Distinct and Quantitative Validation Method for Predictive Process Modelling in Preparative Chromatography of Synthetic and Bio-Based Feed Mixtures Following a Quality-by-Design (QbD) Approach

Abstract

Process development, especially in regulated industries, where quality-by-design approaches have become a prerequisite, is cost intensive and time consuming. A main factor is the large number of experiments needed. Process modelling can reduce this number significantly by replacing experiments with simulations. However, this requires a validated model. In this paper, a process and model development workflow is presented, which focuses on implementing, parameterizing, and validating the model in four steps. The presented methods are laid out to gain, create, or generate the maximum information and process knowledge needed for successful process development. This includes design of experiments and statistical evaluations showing process robustness, sensitivity of target values to process parameters, and correlations between process and target values. Two case studies are presented. An ion exchange capture step for monoclonal antibodies focusing on high accuracy and low feed consumption; and one case study for small molecules focusing on rapid process development, emphasizing speed of parameter determination.

Distinct and Quantitative Validation for Predictive Process Modelling in Steam Distillation of Caraway Fruits and Lavender Flower Following a Quality-By-Design (QbD) Approach

“…Other models, which are verified and validated with this process model development workflow, summarised schematically in Figure 3, cover a solid-liquid (phyto-) extraction [12], upstream fermentation [15], liquid-liquid extraction [16], continuous single-pass tangential flow filtration [17], precipitation [18] and chromatography [19]. This demonstrates the benefit of a methodical approach to model development.…”

Digital Twin of mRNA-Based SARS-COVID-19 Vaccine Manufacturing towards Autonomous Operation for Improvements in Speed, Scale, Robustness, Flexibility and Real-Time Release Testing

“…The processes reported in literature and the process framework depicted in this work are both summarized in Figure 4. For this total pDNA to mRNA process, a digital twin is proposed based on literature data, pre-existing knowledge and experimental experience as well as existing basically validated process models [41][42][43][44][45][46][47].…”

“…This was done since for more sophisticated adsorption models such as competitive Langmuir or steric mass action (SMA), as a bigger data set for parameter determination is required [65,66]. Langmuir, however, has shown for different target molecules an accurate description of adsorption for different working groups [44,67,68].…”

Modeling and Simulation of Reaction and Fractionation Systems for the Industrial Residue Hydrotreating Process

“…(4) Delump the effluent from the reactor to build the fractionator. (5) Test the effectiveness of the model by comparing the model results with actual plant data.…”

“…Since vacuum residue accounts for about half of the crude oil, more attention has been focused on vacuum residue hydroconversion processes, which are capable of converting heavy, inferior petroleum into light, valuable products such as gasoline, jet fuel, and diesel [3,4]. A good process model is important for monitoring the plant-level operation status, optimizing operating conditions, verifying the dynamic adjustment scheme, and maximizing the profit [5][6][7].…”