Sharma, Paras;
Robbel, Lars;
Schmitt, Michael;
Dikicioglu, Duygu;
Bracewell, Daniel G;
(2024)
Integrated micro-scale protein a chromatography and Low pH viral inactivation unit operations on an automated platform.
Biotechnology Progress
, Article e3476. 10.1002/btpr.3476.
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Abstract
High throughput process development (HTPD) is established for time- and resource- efficient chromatographic process development. However, integration with non-chromatographic operations within a monoclonal antibody (mAb) purification train is less developed. An area of importance is the development of low pH viral inactivation (VI) that follows protein A chromatography. However, the lack of pH measurement devices at the micro-scale represents a barrier to implementation, which prevents integration with the surrounding unit operations, limiting overall process knowledge. This study is based upon the design and testing of a HTPD platform for integration of the protein A and low pH VI operations. This was achieved by using a design and simulation software before execution on an automated liquid handler. The operations were successfully translated to the micro-scale, as assessed by analysis of recoveries and molecular weight content. The integrated platform was then used as a tool to assess the effect of pH on HMWC during low pH hold. The laboratory-scale and micro-scale elution pools showed comparable HMWC across the pH range 3.2-3.7. The investigative power of the platform is highlighted by evaluating the resources required to conduct a hypothetical experiment. This results in lower resource demands and increased labor efficiency relative to the laboratory-scale. For example, the experiment can be conducted in 7 h, compared to 105 h, translating to labor hours, 3 h and 28 h for the micro-scale and laboratory-scale, respectively. This presents the opportunity for further integration beyond chromatographic operations within the purification sequence, to establish a fit-to-platform assessment tool for mAb process development.
| Type: | Article |
|---|---|
| Title: | Integrated micro-scale protein a chromatography and Low pH viral inactivation unit operations on an automated platform |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/btpr.3476 |
| Publisher version: | http://dx.doi.org/10.1002/btpr.3476 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. |
| Keywords: | downstream processing, high throughput process development, micro‐scale, monoclonal antibodies, scale‐down |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191588 |
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