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High-Throughput Process Development: I-Process Chromatography.
- Source :
-
Methods in molecular biology (Clifton, N.J.) [Methods Mol Biol] 2021; Vol. 2178, pp. 11-20. - Publication Year :
- 2021
-
Abstract
- Chromatographic separation serves as "a workhorse" for downstream process development and plays a key role in the removal of product-related, host-cell-related, and process-related impurities. Complex and poorly characterized raw materials and feed material, low feed concentration, product instability, and poor mechanistic understanding of the processes are some of the critical challenges that are faced during the development of a chromatographic step. Traditional process development is performed as a trial-and-error-based evaluation and often leads to a suboptimal process. A high-throughput process development (HTPD) platform involves the integration of miniaturization, automation, and parallelization and provides a systematic approach for time- and resource-efficient chromatographic process development. Creation of such platforms requires the integration of mechanistic knowledge of the process with various statistical tools for data analysis. The relevance of such a platform is high in view of the constraints with respect to time and resources that the biopharma industry faces today.This protocol describes the steps involved in performing the HTPD of chromatography steps. It describes the operation of a commercially available device (PreDictor™ plates from GE Healthcare). This device is available in 96-well format with 2 or 6 μL well size. We also discuss the challenges that one faces when performing such experiments as well as possible solutions to alleviate them. Besides describing the operation of the device, the protocol also presents an approach for statistical analysis of the data that are gathered from such a platform. A case study involving the use of the protocol for examining ion exchange chromatography of the Granulocyte Colony Stimulating Factor (GCSF), a therapeutic product, is briefly discussed. This is intended to demonstrate the usefulness of this protocol in generating data that are representative of the data obtained at the traditional lab scale. The agreement in the data is indeed very significant (regression coefficient 0.93). We think that this protocol will be of significant value to those involved in performing the high-throughput process development of the chromatography process.
- Subjects :
- Animals
Chromatography, Ion Exchange instrumentation
Equipment Design
High-Throughput Screening Assays instrumentation
High-Throughput Screening Assays methods
Humans
Receptors, Granulocyte Colony-Stimulating Factor analysis
Receptors, Granulocyte Colony-Stimulating Factor isolation & purification
Chromatography, Ion Exchange methods
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6029
- Volume :
- 2178
- Database :
- MEDLINE
- Journal :
- Methods in molecular biology (Clifton, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 33128739
- Full Text :
- https://doi.org/10.1007/978-1-0716-0775-6_2