Different options are available for the in vitro genetic modification of cells, including viral vectors, plasmids and bacteria. Each of these modifying agents has distinct physical characteristics and therefore requires a tailored approach to demonstrate appropriate quality and application during the manufacture of GM cells. Different modifying agents are discussed in terms of their risk profile, and regulatory considerations are explained.

This talk will discuss how gene editing is instrumental in moving cell therapies from grafts to off-the-shelf pharmaceuticals, evolving production and control concepts for gene-edited allogeneic cell product candidates, and how to approach manufacturing of genomically engineered designer cells.

Kiadis’ NK-cell program consists of off-the-shelf and haplo donor cell therapy products for the treatment of liquid and solid tumors. Our proprietary off-the-shelf NK-cell platform is based on NK-cells from a unique universal donor, expanded and activated ex vivo using our PM21 particle technology. The Kiadis off-the-shelf platform has the potential to make NK-cell therapy products rapidly and economically available for a broad patient population across a potentially wide range of indications.

Using public information, we constructed a cost of goods model for an autologous gene-modified cell therapy product, evaluated the relationship of estimated manufacturing costs to list prices of CAR-T products, and investigated the potential impact of various factors on manufacturing costs. 

Most manufacturing processes for cell-based therapies remain reliant on manual, open and poorly scalable technologies with limited in-process monitoring, increasing the risks of batch failure. We will present a number of solutions to close and automate bioprocessing for autologous cellular immunotherapies and iPSC and demonstrate the utility of novel process analytical technologies in driving manufacturing decisions, enabling better control and reduced risk of failure.

Immatics utilizes target discovery platform, XPRESIDENT®, which identifies tumor targets and screen cognate TCRs for off-target toxicities. TCRs against these tumor targets are used in various Immatics’ adoptive cellular therapy programs that include endogenous autologous, engineered autologous, and engineered allogeneic products for various cancer indications. Extensive process development led to the manufacturing approaches for the various product platforms and exemplary manufacturing and/or clinical data from various trials will be presented for the various platforms.

This presentation will provide an overview of some of the analytical tools that are used to assess the quality control strategies of advanced therapies. Specifically, we will discuss global efforts for standardization of methodologies that will support product consistency.

Advanced therapeutics now attract significant interest due to the increasing number of exciting and high-profile products on the market and in clinical development. With over 20 years’ experience, the presentation will outline Oxford Biomedica’s (OXB) strategies to develop the next-generation manufacturing processes yielding suitable product quality attributes, in order to maximise capacity and advance development of a diverse product portfolio in therapeutic areas which currently present significant challenges.

Before market approval, it is necessary to complete process validation of the commercial process. This can only be undertaken if sufficient process knowledge has been accrued to build on earlier process qualification activities to develop a suitable validation approach. This talk will explore some of the challenges with validation of manufacturing processes for cell-based medicines, and consider the various approaches that can be taken.

One of the biggest challenges for AAV gene therapy products is establishing an appropriate analytical strategy to support product manufacture, release, stability, comparability and characterization at different stages of development. This presentation will highlight some of the existing analytical challenges and provide guidance on development of an appropriate strategy to help overcome these.

Gene therapy delivery of a drug product requires precise determination of vector titre by a suitably qualified analytical method. Despite the importance of titre assays for product release, optimisation of R&D methods is also crucial to allow for better understanding of the changes in rAAV titre and yield from upstream to downstream unit operations. qPCR is widely considered the gold standard for this purpose. In addition, we adopted orthogonal analytical tools including ddPCR and HPLC as robust and rapid titration alternatives to qPCR.

Currently, static and shake flasks for suspension processes are widely used in the process development of advanced therapies. However, these cell expansion approaches are labor-intensive and require a high level of highly skilled operator manipulation and offer only a low level of cell culture monitoring and control. Here we demonstrate the utility of the ambr250 modular and the newly designed unbaffled single impeller vessel as a process evaluation tool for the expansion of CAR-T cells.