Abstract
Increased pressure on upstream processes to maximize productivity has been crowned with great success, although at the cost of shifting the bottleneck to purification. As drivers were economical, focus is on now on debottlenecking downstream processes as the main drivers of high manufacturing cost. Devising a holistically efficient and economical process remains a key challenge. Traditional and emerging protein purification strategies with particular emphasis on methodologies implemented for the production of recombinant proteins of biopharmaceutical importance are reviewed. The breadth of innovation is addressed, as well as the challenges the industry faces today, with an eye to remaining impartial, fair, and balanced. In addition, the scope encompasses both chromatographic and non-chromatographic separations directed at the purification of proteins, with a strong emphasis on antibodies. Complete solutions such as integrated USP/DSP strategies (i.e., continuous processing) are discussed as well as gains in data quantity and quality arising from automation and high-throughput screening (HTS). Best practices and advantages through design of experiments (DOE) to access a complex design space such as multi-modal chromatography are reviewed with an outlook on potential future trends. A discussion of single-use technology, its impact and opportunities for further growth, and the exciting developments in modeling and simulation of DSP rounds out the overview. Lastly, emerging trends such as 3D printing and nanotechnology are covered.
References
Wilson ID, Allard ER, Cooke M, Poole CF (2000) Encyclopedia of separation science. Academic, San Diego
Cohn EJ (1947) The separation of blood into fractions of therapeutic value. Ann Int Med 26:341–352
Constantino P (2002) Basel, Switzerland Patent No 20050106181 A1
Hagen AJ, Oliver CN, Sitrin R (1997) Optimization and scale-up of solvent extraction in purification of hepatitis A virus (VAQTA™). Biotechnol Bioeng 56:83–88
Kniskern PJ, Miller WJ, Hagopian A, Charlotte C, Hennessey J, John P et al (1998) US Patent No 5,847,112
Merieux I (1980) Belgium Patent No B74899
Yavordios D, Cousin M (1983) France Patent No. 0071515A1
Stern SA, Noble RD (1995) Membrane separations technology. Principles and applications. Elsevier, Amsterdam
Peterson EA, Sober HA (1954) Chromatography of proteins. I Cellulose ion-exchange; adsorbents. J Am Chem Soc 78(4):751–755
Porath J, Flodin P (1959) Gel filtration: a method for desalting and group separation. Nature 183:1657
Lea DJ, Sehon AH (1961) Preparation of synthetic gels for chromatography of macromolecules. Can J Chem 40:159
Vaughan MF (1960) Fractionation of polystyrene by gel filtration. Nature 188:55
Hjerten S (1961) Agarose as an anticonvection agent in zone electrophoresis. Biochim Biophys Acta 53(3):514–517
Hjerten S (1964) The preparation of agarose spheres for the chromatography of molecules and particles. Biochim Biophys Acta 79:393–398
March SC, Parikh I, Cuatrecasas P (1974) Affinity chromatography — old problems and new approaches- in immobilized biochemicals and affinity chromatography- part of the series Advances in Experimental Medicine and Biology (Vol. 42): Springer
Williams KW, Smith RC (1975) Recent advances in column chromatography. Prog Med Chem 12:105–158
Hofstee BH (1973) Protein binding by agarose carrying hydrophobic groups in conjunction with charges. Biochem Biophys Res Commun 50(3):751–757
Er-El Z, Zaidenzaig Y, Shaltiel S (1972) Hydrocarbon-coated sepharoses. Use in the purification of glycogen phosphorylase. Biochem Biophys Res Commun 49(2):383–390
Hjerten S (1973) Some general aspects of hydrophobic interaction chromatography. J Chromatogr A:325–331
Yon RJ (1972) Chromatography of lipophilic proteins on adsorbents containing mixed hydrophobic and ionic groups. Biochem J 126(3):765–767
Gagnon P (2012) Technology trends in antibody purification. J Chromatogr A 1221:57–70
Gottschalk U (2011) The future of downstream processing. pharmtech.com. Retrieved from http://www.pharmtech.com/print/212418?page=full
Jon HC, Zarbis-Papastoitsis G (2011) Advances in the production and downstream processing of antibodies. N Biotechnol 28(5)
Low D, O’Leary R, Pujar NS (2007) Future of antibody purification. J Chromatogr B 848:48–63
Marichal-Gallardo PA, Alvarez MM (2012) State-of-the-art in downstream processing of monoclonal antibodies: process trends in design and validation. Biotechnol Prog 28(4):899–916
Zhou JX, Tressel T, Yang X, Seewoester T (2008) Implementation of advanced technologies in commercial monoclonal antibody production. Biotechnol J 3:1185–1200
Kelley B (2007) Very large scale monoclonal antibody purification: the case for conventional unit operations. Biotechnol Prog 23(5):995–1008. doi:10.1021/bp070117s
Shukla AA, Thoemmes J (2010) Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 28(5):253–261
Banholzer WF, Vosejpka LJ (2011) Risk taking and effective R&D management. Annu Rev Chem Biomol Eng 2:173–188
Hueske A-K, Endrikat J, Guenther E (2015) External environment, the innovating organization, and its individuals: a multilevel model for identifying innovation barriers accounting for social uncertainties. J Eng Technol Manage 35:45–70
Rogers M (2012) Energy = Innovation: 10 disruptive technologies. Sustainability & Resource Productivity Summer
Saunila M, Ukko J (2014) Intangible aspects of innovation capability in SMEs: impacts of size and industry. J Eng Technol Manage 33:32–46
Story VM, Daniels K, Zolkiewski J, Daintyd AJ (2014) The barriers and consequences of radical innovations: introduction to the issue. Ind Mark Manag 24:1271–1277
Weiss JC, Dale BC (1998) Diffusing against mature technology: Issues and Strategy. Ind Mark Manag 27:293–304
Tswett M (1903) O novoy kategorii adsorbtsionnykh yavleny i o primenenii ikh k biokkhimicheskomu analizu (A new category of adsorption phenomena and their use in biochemical analysis). Trudy Varhavskago Obshchestva estevoispytatelei Otd B 14:20–39
Curling J (2007) Process chromatography: five decades of innovation. BioPharm Int 13–18:48
Guiochon G, Felinger A, Shirazi DG, Katti AM (2006) Introduction. In: Fundamentals of preparative and nonlinear chromatography. Academic
Grace JR, Leckner B, Zhu J, Cheng Y (2005) Fluidized beds. In: Multiphase flow handbook. CRC Press
Bartels CR, Kleiman G, Irish DB, Korzun JN (1957) United States/New York Patent No. US 2786831 A
Buiis A, Wesselingh JA (1980) Batch fluidized ion-exchange columns for streams containing suspended particles. J Chromatogr 201:319–327
Burns MA, Graves DJ (1985) Continuous affinity chromatography using a magnetically stabilized fluidized bed. Biotechnol Prog 1:95–103
Draeger MN, Chase HA (1990) Liquid fluidized beds for protein purification. Chem Eng Symp Ser No, 1, 12.11–12.12
Nixon L, Koval CA, Xu L, Noble RD, Slaff GS (1991) The effects of magnetic stabilization on the structure and performance of fluidized beds. Bioseparations 2:217–230
Hjorth R (1997) Expanded-bed adsorption in industrial bioprocessing: recent developments. Trends Biotechnol 15:230–235
Noppe W, Van Damme U, Gent N, Geeraerts F, Vanhoorelbeke K, Deckmyn H (2003) Biology and life sciences. In: Downstream: EBA '02 abstracts: Extended reports from the 4th international conference on expanded bed adsorption, St Petersburg, 2002. Amersham Biosciences, Uppsala
Flickinger MC (2013) Downstream industrial biotechnology: recovery and purification. Wiley
Silver N (2012) The signal and the noise. The Penguin Press, New York
Fee CJ, Nawada S, Dimartino S (2014) 3D printed porous media columns with fine control of column packing geometry. J Chromatogr A 1333:18–24
Rathore AV, Velayudhan A (2003) In: Cazes J (ed) Scale-up and optimization in preparative chromatography. Marcel Dekker, Inc
Allmendinger R, Simaria AS, Turner R, Farid SS (2014) Closed-loop optimization of chromatography column sizing strategies in biopharmaceutical manufacture. J Chem Technol Biotechnol 89(10):1481–1490. doi:10.1002/jctb.4267
Farid SS (2007) Process economics of industrial monoclonal antibody manufacture. J Chromatogr B Analyt Technol Biomed Life Sci 848(1):8–18. doi:10.1016/j.jchromb.2006.07.037
Hammerschmidt N, Tscheliessnig A, Sommer R, Helk B, Jungbauer A (2014) Economics of recombinant antibody production processes at various scales: industry-standard compared to continuous precipitation. Biotechnol J 9(6):766–775. doi:10.1002/biot.201300480
Liu S, Simaria AS, Farid SS, Papageorgiou LG (2013) Designing cost-effective biopharmaceutical facilities using mixed-integer optimization. Biotechnol Prog 29(6):1472–1483. doi:10.1002/btpr.1795
Schugerl K, Hubbuch J (2005) Integrated bioprocesses. Curr Opin Microbiol 8(3):294–300. doi:10.1016/j.mib.2005.01.002
Kelley B (2009) Industrialization of mAb production technology: the bioprocessing industry at a crossroads. MAbs 1(5):443–452
Werner RG (2004) Economic aspects of commercial manufacture of biopharmaceuticals. J Biotechnol 113(1-3):171–182. doi:10.1016/j.jbiotec.2004.04.036
Liu HF, Ma J, Winter C, Bayer R (2010) Recovery and purification process development for monoclonal antibody production. MAbs 2(5):480–499
Lu Y, Williamson B, Gillespie R (2009) Recent advancement in application of hydrophobic interaction chromatography for aggregate removal in industrial purification process. Curr Pharm Biotechnol 10(4):427–433
Nfor BK, Verhaert PD, van der Wielen LA, Hubbuch J, Ottens M (2009) Rational and systematic protein purification process development: the next generation. Trends Biotechnol 27(12):673–679. doi:10.1016/j.tibtech.2009.09.002
Shukla AA, Hubbard B, Tressel T, Guhan S, Low D (2007) Downstream processing of monoclonal antibodies--application of platform approaches. J Chromatogr B Analyt Technol Biomed Life Sci 848(1):28–39. doi:10.1016/j.jchromb.2006.09.026
Singh N, Arunkumar A, Chollangi S, Tan ZG, Borys M, Li ZJ (2015) Clarification technologies for monoclonal antibody manufacturing processes: current state and future perspectives. Biotechnol Bioeng. doi:10.1002/bit.25810
Tao Y, Ibraheem A, Conley L, Cecchini D, Ghose S (2014) Evaluation of high-capacity cation exchange chromatography for direct capture of monoclonal antibodies from high-titer cell culture processes. Biotechnol Bioeng 111(7):1354–1364. doi:10.1002/bit.25192
Wang F, Yan X, Song L, Wang P, Lu D, Feng J, et al. (2013) A novel ‘pipeline’ system for downstream preparation of therapeutic monoclonal antibodies. Biotechnol Lett 35(9):1411–1418. doi:10.1007/s10529-013-1234-2
