In the Stuttgart/Heidelberg ProCell for Patient model, essential steps (blue) in the production of cell therapeutics are performed in an isolator in a fully automated process. The prototype will be installed at the Robert-Bosch-Krankenhaus in Stuttgart. Credit: Optima
“ With the help of the ProCell for Patient system, it will probably be possible to reduce the amount of work, i.e. the number of hours that qualified staff are spending today on the production of CAR-T cells, by at least 50 percent.” Univ.-Prof. Dr. med. Michael Schmitt, MHBA, Siebeneicher-Endowment Professor for Cellular Immunotherapy, Head of GMP Core Facility, Universitätsklinikum Heidelberg.
“ProCell for Patient” at the heart of a future reference centre
The “ProCell for Patient” project started in October 2020, and is funded by the Ministry of Economic Affairs, Labour and Housing Baden-Württemberg as part of the “Forum Health Region Baden-Wuerttemberg” initiative. From Optima Pharma, Dr. Andrea Traube, who heads up Market Development with a focus on system solutions for cell and gene therapeutics at Optima Pharma, is accompanying the project. As Dr. Traube says: “The first steps have been mastered. These are the detailed process analysis of the CAR-T process in Heidelberg and the creation of the User Requirement Specification (URS).”
Her expertise in automating cell culture processes, according to Prof. Aulitzky, is to ensure “that we not only map the manual process 1:1, but also make potential adjustments to the process to exploit the full potential of automation to optimize the manufacturing process”. Optima has unique expertise in this area.
There are six main steps to the process: cell selection, cell activation, genetic modification to CAR-T cells, cell expansion, cell harvesting and formulation, and fill & finish. By using isolator technology from Optima, the plant does not have to be installed in the highest clean room class, as is the case in the Heidelberg GMP laboratory, but in class C or D clean rooms. The first challenges were already overcome during the preparation of the URS. Prof. Schmitt remembers: “To translate the manual process into a cybernetics format, a new way of thinking was required.”
Some process steps proved to be particularly challenging, such as the introduction of biological material. This is because isolator technology requires gassing by hydrogen peroxide, which can be damaging to unprotected cell material.
Operating concept to be integrated into hospital processes
Now Optima and RBK are in the driver’s seat. The experts at Optima Pharma are working on developing functional modules, while the RBK is working on the operating concept and developing a concept for a clinical trial to demonstrate the suitability of the system for use in decentralized CAR-T cell production.
In Q2 2021, work began on building and testing the first functional modules. As a result, it is assured at an early stage that the living cells are not damaged, for example by excessive shear forces. At RBK, test operations will start in the summer of 2022. Even then, UKHD experts will still have an important role to play in making appropriate adjustments to any slight deviation. The ultimate goal is to produce a safe product that is given to the patient as an intravenous drip.
Possible use in hospitals and industry
If the ProCell for Patient model is a successful one, the intention is then to turn the prototype into a marketable product. Dr. Traube explains: “The system can be used in the future in both tumour treatment centres and in the pharmaceutical industry.” Because of its modular design the project partners are anticipating that the production platform can be used to produce different types of cell and gene therapeutics. These have great potential. By 2025, EU and US regulatory authorities anticipate ten to 20 new products per year.
In the long term, multiple hospitals and their patients may benefit from the ProCell for Patient project. First and foremost is the RBK. Prof. Aulitzky expects to obtain manufacturing approval three to six months after the project ends. The Universitätsklinikum Heidelberg, which will initially be supplied by the RBK, will also benefit from this. However, in the medium term, Prof. Schmitt wants to be one of the first to roll out the technology: “We want to set up a number of robot production isolators on a factory floor.” Other clinics are also interested. Consequently, Baden- Württemberg as a location will benefit by becoming a leader in technology for the decentralized production of personalized cell and gene therapeutics, and will help in gaining acceptance by healthcare providers and regulatory authorities. This means that in the future, patients will receive treatment more quickly, with the promise of successful treatment even when all other options have failed.