Formulation Considerations for Autologous T Cell Drug Products

• Main Authors: Christopher F. van der Walle, Sonya Godbert, Gabriele Saito, Zein Azhari
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Pharmaceutics
• Subjects: closed process; fill–finish; design space; primary container; cryopreservation; freeze–thaw
• Online Access: https://www.mdpi.com/1999-4923/13/8/1317

Genetically modified autologous T cells have become an established immunotherapy in the fight against cancer. The manufacture of chimeric antigen receptor (CAR) and αβ-T cell receptor (TCR) transduced T cells poses unique challenges, including the formulation, cryopreservation and fill–finish steps, which are the focus of this review. With an increasing number of marketing approvals for CAR-T cell therapies, comparison of their formulation design and presentation for administration can be made. These differences will be discussed alongside the emergence of automated formulation and fill-finish processes, the formulation design space, Monte Carlo simulation applied to risk analysis, primary container selection, freezing profiles and thaw and the use of dimethyl sulfoxide and alternative solvents/excipients as cryopreservation agents. The review will conclude with a discussion of the pharmaceutical solutions required to meet the simplification of manufacture and flexibility in dosage form for clinical treatment.