Aaberg PM, Houshmand H, Ljungloef A, Van AJ (2005) A method for chromatographic purification, US20,070,213,513 A1
Agner E (2003) Method for displacement chromatography, US6,576,134 B1
Cramer SM, Moore JA, Kundu A, Li Y, Jayaraman G (1995) Displacement chromatography of proteins using low molecular weight displacers, US5,478,924 A
Cramer SM, Shukla AA, Sunasara KM (2001) Low molecular weight displacers for protein purification in hydrophobic interaction and reversed phase chromatographic systems, US6,239,262 B1
Eriksson K, Johansson HJ, Olsson U (2007) Method of separating monomeric protein(s), US20,090,264,630 A1
Godavarti R, Iskra T (2006) Methods of purifying fc region containing proteins, US20,070,082,367 A1
Poll DJ, Harding DRK, Hancock WS (1986) High performance liquid chromatography mobile phase, US4,909,941 A
Shujun S (2013) Arginine wash in protein purification using affinity chromatography. US Patents No. 8,350,013 B2
Staby A (2000) Ion exchange chromatography of proteins and peptides with an organic modifier in the elution step, US6,451,987 B1
Sun S, Gallo C (2011) Arginine derivative wash in protein purification using affinity chromatography. US Patent No. 7,714,111
Sundberg R, Hopfer R (2004) Removal of bacterial endotoxin in a protein solution by immobilized metal affinity chromatography, US20,040,112,832 A1
Gillespie R, Vunnum S, Nguyen T, Macneil S (2012). J Chromatogr A 1251:101–110
Van Alstine J, Houshmand H, Ljunglof A, Aberg PM (2007) Method for chromatographic purification, US20,070,213,513 A1
Wang C, Coppola G, Chumsae C (2015) Protein purification using displacement chromatography: Google Patents
Satzer P, Tscheließnigg A, Sommer R, Jungbauer A (2014) Separation of recombinant antibodies from DNA using divalent cations. Eng Life Sci 14(5)
Tsumoto K, Ejima D, Senczuk AM, Kita Y, Arakawa T (2007) Effects of salts on protein–surface interactions: applications for column chromatography. J Pharm Sci 96(7):1677–1690. doi:10.1002/jps.20821
Johansson K, Frederiksen SS, Degerman M, Breil MP, Mollerup JM, Nilsson B (2015) Combined effects of potassium chloride and ethanol as mobile phase modulators on hydrophobic interaction and reversed-phase chromatography of three insulin variants. J Chromatogr A 1381:64–73. doi:10.1016/j.chroma.2014.12.081
Ngo TT, Narinesingh D (2008) Kosmotropes enhance the yield of antibody purified by affinity chromatography using immobilized bacterial immunoglobulin binding proteins. J Immunoassay Immunochem 29(1):105–115. doi:10.1080/15321810701735203
Arakawa T, Tsumoto K, Nagase K, Ejima D (2007) The effects of arginine on protein binding and elution in hydrophobic interaction and ion-exchange chromatography. Protein Expr Purif 54(1):110–116. doi:10.1016/j.pep.2007.02.010
Cochet S, Hasnaoui MH, Debbia M, Kroviarski Y, Lambin P, Cartron JP, Bertrand O (1994) Chromatography of human immunoglobulin G on immobilized drimarene rubine R/K-5BL. Study of mild, efficient elution procedures. J Chromatogr A 663(2):175–186
Lin M-F, Williams C, Murray MV, Ropp PA (2005) Removal of lipopolysaccharides from protein–lipopolysaccharide complexes by nonflammable solvents. J Chromatogr B 816(1–2):167–174. doi:10.1016/j.jchromb.2004.11.029
Hou Y, Cramer SM (2011) Evaluation of selectivity in multimodal anion exchange systems: a priori prediction of protein retention and examination of mobile phase modifier effects. J Chromatogr A 1218(43):7813–7820. doi:10.1016/j.chroma.2011.08.080
Hirano A, Arakawa T, Kameda T (2014) Interaction of arginine with Capto MMC in multimodal chromatography. J Chromatogr A 1338:58–66. doi:10.1016/j.chroma.2014.02.053
Hirano A, Maruyama T, Shiraki K, Arakawa T, Kameda T (2014) Mechanism of protein desorption from 4-mercaptoethylpyridine resins by arginine solutions. J Chromatogr A 1373:141–148. doi:10.1016/j.chroma.2014.11.032
Holstein MA, Parimal S, McCallum SA, Cramer SM (2012) Mobile phase modifier effects in multimodal cation exchange chromatography. Biotechnol Bioeng 109(1):176–186. doi:10.1002/bit.23318
Herzer S, Bhangale A, Barker G, Chowdhary I, Conover M, O’Mara BW, et al. (2015) Development and scale-up of the recovery and purification of a domain antibody Fc fusion protein-comparison of a two and three-step approach. Biotechnol Bioeng 112(7):1417–1428. doi:10.1002/bit.25561
Liu Z, Gurgel PV, Carbonell RG (2012) Purification of human immunoglobulins A, G and M from Cohn fraction II/III by small peptide affinity chromatography. J Chromatogr A 1262:169–179. doi:10.1016/j.chroma.2012.09.026
Ishihara T, Hosono M (2015) Improving impurities clearance by amino acids addition to buffer solutions for chromatographic purifications of monoclonal antibodies. J Chromatogr B Analyt Technol Biomed Life Sci 995-996:107–114. doi:10.1016/j.jchromb.2015.05.018
Bolton GR, Boesch AW, Basha J, Lacasse DP, Kelley BD, Acharya H (2011) Effect of protein and solution properties on the Donnan effect during the ultrafiltration of proteins. Biotechnol Prog 27(1):140–152. doi:10.1002/btpr.523
Miao F, Velayudhan A, DiBella E, Shervin J, Felo M, Teeters M, Alred P (2009) Theoretical analysis of excipient concentrations during the final ultrafiltration/diafiltration step of therapeutic antibody. Biotechnol Prog 25(4):964–972. doi:10.1002/btpr.168
Stoner MR, Fischer N, Nixon L, Buckel S, Benke M, Austin F, et al. (2004) Protein-solute interactions affect the outcome of ultrafiltration/diafiltration operations. J Pharm Sci 93(9):2332–2342. doi:10.1002/jps.20145
Shukla D, Zamolo L, Cavallotti C, Trout BL (2011) Understanding the role of arginine as an eluent in affinity chromatography via molecular computations. J Phys Chem B 115(11):2645–2654. doi:10.1021/jp111156z
Bolton GR, Selvitelli KR, Iliescu I, Cecchini DJ (2015) Inactivation of viruses using novel protein A wash buffers. Biotechnol Prog 31(2):406–413. doi:10.1002/btpr.2024
Chollangi S, Parker R, Singh N, Li Y, Borys M, Li Z (2015) Development of robust antibody purification by optimizing protein-A chromatography in combination with precipitation methodologies. Biotechnol Bioeng 112(11):2292–2304. doi:10.1002/bit.25639
Frauenschuh A, Bill K (2011) Wash solution and method for affinity chromatography, US20,120,283,416 A1
Gillespie R, Vunnum S, Nguyen T, Macneil S (2012) Protein purification, US20,120,149,878 A1
Srajer Gajdosik M, Clifton J, Josic D (2012) Sample displacement chromatography as a method for purification of proteins and peptides from complex mixtures. J Chromatogr A 1239:1–9. doi:10.1016/j.chroma.2012.03.046
Huang B, Liu FF, Dong XY, Sun Y (2011) Molecular mechanism of the affinity interactions between protein A and human immunoglobulin G1 revealed by molecular simulations. J Phys Chem B 115(14):4168–4176. doi:10.1021/jp111216g
Schuler G, Reinacher M (1991) Development and optimization of a single-step procedure using protein A affinity chromatography to isolate murine IgG1 monoclonal antibodies from hybridoma supernatants. J Chromatogr 587(1):61–70
Lund LN, Christensen T, Toone E, Houen G, Staby A, St Hilaire PM (2011) Exploring variation in binding of protein A and protein G to immunoglobulin type G by isothermal titration calorimetry. J Mol Recognit 24(6):945–952. doi:10.1002/jmr.1140
Baumgartner K, Oelmeier SA, Hubbuch J (2015) The influence of mixed salts on the capacity of hic adsorbers: a predictive correlation to the surface tension and the aggregation temperature. Biotechnol Prog. doi:10.1002/btpr.2166
Werner A, Hasse H (2013) Experimental study and modeling of the influence of mixed electrolytes on adsorption of macromolecules on a hydrophobic resin. J Chromatogr A 1315:135–144. doi:10.1016/j.chroma.2013.09.071
Wolfe LS, Barringer CP, Mostafa SS, Shukla AA (2014) Multimodal chromatography: characterization of protein binding and selectivity enhancement through mobile phase modulators. J Chromatogr A 1340:151–156. doi:10.1016/j.chroma.2014.02.086
Sipple et al., in preparation
Duhamel RC, Schur PH, Brendel K, Meezan E (1979) pH gradient elution of human IgG1, IgG2 and IgG4 from protein A-sepharose. J Immunol Methods 31(3-4):211–217
Gaza-Bulseco G, Hickman K, Sinicropi-Yao S, Hurkmans K, Chumsae C, Liu H (2009) Effect of the conserved oligosaccharides of recombinant monoclonal antibodies on the separation by protein A and protein G chromatography. J Chromatogr A 1216(12):2382–2387. doi:10.1016/j.chroma.2009.01.014
Ejima D, Yumioka R, Tsumoto K, Arakawa T (2005) Effective elution of antibodies by arginine and arginine derivatives in affinity column chromatography. Anal Biochem 345(2):250–257. doi:10.1016/j.ab.2005.07.004
Roben PW, Salem AN, Silverman GJ (1995) VH3 family antibodies bind domain D of staphylococcal protein A. J Immunol 154(12):6437–6445
Hogwood CE, Ahmad SS, Tarrant RD, Bracewell DG, Smales CM (2015) An ultra scale-down approach identifies host cell protein differences across a panel of mAb producing CHO cell line variants. Biotechnol J. doi:10.1002/biot.201500010
Levy NE, Valente KN, Choe LH, Lee KH, Lenhoff AM (2014) Identification and characterization of host cell protein product-associated impurities in monoclonal antibody bioprocessing. Biotechnol Bioeng 111(5):904–912. doi:10.1002/bit.25158
Levy NE, Valente KN, Lee KH, Lenhoff AM (2015) Host cell protein impurities in chromatographic polishing steps for monoclonal antibody purification. Biotechnol Bioeng. doi:10.1002/bit.25882
Lewus RA, Levy NE, Lenhoff AM, Sandler SI (2015) A comparative study of monoclonal antibodies. 1. Phase behavior and protein-protein interactions. Biotechnol Prog 31(1):268–276. doi:10.1002/btpr.2011
Tarrant RD, Velez-Suberbie ML, Tait AS, Smales CM, Bracewell DG (2012) Host cell protein adsorption characteristics during protein A chromatography. Biotechnol Prog 28(4):1037–1044. doi:10.1002/btpr.1581
Zhang S, Daniels W, Salm J, Glynn J, Martin J, Gallo C, et al. (2016) Nature of foulants and fouling mechanism in the protein A MabSelect resin cycled in a monoclonal antibody purification process. Biotechnol Bioeng 113(1):141–149. doi:10.1002/bit.25706
Liu Z, Mostafa SS, Shukla AA (2015) A comparison of protein A chromatographic stationary phases: performance characteristics for monoclonal antibody purification. Biotechnol Appl Biochem 62(1):37–47. doi:10.1002/bab.1243
Swinnen K, Krul A, Van Goidsenhoven I, Van Tichelt N, Roosen A, Van Houdt K (2007) Performance comparison of protein A affinity resins for the purification of monoclonal antibodies. J Chromatogr B Analyt Technol Biomed Life Sci 848(1):97–107. doi:10.1016/j.jchromb.2006.04.050
