TY - JOUR

T1 - Membrane Adsorber for the Fast Purification of a Monoclonal Antibody Using Protein A Chromatography

AU - Brämer, Chantal

AU - Tünnermann, Lisa

AU - Salcedo, Alina Gonzalez

AU - Reif, Oscar Werner

AU - Solle, Dörte

AU - Scheper, Thomas

AU - Beutel, Sascha

N1 - Funding information: We acknowledge financial support by the BMBF within the project ProzessallianzWiPro (031B0475I). We would like to thank Florian Taft, Patrick Adametz and Katrin Töppner from Sartorius Stedim Biotech for their support in this project. The publication of this article was funded by the Open Access fund of Leibniz Universität Hannover. using DoE, the number of experiments could be reduced and thus the optimization was very fast. The use of membrane adsorbers has the advantage that the process is easily scalable and the disposable MA can be disposed of after use. Furthermore, the transfer of the batch to continuous DoE,operathetionumbern modeofwexperimentsas describecouldd, anbedrteducedhis isandverythusreltheevanoptimizationt to currenwast deveryvelofast.pmenThets iusen tofhe membranebiotechnologadsorbersical induhasstrythe. advantage that the process is easily scalable and the disposable MA can be disposed of after use. Furthermore, the transfer of the batch to continuous operation mode was dAeuscthriobreCdo, natnrdibuthtiiosniss:vCeornycreeplteuvaalinzatttioonc,u Cr.rBe.n atndde Sv.Be.l;o mpmetheondtsoliongyth, eC.bBi.o; ftoercmhnalo alongaliycsails,i nS.dBu.; sitnrvye.stigation, C.B., L.T., A.G.S.; resources, S.B. and T.S.; writing—original draft preparation, C.B.; writing—review and editing, A.S.G., D.S., T.S., S.B.; visualization, C.B.; supervision, T.S. and S.B.; project administration, S.B.; funding C.B., L.T., A.G.S.; resources, S.B., O.-W.R. and T.S.; writing—original draft preparation, C.B.; writing—review and acquisition, D.S. editing, A.G.S., D.S., T.S., S.B.; visualization, C.B.; supervision, T.S. and S.B.; project administration, S.B.; funding Funding: We acknowledge financial support by the BMBF within the project Prozessallianz WiPro (031B0475I). FNuno dfuinrgth: eWr eexatcekrnnaolw fulenddgiengfi nwaansc riaelcesuivpepdo. rt by the BMBF within the project Prozessallianz WiPro (031B0475I). No further external funding was received. Acknowledgments: We would like to thank Dr. Florian Taft, Patrick Adametz and Katrin Töppner from Sartorius Stedim Biotech for their support in this project. The publication of this article was funded by the Open Stedim Biotech for their support in this project. The publication of this article was funded by the Open Access Access fund of Leibniz Universität Hannover. fund of Leibniz Universität Hannover. Conflicts of Interest: The authors have declared no conflict of interest.

PY - 2019/12

Y1 - 2019/12

N2 - Monoclonal antibodies are conquering the biopharmaceutical market because they can be used to treat a variety of diseases. Therefore, it is very important to establish robust and optimized processes for their production. In this article, the first step of chromatography (Protein A chromatography) in monoclonal antibody purification was optimized with a focus on the critical elution step. Therefore, different buffers (citrate, glycine, acetate) were tested for chromatographic performance and product quality. Membrane chromatography was evaluated because it promises high throughputs and short cycle times. The membrane adsorber Sartobind® Protein A 2 mL was used to accelerate the purification procedure and was further used to perform a continuous chromatographic run with a four-membrane adsorber-periodic counter-current chromatography (4MA-PCCC) system. It was found that citrate buffer at pH 3.5 and 0.15 M NaCl enabled the highest recovery of >95% and lowest total aggregate content of 0.26%. In the continuous process, the capacity utilization of the membrane adsorber was increased by 20%.

AB - Monoclonal antibodies are conquering the biopharmaceutical market because they can be used to treat a variety of diseases. Therefore, it is very important to establish robust and optimized processes for their production. In this article, the first step of chromatography (Protein A chromatography) in monoclonal antibody purification was optimized with a focus on the critical elution step. Therefore, different buffers (citrate, glycine, acetate) were tested for chromatographic performance and product quality. Membrane chromatography was evaluated because it promises high throughputs and short cycle times. The membrane adsorber Sartobind® Protein A 2 mL was used to accelerate the purification procedure and was further used to perform a continuous chromatographic run with a four-membrane adsorber-periodic counter-current chromatography (4MA-PCCC) system. It was found that citrate buffer at pH 3.5 and 0.15 M NaCl enabled the highest recovery of >95% and lowest total aggregate content of 0.26%. In the continuous process, the capacity utilization of the membrane adsorber was increased by 20%.

KW - Membrane adsorber

KW - Monoclonal antibody

KW - Periodic counter-current chromatography

KW - Protein A chromatography

UR - http://www.scopus.com/inward/record.url?scp=85076091867&partnerID=8YFLogxK

U2 - 10.3390/membranes9120159

DO - 10.3390/membranes9120159

M3 - Article

AN - SCOPUS:85076091867

VL - 9

JO - Membranes

JF - Membranes

IS - 12

M1 - 159

ER -