Requiring Refinement and Control of Complexity and Cost
Affordability and accessibility are critical factors for commercial success of next-gen therapies; however, greater industry collaboration is needed to reduce inefficiencies in the development of advanced technologies.
Next-generation therapies are offering new hope to patients with unmet clinical need around the world; however, approaching the development and manufacture of these complex, novel modalities can be fraught with obstacles. To learn more about the challenges of developing and manufacturing next-gen therapies, how advanced technologies can help to overcome these hurdles, and the importance of flexibility and collaboration, The Pharma Navigator chatted with Jon Ellis, CEO Trenchant BioSystems.
Two Main Challenges Remain
TPN: Could you give an overview of the specific challenges pertaining to the development and manufacture of next-generation therapies?
Ellis: Within the industry, two main challenges remain: manufacturing complexity and cost. Next-generation therapies will not be commercially viable unless they can be made more affordable and accessible.
As a greater understanding of product characteristics that drive clinical efficacy develops, there will be a need to further refine and control them in both autologous and allogeneic settings. A lack of integration of quality control assays with manufacturing often prevents capture of real-time data, inhibiting data-based manufacturing decisions.
Optimizing Processes
TPN: How can advanced technologies help to overcome these development and manufacturing challenges?
Ellis: New technologies that can further refine cell populations to a more defined phenotype will help control variability for autologous products and enable greater characterization of allogeneic products, ideally though sequential, or multi-parametric selection at clinical scale.
Automation of manufacturing is essential to reduce both cost and complexity through simplification of training and a reduction in operator interactions. This enables greater output in a centralized manufacturing model and makes decentralized manufacturing feasible.
Integration of analytics with manufacturing platforms will enable optimized manufacturing processes through usage of real-time data and capture within the batch record.
New Tools Are Needed
TPN: Are there any potential areas where advanced technologies are not yet suitable for use or where further development is needed?
Ellis: Most recently, new manufacturing platform technologies have been bioreactors with few new platforms across the rest of the unit operations. Cell selection, gene modification, and formulation and fill operations need new tools to ensure consistent performance and a reduction in COGs [cost of goods]:
· New cell selection tools should be capable of improved recovery and purity performance and sequential selections.
· New platform technologies to enable non-viral delivery of cargo should be capable of high efficiency and without cell toxicity. The ability to achieve both high efficiencies, without an impact on cell viability, and achieve scalable performance has been a challenge for many existing tools.
· Fill/finish platforms should be capable of filling bags and vials with variable volumes, control cell concentration and volume, fill within an acceptable timeline to minimize cryoprotectant toxicity, and all operate as a closed system.
Accommodating Variability
TPN: Why is flexibility particularly important for the increasingly complex development pipelines? How can advanced technologies help with this aspect?
Ellis: Cell therapy clinical approaches vary in terms of starting material, therapeutic cell type, dosing regimen, and gene modification methodology. Advanced technologies must have adequate flexibility to accommodate such variability and ensure scalable performance from pre-clinical development through to commercial manufacturing. Being able to leverage one platform technology or process for an entire clinical pipeline will reduce the cost and timeline of development.
Collaboration Can Streamline Progress
TPN: How are CDMOs utilizing advanced technologies to drive forward innovation in next-gen therapies in your opinion? Does more need to be done?
Ellis: CDMOs are looking to differentiate from one another due to current over-capacity in the industry and are well placed to assess new technologies due to their experience across a range of manufacturing processes and technologies. Development of new technologies could be streamlined by collaboration between technology companies and CDMOs to ensure new platforms meet technical and functional requirements. Collaboration across the industry to share knowledge and non-proprietary data would reduce inefficiency.