McCaw TR, Koepf EK, Conley L (2014) Evaluation of a novel methacrylate-based protein A resin for the purification of immunoglobulins and Fc-fusion proteins. Biotechnol Prog 30(5):1125–1136. doi:10.1002/btpr.1951
Meininger DP, Rance M, Starovasnik MA, Fairbrother WJ, Skelton NJ (2000) Characterization of the binding interface between the E-domain of Staphylococcal protein A and an antibody Fv-fragment. Biochemistry 39(1):26–36
Moks T, Abrahmsen L, Nilsson B, Hellman U, Sjoquist J, Uhlen M (1986) Staphylococcal protein A consists of five IgG-binding domains. Eur J Biochem 156(3):637–643
Ghose S, Hubbard B, Cramer SM (2007) Binding capacity differences for antibodies and Fc-fusion proteins on protein A chromatographic materials. Biotechnol Bioeng 96(4):768–779. doi:10.1002/bit.21044
Sjoquist J, Wadso II (1971) A thermochemical study of the reaction between protein A from S. aureus and fragment Fc from immunoglobulin G. FEBS Lett 14(4):254–256
Yang L, Biswas ME, Chen P (2003) Study of binding between protein A and immunoglobulin G using a surface tension probe. Biophys J 84(1):509–522. doi:10.1016/s0006-3495(03)74870-x
Muller E, Vajda J (2016) Routes to improve binding capacities of affinity resins demonstrated for protein A chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. doi:10.1016/j.jchromb.2016.01.036
LIfesciences G Application note (AA ed., Vol. 29190587). GE Lifesciences, Piscataway
Ghose S, Zhang J, Conley L, Caple R, Williams KP, Cecchini D (2014) Maximizing binding capacity for protein A chromatography. Biotechnol Prog 30(6):1335–1340. doi:10.1002/btpr.1980
Gonzalez-Valdez J, Yoshikawa A, Weinberg J, Benavides J, Rito-Palomares M, Przybycien TM (2014) Toward improving selectivity in affinity chromatography with PEGylated affinity ligands: the performance of PEGylated protein A. Biotechnol Prog 30(6):1364–1379. doi:10.1002/btpr.1994
Gulich S, Uhlen M, Hober S (2000) Protein engineering of an IgG-binding domain allows milder elution conditions during affinity chromatography. J Biotechnol 76(2-3):233–244
Pabst TM, Palmgren R, Forss A, Vasic J, Fonseca M, Thompson C, et al. (2014) Engineering of novel Staphylococcal protein A ligands to enable milder elution pH and high dynamic binding capacity. J Chromatogr A 1362:180–185. doi:10.1016/j.chroma.2014.08.046
Watanabe H, Matsumaru H, Ooishi A, Honda S (2013) Structure-based histidine substitution for optimizing pH-sensitive Staphylococcus protein A. J Chromatogr B Analyt Technol Biomed Life Sci 929:155–160. doi:10.1016/j.jchromb.2013.04.029
Xia HF, Liang ZD, Wang SL, Wu PQ, Jin XH (2014) Molecular modification of protein A to improve the elution pH and alkali resistance in affinity chromatography. Appl Biochem Biotechnol 172(8):4002–4012. doi:10.1007/s12010-014-0818-1
Gagnon P, Nian R (2016) Conformational plasticity of IgG during protein A affinity chromatography. J Chromatogr A 1433:98–105. doi:10.1016/j.chroma.2016.01.022
Gagnon P, Nian R, Leong D, Hoi A (2015) Transient conformational modification of immunoglobulin G during purification by protein A affinity chromatography. J Chromatogr A 1395:136–142. doi:10.1016/j.chroma.2015.03.080
Mazzer AR, Perraud X, Halley J, O’Hara J, Bracewell DG (2015) Protein A chromatography increases monoclonal antibody aggregation rate during subsequent low pH virus inactivation hold. J Chromatogr A 1415:83–90. doi:10.1016/j.chroma.2015.08.068
Shukla AA, Gupta P, Han X (2007) Protein aggregation kinetics during protein A chromatography. Case study for an Fc fusion protein. J Chromatogr A 1171(1-2):22–28. doi:10.1016/j.chroma.2007.09.040
Zhang S, Xu K, Daniels W, Salm J, Glynn J, Martin J, et al. (2016) Structural and functional characteristics of virgin and fouled Protein A MabSelect resin cycled in a monoclonal antibody purification process. Biotechnol Bioeng 113(2):367–375. doi:10.1002/bit.25708
Boulet-Audet M, Byrne B, Kazarian SG (2015) Cleaning-in-place of immunoaffinity resins monitored by in situ ATR-FTIR spectroscopy. Anal Bioanal Chem 407(23):7111–7122. doi:10.1007/s00216-015-8871-3
Rogers M, Hiraoka-Sutow M, Mak P, Mann F, Lebreton B (2009) Development of a rapid sanitization solution for silica-based protein A affinity adsorbents. J Chromatogr A 1216(21):4589–4596. doi:10.1016/j.chroma.2009.03.065
Wang L, Dembecki J, Jaffe NE, O’Mara BW, Cai H, Sparks CN, et al. (2013) A safe, effective, and facility compatible cleaning in place procedure for affinity resin in large-scale monoclonal antibody purification. J Chromatogr A 1308:86–95. doi:10.1016/j.chroma.2013.07.096
Gronberg A, Eriksson M, Ersoy M, Johansson HJ (2011) A tool for increasing the lifetime of chromatography resins. MAbs 3(2):192–202
Yang L, Harding JD, Ivanov AV, Ramasubramanyan N, Dong DD (2015) Effect of cleaning agents and additives on protein A ligand degradation and chromatography performance. J Chromatogr A 1385:63–68. doi:10.1016/j.chroma.2015.01.068
Saraswat M, Musante L, Ravida A, Shortt B, Byrne B, Holthofer H (2013) Preparative purification of recombinant proteins: current status and future trends. Biomed Res Int 2013:312709. doi:10.1155/2013/312709
Stonier A, Simaria AS, Smith M, Farid SS (2012) Decisional tool to assess current and future process robustness in an antibody purification facility. Biotechnol Prog 28(4):1019–1028. doi:10.1002/btpr.1569
Liu HF, McCooey B, Duarte T, Myers DE, Hudson T, Amanullah A, et al. (2011) Exploration of overloaded cation exchange chromatography for monoclonal antibody purification. J Chromatogr A 1218(39):6943–6952. doi:10.1016/j.chroma.2011.08.008
Iskra T, Sacramo A, Gallo C, Godavarti R, Chen S, Lute S, Brorson K (2015) Development of a modular virus clearance package for anion exchange chromatography operated in weak partitioning mode. Biotechnol Prog 31(3):750–757. doi:10.1002/btpr.2080
Kelley BD, Jakubik J, Vicik S (2008) Viral clearance studies on new and used chromatography resins: critical review of a large dataset. Biologicals 36(2):88–98. doi:10.1016/j.biologicals.2007.08.001
Miesegaes GR, Lute SC, Read EK, Brorson KA (2014) Viral clearance by flow-through mode ion exchange columns and membrane adsorbers. Biotechnol Prog 30(1):124–131. doi:10.1002/btpr.1832
Norling L, Lute S, Emery R, Khuu W, Voisard M, Xu Y, et al. (2005) Impact of multiple re-use of anion-exchange chromatography media on virus removal. J Chromatogr A 1069(1):79–89
Roush D (2014) Viral clearance using traditional, well-understood unit operations (session I): anion exchange chromatography (AEX). PDA J Pharm Sci Technol 68(1):23–29. doi:10.5731/pdajpst.2014.00963
Roush D (2015) Viral clearance using traditional, well-understood unit operations: session 1.2. Anion exchange chromatography; and session 1.3. Protein a chromatography. PDA J Pharm Sci Technol 69(1):154–162. doi:10.5731/pdajpst.2015.01039
Strauss DM, Cano T, Cai N, Delucchi H, Plancarte M, Coleman D, et al. (2010) Strategies for developing design spaces for viral clearance by anion exchange chromatography during monoclonal antibody production. Biotechnol Prog 26(3):750–755. doi:10.1002/btpr.385
Strauss DM, Gorrell J, Plancarte M, Blank GS, Chen Q, Yang B (2009) Anion exchange chromatography provides a robust, predictable process to ensure viral safety of biotechnology products. Biotechnol Bioeng 102(1):168–175. doi:10.1002/bit.22051
Zhou JX, Solamo F, Hong T, Shearer M, Tressel T (2008) Viral clearance using disposable systems in monoclonal antibody commercial downstream processing. Biotechnol Bioeng 100(3):488–496. doi:10.1002/bit.21781
Yao Y, Lenhoff AM (2006) Pore size distributions of ion exchangers and relation to protein binding capacity. J Chromatogr A 1126(1-2):107–119. doi:10.1016/j.chroma.2006.06.057
DePhillips P, Lenhoff AM (2000) Pore size distributions of cation-exchange adsorbents determined by inverse size-exclusion chromatography. J Chromatogr A 883(1-2):39–54
Tao Y, Carta G (2008) Rapid monoclonal antibody adsorption on dextran-grafted agarose media for ion-exchange chromatography. J Chromatogr A 1211(1-2):70–79. doi:10.1016/j.chroma.2008.09.096
Bowes BD, Lenhoff AM (2011) Protein adsorption and transport in dextran-modified ion-exchange media. II Intraparticle uptake and column breakthrough. J Chromatogr A 1218(29):4698–4708. doi:10.1016/j.chroma.2011.05.054
Lenhoff AM (2011) Protein adsorption and transport in polymer-functionalized ion-exchangers. J Chromatogr A 1218(49):8748–8759. doi:10.1016/j.chroma.2011.06.061
Perez Almodovar EX, Glatz B, Carta G (2012) Counterion effects on protein adsorption equilibrium and kinetics in polymer-grafted cation exchangers. J Chromatogr A 1253:83–93. doi:10.1016/j.chroma.2012.06.100
Perez-Almodovar EX, Wu Y, Carta G (2012) Multicomponent adsorption of monoclonal antibodies on macroporous and polymer grafted cation exchangers. J Chromatogr A 1264:48–56. doi:10.1016/j.chroma.2012.09.064
Xu Z, Li J, Zhou JX (2012) Process development for robust removal of aggregates using cation exchange chromatography in monoclonal antibody purification with implementation of quality by design. Prep Biochem Biotechnol 42(2):183–202. doi:10.1080/10826068.2012.654572
Riordan WT, Heilmann SM, Brorson K, Seshadri K, Etzel MR (2009) Salt tolerant membrane adsorbers for robust impurity clearance. Biotechnol Prog 25(6):1695–1702. doi:10.1002/btpr.256
Yoshimoto N, Itoh D, Isakari Y, Podgornik A, Yamamoto S (2015) Salt tolerant chromatography provides salt tolerance and a better selectivity for protein monomer separations. Biotechnol J 10(12):1929–1934. doi:10.1002/biot.201400550
Gu F, Chodavarapu K, McCreary D, Plitt TA, Tamoria E, Ni M, et al. (2015) Silica-based strong anion exchange media for protein purification. J Chromatogr A 1376:53–63. doi:10.1016/j.chroma.2014.11.082
Fang F, Aguilar MI, Hearn MT (1996) Influence of temperature on the retention behaviour of proteins in cation-exchange chromatography. J Chromatogr A 729(1-2):49–66
Guo J, Carta G (2014) Unfolding and aggregation of a glycosylated monoclonal antibody on a cation exchange column. Part II. Protein structure effects by hydrogen deuterium exchange mass spectrometry. J Chromatogr A 1356:129–137. doi:10.1016/j.chroma.2014.06.038
Guo J, Carta G (2015) Unfolding and aggregation of monoclonal antibodies on cation exchange columns: effects of resin type, load buffer, and protein stability. J Chromatogr A 1388:184–194. doi:10.1016/j.chroma.2015.02.047
