Formulation Development of Therapeutic Monoclonal Antibodies Using High-Throughput Fluorescence and Static Light Scattering Techniques: Role of Conformational and Colloidal Stability

2011 ◽  
Vol 100 (4) ◽  
pp. 1306-1315 ◽  
Author(s):  
Deborah S. Goldberg ◽  
Steven M. Bishop ◽  
Ambarish U. Shah ◽  
Hasige A Sathish
Keyword(s):  
Monoclonal Antibodies ◽  
Light Scattering ◽  
High Throughput ◽  
Colloidal Stability ◽  
Static Light Scattering ◽  
Formulation Development ◽  
Therapeutic Monoclonal Antibodies

scholarly journals Microwell Plate-Based Dynamic Light Scattering as a High-Throughput Characterization Tool in Biopharmaceutical Development

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 172
Author(s):  
Katharina Dauer ◽  
Stefania Pfeiffer-Marek ◽  
Walter Kamm ◽  
Karl G. Wagner
Keyword(s):  
Light Scattering ◽  
High Throughput ◽  
Colloidal Stability ◽  
Active Pharmaceutical Ingredient ◽  
Formulation Development ◽  
Drug Candidates ◽  
Coefficients Of Variation ◽  
Kd Values ◽  
Data Points ◽  
Lower Variability

High-throughput light scattering instruments are widely used in screening of biopharmaceutical formulations and can be easily incorporated into processes by utilizing multi-well plate formats. High-throughput plate readers are helpful tools to assess the aggregation tendency and colloidal stability of biological drug candidates based on the diffusion self-interaction parameter (kD). However, plate readers evoke issues about the precision and variability of determined data. In this article, we report about the statistical evaluation of intra- and inter-plate variability (384-well plates) for the kD analysis of protein and peptide solutions. ANOVA revealed no significant differences between the runs. In conclusion, the reliability and precision of kD was dependent on the plate position of the sample replicates and kD value. Positive kD values (57.0 mL/g, coefficients of variation (CV) 8.9%) showed a lower variability compared to negative kD values (−14.8 mL/g, CV 13.4%). The variability of kD was not reduced using more data points (120 vs. 30). A kD analysis exclusively based on center wells showed a lower CV (<2%) compared to edge wells (5–12%) or a combination of edge and center wells (2–5%). We present plate designs for kD analysis within the early formulation development, screening up to 20 formulations consuming less than 50 mg of active pharmaceutical ingredient (API).

scholarly journals Accelerated Formulation Development of Monoclonal Antibodies (mAbs) and mAb-Based Modalities

2015 ◽  
Vol 20 (4) ◽  
pp. 468-483 ◽  
Author(s):  
Vladimir I. Razinkov ◽  
Michael J. Treuheit ◽  
Gerald W. Becker
Keyword(s):  
Monoclonal Antibodies ◽  
High Throughput ◽  
Drug Product ◽  
Storage Conditions ◽  
Formulation Development ◽  
Long Term Storage ◽  
Therapeutic Monoclonal Antibodies ◽  
Term Storage ◽  
Selection Of

More therapeutic monoclonal antibodies and antibody-based modalities are in development today than ever before, and a faster and more accurate drug discovery process will ensure that the number of candidates coming to the biopharmaceutical pipeline will increase in the future. The process of drug product development and, specifically, formulation development is a critical bottleneck on the way from candidate selection to fully commercialized medicines. This article reviews the latest advances in methods of formulation screening, which allow not only the high-throughput selection of the most suitable formulation but also the prediction of stability properties under manufacturing and long-term storage conditions. We describe how the combination of automation technologies and high-throughput assays creates the opportunity to streamline the formulation development process starting from early preformulation screening through to commercial formulation development. The application of quality by design (QbD) concepts and modern statistical tools are also shown here to be very effective in accelerated formulation development of both typical antibodies and complex modalities derived from them.

Functional role of carbohydrate residues in human immunoglobulin G and therapeutic monoclonal antibodies

2016 ◽  
Vol 81 (8) ◽  
pp. 835-857 ◽  
Author(s):  
Y. L. Dorokhov ◽  
E. V. Sheshukova ◽  
E. N. Kosobokova ◽  
A. V. Shindyapina ◽  
V. S. Kosorukov ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Immunoglobulin G ◽  
Functional Role ◽  
Human Immunoglobulin ◽  
Human Immunoglobulin G ◽  
Therapeutic Monoclonal Antibodies

The Role of Amino Acid Sequence in the Self-Association of Therapeutic Monoclonal Antibodies: Insights from Coarse-Grained Modeling

2013 ◽  
Vol 117 (5) ◽  
pp. 1269-1279 ◽  
Author(s):  
Anuj Chaudhri ◽  
Isidro E. Zarraga ◽  
Sandeep Yadav ◽  
Thomas W. Patapoff ◽  
Steven J. Shire ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
The Self ◽  
Coarse Grained ◽  
Self Association ◽  
Therapeutic Monoclonal Antibodies

scholarly journals Development of a chromatography-free method for high-throughput MS-based bioanalysis of therapeutic monoclonal antibodies

Bioanalysis ◽  
2021 ◽  
Author(s):  
Zhengqi Zhang ◽  
Yuetian Yan ◽  
Shunhai Wang ◽  
Ning Li
Keyword(s):  
Monoclonal Antibodies ◽  
High Throughput ◽  
Solid Phase ◽  
Proof Of Concept ◽  
Direct Infusion ◽  
Monitoring Method ◽  
Parallel Reaction Monitoring ◽  
Human Igg1 ◽  
Surrogate Peptide ◽  
Therapeutic Monoclonal Antibodies

Aim: Our objective was to test the feasibility of developing an LC-free, MS-based approach for high-throughput bioanalysis of humanized therapeutic monoclonal antibodies. Methodology: A universal tryptic peptide from human IgG1, IgG3 and IgG4 was selected as the surrogate peptide for quantitation. After tryptic digestion, the surrogate peptide was fractionated via solid-phase extraction before being subjected to direct infusion-based MS/MS analysis. A high-resolution, multiplexed (MSX = 2) parallel reaction monitoring method was developed for data acquisition. Results & conclusion: This proof-of-concept study demonstrated the feasibility of achieving high-throughput MS-based bioanalysis of monoclonal antibodies using an LC-free workflow with sensitivity comparable to conventional LC–MS/MS-based methods.

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