Developing next generation products to release current bottlenecks in CGT. Technical overview on CMC strategies for real CGT products, presentation of actual scientific data showing the progress done to release current bottlenecks in the manufacture and COGs of CGT products. The critical points in the CMC strategy for CGT products, with real examples. Current bottlenecks in the manufacture of CGT products and development areas to focus on.

There are longstanding challenges in the commercialisation of ATMPs that can be addressed by the implementation of process analytical technologies (PATs). Cell and Gene Therapy Catapult (CGTC) has led a consortium project with 23 collaborators to investigate the application of PAT and advanced analytics for a T cell immunotherapy process. We will discuss the extensive approach we applied to analytical characterisation of the process and the opportunities and challenges it presented.

Over the past decade, the development of cell therapies has gained significant momentum. Processes executed in a hospital setting such as the isolation of tumor infiltrating lymphocytes (TILs), transformed clones of hematopoietic stem cells (HSCs), or other rare cells, are challenging to replicate in a cGMP environment. We will discuss the cell sorting process and analytical development considerations when implementing fluorescence activated cell sorting (FACS) in a cGMP environment.

Manufacturing clinically-relevant cell numbers with desired phenotypes is a major hurdle for ex vivo genetically modified cellular immunotherapies, such as CAR-T. The high cost of goods and inherent variability of gene-modified cell therapies presents a translational and manufacturing challenge. This talk will focus on providing process optimisation and process intensification case studies for CAR-T cell manufacture and how applying these strategies may prove essential for commercial viability. Specifically, this talk will focus on: Identifying critical process parameters for improved, consistent CAR-T expansion, scaling up critical parameters to the stirred-tank bioreactor process and optimizing perfusion parameters to maximize growth and function?. 

Comparability of biological products is always challenging, but even more so when the product is a complex mixture of cells of which a proportion have been genetically modified. The frequently short development timelines for cell and gene therapies mean that comparability is often considered too late during the implementation of process changes. The talk outlines key considerations that ensure that an appropriate comparability plan can be put in place and executed, and that can be adapted throughout the product lifecycle.

Tumor-infiltrating lymphocytes (TIL) are circulating cytotoxic and helper T-cells that have infiltrated a tumor, recognize tumor-specific neoantigens unique to each patient, and mediate tumor cell death. TIL cell therapy involves the adoptive transfer of billions of polyclonal, patient-specific TIL recovered from a patient’s tumor tissue that are amplified and reinvigorated using a proprietary process. I will discuss unique opportunities and challenges in TIL cell therapy manufacturing, logistics and development.

Assessment of cell therapy quality from raw materials to final product is critical to ensuring their safety and efficacy. Lack of standards for cell therapy has slowed down product development since the path and tools to commercialization are not clear. USP continues to publish best practices and methods that support their innovation. Existing standards as well as new work related to plasmid DNA and rapid microbial methods will be shared.

Curating and refining a comprehensive in-process and final product testing plan throughout development is an invaluable and arguably essential tool. This talk will discuss best practices for maintaining the data throughout clinical development, implementation of the proper statistical methodologies and a clearly defined risk-based approach that will lead the way to a data-driven PPQ design and successful execution.

Decentralized manufacturing (DCM) strategy consists of a platform comprising manufacturing and testing units, installed to the same specifications at multiple locations placed close to or at medical centers, networked and managed by a central remote Quality Management System. A regulatory framework is required to enable the development of point of care (POCare) manufacture, providing control measures equivalent to those currently in place, confirming that POCare products have appropriate quality, safety, and efficacy attributes. To ensure compliance to quality and regulatory DCM requirements, Orgenesis has established a comprehensive approach supporting oversight of POCare centers.

The nature of cell therapy products means they cannot be terminally sterilised or even sterile-filtered; this puts a greater onus on other aspects of sterility control. This talk will discuss how a holistic approach is needed to ensure safety of these products, including facilities, testing and methods of sterilisation.

Utilizing a novel platform to overcome poor endogenous costimulation and leverage the diverse TCR repertoire of TILs while amplifying antitumor activity.

Evaluation of critical raw materials should start at early stages of product cycle. This talk will focus on risk analysis and mitigation strategies to support process and analytical development for the manufacture of allogeneic therapies from pluripotent stem cells.

Flow cytometry data analysis is extremely time-consuming and the principal source of variation in the application of the technology. As an alternative, we have developed the best performing automated approach for cell population identification in the peer-reviewed literature. It consistently achieves up to 94% accuracy, and is in use by pharma for clinical studies and cell therapy manufacturing. Looking to the future our preliminary data supports that machine learning will exceed even this, providing a scalable solution for all users of the technology.