A Quality Risk Management Model Approach for Cell Therapy Manufacturing

Fabio Lopez, Chiara Di Bartolo, Tommaso Piazza, Antonino Passannanti, Jörg C. Gerlach, Bruno Gridelli, Fabio Triolo

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)1857-1871
Number of pages15
JournalRisk Analysis
Issue number12
Publication statusPublished - Dec 2010


  • Cell therapy
  • Pareto analysis
  • Quality risk management
  • Regenerative medicine

ASJC Scopus subject areas

  • Physiology (medical)
  • Safety, Risk, Reliability and Quality

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  • Cite this

    Lopez, F., Bartolo, C. D., Piazza, T., Passannanti, A., Gerlach, J. C., Gridelli, B., & Triolo, F. (2010). A Quality Risk Management Model Approach for Cell Therapy Manufacturing. Risk Analysis, 30(12), 1857-1871. https://doi.org/10.1111/j.1539-6924.2010.01465.x