Membrane adsorbers as purification tools for monoclonal antibody purification.

Downstream purification processes for monoclonal antibody production typically involve multiple steps; some of them are conventionally performed by bead-based column chromatography. Affinity chromatography with Protein A is the most selective method for protein purification and is conventionally used for the initial capturing step to facilitate rapid volume reduction as well as separation of the antibody. However, conventional affinity chromatography has some limitations that are inherent with the method, it exhibits slow intraparticle diffusion and high pressure drop within the column. Membrane-based separation processes can be used in order to overcome these mass transfer limitations. The ligand is immobilized in the membrane pores and the convective flow brings the solute molecules very close to the ligand and hence minimizes the diffusional limitations associated with the beads. Nonetheless, the adoption of this technology has been slow because membrane chromatography has been limited by a lower binding capacity than that of conventional columns, even though the high flux advantages provided by membrane adsorbers would lead to higher productivity. This review considers the use of membrane adsorbers as an alternative technology for capture and polishing steps for the purification of monoclonal antibodies. Promising industrial applications as well as new trends in research will be addressed.

[1]  H. Zou,et al.  Affinity membrane chromatography for the analysis and purification of proteins. , 2001, Journal of biochemical and biophysical methods.

[2]  Maria Rossi,et al.  Affinity purification of polyclonal antibodies using a new all-D synthetic peptide ligand: comparison with protein A and protein G. , 2002, Journal of immunological methods.

[3]  Henry C. Thomas,et al.  Heterogeneous Ion Exchange in a Flowing System , 1944 .

[4]  S. Suen,et al.  Sorption kinetics and breakthrough curves for pepsin and chymosin using pepstatin A affinity membranes. , 1994, Journal of chromatography. A.

[5]  M. Etzel,et al.  Purification of Bovine Immunoglobulin G via Protein G Affinity Membranes , 1996 .

[6]  R. Seshadri,et al.  Affinity adsorption devices prepared from microporous poly(amide) hollow fibers and sheet membranes , 1997 .

[7]  C. Lowe,et al.  Affinity chromatography on immobilized "biomimetic" ligands. Synthesis, immobilization and chromatographic assessment of an immunoglobulin G-binding ligand. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[8]  E. Ruckenstein,et al.  Membrane Chromatography: Preparation and Applications to Protein Separation , 1999, Biotechnology progress.

[9]  W Demmer,et al.  Large-scale membrane adsorbers. , 1999, Journal of chromatography. A.

[10]  S. Zale,et al.  Membrane-Based Affinity Technology for Commercial Scale Purifications , 1988, Bio/Technology.

[11]  M. Etzel,et al.  Analysis of Protein Purification Using Ion-Exchange Membranes , 1999 .

[12]  Klaus Huse,et al.  Purification of antibodies by affinity chromatography. , 2002, Journal of biochemical and biophysical methods.

[13]  G. Fassina,et al.  Immunoglobulin specificity of TG19318: a novel synthetic ligand for antibody affinity purification , 1998, Journal of molecular recognition : JMR.

[14]  Chris Antoniou,et al.  Performance of a Novel Viresolve NFR Virus Filter , 2002, Biotechnology progress.

[15]  M. Etzel,et al.  Mass transfer limitations in protein separations using ion-exchange membranes. , 1996, Journal of chromatography. A.

[16]  N. Slater,et al.  Characterisation of a generic monoclonal antibody harvesting system for adsorption of DNA by depth filters and various membranes , 1999, Bioseparation.

[17]  P. Blond,et al.  Purification of immunoglobulins G by protein A/G affinity membrane chromatography. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[18]  J. Talbot,et al.  Analysis of steric hindrance effects on adsorption kinetics and equilibria , 1994 .

[19]  C. Lowe,et al.  New developments in affinity chromatography with potential application in the production of biopharmaceuticals. , 2001, Journal of biochemical and biophysical methods.

[20]  G. Hermanson,et al.  Immobilized Affinity Ligand Techniques , 1992 .

[21]  G. Fassina,et al.  Novel ligands for the affinity-chromatographic purification of antibodies. , 2001, Journal of biochemical and biophysical methods.

[22]  E. Klein Affinity membranes: a 10-year review , 2000 .

[23]  G. Birkenmeier,et al.  Separation of paraproteins from human plasma by membrane chromatography. , 1997, Journal of chromatography. B, Biomedical sciences and applications.

[24]  C. Dowd,et al.  Performance of a membrane adsorber for trace impurity removal in biotechnology manufacturing. , 2005, Journal of chromatography. A.

[25]  R. Ghosh Membrane chromatographic immunoassay method for rapid quantitative analysis of specific serum antibodies. , 2006, Biotechnology and bioengineering.

[26]  Wolf-Dieter Deckwer,et al.  Comparison of affinity membranes for the purification of immunoglobulins , 2002 .

[27]  K. Kroner,et al.  Surface-modified membranes as a matrix for protein purification. , 1992, Journal of chromatography.

[28]  Raja Ghosh,et al.  Protein separation using membrane chromatography: opportunities and challenges. , 2002, Journal of chromatography. A.

[29]  A. Zydney,et al.  Membrane separations in biotechnology. , 2001, Current opinion in biotechnology.

