Pre-competitive
multi-stakeholder collaboration
to optimize manufacturing, lower COGs, and increase patient access
While cell therapies have demonstrated exceptional efficacy, patient access and COGs continue to be a major concern for investors, healthcare systems, and physicians, especially when compared to other modalities, such as T Cell Engagers, Antibody-Drug Conjugates, and radiotherapies. This concern undermines the overall confidence in the sector, impacting investment, insurance coverage, and willingness to prescribe. Imaginably, the sector can mature, as other sectors, such as mAbs, have. However, following a conventional path, maturation of the sector may require decades. During this time, cell therapies, a highly efficacious modality with potential to save patients’ lives, may become abandoned in favor of modalities with lower efficacy, but more straightforward manufacturing.
Understanding and optimizing manufacturability of cell therapies has proven to be a difficult problem to solve. A number of cell therapy developers have been focused on the topic. But due to the overall complexity of the modality, lack of fit-for-purpose analytical technologies, data fragmentation, and the small number of patients who have received cell therapies, optimization of cell therapy manufacturing remains a challenge in the sector shared across therapeutic developers.
Complexity of the modality. Compared to small molecules, traditional Biologics, and even mRNA-based therapies, cell therapies are complex - living cells, capable of cell division, that come in a variety of shifting phenotypes. Identifying parameters (Critical Quality Attributes, or CQAs) that can define the quality of cell therapies has been a challenge. Layered on top of this is the fact that the starting material is obtained from a human, whether the patient themselves or a donor, who interacts with the surrounding environment, which leads to constant changes in the starting material. Identification of patient and donor biomarkers (Critical Donor Attributes, or CDAs) predictive of positive clinical outcomes has presented a profound challenge.
Lack of fit-for-purpose analytical technologies. Given the complexity of the modality, there is a need for advanced analytics. While biophysical characterization tools for small molecules and traditional biologics have been perfected, technologies that can non-invasively characterize cell therapies across relevant parameters in real time are still in nascent stages.
Data fragmentation. Cell therapy manufacturing workflow is spread across a number of stakeholders, including hospitals, blood supply organizations, tools and technologies organizations, therapy developers, and manufacturers. This leads to profound separation of data across organizations. Such fragmentation creates additional barriers to analyses that relate various data pillars to clinical outcomes, leading to challenges when attempting to define critical parameters across materials, manufacturing processes, and logistics (Critical Material Attributes, or CMAs; and Critical Process Parameters, or CPPs), biomarkers pertaining to donors (CDAs), and patient stratification.
Small number of treated patients. The circularity of limited patient access brings on, perhaps, the biggest challenge yet. As each therapy developer has treated only a very small number of patients, attempted analyses invariably run into concerns with reliability of insights due to low statistical power.
Investors and healthcare systems are concerned that cell therapies will remain a high-cost modality incapable of addressing patient demand, particularly for large indications. Disruptive innovation that addresses manufacturing, scalability, and production costs is required in order to deliver change on a relevant timescale.