scholarly journals 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

Processes ◽  
2019 ◽  
Vol 7 (9) ◽  
pp. 580 ◽  
Author(s):  
Steffen Zobel-Roos ◽  
Mourad Mouellef ◽  
Reinhard Ditz ◽  
Jochen Strube
Keyword(s):  
Quality By Design ◽  
Process Development ◽  
Model Development ◽  
Process Modelling ◽  
Feed Consumption ◽  
Parameter Determination ◽  
Preparative Chromatography ◽  
Maximum Information ◽  
Target Values ◽  
Quantitative Validation

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.

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

Processes ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 594 ◽  
Author(s):  
Thorsten Roth ◽  
Lukas Uhlenbrock ◽  
Jochen Strube
Keyword(s):  
Quality By Design ◽  
Steam Distillation ◽  
Process Development ◽  
Model Development ◽  
Chemical Model ◽  
Maximum Information ◽  
Physico Chemical ◽  
Target Values ◽  
Different Types ◽  
Quantitative Validation

A quality by design (QbD) approach as part of process development in the regulated, pharmaceutical industry requires many experiments. Due to the large number, process development is time consuming and cost intensive. A key to modern process development to reduce the number of required experiments is a predictive simulation with a validated physico-chemical model. In order to expand the process expertise of steam distillation through maximum information, a model development workflow is used in this paper, which focuses on implementation, verification, parametrization and validation of a physico-chemical model. Process robustness and sensitivity of target values can be determined from the developed general model and design of experiments with statistical evaluations. The model validation is exemplified by two different types of plant systems, caraway fruits (Carum Carvi) and lavender flowers (Lavandula).

scholarly journals Advanced Process Analytical Technology in Combination with Process Modeling for Endpoint and Model Parameter Determination in Lyophilization Process Design and Optimization

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1600
Author(s):  
Alex Juckers ◽  
Petra Knerr ◽  
Frank Harms ◽  
Jochen Strube
Keyword(s):  
Process Design ◽  
Quality By Design ◽  
Process Development ◽  
Process Analytical Technology ◽  
Parameter Determination ◽  
Design And Optimization ◽  
Manometric Temperature Measurement ◽  
Analytical Technology ◽  
Main Shortcoming

Lyophilization is widely used in the preservation of thermolabile products. The main shortcoming is the long processing time. Lyophilization processes are mostly based on a recipe that is not changed, but, with the Quality by Design (QbD) approach and use of Process Analytical Technology (PAT), the process duration can be optimized for maximum productivity while ensuring product safety. In this work, an advanced PAT approach is used for the endpoint determination of primary drying. Manometric temperature measurement (MTM) and comparative pressure measurement are used to determine the endpoint of the batch while a modeling approach is outlined that is able to calculate the endpoint of every vial in the batch. This approach can be used for process development, control and optimization.

scholarly journals Distinct and Quantitative Validation Method for Predictive Process Modeling with Examples of Liquid-Liquid Extraction Processes of Complex Feed Mixtures

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 298 ◽  
Author(s):  
Axel Schmidt ◽  
Jochen Strube
Keyword(s):  
Process Model ◽  
Process Development ◽  
Scale Up ◽  
Liquid Extraction ◽  
Process Models ◽  
Parameter Determination ◽  
Production Scale ◽  
Liquid Liquid Extraction ◽  
Safety Margins ◽  
Quantitative Validation

As of today, industrial process development for liquid-liquid extraction and scale-up of extraction columns is based on an experimental procedure that requires tests in pilot-scale. This methodology consumes large amounts of material and time and the utilized scale-up equations are crude estimates including considerable safety margins. This approach is practical for well-known systems or low-value products coupled with high production scale, where such a scale-up methodology has less impact on the overall profitability. However, for new high-value products in biologics manufacturing, a process development based on process understanding and the use of validated process models is imperative. Therefore, a distinct and quantitative validation workflow for liquid-liquid extraction modeling is presented on the example of two complex feed mixtures. Monte-Carlo simulations based on the presented model parameter determination concept result for both examples in prediction accuracy comparable to the experiments and prediction precision within the deviation of the respective experiments. Identification of statistically significant parameters is demonstrated. The presented methodology for model validation will support the implementation of liquid-liquid extraction in the manufacturing of new high value biological products in regulated industries by providing a workflow to derive a Quality-by-Design compatible process model.