Gospodarek AM, Hiser DE, O’Connell JP, Fernandez EJ (2014) Unfolding of a model protein on ion exchange and mixed mode chromatography surfaces. J Chromatogr A 1355:238–252. doi:10.1016/j.chroma.2014.06.024
Bracewell DG, Boychyn M, Baldascini H, Storey SA, Bulmer M, More J, Hoare M (2008) Impact of clarification strategy on chromatographic separations: pre-processing of cell homogenates. Biotechnol Bioeng 100(5):941–949. doi:10.1002/bit.21823
Kramarczyk JF, Kelley BD, Coffman JL (2008) High-throughput screening of chromatographic separations: II. Hydrophobic interaction. Biotechnol Bioeng 100(4):707–720. doi:10.1002/bit.21907
McCue JT (2009) Theory and use of hydrophobic interaction chromatography in protein purification applications. Methods Enzymol 463:405–414. doi:10.1016/s0076-6879(09)63025-1
McCue JT, Engel P, Ng A, Macniven R, Thommes J (2008) Modeling of protein monomer/aggregate purification and separation using hydrophobic interaction chromatography. Bioprocess Biosyst Eng 31(3):261–275. doi:10.1007/s00449-008-0200-1
Deitcher RW, O’Connell JP, Fernandez EJ (2010) Changes in solvent exposure reveal the kinetics and equilibria of adsorbed protein unfolding in hydrophobic interaction chromatography. J Chromatogr A 1217(35):5571–5583. doi:10.1016/j.chroma.2010.06.051
Deitcher RW, Xiao Y, O’Connell JP, Fernandez EJ (2009) Protein instability during HIC: evidence of unfolding reversibility, and apparent adsorption strength of disulfide bond-reduced alpha-lactalbumin variants. Biotechnol Bioeng 102(5):1416–1427. doi:10.1002/bit.22171
Gospodarek AM, Smatlak ME, O’Connell JP, Fernandez EJ (2011) Protein stability and structure in HIC: hydrogen exchange experiments and COREX calculations. Langmuir 27(1):286–295. doi:10.1021/la103793r
Muca R, Marek W, Piatkowski W, Antos D (2010) Influence of the sample-solvent on protein retention, mass transfer and unfolding kinetics in hydrophobic interaction chromatography. J Chromatogr A 1217(17):2812–2820. doi:10.1016/j.chroma.2010.02.043
Ueberbacher R, Rodler A, Hahn R, Jungbauer A (2010) Hydrophobic interaction chromatography of proteins: thermodynamic analysis of conformational changes. J Chromatogr A 1217(2):184–190. doi:10.1016/j.chroma.2009.05.033
Eriksson KO, Belew M (2011) Hydrophobic interaction chromatography. Methods Biochem Anal 54:165–181
To BC, Lenhoff AM (2007) Hydrophobic interaction chromatography of proteins. I The effects of protein and adsorbent properties on retention and recovery. J Chromatogr A 1141(2):191–205. doi:10.1016/j.chroma.2006.12.020
To BC, Lenhoff AM (2007) Hydrophobic interaction chromatography of proteins. II Solution thermodynamic properties as a determinant of retention. J Chromatogr A 1141(2):235–243. doi:10.1016/j.chroma.2006.12.022
To BC, Lenhoff AM (2008) Hydrophobic interaction chromatography of proteins III. Transport and kinetic parameters in isocratic elution. J Chromatogr A 1205(1-2):46–59. doi:10.1016/j.chroma.2008.07.079
To BC, Lenhoff AM (2011) Hydrophobic interaction chromatography of proteins. IV Protein adsorption capacity and transport in preparative mode. J Chromatogr A 1218(3):427–440. doi:10.1016/j.chroma.2010.11.051
Mirani MR, Rahimpour F (2015) Thermodynamic modelling of hydrophobic interaction chromatography of biomolecules in the presence of salt. J Chromatogr A 1422:170–177. doi:10.1016/j.chroma.2015.10.019
Nfor BK, Zuluaga DS, Verheijen PJ, Verhaert PD, van der Wielen LA, Ottens M (2011) Model-based rational strategy for chromatographic resin selection. Biotechnol Prog 27(6):1629–1643
Lemmens R, Olsson U, Nyhammar T, Stadler J (2003) Supercoiled plasmid DNA: selective purification by thiophilic/aromatic adsorption. J Chromatogr B Analyt Technol Biomed Life Sci 784(2):291–300
Senczuk AM, Klinke R, Arakawa T, Vedantham G, Yigzaw Y (2009) Hydrophobic interaction chromatography in dual salt system increases protein binding capacity. Biotechnol Bioeng 103(5):930–935. doi:10.1002/bit.22313
Melander W, Horvath C (1977) Salt effect on hydrophobic interactions in precipitation and chromatography of proteins: an interpretation of the lyotropic series. Arch Biochem Biophys 183(1):200–215
Kelley et al (2008) Weak partitioning chromatography for anion exchange purification of monoclonal antibodies. Biotechnol Bioeng 101:553–566
Johansson B-L, Belew M, Eriksson S, Glad G, Lind O, Maloisel J-L, Norrman N (2003) Preparation and characterization of prototypes for multi-modal separation aimed for capture of positively charged biomolecules at high-salt conditions. J Chromatogr A 1016(1):35–49. doi:10.1016/S0021-9673(03)01141-5
Yang T, Malmquist G, Johansson B-L, Maloisel J-L, Cramer S (2007) Evaluation of multi-modal high salt binding ion exchange materials. J Chromatogr A 1157(1–2):171–177. doi:10.1016/j.chroma.2007.04.070
Chen J, Tetrault J, Zhang Y, Wasserman A, Conley G, Dileo M, et al. (2010) The distinctive separation attributes of mixed-mode resins and their application in monoclonal antibody downstream purification process. J Chromatogr A 1217(2):216–224. doi:10.1016/j.chroma.2009.09.047
Kaleas KA, Tripodi M, Revelli S, Sharma V, Pizarro SA (2014) Evaluation of a multimodal resin for selective capture of CHO-derived monoclonal antibodies directly from harvested cell culture fluid. J Chromatogr B Analyt Technol Biomed Life Sci 969:256–263. doi:10.1016/j.jchromb.2014.08.026
Pezzini J, Joucla G, Gantier R, Toueille M, Lomenech A-M, Le Sénéchal C, et al. (2011) Antibody capture by mixed-mode chromatography: a comprehensive study from determination of optimal purification conditions to identification of contaminating host cell proteins. J Chromatogr A 1218(45):8197–8208. doi:10.1016/j.chroma.2011.09.036
Pete G (2009) IgG aggregate removal by charged-hydrophobic mixed mode chromatography. Curr Pharm Biotechnol 10(4):434–439. doi:10.2174/138920109788488888
Li P, Xiu G, Mata VG, Grande CA, Rodrigues AE (2006) Expanded bed adsorption/desorption of proteins with Streamline Direct CST I adsorbent. Biotechnol Bioeng 94(6):1155–1163. doi:10.1002/bit.20952
Mollerup JM, Hansen TB, Kidal S, Staby A (2008) Quality by design—thermodynamic modelling of chromatographic separation of proteins. J Chromatogr A 1177(2):200–206. doi:10.1016/j.chroma.2007.08.059
Nfor BK, Noverraz M, Chilamkurthi S, Verhaert PDEM, van der Wielen LAM, Ottens M (2010) High-throughput isotherm determination and thermodynamic modeling of protein adsorption on mixed mode adsorbents. J Chromatogr A 1217(44):6829–6850. doi:10.1016/j.chroma.2010.07.069
Pitiot O, Folley L, Vijayalakshmi MA (2001) Protein adsorption on histidyl-aminohexyl-sepharose 4B: I. Study of the mechanistic aspects of adsorption for the separation of human serum albumin from its non-enzymatic glycated isoforms (advanced glycosylated end products). J Chromatogr B Biomed Sci Appl 758(2):163–172. doi:10.1016/S0378-4347(01)00176-1
Wang J, Jenkins EW, Robinson JR, Wilson A, Husson SM (2015) A new multimodal membrane adsorber for monoclonal antibody purifications. J Membr Sci 492:137–146. doi:10.1016/j.memsci.2015.05.013
Follman DK, Fahrner RL (2004) Factorial screening of antibody purification processes using three chromatography steps without protein A. J Chromatogr A 1024(1-2):79–85
Komkova EN, Honeyman CH (2014) Mixed-mode chromatography membranes, US20,sss140,238,935 A1
Wang J, Sproul RT, Anderson LS, Husson SM (2014) Development of multimodal membrane adsorbers for antibody purification using atom transfer radical polymerization. Polymer 55(6):1404–1411. doi:10.1016/j.polymer.2013.12.023
Stone MT, Kozlov M (2014) Separating proteins with activated carbon. Langmuir 30(27):8046–8055. doi:10.1021/la501005s
Amara J, Boyle J, Yavorsky D, Cacace B (2016) High surface area fiber media with nano-fibrillated surface features, WO2,016,036,508 A1
Amara J, Cacace B, Yavorsky D, Boyle J (2014) Chromatography media for purifying vaccines and viruses, US20,150,352,465 A1
Yavorsky D, Amara J, Umana J, Cataldo W, Kozlov M, Stone M (2015) Chromatography media and method, US20,120,029,176 A1
Hardick O, Dods S, Stevens B, Bracewell DG (2015) Nanofiber adsorbents for high productivity continuous downstream processing. J Biotechnol 213:74–82. doi:10.1016/j.jbiotec.2015.01.031
Baur D, Angarita M, Muller-Spath T, Steinebach F, Morbidelli M (2016) Comparison of batch and continuous multi-column protein A capture processes by optimal design. Biotechnol J. doi:10.1002/biot.201500481
Konstantinov KB, Cooney CL (2015) White paper on continuous bioprocessing, May 20–21, 2014, Continuous manufacturing symposium. J Pharm Sci 104(3):813–820. doi:10.1002/jps.24268
Muller-Spath T, Aumann L, Strohlein G, Kornmann H, Valax P, Delegrange L, et al. (2010) Two step capture and purification of IgG2 using multicolumn countercurrent solvent gradient purification (MCSGP). Biotechnol Bioeng 107(6):974–984. doi:10.1002/bit.22887
Warikoo V, Godawat R, Brower K, Jain S, Cummings D, Simons E, et al. (2012) Integrated continuous production of recombinant therapeutic proteins. Biotechnol Bioeng 109(12):3018–3029. doi:10.1002/bit.24584
Anderson NG (2001) Practical use of continuous processing in developing and scaling up laboratory processes. Org Process Res Dev 5(6):613–621. doi:10.1021/op0100605
Fletcher N (2010) Turn batch to continuous processing. Manufacturing Chemist Pharma
Laird T (2007) Continuous processes in small-scale manufacture. Org Process Res Dev 11(6):927–927. doi:10.1021/op700233e
Laird T (2014) Process intensification: engineering for efficiency, sustainability and flexibility. Org Process Res Dev 18(1):276–276. doi:10.1021/op400341e
Mazumdar S, Ray SK (2001) Solidification control in continuous casting of steel. Sadhana 26(1):179–198. doi:10.1007/bf02728485
Reay DA, Ramshaw C, Harvey A (2013) Process intensification engineering for efficiency, sustainability and flexibility. Retrieved from http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=486200
Thomas H (2008) Coming of age. Chem Eng (805):38–40. Retrieved from https://www.scopus.com/inward/record.url?eid=2-s2.0-46949110144&partnerID=40&md5=127c830aa56e3a069687fa3af8cc731e
Ruthven DM, Ching CB (1989) Counter-current and simulated counter-current adsorption separation processes. Chem Eng Sci 44(5):1011–1038. doi:10.1016/0009-2509(89)87002-2
Godawat R, Brower K, Jain S, Konstantinov K, Riske F, Warikoo V (2012) Periodic counter-current chromatography -- design and operational considerations for integrated and continuous purification of proteins. Biotechnol J 7(12):1496–1508. doi:10.1002/biot.201200068
