How do you balance manufacturing flexibility with robustness and cost-effectiveness?

Planning for integration and automation in your manufacturing processes as therapeutic demand increases is a good way to manage the high costs of cell therapy manufacturing. This also helps to manage your changing needs for flexibility, scale, and robustness.

The industry is in urgent need of a range of stand-alone modules to automate the performance of unit operations reliably.[2] These stand-alone unit modules also need to be interconnectable, so that CGT manufacturers can connect them as scale demands increase. By having stand-alone modules that can be integrated, cell therapy manufacturers can have both the flexibility to optimize unit processes, and the automation and robustness that is needed with larger scale production.

Currently, the industry does not have a broad menu of systems or modules capable of executing manufacturing operations that support integration. A practical approach is to use a combination of off-the-shelf manufacturing modules, configurable platforms, and a process-specific integration strategy to support progression from process development to GMP manufacturing and ultimately to commercial scale manufacturing. The key is to carefully evaluate and select-off-the shelf technology that can be incorporated into future robust, configurable systems when your demand increases.

This approach can minimize tech transfer costs, because by integrating modular units into a configurable system, the risk of additional qualification and validation studies is minimized as your process scales. By selecting off-the-shelf unit modules that can transition to integrated manufacturing systems, CGT manufacturers can set their manufacturing roadmap to incorporate a high level of flexibility while remaining cost-effective.