Advertisement

Downstream Processing for Biopharmaceuticals Recovery

  • Anu Mehta
Chapter
Part of the Environmental Chemistry for a Sustainable World book series (ECSW, volume 26)

Abstract

The invention of genetic engineering tools has given birth to a new type of pharmaceuticals known as biopharmaceuticals. These are the drug molecules that have therapeutic effects and are synthesised in biological cell systems. Drug like recombinant insulin is a prominent prototype example of biopharmaceutical which is commonly available in the market at cheap prices for diabetic patients, globally. The production of these therapeutic molecules differs from chemically synthesised low molecular weight drugs. Upstream and downstream processes altogether comprise the production process of biopharmaceuticals. The downstream processing costs 70% of the total production cost of a particular biopharmaceutical, largely contributed by expensive chromatographic techniques such as affinity, hydrophobic interaction, ion exchange and size exclusion. Although chromatography is a reliable and conventional approach to carry out single step purification of biopharmaceuticals, the columns are run in a series to increase the purification fold. This makes the process tedious, and problems like diffusional spreading and resolution are also observed with chromatography procedures. The concern is important as we aim to bring various biopharmaceuticals into market that can treat innumerable diseases at a cheap price.

The current chapter emphasises the process and technology related to the upstream process and the three chronological steps – initial recovery, purification and polishing – involved in downstream processing of biopharmaceuticals. The chapter encompasses the hurdles encountered in the downstream processing in particular with chromatography process that makes high-quality production of biopharmaceuticals an expensive affair thus making it difficult to reach the public. New technologies designed to offer faster and cheaper purification such as aqueous two-phase extraction system, and nano-magnetic-based antibodies separation system have been discussed further. Moreover, we have reviewed and emphasised the requirement of using combination of physical, mathematical, biological and computational approaches, which can help to design efficient production and purification systems for the ample, cheap and continuous market supply of this new category of drugs.

Keywords

Biopharmaceuticals Biosimilars Biotechnology Chromatography Downstream process Genetic engineering Monoclonal antibodies Molecular pharming Polishing Purification 

Notes

Acknowledgements

The author is highly thankful to the editor and reviewers for suggesting valuable suggestions.