Gjoka X, Rogler K, Martino RA, Gantier R, Schofield M (2015) A straightforward methodology for designing continuous monoclonal antibody capture multi-column chromatography processes. J Chromatogr A 1416:38–46. doi:10.1016/j.chroma.2015.09.005
Dutta AK, Tran T, Napadensky B, Teella A, Brookhart G, Ropp PA, et al. (2015) Purification of monoclonal antibodies from clarified cell culture fluid using protein A capture continuous countercurrent tangential chromatography. J Biotechnol 213:54–64. doi:10.1016/j.jbiotec.2015.02.026
Napadensky B, Shinkazh O, Teella A, Zydney AL (2013) Continuous countercurrent tangential chromatography for monoclonal antibody purification. Sep Sci Technol 48(9):1289–1297. doi:10.1080/01496395.2013.767837
Shinkazh O, Kanani D, Barth M, Long M, Hussain D, Zydney AL (2011) Countercurrent tangential chromatography for large-scale protein purification. Biotechnol Bioeng 108(3):582–591. doi:10.1002/bit.22960
Casey C, Gallos T, Alekseev Y, Ayturk E, Pearl S (2011) Protein concentration with single-pass tangential flow filtration (SPTFF). J Membr Sci 384(1–2):82–88. doi:10.1016/j.memsci.2011.09.004
Dizon-Maspat J, Bourret J, D’Agostini A, Li F (2012) Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production. Biotechnol Bioeng 109(4):962–970. doi:10.1002/bit.24377
Chenette HCS, Robinson JR, Hobley E, Husson SM (2012) Development of high-productivity, strong cation-exchange adsorbers for protein capture by graft polymerization from membranes with different pore sizes. J Membr Sci 432-424:43–52. doi:10.1016/j.memsci.2012.07.040
Kuczewski M, Schirmer E, Lain B, Zarbis-Papastoitsis G (2011) A single-use purification process for the production of a monoclonal antibody produced in a PER.C6 human cell line. Biotechnol J 6(1):56–65. doi:10.1002/biot.201000292
Orr V, Zhong L, Moo-Young M, Chou CP (2013) Recent advances in bioprocessing application of membrane chromatography. Biotechnol Adv 31(4):450–465. doi:10.1016/j.biotechadv.2013.01.007
Klutz S, Lobedann M, Bramsiepe C, Schembecker G (2016) Continuous viral inactivation at low pH value in antibody manufacturing. Chem Eng Process Process Intensification 102:88–101. doi:10.1016/j.cep.2016.01.002
Klutz S, Magnus J, Lobedann M, Schwan P, Maiser B, Niklas J, et al. (2015) Developing the biofacility of the future based on continuous processing and single-use technology. J Biotechnol 213:120–130. doi:10.1016/j.jbiotec.2015.06.388
Pollock J, Bolton G, Coffman J, Ho SV, Bracewell DG, Farid SS (2013) Optimising the design and operation of semi-continuous affinity chromatography for clinical and commercial manufacture. J Chromatogr A 1284:17–27. doi:10.1016/j.chroma.2013.01.082
Dutta AK, Tan J, Napadensky B, Zydney AL, Shinkazh O (2016) Performance optimization of continuous countercurrent tangential chromatography for antibody capture. Biotechnol Prog 32(2):430–439. doi:10.1002/btpr.2250
Brower KP, Ryakala VK, Bird R, Godawat R, Riske FJ, Konstantinov K, et al. (2014) Single-step affinity purification of enzyme biotherapeutics: a platform methodology for accelerated process development. Biotechnol Prog 30(3):708–717. doi:10.1002/btpr.1870
Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS (2010) Process analytical technology (PAT) for biopharmaceutical products: Part I. Concepts and applications. Biotechnol Bioeng 105(2):276–284. doi:10.1002/bit.22528
Tharmalingam T, Wu CH, Callahan S, T Goudar C (2015) A framework for real-time glycosylation monitoring (RT-GM) in mammalian cell culture. Biotechnol Bioeng 112(6):1146–1154. doi:10.1002/bit.25520
Box GEP, Hunter JS, Hunter WG (2005) Statistics for experimenters: design, innovation, and discovery. Wiley-Interscience
Montgomery DC (2012) Design and analysis of experiments. Wiley
Begley CG (2013) An unappreciated challenge to oncology drug discovery: pitfalls in preclinical research. Am Soc Clin Oncol Educ Book, 466–468. doi:10.1200/EdBook_AM.2013.33.466
Cook DA, Beckman TJ, Bordage G (2007) Quality of reporting of experimental studies in medical education: a systematic review. Med Educ 41(8):737–745. doi:10.1111/j.1365-2923.2007.02777.x
Deming SN (1986) Chemometrics: an overview. Clin Chem 32(9):1702–1706
Ilzarbe L, Álvarez MJ, Viles E, Tanco M (2008) Practical applications of design of experiments in the field of engineering: a bibliographical review. Qual Reliab Eng Int 24(4):417–428. doi:10.1002/qre.909
Tanco M, Viles E, Ilzarbe L, Alvarez MJ (2007) Manufacturing industries need design of experiments (DoE). Proceedings of the World Congress on Engineering, II
Nfor BK, Ripic J, van der Padt A, Jacobs M, Ottens M (2012) Model-based high-throughput process development for chromatographic whey proteins separation. Biotechnol J 7(10):1221–1232. doi:10.1002/biot.201200191
Welsh J (2015) Pushing the limits of high-throughput chromatography process development: current state and future directions. Pharm Bioprocess 3(1):1–3
Hussain M (2015) A direct qPCR method for residual DNA quantification in monoclonal antibody drugs produced in CHO cells. J Pharm Biomed Anal 115:603–606. doi:10.1016/j.jpba.2015.03.005
Nissom PM (2007) Specific detection of residual CHO host cell DNA by real-time PCR. Biologicals 35(3):211–215. doi:10.1016/j.biologicals.2006.09.001
Diederich P, Hoffmann M, Hubbuch J (2015) High-throughput process development of purification alternatives for the protein avidin. Biotechnol Prog 31(4):957–973. doi:10.1002/btpr.2104
Van Cleave VH (2003) Validation of immunoassays for anti-drug antibodies. Dev Biol (Basel) 112:107–112
Antony J (2003) 2 – Fundamentals of design of experiments. In: Design of experiments for engineers and scientists (pp. 6–16). Butterworth-Heinemann, Oxford
Tye H (2004) Application of statistical ‘design of experiments’ methods in drug discovery. Drug Discov Today 9(11):485–491. doi:10.1016/S1359-6446(04)03086-7
Donev AN (2004) Design of experiments in the presence of errors in factor levels. J Stat Plann Inference 126(2):569–585. doi:10.1016/j.jspi.2003.09.002
Franceschini G, Macchietto S (2008) Model-based design of experiments for parameter precision: state of the art. Chem Eng Sci 63(19):4846–4872. doi:10.1016/j.ces.2007.11.034
Rathore AS, Mittal S, Pathak M, Arora A (2014) Guidance for performing multivariate data analysis of bioprocessing data: pitfalls and recommendations. Biotechnol Prog 30(4):967–973. doi:10.1002/btpr.1922
Shen X, Huang H-C (2006) Optimal model assessment, selection, and combination. J Am Stat Assoc 101(474):554–568. doi:10.1198/016214505000001078
Shen X, Ye J (2002) Adaptive model selection. J Am Stat Assoc 97(457):210–221. doi:10.1198/016214502753479356
Zhang B, Shen X, Mumford SL (2012) Generalized degrees of freedom and adaptive model selection in linear mixed-effects models. Comput Stat Data Anal 56(3):574–586. doi:10.1016/j.csda.2011.09.001
Cortina JM (1993) Interaction, nonlinearity, and multicollinearity: implications for multiple regression. J Manag 19(4):915–922. doi:10.1177/014920639301900411
Strobl C, Malley J, Tutz G (2009) An introduction to recursive partitioning: rationale, application and characteristics of classification and regression trees, bagging and random forests. Psychol Methods 14(4):323–348. doi:10.1037/a0016973
Luo L, Yao Y, Gao F (2015) Bayesian improved model migration methodology for fast process modeling by incorporating prior information. Chem Eng Sci 134:23–35. doi:10.1016/j.ces.2015.04.045
Sainani KL (2013) Multivariate regression: the pitfalls of automated variable selection. PM R 5(9):791–794. doi:10.1016/j.pmrj.2013.07.007
Berry EM, Coustere-Yakir C, Grover NB (1998) The significance of non-significance. QJM 91(9):647–653
Gerss J (2006) Not significant--what now? Zentralbl Gynakol 128(6):307–310. doi:10.1055/s-2006-942088
Yan W, Hu S, Yang Y, Gao F, Chen T (2011) Bayesian migration of Gaussian process regression for rapid process modeling and optimization. Chem Eng J 166(3):1095–1103. doi:10.1016/j.cej.2010.11.097
Barker GA, Calzada J, Herzer S, Rieble S (2015) Adaptation to high throughput batch chromatography enhances multivariate screening. Biotechnol J 10(9):1493–1498. doi:10.1002/biot.201400671
Ryan TP (2006) Modern experimental design. Wiley-Interscience
Eriksson L (2008) Design of experiments: principles and applications. Umetrics
Harring JR, Weiss BA, Li M (2015) Assessing spurious interaction effects in structural equation modeling: a cautionary note. Educ Psychol Meas 75(5):721–738. doi:10.1177/0013164414565007
Bedeian AG, Mossholder KW (1994) Simple question, not so simple answer: interpreting interaction terms in moderated multiple regression. J Manag 20(1):159–165
Myers RH, Montgomery DC, Anderson-Cook CM (2016) Response surface methodology: process and product optimization using designed experiments, 3rd edn. Wiley
Dougherty S, Simpson JR, Hill RR, Pignatiello JJ, White ED (2014) Augmentation of definitive screening designs (DSD+). Int J Exp Des Process Optimisation 4(2):91–115. doi:10.1504/IJEDPO.2014.066465
Hecht ES, McCord JP, Muddiman DC (2015) Definitive screening design optimization of mass spectrometry parameters for sensitive comparison of filter and solid phase extraction purified, INLIGHT plasma N-glycans. Anal Chem 87(14):7305–7312. doi:10.1021/acs.analchem.5b01609
Tai M, Ly A, Leung I, Nayar G (2015) Efficient high-throughput biological process characterization: definitive screening design with the Ambr250 bioreactor system. Biotechnol Prog 31(5):1388–1395. doi:10.1002/btpr.2142
Yang Y-P, D’Amore T (2014) Protein subunit vaccine purification. In: Wen EP, Ellis R, Pujar NS (eds) Vaccine development and manufacturing1st edn. Wiley, Hoboken
Goos P (2002) The optimal design of blocked and split-plot experiments. Springer
Barker TB (2005) Quality by experimental design, 3rd edn. CRC Press
Fisher RA (1966) The design of experiments8th edn. Oliver and Boyd, Edinburgh
Lau CY, Zahidi AAA, Liew OW, Ng TW (2015) A direct heating model to overcome the edge effect in microplates. J Pharm Biomed Anal 102:199–202. doi:10.1016/j.jpba.2014.09.021
Close EJ, Salm JR, Bracewell DG, Sorensen E (2014) Modelling of industrial biopharmaceutical multicomponent chromatography. Chem Eng Res Des 92(7):1304–1314. doi:10.1016/j.cherd.2013.10.022
Chhatre S, Bracewell DG, Titchener-Hooker NJ (2009) A microscale approach for predicting the performance of chromatography columns used to recover therapeutic polyclonal antibodies. J Chromatogr A 1216(45):7806–7815. doi:10.1016/j.chroma.2009.09.038
