Retrospective Analysis of Autologous Chondrocyte-Based Cytotherapy Production for Clinical Use: GMP Process-Based Manufacturing Optimization in a Swiss University Hospital
Virginie Philippe,
Alexis Laurent,
Nathalie Hirt-Burri,
Philippe Abdel-Sayed,
Corinne Scaletta,
Valentine Schneebeli,
Murielle Michetti,
Jean-François Brunet,
Lee Ann Applegate,
Robin Martin
Affiliations
Virginie Philippe
Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Alexis Laurent
Manufacturing Department, LAM Biotechnologies SA, CH-1066 Epalinges, Switzerland
Nathalie Hirt-Burri
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Philippe Abdel-Sayed
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Corinne Scaletta
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Valentine Schneebeli
Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Murielle Michetti
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Jean-François Brunet
Cell Production Center, Service of Pharmacy, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Lee Ann Applegate
Regenerative Therapy Unit, Plastic, Reconstructive and Hand Surgery Service, Lausanne University Hospital, University of Lausanne, CH-1066 Epalinges, Switzerland
Robin Martin
Orthopedics and Traumatology Service, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland
Cultured autologous human articular chondrocyte (HAC) implantation has been extensively investigated for safe and effective promotion of structural and functional restoration of knee cartilage lesions. HAC-based cytotherapeutic products for clinical use must be manufactured under an appropriate quality assurance system and follow good manufacturing practices (GMP). A prospective clinical trial is ongoing in the Lausanne University Hospital, where the HAC manufacturing processes have been implemented internally. Following laboratory development and in-house GMP transposition of HAC cell therapy manufacturing, a total of 47 patients have been treated to date. The main aim of the present study was to retrospectively analyze the available manufacturing records of the produced HAC-based cytotherapeutic products, outlining the inter-individual variability existing among the 47 patients regarding standardized transplant product preparation. These data were used to ameliorate and to ensure the continued high quality of cytotherapeutic care in view of further clinical investigations, based on the synthetic analyses of existing GMP records. Therefore, a renewed risk analysis-based process definition was performed, with specific focus set on process parameters, controls, targets, and acceptance criteria. Overall, high importance of the interdisciplinary collaboration and of the manufacturing process robustness was underlined, considering the high variability (i.e., quantitative, functional) existing between the treated patients and between the derived primary HAC cell types.
