Predictive surrogate assays could drive efficient clinical translation and commercialization.
The Centre for Commercialization of Regenerative Medicine (CCRM) envisages its mission in filling the main bottlenecks that a cell therapy product encounters because of the present gap between the existing government programs and the industry investment capital. Michael May, CCRM President and CEO, explained how its company mission connects the two pillars by enabling product development, integrating science and business and engaging with industry and therefore assists the commercialization process from the initial R&D stages down to the marketed product.
"The gap between proof of concept and fundable technologies is wider than ever.", Dr May outlined. Partnerships are important to CCRM and together with industry they are focusing on promising technologies for the development of new technologies that will accelerate regenerative medicine cost reduction and robustness. CCRM strategic plan for the future is to enlarge the network by attracting investors and more partners. Indeed, their GMP facilities will be expanded in 2014 for the translation of cell therapy research, supporting the integration of assay development and process optimization. This will also facilitate CCRM to collaborate internationally on standardization, once again aligning academic innovation and market pull. And to be honest it's no wonder CCRM and Cell Therapy Catapult signed a collaboration at the evening drink reception on the occasion of the first day of the Congress.
Dr May's talk then explained CCRM focus on the evaluation and development of potency assays, which play a pivotal role in defining the quality of cell therapy products. Given the novelty of the field in which regenerative medicine companies are moving in, there is a lack of consensus on those product characteristics assays that have to be performed in order to unequivocally assess the identity of a cell product. Stem and progenitor cells are typically heterogeneous populations easily influenced by variations of the microenvironment niche and therefore only controlling the process ("the product is the process") is vital but not sufficient.
US regulations impose that cell therapy candidates are tested quantitatively to measure the biological activity based on "attributes" of the product which are linked as closely as possible to a relevant biological function. This clearly ensures that only product lots that meet defined acceptance criteria can be administered during all phases of clinical investigation and following market approval. Nevertheless, assessing the biological functions of the product can take days to months and normally require invasive sampling; therefore these assays may not really reflect the needs.
Targeted potency assays, or predictive surrogate assays, will be more favorable as they will define biosimilarity of the product characteristics, be ideally rapid and stable and allow for process optimization and feedback control. Early trials requirements for potency are less stringent but as trials move into the late stages, extensive validation of the product via robust and unequivocal tests is essential to avoid the trial to be put on clinical hold. Dr May said that quality, consistency and stability are often not fully assessed or clearly explained in publications and this issue was recently brought up at a Canada-US-UK workshop in which MSCs identity and nomenclature was discussed. The international scientific debate is committed to the generation of uniform reference lines, and so far the candidate guidelines for human MSCs potency definition have been indicated as the ability to undergo tri-lineage differentiation, CFU-F, to secrete a plethora of cytokines, anti-inflammatory and immunomodulatory factors, as well as anti-microbial peptides and to express an indication-specific miRNA set. Three human MSC products are currently approved (ProchymalÂ® – aGvHD in Canada/New Zealand; CartistemÂ® – traumatic/degenerative OA in South Korea; HeartiCellgram – post-AMI in South Korea) but the assays they underwent are not completely consistent with the actual complete definition of potency assays. A strong potency validaton of every cell therapy product should not be excluded from the whole bioprocesses; in fact, the cell manufacturing challenge lays in a multidimensional optimization problem, in which cost reduction, selective pressure decrease and indeed target cell (identity) output (potency) increase are all interconnected.
The take home message is that a substantial potency evaluation plan can greatly favor cell therapy products commercialization because it reduces the risks of failure in late-stage progression.
Guest blog provided by Giulia Detela