These authors contributed equally to this work.
A Quality Risk Management Model Approach for Cell Therapy Manufacturing
Article first published online: 17 AUG 2010
© 2010 Society for Risk Analysis
Volume 30, Issue 12, pages 1857–1871, December 2010
How to Cite
Lopez, F., Bartolo, C. D., Piazza, T., Passannanti, A., Gerlach, J. C., Gridelli, B. and Triolo, F. (2010), A Quality Risk Management Model Approach for Cell Therapy Manufacturing. Risk Analysis, 30: 1857–1871. doi: 10.1111/j.1539-6924.2010.01465.x
- Issue published online: 1 DEC 2010
- Article first published online: 17 AUG 2010
- Cell therapy;
- Pareto analysis;
- quality risk management;
- regenerative medicine
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.