WP8 - GMP Manufacturing of MSCs

Culture conditions have the potential to change the biological characteristics or functions of the cell and as a result the culturing process is subject to specific quality control checks to ensure the safety and efficacy of the manufactured cells. Serum free manufacture of stem cells requires the use of growth factors and it is necessary to develop protocols for detection of these factors in release assays of the final product to ensure patients are not exposed to potential risks associated with even low levels of growth factor.

 WP 8 aims to identify the potential quality and regulatory risks associated with serum-free stem cell manufacture, within the context of the regulatory framework of the EU for GMP (Good Manufacturing Practice) production of cellular products, leading to the development of quality control methods to ensure the validity, purity and potency of the manufactured MSCs.

These checks will include the screening of donor bone marrow for disease transmission, identification and functional testing of raw materials which comply with GMP requirements, development of final release assays for cells grown in the final media formulation, drafting of Standard Operating Procedures for the manufacturing and quality control of MSCs and benchmarking and standardization against other GMP manufactured MSCs.

The information collected in WP8 will result in regulatory approved and GMP compliant methods for the isolation, expansion and banking of MSCs in a serum free media that will create an accelerated path to approved use in clinical trials and ultimately general clinical use.

Manufacturing and quality control testing will be carried out in a purpose-built (GMP) clean-room facility for the production of cellular therapy agents for clinical use, located at REMEDI, NUI Galway, Ireland. The GMP facility encompasses a working floor space of approximately 250 M2 and possesses two equipped independent production suites comprising of three processing rooms (Preparation Room, Downstream Process Room, Filling Room) for various stages of the mesenchymal stem cell isolation and culturing process.

The facility is serviced by a dedicated CO2 gasline and Liquid N2 generation plant, and highly filtered air is provided to both production suites by independent air handling systems. As dictated by current European Union legislation, the processing rooms are classified as Grade B according to Annex I of the EU manufacturing guidelines for medicinal products, with open manipulations of the product being performed in a Grade A environment.

Figure 8: GMP-grade cellular processing using a clean room facility to culture bone marrow derived MSCs as well as characterize their morphology by microscopy.