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A Quality Risk Management Model Approach for Cell Therapy Manufacturing

Authors

  • Fabio Lopez,

    1. Dipartimento di Tecnologia Meccanica, Produzione e Ingegneria Gestionale, Università di Palermo, Palermo, Italy.
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    • These authors contributed equally to this work.

  • Chiara Di Bartolo,

    1. Fondazione Ri.MED, Palermo, Italy.
    2. Regenerative Medicine and Cell Therapy Unit, ISMETT-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
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    • These authors contributed equally to this work.

  • Tommaso Piazza,

    1. IT Department, ISMETT-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
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  • Antonino Passannanti,

    1. Dipartimento di Tecnologia Meccanica, Produzione e Ingegneria Gestionale, Università di Palermo, Palermo, Italy.
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  • Jörg C. Gerlach,

    1. Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
    2. Department of Bioengineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
    3. AG Experimental Surgery, Charité, Medical Faculty of the Berlin Universities, Berlin, Germany.
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  • Bruno Gridelli,

    1. Department of Surgery, ISMETT-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
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  • Fabio Triolo

    Corresponding author
    1. Regenerative Medicine and Cell Therapy Unit, ISMETT-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy.
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Address correspondence to Fabio Triolo, ISMETT, via E. Tricomi 1, 90127 Palermo, Italy; tel: +39-091-2192484; fax: +39-091-2192422; ftriolo@ismett.edu.

Abstract

International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell-based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator-introduced variations, and affected by heterogeneity of the processed organs/tissues and lot-dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell-based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo-quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed.

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