Continuous Preparative SEC for Purification of “Difficult-to-Manufacture” Proteins–A Feasibility Study

November 2, 2020
Kilian Brand

Kilian Brand is lab technician downstream process development at at Sanofi-Aventis Deutschland GmbH.

,
Florian Capito

Florian Capito is lab head downstream process development at Sanofi-Aventis Deutschland GmbH.

,
Verena Oeinck

Verena Oeinck is lab technician downstream process development at Sanofi-Aventis Deutschland GmbH.

,
Hendrik Flato

Hendrik Flato is lab engineer downstream process development at Sanofi-Aventis Deutschland GmbH.

,
Marc Bisschops

Marc Bisschops is director at Pall Medistad.

,
Martin Glenz

Martin Glenz is principal scientist at Pall GmbH.

,
Ralf Ehret

Ralf Ehret is vice dean at Provadis School of International Management and Technology.

BioPharm International, BioPharm International-11-01-2020, Volume 33, Issue 11
Page Number: 28–35

Continuous SEC was shown to increase productivity with the same product quality and yield.

The advent of new antibody formats, such as multispecific antibodies or Fc-fusion proteins, imposes new challenges on downstream processing. Classical Protein A or ion exchange chromatography may not be capable of delivering adequate product quality if impurities display similar physicochemical properties compared to the target product. Size exclusion chromatography (SEC) with the possibility to purify according to the molecule size suffers from low productivity and is, thus, rarely used in commercial antibody purification. In this feasibility study, the principle suitability of continuous SEC using simulated moving bed chromatography to separate bovine serum albumin (BSA) and myoglobin, as model proteins, is shown. The applicability of this approach for separation of high molecular weight species (HMWs) from a multispecific antibody is then further evaluated. Compared to batch SEC, productivity is increased by a factor of 2.2 while maintaining higher product quality and yield. Additionally, BSA and myoglobin are separated with a productivity increase of factor 3.3–3.4, showing the feasibility of considering continuous SEC as an emerging viable option for “difficult-to-manufacture” proteins, especially for purification of a specific molecule in larger quantities.

Peer-Reviewed

Submitted: March 13, 2020
Accepted: June 23, 2020

About the authors

Kilian Brand is lab technician downstream process development, Florian Capito*, Florian.capito@sanofi.com, is lab head downstream process development, Verena Oeinck is lab technician downstream process development, and Hendrik Flato is lab engineer downstream process development; all at Sanofi-Aventis Deutschland GmbH. Marc Bisschops is director at Pall Medistad, and Martin Glenz is principal scientist at Pall GmbH. Ralf Ehret is vice dean at Provadis School of International Management and Technology.

*To whom all correspondence should be addressed.

Article Details

BioPharm International
Vol. 33, No. 11
November 2020
Pages: 28–35

Citation

When referring to this article, please cite it as K. Brand et al., “Continuous Preparative SEC for Purification of ‘Difficult-to-Manufacture’ Proteins–A Feasibility Study,” BioPharm International 33 (11) 2020.

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