A review on the modernization of pharmaceutical development and manufacturing – Trends, perspectives, and the role of mathematical modeling

Quality‐by‐control of intensified continuous filtration‐drying of active pharmaceutical ingredients

“…the MATLAB fmincon optimizer (from MATLAB Optimization Toolbox, version 9.1) for achieving the solution of the optimization problem of Equation (7). The estimation uncertainty is obtained through the calculation of the variance-covariance matrix at the solution.…”

“…Level 2 and Level 3 control strategies, both controlling quality at open-loop, are the current standard in pharmaceutical manufacturing. 7 In a Level 1 control strategy, instead, the product quality is actively controlled by making use of process control techniques. The CPPs are automatically adjusted in response to measured changes of the CMAs (feedforward control) or of the CQAs (feedback control).…”

“…11 McKinsey 12 even estimated that introducing an advanced quality control system for process development and manufacturing could reduce the product launch time by up to 30%, with a very strong impact on profit of pharmaceutical companies. 10 Even though the adoption of Level 1 control strategies is still in embryonic phase, many recent academic publications 7,[13][14][15] demonstrated the advantages of closed-loop quality control in different pharmaceutical processes, including plant-wide applications. 16 The recent interest toward control strategies comprising elements of active process control has led to the establishment of a novel paradigm in pharmaceutical development and manufacturing, which has been named quality-by-control (QbC).…”

“…A Level 1 control strategy is made up of multiple layers. The figure is taken from Destro and Barolo 7 on continuous processing and QbC have been published around the topics of reacting systems, 23,24 crystallization, [25][26][27] and of solid-dosage form manufacturing lines. 28,29 However, end-to-end continuous pharmaceutical processes with active quality control have been somewhat overlooked.…”

Mathematical Modeling and Optimization to Inform Impurity Control in an Industrial Active Pharmaceutical Ingredient Manufacturing Process

“…Moreover, DoE does not fully capture the inherent nonlinearities of the physical mechanisms underpinning pharmaceutical manufacturing processes. 11 Besides the purity, ensuring a product's manufacturability (e.g., acceptable yields are attainable) and accelerating the process' development are also essential in an industrial context, 15 as multiple assets in a company's portfolio will be simultaneously under development. 2 1.2.…”