Application of the Steric Mass Action formalism for modeling under high loading conditions: Part 1. Investigation of the influence of pH on the steric shielding factor

Seelinger, Felix; Wittkopp, Felix; Hirschheydt, Thomas von; Hafner, Mathias; Frech, Christian

doi:10.1016/j.chroma.2022.463265

Cited by 2 publications

(1 citation statement)

References 68 publications

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“…[6,9] However, the accurate calculation of σ was a complex and challenging task, and various approaches have been explored in recent studies. [33,34,57,58]…”

Section: F I G U R Ementioning

confidence: 99%

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Chen,

Lu,

Wang

et al. 2024

Biotechnology Journal

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Developing an accurate and reliable model for chromatographic separation that meets regulatory requirements and ensures consistency in model development remains challenging. In order to address this challenge, a standardized approach was proposed in this study with ion‐exchange chromatography (IEC). The approach includes the following steps: liquid flow identification, system and column‐specific parameters determination and validation, multi‐component system identification, protein amount validation, steric mass action parameters determination and evaluation, and validation of the calibrated model's generalization ability. The parameter‐by‐parameter (PbP) calibration method and the consideration of extra‐column effects were integrated to enhance the accuracy of the developed models. The experiments designed for implementing the PbP method (five gradient experiments for model calibration and one stepwise experiment for model validation) not only streamline the experimental workload but also ensure the extrapolation abilities of the model. The effectiveness of the standardized approach is successfully validated through an application about the IEC separation of industrial antibody variants, and satisfactory results were observed with R2 ≈ 0.9 for the majority of calibration and validation experiments. The standardized approach proposed in this work contributes significantly to improve the accuracy and reliability of the developed IEC models. Models developed using this standardized approach are ready to be applied to a broader range of industrial separation systems, and are likely find further applications in model‐assisted decision‐making of process development.

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“…[6,9] However, the accurate calculation of σ was a complex and challenging task, and various approaches have been explored in recent studies. [33,34,57,58]…”

Section: F I G U R Ementioning

confidence: 99%

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Chen,

Lu,

Wang

et al. 2024

Biotechnology Journal

View full text Add to dashboard Cite

show abstract

Current state of implementation of in silico tools in the biopharmaceutical industry—Proceedings of the 5th modeling workshop

Wittkopp,

Welsh,

Todd

et al. 2024

Biotech & Bioengineering

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The fifth modeling workshop (5MW) was held in June 2023 at Favrholm, Denmark and sponsored by Recovery of Biological Products Conference Series. The goal of the workshop was to assemble modeling practitioners to review and discuss the current state, progress since the last fourth mini modeling workshop (4MMW), gaps and opportunities for development, deployment and maintenance of models in bioprocess applications. Areas of focus were four categories: biophysics and molecular modeling, mechanistic modeling, computational fluid dynamics (CFD) and plant modeling. Highlights of the workshop included significant advancements in biophysical/molecular modeling to novel protein constructs, mechanistic models for filtration and initial forays into modeling of multiphase systems using CFD for a bioreactor and mapped strategically to cell line selection/facility fit. A significant impediment to more fully quantitative and calibrated models for biophysics is the lack of large, anonymized datasets. A potential solution would be the use of specific descriptors in a database that would allow for detailed analyzes without sharing proprietary information. Another gap identified was the lack of a consistent framework for use of models that are included or support a regulatory filing beyond the high‐level guidance in ICH Q8–Q11. One perspective is that modeling can be viewed as a component or precursor of machine learning (ML) and artificial intelligence (AI). Another outcome was alignment on a key definition for “mechanistic modeling.” Feedback from participants was that there was progression in all of the fields of modeling within scope of the conference. Some areas (e.g., biophysics and molecular modeling) have opportunities for significant research investment to realize full impact. However, the need for ongoing research and development for all model types does not preclude the application to support process development, manufacturing and use in regulatory filings. Analogous to ML and AI, given the current state of the four modeling types, a prospective investment in educating inter‐disciplinary subject matter experts (e.g., data science, chromatography) is essential to advancing the modeling community.

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Application of the Steric Mass Action formalism for modeling under high loading conditions: Part 1. Investigation of the influence of pH on the steric shielding factor

Cited by 2 publications

References 68 publications

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

Current state of implementation of in silico tools in the biopharmaceutical industry—Proceedings of the 5th modeling workshop

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