Harmonisation of quality control tests for academic production of CAR-T cells: a position paper from the WP-bioproduction of the UNITC consortium
Chrystel Marton, Béatrice Clemenceau, Guillaume Dachy, Clémence Demerle, Sophie Derenne, Christophe Ferrand, Camille Giverne, Jean‐Baptiste Latouche, Ludovic Lemée, J. Martinet, Halvard Bönig, Danièle Bensoussan, Christian Chabannon, Ulrike Koehl, Marina Deschamps, John De Vos, Jean‐Sébastien Diana, Aurore Dougé, Édouard Forcade, Jeanne Galaine, Stéphanie Thiant, Anne Galy, Jérôme Larghero, Loïc Reppel, Sébastien Viel, Olivier Boyer, Ibrahim Yakoub‐Agha
Abstract
This position paper from the Bioproduction Working Group of the UNITC Consortium seeks to harmonize quality control (QC) procedures for academic production of autologous CAR-T cells. The primary objective is to standardize QC testing for batch release in academic cell therapy units. Academic CAR-T manufacturing under the hospital exemption pathway enables faster, more cost-effective production and the use of fresh cells, eliminating the need for cryopreservation. Standardized QC processes are critical to ensure consistent product quality and safety. This paper focuses on key QC measures, including mycoplasma detection using validated commercial kits or in-house methods with on-site validation, endotoxin testing via Limulus Amebocyte Lysate (LAL) or Recombinant Factor C (rFC) assays with validated protocols to prevent matrix interference, vector copy number (VCN) quantification through validated qPCR or ddPCR techniques, and potency assessment through IFN-γ ELISA following antigenic stimulation. Emphasizing method validation and standardized testing, this work underscores the importance of robust QC strategies to ensure the safety and efficacy of CAR-T cell therapies, with ongoing efforts dedicated to optimizing these processes. This workshop focuses on addressing the harmonization of some quality control (QC) measures required for the validation of academic CAR-T cell production :mycoplasma detection; endotoxin testing; vector copy number (VCN) quantification; potency testing and the use of surrogate markers, if applicable. Sterility testing and characterization/identity/purity assessments are not covered in this work.