A Quality Risk Management Model Approach for Cell Therapy Manufacturing

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.     

基于TRIZ的复杂系统FMECA分析流程和方法研究

大型复杂系统具有结构复杂和功能多样化的特点,严重故障的发生将会造成巨大损失,而现有的故障分析方法和管理手段明显不足。基于传统FMECA方法,结合TRIZ理论和方法,以神光系列激光装置为研究对象,本文提出改进的FMECA分析流程和方法,目的是开展故障模式及影响的多样性分析以及寻找完善的问题纠正措施,从而提高故障归零率,降低系统运行风险。