scholarly journals Process Analytical Technology for Precipitation Process Integration into Biologics Manufacturing towards Autonomous Operation—mAb Case Study

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 488
Author(s):  
Lara Julia Lohmann ◽  
Jochen Strube
Keyword(s):  
Process Control ◽  
Real Time ◽  
Process Analytical Technology ◽  
Measurement Techniques ◽  
Array Detector ◽  
Precipitation Process ◽  
Suitable Model ◽  
Process Data ◽  
Autonomous Operation ◽  
Analytical Technology

The integration of real time release testing into an advanced process control (APC) concept in combination with digital twins accelerates the process towards autonomous operation. In order to implement this, on the one hand, measurement technology is required that is capable of measuring relevant process data online, and on the other hand, a suitable model must be available to calculate new process parameters from this data, which are then used for process control. Therefore, the feasibility of online measurement techniques including Raman-spectroscopy, attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR), diode array detector (DAD) and fluorescence is demonstrated within the framework of the process analytical technology (PAT) initiative. The best result is achieved by Raman, which reliably detected mAb concentration (R2 of 0.93) and purity (R2 of 0.85) in real time, followed by DAD. Furthermore, the combination of DAD and Raman has been investigated, which provides a promising extension due to the orthogonal measurement methods and higher process robustness. The combination led to a prediction for concentration with a R2 of 0.90 ± 3.9% and for purity of 0.72 ± 4.9%. These data are used to run simulation studies to show the feasibility of process control with a suitable digital twin within the APC concept.

scholarly journals Multi-angle light scattering as a process analytical technology measuring real-time molecular weight for downstream process control

mAbs ◽  
2018 ◽  
pp. 1-6
Author(s):  
Bhumit A. Patel ◽  
Adrian Gospodarek ◽  
Michael Larkin ◽  
Sophia A. Kenrick ◽  
Mark A. Haverick ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Light Scattering ◽  
Process Control ◽  
Real Time ◽  
Process Analytical Technology ◽  
Downstream Process ◽  
Analytical Technology

In-Process Data Fusion for Process Monitoring and Control of Metal Additive Manufacturing

2021 ◽  
Author(s):  
Zhuo Yang ◽  
Yan Lu ◽  
Simin Li ◽  
Jennifer Li ◽  
Yande Ndiaye ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Process Control ◽  
Data Fusion ◽  
Real Time ◽  
Process Data ◽  
Multi Scale ◽  
And Control ◽  
Fusion Framework ◽  
Scale Data ◽  
Metal Additive

Abstract To accelerate the adoption of Metal Additive Manufacturing (MAM) for production, an understanding of MAM process-structure-property (PSP) relationships is indispensable for quality control. A multitude of physical phenomena involved in MAM necessitates the use of multi-modal and in-process sensing techniques to model, monitor and control the process. The data generated from these sensors and process actuators are fused in various ways to advance our understanding of the process and to estimate both process status and part-in-progress states. This paper presents a hierarchical in-process data fusion framework for MAM, consisting of pointwise, trackwise, layerwise and partwise data analytics. Data fusion can be performed at raw data, feature, decision or mixed levels. The multi-scale data fusion framework is illustrated in detail using a laser powder bed fusion process for anomaly detection, material defect isolation, and part quality prediction. The multi-scale data fusion can be generally applied and integrated with real-time MAM process control, near-real-time layerwise repairing and buildwise decision making. The framework can be utilized by the AM research and standards community to rapidly develop and deploy interoperable tools and standards to analyze, process and exploit two or more different types of AM data. Common engineering standards for AM data fusion systems will dramatically improve the ability to detect, identify and locate part flaws, and then derive optimal policies for process control.

scholarly journals Fast and Flexible mRNA Vaccine Manufacturing as a Solution to Pandemic Situations by Adopting Chemical Engineering Good Practice—Continuous Autonomous Operation in Stainless Steel Equipment Concepts

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1874
Author(s):  
Axel Schmidt ◽  
Heribert Helgers ◽  
Florian Lukas Vetter ◽  
Alex Juckers ◽  
Jochen Strube
Keyword(s):  
Stainless Steel ◽  
Chemical Engineering ◽  
Process Analytical Technology ◽  
Good Practice ◽  
Operation Mode ◽  
Continuous Manufacturing ◽  
Efficient Operation ◽  
Messenger Ribonucleic Acid ◽  
Autonomous Operation ◽  
Analytical Technology

SARS-COVID-19 vaccine supply for the total worldwide population has a bottleneck in manufacturing capacity. Assessment of existing messenger ribonucleic acid (mRNA) vaccine processing shows a need for digital twins enabled by process analytical technology approaches in order to improve process transfer for manufacturing capacity multiplication, a reduction in out-of-specification batch failures, qualified personal training for faster validation and efficient operation, optimal utilization of scarce buffers and chemicals and speed-up of product release by continuous manufacturing. In this work, three manufacturing concepts for mRNA-based vaccines are evaluated: Batch, full-continuous and semi-continuous. Technical transfer from batch single-use to semi-continuous stainless-steel, i.e., plasmid deoxyribonucleic acid (pDNA) in batch and mRNA in continuous operation mode, is recommended, in order to gain: faster plant commissioning and start-up times of about 8–12 months and a rise in dose number by a factor of about 30 per year, with almost identical efforts in capital expenditures (CAPEX) and personnel resources, which are the dominant bottlenecks at the moment, at about 25% lower operating expenses (OPEX). Consumables are also reduceable by a factor of 6 as outcome of this study. Further optimization potential is seen at consequent digital twin and PAT (Process Analytical Technology) concept integration as key-enabling technologies towards autonomous operation including real-time release-testing.

In situ real time monitoring of emulsification and homogenization processes for vaccine adjuvants

The Analyst ◽  
2022 ◽  
Author(s):  
Nicole M. Ralbovsky ◽  
Randal J. Soukup ◽  
Justin P. Lomont ◽  
Mackenzie L. Lauro ◽  
Amanda Gulasarian ◽  
...  
Keyword(s):  
Real Time ◽  
Process Analytical Technology ◽  
Vaccine Adjuvant ◽  
Formation Processes ◽  
Vaccine Adjuvants ◽  
Stable Emulsion ◽  
Real Time Monitoring ◽  
Analytical Technology

Process analytical technology was used to monitor formation of a stable emulsion product, with results providing improved understanding of emulsion-based vaccine adjuvant formation processes.

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