Cutting Tool Temperatures in Contour Turning: Transient Analysis and Experimental Verification

1997 ◽  
Vol 119 (4A) ◽  
pp. 494-501 ◽  
Author(s):  
D. A. Stephenson ◽  
T.-C. Jen ◽  
A. S. Lavine
Keyword(s):  
Transient Analysis ◽  
Cutting Tool ◽  
Process Development ◽  
Thermal Contact ◽  
Model Development ◽  
Cutting Speed ◽  
Depth Of Cut ◽  
Transient Conditions ◽  
Trouble Shooting ◽  
Model Predictions

This paper describes a model for predicting cutting tool temperatures under transient conditions. It is applicable to processes such as contour turning, in which the cutting speed, feed rate, and depth of cut may vary continuously with time. The model is intended for use in process development and trouble shooting. Therefore, emphasis is given in the model development to enable rapid computation and to avoid the need to specify parameters such as thermal contact resistances and convection coefficients which are not known in practice. Experiments were conducted to validate the predictive model. The model predictions with two different boundary conditions bound the experimental results. An example is presented which shows the utility of the model for process planning.

Process development in the Quality by Design paradigm: Modeling of Protein A chromatography resin fouling

2018 ◽  
Vol 1570 ◽  
pp. 56-66 ◽  
Author(s):  
Lalita Kanwar Shekhawat ◽  
Mili Pathak ◽  
Jayati Sakar ◽  
Anurag S. Rathore
Keyword(s):  
Quality By Design ◽  
Process Development ◽  
Protein A ◽  
Design Paradigm

Quality by Design-Driven Process Development of Cell Culture in Bioreactor for the Production of Foot-And-Mouth Veterinary Vaccine

2019 ◽  
Vol 108 (7) ◽  
pp. 2288-2295 ◽  
Author(s):  
Xinran Li ◽  
Xuerong Liu ◽  
Rongbin Wang ◽  
Fanglan An ◽  
Jianqi Nie ◽  
...  
Keyword(s):  
Cell Culture ◽  
Quality By Design ◽  
Process Development ◽  
Veterinary Vaccine ◽  
Foot And Mouth

scholarly journals Exploring Macroporosity of Additively Manufactured Titanium Metamaterials for Bone Regeneration with Quality by Design: A Systematic Literature Review

Materials ◽  
2020 ◽  
Vol 13 (21) ◽  
pp. 4794
Author(s):  
Daniel Martinez-Marquez ◽  
Ylva Delmar ◽  
Shoujin Sun ◽  
Rodney A. Stewart
Keyword(s):  
Bone Regeneration ◽  
Design Process ◽  
Quality By Design ◽  
Biological Properties ◽  
Future Research ◽  
Material Strength ◽  
Porous Scaffolds ◽  
Design Decision ◽  
Bone Properties ◽  
Target Values

Additive manufacturing facilitates the design of porous metal implants with detailed internal architecture. A rationally designed porous structure can provide to biocompatible titanium alloys biomimetic mechanical and biological properties for bone regeneration. However, increased porosity results in decreased material strength. The porosity and pore sizes that are ideal for porous implants are still controversial in the literature, complicating the justification of a design decision. Recently, metallic porous biomaterials have been proposed for load-bearing applications beyond surface coatings. This recent science lacks standards, but the Quality by Design (QbD) system can assist the design process in a systematic way. This study used the QbD system to explore the Quality Target Product Profile and Ideal Quality Attributes of additively manufactured titanium porous scaffolds for bone regeneration with a biomimetic approach. For this purpose, a total of 807 experimental results extracted from 50 different studies were benchmarked against proposed target values based on bone properties, governmental regulations, and scientific research relevant to bone implants. The scaffold properties such as unit cell geometry, pore size, porosity, compressive strength, and fatigue strength were studied. The results of this study may help future research to effectively direct the design process under the QbD system.

Sign in / Sign up

Export Citation Format

Share Document