[30]  Richard Francis,et al.  Optimised affinity purification of polyclonal antibodies from hyper immunised ovine serum using a synthetic Protein A adsorbent, MAbsorbent A2P. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[31]  G. Bayramoglu,et al.  Preparation and characterisation of surfaces properties of poly(hydroxyethylmethacrylate-co-methacrylolyamido-histidine) membranes: application for purification of human immunoglobulin G. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[32]  M. Kula,et al.  Application of thiophilic membranes for the purification of monoclonal antibodies from cell culture media. , 1995, Journal of chromatography. B, Biomedical applications.

[33]  K. Kojima,et al.  Selective removal of immunoglobulin E from rat blood by membrane-immobilized antibody. , 1995, Journal of chromatography. B, Biomedical applications.

[34]  Z. Su,et al.  Protein A immunoaffinity hollow fiber membranes for immunoglobulin G purification: experimental characterization. , 1995, Biotechnology and bioengineering.

[35]  M Angela Taipa,et al.  Antibodies and Genetically Engineered Related Molecules: Production and Purification , 2004, Biotechnology progress.

[36]  M. Vijayalakshmi,et al.  Interaction of human immunoglobulin G with l-histidine immobilized onto poly(ethylene vinyl alcohol) hollow-fiber membranes. , 1995, Journal of chromatography. B, Biomedical applications.

[37]  C. Lowe,et al.  Design, synthesis, and application of a Protein A mimetic , 1998, Nature Biotechnology.

[38]  M. Vijayalakshmi,et al.  Separation of immunoglobulin G from human serum by pseudobioaffinity chromatography using immobilized L-histidine in hollow fibre membranes. , 1995, Journal of chromatography. B, Biomedical applications.

[39]  Kyoichi Saito,et al.  Adsorption Characteristics of an Immobilized Metal Affinity Membrane , 1991, Biotechnology progress.

[40]  P. Viot,et al.  From car parking to protein adsorption: an overview of sequential adsorption processes , 1999, cond-mat/9906428.

[41]  G. Smejkal,et al.  Separation Methods In Proteomics , 2005 .

[42]  G. Fassina,et al.  Affinity purification of immunoglobulin M using a novel synthetic ligand. , 1998, Journal of chromatography. B, Biomedical sciences and applications.

[43]  Haiou Yang,et al.  Hexamer peptide affinity resins that bind the Fc region of human immunoglobulin G , 2008 .

[44]  C. Bamford,et al.  Studies of a novel membrane for affinity separations: I. Functionalisation and protein coupling , 1992 .

[45]  R L Fahrner,et al.  Membrane ion-exchange chromatography for process-scale antibody purification. , 2001, Journal of chromatography. A.

[46]  G. Fassina,et al.  Affinity purification of polyclonal antibodies using immobilized multimeric peptides. , 1995, Journal of chromatography. B, Biomedical applications.

[47]  S. Suen,et al.  A mathematical analysis of affinity membrane bioseparations , 1992 .

[48]  L. Castilho Influence of matrix activation and polymer coating on the purification of human IgG with protein A affinity membranes , 2000 .

[49]  D. Keith Roper,et al.  Separation of biomolecules using adsorptive membranes , 1995 .

[50]  I. Lundström Models of protein adsorption on solid surfaces , 1985 .

[51]  E. Klein,et al.  Affinity membranes prepared from hydrophilic coatings on microporous polysulfone hollow fibers , 1994 .

[52]  S. Suen,et al.  Sorption kinetics and axial diffusion in binary-solute affinity-membrane bioseparations , 1993 .

[53]  G. Belfort,et al.  Protein fractionation using fast flow immobilized metal chelate affinity membranes , 1994, Biotechnology and bioengineering.

[54]  C. Lowe,et al.  New strategy for the design of ligands for the purification of pharmaceutical proteins by affinity chromatography. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[55]  M. Kula,et al.  Fast protein chromatography on analytical and preparative scale using modified microporous membranes , 1992 .

[56]  M. Nachman Kinetic aspects of membrane-based immunoaffinity chromatography. , 1992, Journal of chromatography.

[57]  T. Przybycien,et al.  Alternative bioseparation operations: life beyond packed-bed chromatography. , 2004, Current opinion in biotechnology.

[58]  J. L. Manganaro,et al.  Protein Purification with Novel Porous Sheets Containing Derivatized Cellulose , 1993, Biotechnology progress.

[59]  Mark R. Etzel,et al.  Purification of a large protein using ion-exchange membranes , 2002 .

[60]  M. Etzel,et al.  Evaluation of an ion‐exchange membrane for the purification of plasmid DNA , 2003, Biotechnology and applied biochemistry.

[61]  M. Etzel,et al.  Evaluation of Three Kinetic Equations in Models of Protein Purification Using Ion-Exchange Membranes , 2003 .

[62]  U. Palanisamy,et al.  Design, synthesis and characterisation of affinity ligands for glycoproteins , 1999, Journal of molecular recognition : JMR.

[63]  Jörg Thömmes,et al.  Membrane Chromatography—An Integrative Concept in the Downstream Processing of Proteins , 1995 .