Hutchinson N, Chhatre S, Baldascini H, Davies JL, Bracewell DG, Hoare M (2009) Ultra scale-down approach to correct dispersive and retentive effects in small-scale columns when predicting larger scale elution profiles. Biotechnol Prog 25(4):1103–1110. doi:10.1002/btpr.172
Lacki KM (2012) High throughput process development of chromatography steps: advantages and limitations of different formats used. Biotechnol J 7(10):1192–1202
Kelley BD, Switzer M, Bastek P, Kramarczyk JF, Molnar K, Yu T, Coffman J (2008) High-throughput screening of chromatographic separations: IV. Ion-exchange. Biotechnol Bioeng 100(5):950–963. doi:10.1002/bit.21905
Creasy A, Barker G, Yao Y, Carta G (2015) Systematic interpolation method predicts protein chromatographic elution from batch isotherm data without a detailed mechanistic isotherm model. Biotechnol J 10:1400–1411
Coffman JL, Kramarczyk JF, Kelley BD (2008) High-throughput screening of chromatographic separations: I. Method development and column modeling. Biotechnol Bioeng 100(4):605–618. doi:10.1002/bit.21904
Boning DS, Mozumder PK (1994) DOE/Opt: a system for design of experiments, response surface modeling, and optimization using process and device simulation. IEEE Trans Semiconductor Manuf 7(2):233–244. doi:10.1109/66.286858
Wu JCW, Hamada MS (2009) Experiments: planning, analysis, and optimization, 2nd edn. Wiley
Ladd Effio C, Baumann P, Weigel C, Vormittag P, Middelberg A, Hubbuch J (2016) High-throughput process development of an alternative platform for the production of virus-like particles in Escherichia coli. J Biotechnol 219:7–19. doi:10.1016/j.jbiotec.2015.12.018
Staby A, Jensen RH, Bensch M, Hubbuch J, Dunweber DL, Krarup J, et al. (2007) Comparison of chromatographic ion-exchange resins VI. Weak anion-exchange resins. J Chromatogr A 1164(1-2):82–94. doi:10.1016/j.chroma.2007.06.048
Wensel DL, Kelley BD, Coffman JL (2008) High-throughput screening of chromatographic separations: III. Monoclonal antibodies on ceramic hydroxyapatite. Biotechnol Bioeng 100(5):839–854. doi:10.1002/bit.21906
Traylor SJ, Xu X, Li Y, Jin M, Li ZJ (2014) Adaptation of the pore diffusion model to describe multi-addition batch uptake high-throughput screening experiments. J Chromatogr A 1368:100–106. doi:10.1016/j.chroma.2014.09.058
Carta G (2012) Predicting protein dynamic binding capacity from batch adsorption tests. Biotechnol J 7(10):1216–1220. doi:10.1002/biot.201200136
Luo H, Cao M, Newell K, Afdahl C, Wang J, Wang WK, Li Y (2015) Double-peak elution profile of a monoclonal antibody in cation exchange chromatography is caused by histidine-protonation-based charge variants. J Chromatogr A 1424:92–101. doi:10.1016/j.chroma.2015.11.008
Ho SV, McLaughlin JM, Cue BW, Dunn PJ (2010) Environmental considerations in biologics manufacturing. Green Chem 12(5):755–766. doi:10.1039/B927443J
Lopes AG (2015) Single-use in the biopharmaceutical industry: a review of current technology impact, challenges and limitations. Food Bioprod Process 93:98–114
Shukla AA, Gottschalk U (2013) Single-use disposable technologies for biopharmaceutical manufacturing. Trends Biotechnol 31(3):147–154. doi:10.1016/j.tibtech.2012.10.004
Langer ES, Rader R (2015) Future proofing biopharmaceutical manufacturing: the industry seeks a leaner version of itself. Pharm Bioprocess 1(5):415–418
McNerney T, Thomas A, Senczuk A, Petty K, Zhao X, Piper R, et al. (2015) PDADMAC flocculation of Chinese hamster ovary cells: enabling a centrifuge-less harvest process for monoclonal antibodies. MAbs 7(2):413–428. doi:10.1080/19420862.2015.1007824
Weaver J, Husson SM, Murphy L, Wickramasinghe SR (2013) Anion exchange membrane adsorbers for flow-through polishing steps: Part I. Clearance of minute virus of mice. Biotechnol Bioeng 110(2):491–499. doi:10.1002/bit.24720
Weaver J, Husson SM, Murphy L, Wickramasinghe SR (2013) Anion exchange membrane adsorbers for flow-through polishing steps: Part II. Virus, host cell protein, DNA clearance, and antibody recovery. Biotechnol Bioeng 110(2):500–510. doi:10.1002/bit.24724
Smrekar V, Smrekar F, Strancar A, Podgornik A (2013) Single step plasmid DNA purification using methacrylate monolith bearing combination of ion-exchange and hydrophobic groups. J Chromatogr A 1276:58–64. doi:10.1016/j.chroma.2012.12.029
Sousa A, Almeida AM, Cernigoj U, Sousa F, Queiroz JA (2014) Histamine monolith versatility to purify supercoiled plasmid deoxyribonucleic acid from Escherichia coli lysate. J Chromatogr A 1355:125–133. doi:10.1016/j.chroma.2014.06.003
Teeters MA, Conrardy SE, Thomas BL, Root TW, Lightfoot EN (2003) Adsorptive membrane chromatography for purification of plasmid DNA. J Chromatogr A 989(1):165–173
Ladd Effio C, Hahn T, Seiler J, Oelmeier SA, Asen I, Silberer C, et al. (2016) Modeling and simulation of anion-exchange membrane chromatography for purification of Sf9 insect cell-derived virus-like particles. J Chromatogr A 1429:142–154. doi:10.1016/j.chroma.2015.12.006
Nestola P, Peixoto C, Villain L, Alves PM, Carrondo MJ, Mota JP (2015) Rational development of two flowthrough purification strategies for adenovirus type 5 and retro virus-like particles. J Chromatogr A 1426:91–101. doi:10.1016/j.chroma.2015.11.037
Banjac M, Roethl E, Gelhart F, Kramberger P, Jarc BL, Jarc M, Peterka M (2014) Purification of Vero cell derived live replication deficient influenza A and B virus by ion exchange monolith chromatography. Vaccine 32(21):2487–2492. doi:10.1016/j.vaccine.2014.02.086
Mundle ST, Giel-Moloney M, Kleanthous H, Pugachev KV, Anderson SF (2015) Preparation of pure, high titer, pseudoinfectious Flavivirus particles by hollow fiber tangential flow filtration and anion exchange chromatography. Vaccine 33(35):4255–4260. doi:10.1016/j.vaccine.2014.09.074
Thömmes J, Kula MR (1995) Membrane chromatography—an integrative concept in the downstream processing of proteins. Biotechnol Prog 11(4):357–367. doi:10.1021/bp00034a001
Francis P, von Lieres E, Haynes CA (2011) Zonal rate model for stacked membrane chromatography. I. Characterizing solute dispersion under flow-through conditions. J Chromatogr A 1218(31):5071–5078. doi:10.1016/j.chroma.2011.05.017
Zhou JX, Tressel T, Gottschalk U, Solamo F, Pastor A, Dermawan S, et al. (2006) New Q membrane scale-down model for process-scale antibody purification. J Chromatogr A 1134(1-2):66–73. doi:10.1016/j.chroma.2006.08.064
Ghosh P, Vahedipour K, Leuthold M, von Lieres E (2014) Model-based analysis and quantitative prediction of membrane chromatography: extreme scale-up from 0.08 ml to 1200 ml. J Chromatogr A 1332:8–13. doi:10.1016/j.chroma.2014.01.047
Tatarova I, Faber R, Denoyel R, Polakovic M (2009) Characterization of pore structure of a strong anion-exchange membrane adsorbent under different buffer and salt concentration conditions. J Chromatogr A 1216(6):941–947. doi:10.1016/j.chroma.2008.12.018
Borsoi-Ribeiro M, Bresolin IT, Vijayalakshmi M, Bueno SM (2013) Behavior of human immunoglobulin G adsorption onto immobilized Cu(II) affinity hollow-fiber membranes. J Mol Recognit 26(10):514–520. doi:10.1002/jmr.2296
Yavuz H, Bereli N, Yilmaz F, Armutcu C, Denizli A (2015) Antibody purification from human plasma by metal-chelated affinity membranes. Methods Mol Biol 1286:43–46. doi:10.1007/978-1-4939-2447-9_4
Francis P, Haynes CA (2009) Scale-up of controlled-shear affinity filtration using computational fluid dynamics. Biotechnol J 4(5):665–673. doi:10.1002/biot.200800331
Francis P, Martinez DM, Taghipour F, Bowen BD, Haynes CA (2006) Optimizing the rotor design for controlled-shear affinity filtration using computational fluid dynamics. Biotechnol Bioeng 95(6):1207–1217. doi:10.1002/bit.21090
Hou Y, Brower M, Pollard D, Kanani D, Jacquemart R, Kachuik B, Stout J (2015) Advective hydrogel membrane chromatography for monoclonal antibody purification in bioprocessing. Biotechnol Prog 31(4):974–982. doi:10.1002/btpr.2113
Nachman M, Azad AR, Bailon P (1992) Efficient recovery of recombinant proteins using membrane-based immunoaffinity chromatography (MIC). Biotechnol Bioeng 40(5):564–571. doi:10.1002/bit.260400503
Kuczewski M, Fraud N, Faber R, Zarbis-Papastoitsis G (2010) Development of a polishing step using a hydrophobic interaction membrane adsorber with a PER.C6-derived recombinant antibody. Biotechnol Bioeng 105(2):296–305. doi:10.1002/bit.22538
Kanavova N, Kosior A, Antosova M, Faber R, Polakovic M (2012) Application of a micromembrane chromatography module to the examination of protein adsorption equilibrium. J Sep Sci 35(22):3177–3183. doi:10.1002/jssc.201200396
Rathore AS, Muthukumar S (2014) High-throughput process development: II. Membrane chromatography. Methods Mol Biol 1129:39–44. doi:10.1007/978-1-62703-977-2_4
Close EJ, Salm JR, Iskra T, Sorensen E, Bracewell DG (2013) Fouling of an anion exchange chromatography operation in a monoclonal antibody process: visualization and kinetic studies. Biotechnol Bioeng 110(9):2425–2435. doi:10.1002/bit.24898
Corbett R, Carta G, Iskra T, Gallo C, Godavarti R, Salm JR (2013) Structure and protein adsorption mechanisms of clean and fouled tentacle-type anion exchangers used in a monoclonal antibody polishing step. J Chromatogr A 1278:116–125. doi:10.1016/j.chroma.2013.01.006
Cheong WJ, Yang SH, Ali F (2013) Molecular imprinted polymers for separation science: a review of reviews. J Sep Sci 36(3):609–628. doi:10.1002/jssc.201200784
Bhut BV, Christensen KA, Husson SM (2010) Membrane chromatography: protein purification from E. coli lysate using newly designed and commercial anion-exchange stationary phases. J Chromatogr A 1217(30):4946–4957. doi:10.1016/j.chroma.2010.05.049
Boi C (2007) Membrane adsorbers as purification tools for monoclonal antibody purification. J Chromatogr B Analyt Technol Biomed Life Sci 848(1):19–27. doi:10.1016/j.jchromb.2006.08.044
Herigstad MO, Gurgel PV, Carbonell RG (2011) Transport and binding characterization of a novel hybrid particle impregnated membrane material for bioseparations. Biotechnol Prog 27(1):129–139. doi:10.1002/btpr.502
Nestola P, Villain L, Peixoto C, Martins DL, Alves PM, Carrondo MJ, Mota JP (2014) Impact of grafting on the design of new membrane adsorbers for adenovirus purification. J Biotechnol 181:1–11. doi:10.1016/j.jbiotec.2014.04.003
Sum CH, Chong JY, Wettig S, Slavcev RA (2014) Separation and purification of linear covalently closed deoxyribonucleic acid by Q-anion exchange membrane chromatography. J Chromatogr A 1339:214–218. doi:10.1016/j.chroma.2014.03.016
