This paper presents a new method for process synthesis and economic assessment for solid drug product manufacturing, considering continuous manufacturing as a prominent process alternative. Of the three phases of drug development, phase II was targeted where the dosage form, formulation, and processing technology are determined. For a comprehensive alternative generation, a superstructure was developed that covered 9452 options for the unit level, which was combined with two options on the formulation strategy. The generated alternative was assessed by a net present value calculation model, which was adapted for dynamic cash flow consideration in the drug lifecycle. The model can incorporate uncertainty in the drug development and manufacturing in the result, and can perform global sensitivity analysis by Monte Carlo simulation. The method was demonstrated in a case study where two different scenarios regarding the price of the active pharmaceutical ingredient and the demand for the product were assumed. The results showed that when the demand and price are both low, the labor-related costs are dominant, and in the opposite case, the material-related costs become relevant. We also introduce the prototype version of the software “SoliDecision,” by which the presented method was implemented for industrial application.

中文翻译：

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不确定性下基于上层建筑的过程综合与经济评估

本文提出了一种新的方法，用于固体药物产品的生产过程综合和经济评估，并将连续生产作为一种重要的工艺方法。在药物开发的三个阶段中，第二阶段的目标是确定剂型，制剂和加工技术。为了产生全面的替代能源，开发了一种上层建筑，其中涵盖了9452个单位级别的选项，并结合了制定策略的两个选项。通过净现值计算模型评估产生的替代方案，该模型适用于药物生命周期中的动态现金流量考虑。该模型可以将不确定性纳入药物开发和制造的结果中，并且可以通过蒙特卡洛模拟进行全局敏感性分析。在案例研究中演示了该方法，其中假设了两种有关活性药物成分价格和产品需求的不同方案。结果表明，当需求和价格都较低时，与劳动力相关的成本占主导，而与之相反，与材料相关的成本则成为相关成本。我们还将介绍软件“ SoliDecision”的原型版本，通过该原型版本，所提出的方法可用于工业应用。