Purpose

With the applications of more advanced manufacturing technologies being applied to the pharmaceutical industry, continuous processes are at the forefront of innovation. One area that is highly desired to be systematically investigated is material traceability in continuous manufacturing systems. By following federal guidelines already in place, the goal was to address the issue of material traceability in a continuous direct compression tablet manufacturing process.

Methods

The residence time distribution (RTD) method has been used for material traceability in continuous pharmaceutical tablet manufacturing process. Utilizing the minimum and maximum residence times for the continuous line pre-production, raw material batch changes that occur during feeder refill can be traced at the outlet of the process. MATLAB programing was used to develop software prototype to trace material components.

Results

Developed framework for implementation of material traceability into continuous manufacturing pilot-plant. To demonstrate the application of this framework, a software prototype was developed, which allows the operator to input residence time attributes for each component in the formulation. Using the minimum and maximum residence time values for that component, the lot number is incremented when the change in material batch is predicted to be present in the tablets at the outlet. The tablet lot number is recorded by the control system in real-time.

Conclusions

Developed framework and corresponding software allows the material traceability to be fully accounted for during a continuous drug product manufacturing process. A proof of concept was created to demonstrate feasibility of such a system, which has a wide range of applications.

中文翻译：

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实现材料可追溯性到连续药物片剂制造过程中的系统框架

目的

随着将更先进的制造技术应用于制药行业，连续过程已成为创新的最前沿。迫切需要系统研究的一个领域是连续制造系统中的材料可追溯性。通过遵循已经制定的联邦指南，目标是解决连续直接压片生产过程中材料可追溯性的问题。

方法

停留时间分布（RTD）方法已用于连续药物片剂制造过程中的材料可追溯性。利用最小和最大停留时间进行连续生产线的预生产，可以在过程出口处跟踪进料器重新填充过程中发生的原料批次变化。使用MATLAB编程来开发软件原型以跟踪材料成分。

结果

为实现将材料追溯到连续制造中试工厂而开发的框架。为了演示该框架的应用，开发了一个软件原型，该原型允许操作员输入配方中每个成分的停留时间属性。使用该组件的最小和最大停留时间值，当预计出口处的片剂中物料批次变化时，批号会增加。片剂批号由控制系统实时记录。

结论

开发的框架和相应的软件可以在连续药品生产过程中充分考虑材料的可追溯性。创建了概念验证来证明这种系统的可行性，该系统具有广泛的应用范围。