Unlike traditional pharmaceuticals, cell therapy products (CTPs) require geographically dispersed networks of cell/tissue collection, manufacture, distribution, and clinical treatment facilities. Regardless of source (allogeneic, autologous) or formulation (e.g., fresh, frozen, scaffold), the vast majority of CTPs are clinically administered on a per-patient basis. A CTP will be clinically effective, and therefore commercially viable, only if it is robust enough to be delivered to the patient in an efficient, controlled, and reproducible manner.

In the context of CTPs, delivery is not a synonym for shipping. It entails some (or all) of the following: QC release and shipping from the manufacturing site, receipt and storage at the clinical site, preadministration processing, formulation and QC release at the clinical site, and administration by the clinicians.

Based on our experience and understanding of CTP delivery, Progenitor Cell Therapy coined the term direct delivery for CTPs formulated and QC-released at the time of manufacture into the final formulation without requiring additional clinical site processing prior to patient administration. However, this comes at the operational cost of CTP manufacturing being driven by a per-patient clinical need (not suitable for acute indications), and requires a suitable CTP stability profile if the product is not manufactured at the clinical site. Meanwhile, multi-step delivery CTPs require additional clinical-site processing, QC, and logistics before patient administration. Although this creates significant risks and resource requirements (which increase with the addition of each new clinical site), it allows for the flexibility and efficiency of CTP manufacturing on a campaign basis, easier engagement of off-site/centralized manufacturing, and creation of inventory at clinical sites (suitable for acute indications). Importantly, it also allows for the use of final formulations with shorter stability.

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. In the context of point-of-care vs. centralized manufacturing, the clinical site risk mitigation and resource requirement reduction is achieved by transitioning to a centralized model, moving the majority of the process to a single manufacturing site or a limited number of sites. Looking at delivery as an extension of manufacturing, a hybrid delivery model — moving as many delivery steps to the (limited number of) manufacturing site(s) where 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 — would provide the ideal commercial solution.

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 amendable 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.

About the Author

Author Details
Sanjin Zvonic, PhD, is director of technology and business development at PCT (Progenitor Cell Therapy); 1-201-677-CELL; [email protected]; www.pctcelltherapy.com.