Application of a High-Throughput Screening Procedure with PEG-Induced Precipitation to Compare Relative Protein Solubility During Formulation Development with IgG1 Monoclonal Antibodies

2011 ◽  
Vol 100 (3) ◽  
pp. 1009-1021 ◽  
Author(s):  
Todd J. Gibson ◽  
Katie Mccarty ◽  
Iain J. McFadyen ◽  
Ethan Cash ◽  
Paul Dalmonte ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
High Throughput ◽  
High Throughput Screening ◽  
Protein Solubility ◽  
Screening Procedure ◽  
Formulation Development

scholarly journals High-Throughput Screening and Analysis of Charge Variants of Monoclonal Antibodies in Multiple Formulations

2017 ◽  
Vol 22 (8) ◽  
pp. 1044-1052
Author(s):  
Larysa Alekseychyk ◽  
Cheng Su ◽  
Gerald W. Becker ◽  
Michael J. Treuheit ◽  
Vladimir I. Razinkov
Keyword(s):  
Monoclonal Antibodies ◽  
High Throughput ◽  
High Throughput Screening ◽  
Time Frame ◽  
Exchange Chromatography ◽  
Rapid Screening ◽  
Formulation Development ◽  
Charge Variants ◽  
The Right ◽  
High Level

Among different biopharmaceutical products, monoclonal antibodies (mAbs) show a high level of complexity, including heterogeneity due to differences in size, hydrophobicity, charge, and so forth. Such heterogeneity can be related to both cell-based production and any of the stages of purification, storage, and delivery that the mAb is subjected to. Choosing the right formulation composition providing both physical and chemical stabilities can be a very challenging process, especially when done in the limited time frame required for a typical drug development cycle. Charge variants, a common type of heterogeneity for mAbs, are easy to detect by ion exchange, specifically cation exchange chromatography (CEX). We have developed and implemented a high-throughput CEX-based approach for the rapid screening and analysis of charge modifications in multiple formulation conditions. In this work, 96 different formulations of antistreptavidin IgG1 and IgG2 molecules were automatically prepared and analyzed after incubation at high temperature. Design of experiment and statistical analysis tools have been utilized to determine the major formulation factors responsible for chemical stability of antibodies. Regression models were constructed to find the optimal formulation conditions. The methodology can be applied to different stages of preformulation and formulation development of mAbs.

A novel method to evaluate protein solubility using a high throughput screening approach

2009 ◽  
Vol 64 (17) ◽  
pp. 3778-3788 ◽  
Author(s):  
Matthias Wiendahl ◽  
Christiane Völker ◽  
Ilka Husemann ◽  
Janus Krarup ◽  
Arne Staby ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Protein Solubility ◽  
Screening Approach ◽  
Novel Method

scholarly journals High-Throughput Screening and Stability Optimization of Anti-Streptavidin IgG1 and IgG2 Formulations

2014 ◽  
Vol 19 (9) ◽  
pp. 1290-1301 ◽  
Author(s):  
Larysa Alekseychyk ◽  
Cheng Su ◽  
Gerald W. Becker ◽  
Michael J. Treuheit ◽  
Vladimir I. Razinkov
Keyword(s):  
High Throughput ◽  
Conformational Changes ◽  
High Throughput Screening ◽  
Multivariate Regression Analysis ◽  
Chemical Degradation ◽  
Formulation Development ◽  
Long Term Storage ◽  
Formulation Factors ◽  
Type Of Stability ◽  
And Control

Selection of a suitable formulation that provides adequate product stability is an important aspect of the development of biopharmaceutical products. Stability of proteins includes not only resistance to chemical modifications but also conformational and colloidal stabilities. While chemical degradation of antibodies is relatively easy to detect and control, propensity for conformational changes and/or aggregation during manufacturing or long-term storage is difficult to predict. In many cases, the formulation factors that increase one type of stability may significantly decrease another type under the same or different conditions. Often compromise is necessary to minimize the adverse effects of an antibody formulation by careful optimization of multiple factors responsible for overall stability. In this study, high-throughput stress and characterization techniques were applied to 96 formulations of anti-streptavidin antibodies (an IgG1 and an IgG2) to choose optimal formulations. Stress and analytical methods applied in this study were 96-well plate based using an automated liquid handling system to prepare the different formulations and sample plates. Aggregation and clipping propensity were evaluated by temperature and mechanical stresses. Multivariate regression analysis of high-throughput data was performed to find statistically significant formulation factors that alter measured parameters such as monomer percentage or unfolding temperature. The results of the regression models were used to maximize the stabilities of antibodies under different formulations and to find the optimal formulation space for each molecule. Comparison of the IgG1 and IgG2 data indicated an overall greater stability of the IgG1 molecule under the conditions studied. The described method can easily be applied to both initial preformulation screening and late-stage formulation development of biopharmaceutical products.

High throughput screening of ultrafiltration and diafiltration processing of monoclonal antibodies via the ambr® crossflow system

2020 ◽  
Vol 36 (2) ◽  
Author(s):  
Lara Fernandez‐Cerezo ◽  
Michael K. Wismer ◽  
InKwan Han ◽  
Jennifer M. Pollard
Keyword(s):  
Monoclonal Antibodies ◽  
High Throughput ◽  
High Throughput Screening
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