Zhong L, Scharer J, Moo-Young M, Fenner D, Crossley L, Honeyman CH, et al. (2011) Potential application of hydrogel-based strong anion-exchange membrane for plasmid DNA purification. J Chromatogr B Analyt Technol Biomed Life Sci 879(9-10):564–572. doi:10.1016/j.jchromb.2011.01.017
Mould DL, Synge RLM (1952) Electrokinetic ultrafiltration analysis of polysaccharides. A new approach to the chromatography of large molecules. Analyst 77(921):964–969. doi:10.1039/AN9527700964
Hahn R, Jungbauer A (2001) Control method for integrity of continuous beds. J Chromatogr A 908(1-2):179–184
Xie S, Allington RW, Frechet JM, Svec F (2002) Porous polymer monoliths: an alternative to classical beads. Adv Biochem Eng Biotechnol 76:87–125
Barroso T, Hussain A, Roque AC, Aguiar-Ricardo A (2013) Functional monolithic platforms: chromatographic tools for antibody purification. Biotechnol J 8(6):671–681. doi:10.1002/biot.201200328
Rajamanickam V, Herwig C, Spadiut O (2015) Monoliths in bioprocess technology. Chromatography 2(2):195–212
Trilisky EI, Lenhoff AM (2009) Flow-dependent entrapment of large bioparticles in porous process media. Biotechnol Bioeng 104(1):127–133. doi:10.1002/bit.22370
Trilisky EI, Lenhoff AM (2010) Effect of bioparticle size on dispersion and retention in monolithic and perfusive beds. J Chromatogr A 1217(47):7372–7384. doi:10.1016/j.chroma.2010.09.040
Herigstad MO, Dimartino S, Boi C, Sarti GC (2015) Experimental characterization of the transport phenomena, adsorption, and elution in a protein A affinity monolithic medium. J Chromatogr A 1407:130–138. doi:10.1016/j.chroma.2015.06.045
Barroso T, Branco RJ, Aguiar-Ricardo A, Roque AC (2014) Structural evaluation of an alternative Protein A biomimetic ligand for antibody purification. J Comput Aided Mol Des 28(1):25–34. doi:10.1007/s10822-013-9703-1
Dean PD, Watson DH (1979) J Chromatogr 165:301–319
Regnault V, Rivat C, Vallar L, Geschier C, Stolz JF (1992) Purification of biologically active human plasma transthyretin by dye-affinity chromatography: studies on dye leakage and possibility of heat treatment for virus inactivation. J Chromatogr 584(1):93–99
Ongkudon CM, Kansil T, Wong C (2014) Challenges and strategies in the preparation of large-volume polymer-based monolithic chromatography adsorbents. J Sep Sci 37(5):455–464. doi:10.1002/jssc.201300995
Arrua RD, Haddad PR, Hilder EF (2013) Monolithic cryopolymers with embedded nanoparticles. II Capillary liquid chromatography of proteins using charged embedded nanoparticles. J Chromatogr A 1311:121–126. doi:10.1016/j.chroma.2013.08.077
Guo SZ, Yang X, Heuzey MC, Therriault D (2015) 3D printing of a multifunctional nanocomposite helical liquid sensor. Nanoscale 7(15):6451–6456. doi:10.1039/c5nr00278h
Krejcova L, Nejdl L, Rodrigo MA, Zurek M, Matousek M, Hynek D, et al. (2014) 3D printed chip for electrochemical detection of influenza virus labeled with CdS quantum dots. Biosens Bioelectron 54:421–427. doi:10.1016/j.bios.2013.10.031
Lee W, Kwon D, Choi W, Jung GY, Jeon S (2015) 3D-printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid cross-section. Sci Rep 5:7717. doi:10.1038/srep07717
Xu L, Gutbrod SR, Bonifas AP, Su Y, Sulkin MS, Lu N, et al. (2014) 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat Commun 5:3329. doi:10.1038/ncomms4329
Guo SZ, Heuzey MC, Therriault D (2014) Properties of polylactide inks for solvent-cast printing of three-dimensional freeform microstructures. Langmuir 30(4):1142–1150. doi:10.1021/la4036425
Liu W, Li Y, Feng S, Ning J, Wang J, Gou M, et al. (2014) Magnetically controllable 3D microtissues based on magnetic microcryogels. Lab Chip 14(15):2614–2625. doi:10.1039/c4lc00081a
Wang X, Schroder HC, Feng Q, Draenert F, Muller WE (2013) The deep-sea natural products, biogenic polyphosphate (Bio-PolyP) and biogenic silica (Bio-Silica), as biomimetic scaffolds for bone tissue engineering: fabrication of a morphogenetically-active polymer. Mar Drugs 11(3):718–746. doi:10.3390/md11030718
Wang X, Schroder HC, Grebenjuk V, Diehl-Seifert B, Mailander V, Steffen R, et al. (2014) The marine sponge-derived inorganic polymers, biosilica and polyphosphate, as morphogenetically active matrices/scaffolds for the differentiation of human multipotent stromal cells: potential application in 3D printing and distraction osteogenesis. Mar Drugs 12(2):1131–1147. doi:10.3390/md12021131
Yao Q, Wei B, Liu N, Li C, Guo Y, Shamie AN, et al. (2015) Chondrogenic regeneration using bone marrow clots and a porous polycaprolactone-hydroxyapatite scaffold by three-dimensional printing. Tissue Eng Part A 21(7-8):1388–1397. doi:10.1089/ten.TEA.2014.0280
Farahani RD, Chizari K, Therriault D (2014) Three-dimensional printing of freeform helical microstructures: a review. Nanoscale 6(18):10470–10485. doi:10.1039/c4nr02041c
Guo SZ, Gosselin F, Guerin N, Lanouette AM, Heuzey MC, Therriault D (2013) Solvent-cast three-dimensional printing of multifunctional microsystems. Small 9(24):4118–4122. doi:10.1002/smll.201300975
Lee H, Fang NX (2012) Micro 3D printing using a digital projector and its application in the study of soft materials mechanics. J Vis Exp 69:e4457. doi:10.3791/4457
Qin Z, Compton BG, Lewis JA, Buehler MJ (2015) Structural optimization of 3D-printed synthetic spider webs for high strength. Nat Commun 6:7038. doi:10.1038/ncomms8038
Shin D, Kim J, Yoo DS, Kim K (2015) Design of 3D isotropic metamaterial device using smart transformation optics. Opt Express 23(17):21892–21898. doi:10.1364/oe.23.021892
Amor-Coarasa A, Kelly JM, Babich JW (2015) Synthesis of [11C]palmitic acid for PET imaging using a single molecular sieve 13X cartridge for reagent trapping, radiolabeling and selective purification. Nucl Med Biol 42(8):685–690. doi:10.1016/j.nucmedbio.2015.03.008
Gross BC, Anderson KB, Meisel JE, McNitt MI, Spence DM (2015) Polymer coatings in 3D-printed fluidic device channels for improved cellular adherence prior to electrical lysis. Anal Chem 87(12):6335–6341. doi:10.1021/acs.analchem.5b01202
Liu X, Lei Z, Liu F, Liu D, Wang Z (2014) Fabricating three-dimensional carbohydrate hydrogel microarray for lectin-mediated bacterium capturing. Biosens Bioelectron 58:92–100. doi:10.1016/j.bios.2014.02.056
Chae MP, Rozen WM, McMenamin PG, Findlay MW, Spychal RT, Hunter-Smith DJ (2015) Emerging applications of bedside 3D printing in plastic surgery. Front Surg 2:25. doi:10.3389/fsurg.2015.00025
Truskett VN, Watts MP (2006) Trends in imprint lithography for biological applications. Trends Biotechnol 24(7):312–317. doi:10.1016/j.tibtech.2006.05.005
Tseng P, Murray C, Kim D, Di Carlo D (2014) Research highlights: printing the future of microfabrication. Lab Chip 14(9):1491–1495. doi:10.1039/c4lc90023e
Cheong WJ, Ali F, Kim YS, Lee JW (2013) Comprehensive overview of recent preparation and application trends of various open tubular capillary columns in separation science. J Chromatogr A 1308:1–24. doi:10.1016/j.chroma.2013.07.107
Thayer JR, Flook KJ, Woodruff A, Rao S, Pohl CA (2010) New monolith technology for automated anion-exchange purification of nucleic acids. J Chromatogr B Analyt Technol Biomed Life Sci 878(13-14):933–941. doi:10.1016/j.jchromb.2010.01.030
Dinh NP, Cam QM, Nguyen AM, Shchukarev A, Irgum K (2009) Functionalization of epoxy-based monoliths for ion exchange chromatography of proteins. J Sep Sci 32(15-16):2556–2564. doi:10.1002/jssc.200900243
Du K (2014) Peptide immobilized monolith containing tentacle-type functionalized polymer chains for high-capacity binding of immunoglobulin G. J Chromatogr A 1374:164–170. doi:10.1016/j.chroma.2014.11.060
Hanora A, Savina I, Plieva FM, Izumrudov VA, Mattiasson B, Galaev IY (2006) Direct capture of plasmid DNA from non-clarified bacterial lysate using polycation-grafted monoliths. J Biotechnol 123(3):343–355. doi:10.1016/j.jbiotec.2005.11.017
Savina IN, Galaev IY, Mattiasson B (2006) Ion-exchange macroporous hydrophilic gel monolith with grafted polymer brushes. J Mol Recognit 19(4):313–321. doi:10.1002/jmr.774
Singh NK, Dsouza RN, Grasselli M, Fernandez-Lahore M (2014) High capacity cryogel-type adsorbents for protein purification. J Chromatogr A 1355:143–148. doi:10.1016/j.chroma.2014.06.008
Tao SP, Zheng J, Sun Y (2015) Grafting zwitterionic polymer onto cryogel surface enhances protein retention in steric exclusion chromatography on cryogel monolith. J Chromatogr A 1389:104–111. doi:10.1016/j.chroma.2015.02.051
Gagnon P (2010) Monoliths open the door to key growth sectors. Bioprocess Int
Martin C, Coyne J, Carta G (2005) Properties and performance of novel high-resolution/highpermeability ion-exchange media for protein chromatography. J Chromatogr A 1069(1):43–52
Hoshino Y, Kodama T, Okahata Y, Shea KJ (2008) Peptide imprinted polymer nanoparticles: a plastic antibody. J Am Chem Soc 130:15242–15243
Hoshino Y, Urakami T, Kodama T, Koide H, Oku N, Okahata Y, Shea KJ (2009) Design of synthetic polymer nanoparticles that capture and neutralize a toxic peptide. Small 5(13):1562–1568
Zeng Z, Hoshino Y, Rodriguez A, Yoo H, Shea KJ (2010) Synthetic polymer nanoparticles with antibody-like affinity for a hydrophilic peptide. ACS Nano 4(1):199–204
Wong G (2009) Biotech scientists bank on big pharma’s biologics push. Nat Biotechnol 27(3):293–295. doi:10.1038/nbt0309-293
Dinon F, Salvalaglio M, Gallotta A, Beneduce L, Pengo P, Cavallotti C, Fassina G (2011) Structural refinement of protein A mimetic peptide. J Mol Recognit 24(6):1087–1094. doi:10.1002/jmr.1157
Thompson AD, Dugan A, Gestwicki JE, Mapp AK (2012) Fine-tuning multiprotein complexes using small molecules. ACS Chem Biol 7(8):1311–1320. doi:10.1021/cb300255p
Ulucan O, Eyrisch S, Helms V (2012) Druggability of dynamic protein-protein interfaces. Curr Pharm Des 18(30):4599–4606
Lee S-H, Hoshino Y, Randall AJ, Zeng Z, Baldi PJ, Doong R-a, Shea KJ (2012) Engineered synthetic polymer nanoparticles as IgG affinity ligands. J Am Chem Soc 134(38):15765–15772
Hoshino Y, Arata Y, Yonamine Y, Lee S-H, Yamasaki A, Tsuhara R, et al. (2015) Preparation of nanogel-immobilized porous gel beads for affinity separation of proteins: fusion of nano and micro gel materials. Polym J 47(2):220–225. doi:10.1038/pj.2014.101
Box GEP (1976) Science and statistics. J Am Stat Assoc 71(356):791–799
Whitehead AN, Russell B (1963) Principia mathematica, vol III. 2nd edn. Cambridge University Press, New York
