Mesenchymal Stromal Cells
GMP-compliant infrastructure and production in a hospital-setting of mesenchymal stromal cells from lipoaspirate for use in clinical trials
The project aims for the establishment of GMP-manufacturing of mesenchymal stromal cells in closed cultivation system.
Time period: 06/2020 – 06/2023
Lead: Gisela Helenius, Region Örebro Län
Involved partners: VivaBioCell, Acousort, Region Västerbotten
In this project, adipose derived MSCs will be used as a model system for minimally-manipulated cellular ATMPs produced in a hospital setting. While transplant of minimally manipulated cells is standard therapy for many conditions eg. blood transplants, when autologous or allogeneic cells are returned to the body for a different essential function, they are now regulated as ATMPs. An example of this is the use of fat derived Mesenchymal Stromal Cells (MSCs) for treatment of xerostomia, chronic wounds, knee osteoarthritis and immunosuppressive treatment to graft vs host reactions.
Production of ATMPs requires infrastructures to achieve medicinal drug production compliant with EU legislation. Key roles and functions such as qualified person, quality controller and quality assurance need to gain knowledge and expertise in cell biologics, clean room technology, pharmaceutical quality systems and the application process for regulatory approval for the manufacturing of ATMPs from the national competent authority (Läkemedelsverket).
By developing a GMP-compliant production line using closed bioreactors, a scalable system for producing off-the-shelf/ready-to-use cell therapy products can be put in place. By using easy-to-operate scalable bioreactors for cell expansion and by developing robust GMP-compliant expansion methods, a cost-effective production can be up-and-running in a relatively short time frame.
This project ends with the initiation of clinical trials using expanded MSCs from closed bioreactors. Patients with xerostomia following radiotherapy will be treated in a randomized placebo-controlled study, with change in unstimulated whole salivary flow rate as primary outcome. Moreover, in a separate clinical trial, patients with chronic wounds will be treated with the same ATMP. Further applications are currently considered. Expected outcome overall from this project is access to cell based therapy for chronic diseases for Swedish patients, in a model system suitable for implementation in hospitals with GMP-facility access.
Examples of tasks and actions:
- Validated SOPs for lipoaspirate procurement suited for MSC expansion as starting material for ATMP production. The starting material needs to meet GMP-standard and fulfill requirement of labelling and traceability.
- Validated SOP for GMP-compliant expansion of MSCs from lipoaspirate in a closed bioreactor.
- Validated SOPs for exosome testing including a potency assay and quality control tests that fulfill demands of speed and accuracy for immediate release of ATMP Detection of exosomes in cell suspension post expansion, determination of yield and size.
- GMP-compliant produced autologous MSCs ready for use in clinical trial (combination of milestone 1-3), complete with validated process using closed bioreactor and exosome release criteria.
- For this project, the end outcome is initiated clinical trials using autologous MSCs.