By Sanjin Zvonic, PhD, Director, Technology & Business Development
If we look back at our chart of the resource demand as we move through the phases of development and commercialization, we can see that direct delivery will be more resource intensive than the so-called “ideal scenario,” and multi-step delivery somewhat less so. So, multi-step delivery offers a potential advantage in terms of overall resource demand.
Resource Demand During Commercialization
Delivery as an Extension of Manufacturing – The Multi-Step/Centralized Hybrid Delivery Model
Practically speaking, due to the limitations inherent in each delivery type, neither provides an opportunity to develop true economy of scale or the operational parameters required for commercial viability and marketplace acceptance of a CTP. Thus, a model that would combine the upstream advantages of multi-step delivery with the downstream efficiency and risk reduction of the direct delivery would be ideal for commercial CTPs. We have to look at delivery as an extension of manufacturing, in the context of point-of-care versus centralized manufacturing. Shifting as many of the multi-step delivery activities as possible back to a manufacturing site (or a limited number of sites) further reduces clinical-end resource requirements and mitigates clinical site risks. In this case, large lots of centrally-manufactured CTP can be stored, processed and then formulated on a per-patient basis prior to shipping to the clinical site for administration. This would provide the ideal commercial solution.
If we start by considering the multi-step/point-of-care hybrid delivery model, the CMO will provide the shipping, allowing for on-demand capacity, validated systems, in-house trained staff, and in-house Quality oversight. However, as the other steps are carried out at clinical sites, the demands on those clinical sites still remain extensive. The developer must ensure capacity for each activity, implement multiple validated systems, place and maintain trained staff for multiple functions, and place and maintain Quality oversight and compliance for multiple functions, all at each site providing the therapy.
Alternatively, with the multi-step/centralized hybrid model, the requirements at the clinical sites are greatly reduced. The developer only needs to ensure capacity for limited activity, implement a limited number of validated systems, place and maintain trained staff for a limited number of functions, and place and maintain Quality oversight and compliance for a limited number of functions at each site. All of the steps of the process are handled by the CMO up to receipt and administration of the cell product at the clinical site.
Thus, we believe that (in most situation) a multi-step delivery process will yield lower overall resource demands than a direct delivery process. If we further extend this model to a multi-step/centralized hybrid model, using a CMO will further reduce resource demands, providing a greater advantage to the cell therapy development company.
Resource Demand During Commercialization
Conclusion
Overall, delivery can have a direct impact on the top 5 unanticipated commercialization obstacles mentioned earlier. Controlled and consistent delivery is crucial for product quality, consistency and efficacy. The delivery method utilized can have a significant impact on the resources and cost associated with controlling delivery, thus directly affecting the clinical and commercial success of the product.
At PCT, we have successfully implemented this approach and are currently enabling it in an active clinical trial. The inventory of the CTP manufactured on a campaign basis is stored and later formulated at our manufacturing site, followed by delivery as individual doses on a per-patient basis. The key to the success of this project is the fact that the CTP manufacturing process and final formulation/stability are amenable to the hybrid delivery approach because the CTP was developed, from early stages, with this crucial consideration in mind.
After more than 12 years of operation and working with more than 100 clients, our team has learned how critical it is to build CTP processes and products with commercialization in mind, and thus our expertise in this regard is invaluable. This is one important message and lesson that we continue to pass on to our clients at any stage of CTP development in which we are fortunate enough to be involved.