Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins: Effects of physical properties

Youngbin Baek, Nripen Singh, Abhiram Arunkumar, Michael Borys, Zheng J. Li, Andrew L. Zydney

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ultrafiltration (UF) is used for the final concentration and formulation of essentially all antibody-based therapeutics including both monoclonal antibodies (mAbs) and Fc-fusion proteins. The objective of this study was to quantitatively compare the filtrate flux behavior for two highly purified mAbs and an Fc-fusion protein under identical flow and buffer conditions. Filtrate flux data were obtained using a Pellicon 3 tangential flow filtration cassette over a wide range of transmembrane pressures and bulk protein concentrations. Independent experimental measurements were performed to evaluate the protein osmotic pressure and solution viscosity. The maximum achievable protein concentration was directly correlated with the solution viscosity, which controls the pressure drop and extent of back-filtration in the cassette. The filtrate flux data were analyzed using a recently developed model that accounts for the effects of intermolecular interactions and transmembrane pressure gradients on the extent of concentration polarization. These results provide important insights into the factors controlling the filtrate flux during the UF of concentrated protein solutions and an effective framework for the design/analysis of UF processes for the formulation of antibody-based therapeutics. Biotechnol. Bioeng. 2017;114: 2057–2065.

Original languageEnglish (US)
Pages (from-to)2057-2065
Number of pages9
JournalBiotechnology and bioengineering
Volume114
Issue number9
DOIs
StatePublished - Sep 2017

Fingerprint

Monoclonal antibodies
Ultrafiltration
Fusion reactions
Physical properties
Monoclonal Antibodies
Proteins
Fluxes
Pressure
Antibodies
Viscosity
Osmotic Pressure
Pressure gradient
Pressure drop
Buffers
Polarization
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Baek, Youngbin ; Singh, Nripen ; Arunkumar, Abhiram ; Borys, Michael ; Li, Zheng J. ; Zydney, Andrew L. / Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins : Effects of physical properties. In: Biotechnology and bioengineering. 2017 ; Vol. 114, No. 9. pp. 2057-2065.
@article{a35dfe65e4e1415abe863606500a7dbe,
title = "Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins: Effects of physical properties",
abstract = "Ultrafiltration (UF) is used for the final concentration and formulation of essentially all antibody-based therapeutics including both monoclonal antibodies (mAbs) and Fc-fusion proteins. The objective of this study was to quantitatively compare the filtrate flux behavior for two highly purified mAbs and an Fc-fusion protein under identical flow and buffer conditions. Filtrate flux data were obtained using a Pellicon 3 tangential flow filtration cassette over a wide range of transmembrane pressures and bulk protein concentrations. Independent experimental measurements were performed to evaluate the protein osmotic pressure and solution viscosity. The maximum achievable protein concentration was directly correlated with the solution viscosity, which controls the pressure drop and extent of back-filtration in the cassette. The filtrate flux data were analyzed using a recently developed model that accounts for the effects of intermolecular interactions and transmembrane pressure gradients on the extent of concentration polarization. These results provide important insights into the factors controlling the filtrate flux during the UF of concentrated protein solutions and an effective framework for the design/analysis of UF processes for the formulation of antibody-based therapeutics. Biotechnol. Bioeng. 2017;114: 2057–2065.",
author = "Youngbin Baek and Nripen Singh and Abhiram Arunkumar and Michael Borys and Li, {Zheng J.} and Zydney, {Andrew L.}",
year = "2017",
month = "9",
doi = "10.1002/bit.26326",
language = "English (US)",
volume = "114",
pages = "2057--2065",
journal = "Biotechnology and Bioengineering",
issn = "0006-3592",
publisher = "Wiley-VCH Verlag",
number = "9",

}

Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins : Effects of physical properties. / Baek, Youngbin; Singh, Nripen; Arunkumar, Abhiram; Borys, Michael; Li, Zheng J.; Zydney, Andrew L.

In: Biotechnology and bioengineering, Vol. 114, No. 9, 09.2017, p. 2057-2065.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ultrafiltration behavior of monoclonal antibodies and Fc-fusion proteins

T2 - Effects of physical properties

AU - Baek, Youngbin

AU - Singh, Nripen

AU - Arunkumar, Abhiram

AU - Borys, Michael

AU - Li, Zheng J.

AU - Zydney, Andrew L.

PY - 2017/9

Y1 - 2017/9

N2 - Ultrafiltration (UF) is used for the final concentration and formulation of essentially all antibody-based therapeutics including both monoclonal antibodies (mAbs) and Fc-fusion proteins. The objective of this study was to quantitatively compare the filtrate flux behavior for two highly purified mAbs and an Fc-fusion protein under identical flow and buffer conditions. Filtrate flux data were obtained using a Pellicon 3 tangential flow filtration cassette over a wide range of transmembrane pressures and bulk protein concentrations. Independent experimental measurements were performed to evaluate the protein osmotic pressure and solution viscosity. The maximum achievable protein concentration was directly correlated with the solution viscosity, which controls the pressure drop and extent of back-filtration in the cassette. The filtrate flux data were analyzed using a recently developed model that accounts for the effects of intermolecular interactions and transmembrane pressure gradients on the extent of concentration polarization. These results provide important insights into the factors controlling the filtrate flux during the UF of concentrated protein solutions and an effective framework for the design/analysis of UF processes for the formulation of antibody-based therapeutics. Biotechnol. Bioeng. 2017;114: 2057–2065.

AB - Ultrafiltration (UF) is used for the final concentration and formulation of essentially all antibody-based therapeutics including both monoclonal antibodies (mAbs) and Fc-fusion proteins. The objective of this study was to quantitatively compare the filtrate flux behavior for two highly purified mAbs and an Fc-fusion protein under identical flow and buffer conditions. Filtrate flux data were obtained using a Pellicon 3 tangential flow filtration cassette over a wide range of transmembrane pressures and bulk protein concentrations. Independent experimental measurements were performed to evaluate the protein osmotic pressure and solution viscosity. The maximum achievable protein concentration was directly correlated with the solution viscosity, which controls the pressure drop and extent of back-filtration in the cassette. The filtrate flux data were analyzed using a recently developed model that accounts for the effects of intermolecular interactions and transmembrane pressure gradients on the extent of concentration polarization. These results provide important insights into the factors controlling the filtrate flux during the UF of concentrated protein solutions and an effective framework for the design/analysis of UF processes for the formulation of antibody-based therapeutics. Biotechnol. Bioeng. 2017;114: 2057–2065.

UR - http://www.scopus.com/inward/record.url?scp=85032826739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032826739&partnerID=8YFLogxK

U2 - 10.1002/bit.26326

DO - 10.1002/bit.26326

M3 - Article

C2 - 28464237

AN - SCOPUS:85032826739

VL - 114

SP - 2057

EP - 2065

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 9

ER -