Quantitative FTA using Monte Carlo analyses in a pharmaceutical plant.,European Journal of Pharmaceutical Sciences

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Quantitative FTA using Monte Carlo analyses in a pharmaceutical plant.
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2020-02-13 , DOI: 10.1016/j.ejps.2020.105265
Mayre Aparecida Borges da Costa ₁ , Amanda Lemette T Brandão ₂ , Jorge G F Santos ₃ , José Carlos Pinto ₃ , Márcio Nele ₄

Affiliation

The evaluation of faults in a multipurpose pharmaceutical pilot plant used for production of polymer particles was performed, integrating traditional Fault Tree Analyses (FTA) and Monte Carlo procedures and employing tools of the quality risk management methodology for production of medicines. The plant was divided into four basic processes: (i) receipt and sampling of materials; (ii) treatment of purified water; (iii) reaction; and (iv) lyophilization and purification. For each process, the most critical failure was selected, and the FTA was built. Selection of basic events considered the most important effects on the final quality of the medicine. Then, the FTA was reduced to basic events using Boolean algebra. The quantitative assessment was made by assigning failure rate values for each event. The reliability data of the failure rates were based on the literature that deals with similar processes. The frequencies for each fault were determined through Monte Carlo simulations, considering that fault probability distributions followed the exponential distribution. When failure rate (ʎ) data are available, the quality management can establish a prediction of plant behavior over a period. This scenario is consistent and coherent with practices of pharmaceutical sites, since occurrence of high rates of failure must be corrected immediately in order to preserve the safety of the operation.

中文翻译：

在制药厂中使用蒙特卡洛分析进行定量FTA。

结合传统的故障树分析（FTA）和蒙特卡洛程序，并采用质量风险管理方法学的工具来生产药品，从而对用于生产聚合物颗粒的多功能制药中试工厂的故障进行了评估。该工厂分为四个基本过程：（i）物料的接收和抽样；（ii）处理纯净水；（iii）反应；（iv）冻干和纯化。对于每个过程，都选择了最关键的故障，并建立了FTA。选择基本事件被认为是对药物最终质量的最重要影响。然后，使用布尔代数将FTA简化为基本事件。通过为每个事件分配失败率值来进行定量评估。故障率的可靠性数据基于处理相似过程的文献。考虑到故障概率分布遵循指数分布，通过蒙特卡洛模拟确定了每个故障的频率。当故障率（ʎ）数据可用时，质量管理人员可以建立一段时间内工厂行为的预测。这种情况与制药厂的做法是一致且一致的，因为必须立即纠正高失败率的发生，以维护手术的安全性。当故障率（ʎ）数据可用时，质量管理人员可以建立一段时间内工厂行为的预测。这种情况与制药厂的做法是一致且一致的，因为必须立即纠正高失败率的发生，以维护手术的安全性。当故障率（ʎ）数据可用时，质量管理人员可以建立一段时间内工厂行为的预测。这种情况与制药厂的做法是一致且一致的，因为必须立即纠正高失败率的发生，以维护手术的安全性。

更新日期：2020-02-20

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