Design of an Integrated Continuous Manufacturing System

Oka, Sarang; Escotet‐Espinoza, M. Sebastian; Singh, Ravendra; Scicolone, James V.; Hausner, Douglas B.; Ierapetritou, Marianthi G.; Muzzio, Fernando J.

doi:10.1002/9781119001348.ch12

Cited by 9 publications

(4 citation statements)

References 50 publications

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“…Mean residence time describes the amount of time an average particle will spend within a process/unit operation(s). For an RTD model, assuming negligible non-ideality such as dead volume in the system, the mean residence time within a unit operation may be expressed in terms of space time, which is defined as a ratio of the mass holdup in the unit operation and overall line mass throughput (42,43). Therefore, the RTD model can account for the dynamics of mass holdup and mass throughput.…”

Section: Description Of Rtd-based Flowsheet Modeling Frameworkmentioning

confidence: 99%

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

Tian

Koolivand

et al. 2021

AAPS PharmSciTech

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Continuous manufacturing (CM) is an emerging technology which can improve pharmaceutical manufacturing and reduce drug product quality issues. One challenge that needs to be addressed when adopting CM technology is material traceability through the entire continuous process, which constitutes one key aspect of control strategy. Residence time distribution (RTD) play an important role in material traceability as it characterizes the material spreading through the process. The propagation of upstream disturbances could be predictively tracked through the entire process by convolution of the disturbance and the RTD. The present study sets up the RTD-based modeling framework in a commonly used process modeling environment, gPROMS, and integrates it with existing modules and built-in tools (e.g. parameter estimation). Concentration calculations based on the convolution integral requires access to historical stream property information, which is not readily available in flowsheet modeling platforms. Thus, a novel approach is taken whereby a partial differential equation is used to propagate and store historical data as the simulation marches forward in time. Other stream properties not modeled by an RTD are determined in auxiliary modules. To illustrate the application of the framework, an integrated RTD-auxiliary model for a continuous direct compression manufacturing line was developed. An excellent agreement was found between the model predictions and experiments. The validated model was subsequently used to assess in-process control strategies for feeder and material traceability through the process. Our simulation results show the employed modeling approach facilitates risk-based assessment of the continuous line by promoting our understanding on the process.

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Section: Description Of Rtd-based Flowsheet Modeling Frameworkmentioning

confidence: 99%

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

Tian

Koolivand

et al. 2021

AAPS PharmSciTech

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“…Traditional pharmaceutical oral dosage manufacturing is carried out in a series of batch unit operations. In the past 10 years, the pharmaceutical industry has been transitioning the manufacturing of a number of products from traditional batch processes to continuous processes due to the improved agility, flexibility, and robustness in continuous operation . There is a large amount of existing “know‐how” for batch pharmaceutical processes, and batch manufacturing can offer advantages over continuous manufacturing for products that are produced in small quantities.…”

Section: Introductionmentioning

confidence: 99%

“…In the past 10 years, the pharmaceutical industry has been transitioning the manufacturing of a number of products from traditional batch processes to continuous processes due to the improved agility, flexibility, and robustness in continuous operation. 1 There is a large amount of existing "knowhow" for batch pharmaceutical processes, and batch manufacturing can offer advantages over continuous manufacturing for products that are produced in small quantities. However, once large quantities of a product are required, a continuous process allows for a smaller footprint and smaller equipment compared with a batch process.…”

Section: Introductionmentioning

confidence: 99%

Continuous fluidized bed drying: Residence time distribution characterization and effluent moisture content prediction

et al. 2020

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The mixing and drying behavior in a continuous fluidized bed dryer were investigated experimentally by characterizing the residence time distribution (RTD) and incorporating a micromixing model together with the drying kinetics obtained from batch drying. The RTD of the dryer was modeled using a tank‐in‐series model. It was found that a high initial material loading and a low material flow rate resulted in a reduced peak height and broaded peak width of the RTD curve. To predict the continuous dryer effluent moisture content, we combined: (a) the drying kinetics as determined in a batch fluidized bed dryer, (b) the RTD model, and (c) micromixing models—segregation and maximum mixedness models. It was found that the segregation model overpredicted the effluent moisture content by up to 5% for the cases we have studied while the maximum mixedness model gave a good prediction of the effluent moisture content.

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“…Once the appropriate sample size is determined for the intended use of an analytical method, the integration time and number of co-adds of the PAT sensors need to be specified to meet the sampling needs of the process and product. 22…”

Section: Introductionmentioning

confidence: 99%

Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame

Anderson

Drennen

et al. 2019

Appl Spectrosc

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Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An in-line NIR method was developed after careful evaluation of the impact of potential experimental factors on the robustness and model accuracy and precision. The NIR method was validated according to the principles outlined in International Conference on Harmonization–Q2 for validation of analytical procedures and was demonstrated to be suitable for monitoring blend content for the formulation under evaluation. Reliable measurements of blend homogeneity rely on representative sampling. To reach the appropriate scale of scrutiny for a unit dose, the study assessed factors that influence the effective sample size measured by NIR. Spectral averaging, integration time, and feed frame paddle wheel speed were found to influence the effective sample size measured by the NIR probe. The effective sampling size was also estimated by comparing the distribution of predicted values with the reference values. The development of a robust, in-line PAT method was facilitated by thorough understanding of the sensitivity of PAT sensors to factors affecting pharmaceutical processes and products.

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Design of an Integrated Continuous Manufacturing System

Cited by 9 publications

References 50 publications

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

Development of an RTD-Based Flowsheet Modeling Framework for the Assessment of In-Process Control Strategies

Continuous fluidized bed drying: Residence time distribution characterization and effluent moisture content prediction

Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame

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