Successfully automating a cell therapy manufacturing program requires flexibility, process understanding, and collaboration to push boundaries and unlock new possibilities. During our breakfast briefing at the 2024 Phacilitate Advanced Therapies Week conference, our moderator Michelle Duquette, PhD, along with our panelists Robert Tressler (Excellos), Matthew Hewitt (Charles River Laboratories), Emily Titus (Notch Therapeutics), and Thorsten Gorba (Aspen Neuroscience) explored considerations for making the transition to automated systems and how collaborative partnerships can assist in navigating this path.
Continue reading for some of the key highlights we covered in this session titled “Bridging the Gap: How Innovation-driven Partnerships Fuel the Pace of Cell Therapy Manufacturing Development.”
Transitioning to Automated Systems
We explored the driving factors for transitioning to automated systems at different stages of the development journey and how the decision is made on what approach to take. Emily Titus highlighted that for Notch as an early-stage company, they need to balance the priority of getting to the clinic quickly to gather first-in-human data, while also considering the long-term scalability of the process. She emphasized the importance of surveying the process and evaluating each unit operation for its effect on the biology of the cells being produced and using that to prioritize which solutions to invest in early on, to build a process that can scale and have longevity.
Thorsten Gorba mentioned that when they made the decision to close, scale and automate their autologous IPSC derived cell therapy process, they explored solutions and providers before concluding that there was nothing readily available that was going to meet their needs, especially given required cell counts are in the millions, not billions. They opted to take a more creative approach by partnering and co-investing with an early-stage company because it was the only way to develop the custom solution they needed for their autologous therapy. Michelle Duquette followed up by asking if other autologous cell therapy manufacturers might be finding themselves in a similar situation where off the shelf solutions don’t fit them. Thorsten commented that outside of CAR-T and immuno-oncology there aren’t a lot of off-the-shelf options that are a good fit, even if you aren’t producing at a smaller scale like they are. Emily chimed in that the reprogramming with the IPSC is the one step they wouldn’t automate since they only have to do it a couple of times. It is really the scale-up of the drug product manufacturing that is the bottleneck.
Rob Tressler emphasized the importance of engaging with clients on the scientific and technical levels of process development to optimize the product for the patient. He cautioned that automation should not be implemented for the sake of automation itself without rigorous assessment of the different systems and platforms being used. Rob stressed the importance of evaluating the impact of automation on cell potency and product variability. “We need to think about if we are helping the cells or hurting the cells,” he said. He also discussed the need for novel approaches and continuous innovation to improve the efficacy of these therapies. Excellos uses a mix of standard platforms and custom approaches they tailor to the clients’ needs and that they think will allow their clients to succeed clinically.
Balancing Standardization and Customization
Matt Hewitt discussed the delicate balance between innovation and standardization in manufacturing processes. He highlighted the challenge of standardizing too much, as it can limit innovation and confine companies within a narrow framework. Instead, a balance should be struck between off-the-shelf and customized solutions, with a pragmatic approach to manufacturing. Hewitt also stressed that the market penetration of cell therapies is primarily limited by the number of batches that can be produced, rather than patient adoption. He believes we can innovate our way out of this and there isn’t just one solution but multiple solutions available. The application of modular systems was also mentioned, with an emphasis on analyzing process fit for purpose and selecting the most suitable approach for each specific process. Hewitt believes that finding the right balance between standardization and customization is crucial for enabling sufficient scale in the production of cell therapies. He advocated for a case-by-case evaluation of each unit operation and a deep understanding of the cell product before adopting standardization or customization of the unit operation.
Making the Case for Automation Investment
A question from the audience on how to balance investment and making the case for automation prompted an interesting discussion on how to manage this. Emily shared that they have looked at some different avenues for investment including government grants and other programs.
Matt commented that one of the key drawbacks with any automated piece of equipment is there is no true scaled down PD versions and the costs to run the available equipment can be prohibitive for start-up companies. We need some simplified PD versions that still have the major characteristics of the GMP versions so that we can do process development, Design of Experiments (DOE), etc.
Collaboration and Flexibility
During the entire session, the panelists highlighted the importance of collaboration and flexibility in cell therapy manufacturing. They emphasized the benefits of working together to achieve the best outcomes. By collaborating with partners, organizations can leverage their expertise and access the necessary resources to drive innovation and overcome manufacturing challenges. Emily Titus highlighted the need to balance the urgency of getting to the clinic with the long-term scalability and sustainability of their manufacturing process and working with internal and external groups to accomplish this. Thorsten Gorba shared the approach for their autologous therapy and how they are working together with their partner and co-investing in order to develop a very custom solution to meet their needs. Rob Tressler emphasized the importance of mobilizing and actively supporting therapeutics companies in this space. Matt Hewitt talked about how they work with their clients to determine the best path forward and fit for each process, and the importance of balancing standardization and customization.
The panelists also discussed the need for flexible and adaptable platforms that can scale to meet the growing demands of cell therapy manufacturing. By considering scalability early in the process and fostering collaborative partnerships, organizations can ensure they have the flexibility and adaptability necessary to succeed in the rapidly evolving field of cell therapy manufacturing.
Participants:
Michelle Duquette, PhD, Chief Scientist – Cell Therapy at Invetech (Moderator)
Rob Tressler, Chief Scientific Officer of Excellos
Matthew Hewitt, Vice President, Technical Officer CGT & Biologics at Charles River Laboratories
Emily Titus, Senior Vice President at Notch Therapeutics
Thorsten Gorba, Vice President of Process & Analytical Development at Aspen Neuroscience