Hillestad M, Nesvik GO (1994) A comparison of deductive and inductive models for product quality estimation. In: Bonvin D (ed) IFAC advanced control of chemical processes. Pergamon, Kyoto, pp 327–332
Hurford A (2012) Mechanistic models: what is the value of understanding? Just simple enough: the art of mathematical modelling, vol 2016
Burden F, Winkler D (2008) Bayesian regularization of neural networks. Methods Mol Biol 458:25–44
Insaidoo FK, Rauscher MA, Smithline SJ, Kaarsholm NC, Feuston BP, Ortigosa AD, et al. (2015) Targeted purification development enabled by computational biophysical modeling. Biotechnol Prog 31(1):154–164. doi:10.1002/btpr.2023
Kayala MA, Azencott CA, Chen JH, Baldi P (2011) Learning to predict chemical reactions. J Chem Inf Model 51(9):2209–2222. doi:10.1021/ci200207y
Kayala MA, Baldi P (2012) ReactionPredictor: prediction of complex chemical reactions at the mechanistic level using machine learning. J Chem Inf Model 52(10):2526–2540. doi:10.1021/ci3003039
Osberghaus A, Hepbildikler S, Nath S, Haindl M, von Lieres E, Hubbuch J (2012) Optimizing a chromatographic three component separation: a comparison of mechanistic and empiric modeling approaches. J Chromatogr A 1237:86–95. doi:10.1016/j.chroma.2012.03.029
Hanke AT, Ottens M (2014) Purifying biopharmaceuticals: knowledge-based chromatographic process development. Trends Biotechnol 32(4):210–220. doi:10.1016/j.tibtech.2014.02.001
Heinonen J, Kukkonen S, Sainio T (2014) Evolutionary multi-objective optimization based comparison of multi-column chromatographic separation processes for a ternary separation. J Chromatogr A 1358:181–191. doi:10.1016/j.chroma.2014.07.004
Korifi R, Le Dreau Y, Dupuy N (2014) Comparative study of the alignment method on experimental and simulated chromatographic data. J Sep Sci 37(22):3276–3291. doi:10.1002/jssc.201400700
Marks RE, Schnabl H (1999) Genetic algorithms and neural networks: a comparison based on the repeated prisoners dilemma. In: Brenner T (ed) Computational techniques for modelling learning in economics, vol 11. Springer, pp 197–219
Brooks CA, Cramer SM (1992) Steric mass-action ion exchange: displacement profiles and induced salt gradients. AIChE J 38(12):1969–1978. doi:10.1002/aic.690381212
Jungbauer A, Carta G (2010) Protein chromatography: process development and scale-up, 1st edn. Wiley
Guiochon GF, Felinger A, Shirazi DG (2006) Fundamentals of preparative and nonlinear chromatography, 2nd edn. Academic
Guiochon GL, Lin B (2003) Modeling for preparative chromatography, 1st edn. Academic
Lopez ZK, Tejeda A, Montesinos RM, Magana I, Guzman R (1997) Modeling column regeneration effects on ion-exchange chromatography. J Chromatogr A 791(1-2):99–107
Karlsson D, Jakobsson N, Axelsson A, Nilsson B (2004) Model-based optimization of a preparative ion-exchange step for antibody purification. J Chromatogr A 1055(1-2):29–39
Edwards-Parton S, Thornhill NF, Bracewell DG, Liddell JM, Titchener-Hooker NJ (2008) Principal component score modeling for the rapid description of chromatographic separations. Biotechnol Prog 24(1):202–208. doi:10.1021/bp070240j
Susanto A, Herrmann T, von Lieres E, Hubbuch J (2007) Investigation of pore diffusion hindrance of monoclonal antibody in hydrophobic interaction chromatography using confocal laser scanning microscopy. J Chromatogr A 1149(2):178–188. doi:10.1016/j.chroma.2007.03.002
Ishihara T, Kadoya T, Endo N, Yamamoto S (2006) Optimization of elution salt concentration in stepwise elution of protein chromatography using linear gradient elution data. Reducing residual protein A by cation-exchange chromatography in monoclonal antibody purification. J Chromatogr A 1114(1):97–101. doi:10.1016/j.chroma.2006.02.042
Ishihara T, Kadoya T, Yamamoto S (2007) Application of a chromatography model with linear gradient elution experimental data to the rapid scale-up in ion-exchange process chromatography of proteins. J Chromatogr A 1162(1):34–40. doi:10.1016/j.chroma.2007.03.016
Ishihara T, Yamamotob S (2005) Optimization of monoclonal antibody purification by ion-exchange chromatography. Application of simple methods with linear gradient elution experimental data. J Chromatogr A 1069(1):99–106
Muller-Spath T, Strohlein G, Aumann L, Kornmann H, Valax P, Delegrange L, et al. (2011) Model simulation and experimental verification of a cation-exchange IgG capture step in batch and continuous chromatography. J Chromatogr A 1218(31):5195–5204. doi:10.1016/j.chroma.2011.05.103
Osberghaus A, Hepbildikler S, Nath S, Haindl M, von Lieres E, Hubbuch J (2012) Determination of parameters for the steric mass action model--a comparison between two approaches. J Chromatogr A 1233:54–65. doi:10.1016/j.chroma.2012.02.004
Westerberg K, Broberg-Hansen E, Sejergaard L, Nilsson B (2013) Model-based risk analysis of coupled process steps. Biotechnol Bioeng 110(9):2462–2470. doi:10.1002/bit.24909
Lapelosa M, Patapoff TW, Zarraga IE (2015) Modeling of protein-anion exchange resin interaction for the human growth hormone charge variants. Biophys Chem 207:1–6. doi:10.1016/j.bpc.2015.07.004
Kluters S, Wittkopp F, Johnck M, Frech C (2015) Application of linear pH gradients for the modeling of ion exchange chromatography: separation of monoclonal antibody monomer from aggregates. J Sep Sci. doi:10.1002/jssc.201500994
Mazumder J, Zhu J, Bassi AS, Ray AK (2009) Modeling and simulation of liquid-solid circulating fluidized bed ion exchange system for continuous protein recovery. Biotechnol Bioeng 104(1):111–126. doi:10.1002/bit.22368
Xenopoulos A (2015) A new, integrated, continuous purification process template for monoclonal antibodies: process modeling and cost of goods studies. J Biotechnol 213:42–53. doi:10.1016/j.jbiotec.2015.04.020
Teeters M, Benner T, Bezila D, Shen H, Velayudhan A, Alred P (2009) Predictive chromatographic simulations for the optimization of recovery and aggregate clearance during the capture of monoclonal antibodies. J Chromatogr A 1216(33):6134–6140. doi:10.1016/j.chroma.2009.06.066
Ladiwala A, Rege K, Breneman CM, Cramer SM (2005) A priori prediction of adsorption isotherm parameters and chromatographic behavior in ion-exchange systems. Proc Natl Acad Sci U S A 102(33):11710–11715. doi:10.1073/pnas.0408769102
Guelat B, Strohlein G, Lattuada M, Delegrange L, Valax P, Morbidelli M (2012) Simulation model for overloaded monoclonal antibody variants separations in ion-exchange chromatography. J Chromatogr A 1253:32–43. doi:10.1016/j.chroma.2012.06.081
Sarangapani PS, Hudson SD, Jones RL, Douglas JF, Pathak JA (2015) Critical examination of the colloidal particle model of globular proteins. Biophys J 108(3):724–737. doi:10.1016/j.bpj.2014.11.3483
Lang KM, Kittelmann J, Durr C, Osberghaus A, Hubbuch J (2015) A comprehensive molecular dynamics approach to protein retention modeling in ion exchange chromatography. J Chromatogr A 1381:184–193. doi:10.1016/j.chroma.2015.01.018
Paloni M, Cavallotti C (2015) Molecular modeling of the affinity chromatography of monoclonal antibodies. Methods Mol Biol 1286:321–335. doi:10.1007/978-1-4939-2447-9_25
Kisley L, Chen J, Mansur AP, Dominguez-Medina S, Kulla E, Kang MK, et al. (2014) High ionic strength narrows the population of sites participating in protein ion-exchange adsorption: a single-molecule study. J Chromatogr A 1343:135–142. doi:10.1016/j.chroma.2014.03.075
Kisley L, Poongavanam M-V, Kourentzi K, Willson RC, Landes CF (2015) pH-dependence of single-protein adsorption and diffusion at a liquid chromatographic interface. J Separation Sci. doi:10.1002/jssc.201500809
Marek W, Muca R, Wos S, Piatkowski W, Antos D (2013) Isolation of monoclonal antibody from a Chinese hamster ovary supernatant. II: Dynamics of the integrated separation on ion exchange and hydrophobic interaction chromatography media. J Chromatogr A 1305:64–75. doi:10.1016/j.chroma.2013.06.076
Baumann P, Hahn T, Hubbuch J (2015) High-throughput micro-scale cultivations and chromatography modeling: powerful tools for integrated process development. Biotechnol Bioeng 112(10):2123–2133. doi:10.1002/bit.25630
Huuk TC, Hahn T, Osberghaus A, Hubbuch J (2014) Model-based integrated optimization and evaluation of a multi-step ion exchange chromatography. Separation and Purification Technology 136:207–222. doi:10.1016/j.seppur.2014.09.012
Sharma C, Malhotra D, Rathore AS (2011) Review of computational fluid dynamics applications in biotechnology processes. Biotechnol Prog 27(6):1497–1510
Joshi V, Shivach T, Kumar V, Yadav N, Rathore A (2014) Avoiding antibody aggregation during processing: establishing hold times. Biotechnol J 9(9):1195–1205. doi:10.1002/biot.201400052
Lapelosa M, Patapoff TW, Zarraga IE (2014) Molecular simulations of the pairwise interaction of monoclonal antibodies. J Phys Chem B 118(46):13132–13141. doi:10.1021/jp508729z
Helling C, Borrmann C, Strube J (2012) Optimal integration of directly combined hydrophobic interaction and ion exchange chromatography purification processes. Chem Eng Technol 35(10):1786–1796. doi:10.1002/ceat.201200043
Buyel JF, Woo JA, Cramer SM, Fischer R (2013) The use of quantitative structure–activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production. J Chromatogr A 1322:18–28. doi:10.1016/j.chroma.2013.10.076
Kruhlak NL, Benz RD, Zhou H, Colatsky TJ (2012) (Q)SAR modeling and safety assessment in regulatory review. Clin Pharmacol Ther 91(3):529–534. doi:10.1038/clpt.2011.300
Acknowledgments
The authors would like to thank Yan Yao, Ph.D., Associate Director, Bristol-Myers Squibb, and Gregory Barker, Ph.D., Senior Engineer, Bristol-Myers Squibb for their critical review and feedback. The authors would also like to thank Professor Giorgio Carta, Ph.D., School of Engineering and Applied Sciences, University of Virginia, Arch Creasy, graduate student at the School of Engineering and Applied Sciences, University of Virginia, and aforementioned colleagues Gregory Barker and Yan Yao for the generous permission to reproduce Fig. 6, and Gregory Barker for the generous provision of Fig. 4.
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Singh, N., Herzer, S. (2017). Downstream Processing Technologies/Capturing and Final Purification. In: Kiss, B., Gottschalk, U., Pohlscheidt, M. (eds) New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins. Advances in Biochemical Engineering/Biotechnology, vol 165. Springer, Cham. https://doi.org/10.1007/10_2017_12
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