eprintid: 10191588 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/19/15/88 datestamp: 2024-05-03 08:17:49 lastmod: 2024-05-03 08:17:49 status_changed: 2024-05-03 08:17:49 type: article metadata_visibility: show sword_depositor: 699 creators_name: Sharma, Paras creators_name: Robbel, Lars creators_name: Schmitt, Michael creators_name: Dikicioglu, Duygu creators_name: Bracewell, Daniel G title: Integrated micro-scale protein a chromatography and Low pH viral inactivation unit operations on an automated platform ispublished: pub divisions: UCL divisions: B04 divisions: C05 divisions: F47 keywords: downstream processing, high throughput process development, micro‐scale, monoclonal antibodies, scale‐down note: 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. 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. date: 2024-04-30 date_type: published publisher: Wiley official_url: http://dx.doi.org/10.1002/btpr.3476 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2271969 doi: 10.1002/btpr.3476 medium: Print-Electronic lyricists_name: Bracewell, Daniel lyricists_name: Dikicioglu, Duygu lyricists_id: DGBRA75 lyricists_id: DDIKI78 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: EP/T517793/1 [Engineering and Physical Sciences Research Council] full_text_status: public publication: Biotechnology Progress article_number: e3476 event_location: United States issn: 8756-7938 citation: 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 <https://doi.org/10.1002/btpr.3476>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10191588/1/Integrated%20micro%20scale%20protein%20a%20chromatography%20and%20Low%20pH%20viral%20inactivation%20unit.pdf