References

  1. Albertsson PA (1970) Partition of cell particles and macromolecules in polymer two-phase system. Adv Protein Chem 24:309–341.  https://doi.org/10.1016/S0065-3233(08)60244-2 CrossRefGoogle Scholar
  2. Alford JR, Kendrick BS, Carpenter JF, Randolph TW (2008) High concentration formulations of recombinant human interleukin-1 receptor antagonist: II. aggregation kinetics. J Pharm Sci 97(8):3005–3021.  https://doi.org/10.1002/jps.21205 CrossRefGoogle Scholar
  3. 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.  https://doi.org/10.1016/j.pep.2007.02.010 CrossRefGoogle Scholar
  4. Aumann L, Morbidelli M (2007) A continuous multicolumn countercurrent solvent gradient purification (MCSGP) process. Biotechnol Bioeng 98(5):1043–1055.  https://doi.org/10.1002/bit.21527 CrossRefGoogle Scholar
  5. Azevedo AM, Aires-Barros MR (2011) New platforms for downstream processing of biopharmaceuticals. 1st Portuguese Meeting in Bioengineering, February 2011 Portuguese chapter of IEEE EMBS Instituto Superior Técnico, Technical University of LisbonGoogle Scholar
  6. Azevedo AM, Rosa PA, Ferreira IF, Aires-Barros MR (2007) Optimisation of aqueous two-phase extraction of human antibodies. J Biotechnol 132(2):209–217.  https://doi.org/10.1016/j.jniotec.2007.04.002 CrossRefGoogle Scholar
  7. Bailey JE, Ollis DF (1986) Biochemical engineering fundamentals, 2nd edn. Tata McGraw-Hill Education, NoidaGoogle Scholar
  8. Beck A (2011) Biosimilar, biobetter and next generation therapeutic antibodies. MAbs 3(2):107–110.  https://doi.org/10.4161/mabs.3.2.14785 CrossRefGoogle Scholar
  9. Bennett AD, Rhind SK, Lowe PA, Hentschel CCG (1984) Eur Pat Appl 0131363Google Scholar
  10. Bhambure R, Kumar K, Rathore AS (2011) High-throughput process development for biopharmaceutical drug substances. Trends Biotechnol 29(3):127–135.  https://doi.org/10.1016/j.tibtech.2010.12.001 CrossRefGoogle Scholar
  11. Biopharma International Editors (2012) Considerations for successful upstream process development. BioPharm Int 25(7)Google Scholar
  12. BIOPHARMA: Biopharmaceutical Products in the U.S. and European Markets (2002) This is a list of new full FDA approvals for biopharmaceutical products. Available from: http://www.biopharma.com/approvals.html
  13. Bloomingburg GF, Bauer JS, Carta G, Byers CH (1991) Continuous separation of proteins by annular chromatography. Ind Eng Chem Res 30(5):1061–1010.  https://doi.org/10.1021/ie00053a031 CrossRefGoogle Scholar
  14. Bonham-Carter J, Shevitz J (2011) A brief history of perfusion bio manufacturing. BioProcess Int. 9(9):28–30Google Scholar
  15. Brouns TM, Elliott ML, Van Wie BJ (1990) U.S. Patent No. 4,939,087. U.S. Patent and Trademark Office, Washington, DCGoogle Scholar
  16. Buchacher A, Iberer G (2006) Purification of intravenous immunoglobulin G from human plasma – aspects of yield and virus safety. Biotechnol J 1(2):148–163.  https://doi.org/10.1002/biot.200500037 CrossRefGoogle Scholar
  17. 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.  https://doi.org/10.1016/j.memsci.2011.09.004 CrossRefGoogle Scholar
  18. Chen J, Tetrault J, Ley A (2008) Comparison of standard and new generation hydrophobic interaction chromatography resins in the monoclonal antibody purification process. J Chromatogr A 1177(2):272–281.  https://doi.org/10.1016/j.chroma.2007.07.083 CrossRefGoogle Scholar
  19. Cheryan M (1986) Ultrafiltration handbook. Technomic, LancasterGoogle Scholar
  20. Chisti Y, Moo-Young M (1986) Disruption of microbial cells for intracellular products. Enzym Microb Technol 8:194–204.  https://doi.org/10.1016/0141-0229(86)90087-6 CrossRefGoogle Scholar
  21. Chon JH, Zarbis-Papastoitsis G (2011) Advances in the production and downstream processing of antibodies. New Biotechnol 28(5):458–463.  https://doi.org/10.1016/j.nbt.2011.03.015 CrossRefGoogle Scholar
  22. Courtney M, Buchwalder A, Tessier LH, Jaye M, Benavente A, Ballard A, Kohli V, Lathe R, Tolstoshev P, Lecocq JP (1984) High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli. 1984. Proc Natl Acad Sci U S A 81(3):669–663.  https://doi.org/10.1073/pnas.81.3.669 CrossRefGoogle Scholar
  23. Crapisi A, Lante A, Pasini G, Spettoli P (1993) Enhanced microbial cell lysis by the use of lysozyme immobilised on different carriers. Process Biochem 28(1):17–21.  https://doi.org/10.1016/0032-9592(94)80031-6 CrossRefGoogle Scholar
  24. Crommelin DJ, Storm G, Verrijk R, de Leede L, Jiskoot W, Hennink WE (2003) Shifting paradigms: biopharmaceuticals versus low molecular weight drugs. Int J Pharm 266(1-2):3–16.  https://doi.org/10.1016/S0378-5173(03)00376-4 CrossRefGoogle Scholar
  25. Dean CR, Ward OP (1992) The use of EDTA or polymyxin with lysozyme for the recovery of intracellular products from Escherichia coli. Biotechnol Tech 6(2):133–138.  https://doi.org/10.1007/BF02438819 CrossRefGoogle Scholar
  26. del Val IJ, Kontoravdi C, Nagy JM (2010) Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns. Biotechnol Prog 26(6):1505–1527.  https://doi.org/10.1002/btpr.470 CrossRefGoogle Scholar
  27. Dunnill P, Lilly MD (1974) Purification of enzymes using magnetic bioaffinity materials. Biotechnol Bioeng 16:987–990.  https://doi.org/10.1002/bit.260160710 CrossRefGoogle Scholar
  28. Durocher Y, Butler M (2009) Expression systems for therapeutic glycoprotein production. Curr Opin Biotechnol 20(6):700–707.  https://doi.org/10.1016/j.copbio.2009.10.008 CrossRefGoogle Scholar
  29. Eiberle MK, Jungbauer A (2010) Technical refolding of proteins: do we have freedom to operate? Biotechnol J 5(6):547–559.  https://doi.org/10.1002/biot.201000001 CrossRefGoogle Scholar
  30. Erikson RA (1984) Disk stack centrifuges in biotechnology. In: American Institute of Chemical Engineers, National Meeting, American Institute of Chemical Engineers, p 9Google Scholar
  31. Ferreira AM, Faustino VFM, Mondal D, Coutinho JAP, Freire MG (2016) Improving the extraction and purification of immunoglobulin G by the use of ionic liquids as adjuvants in aqueous biphasic systems. J Biotechnol 236:166–175.  https://doi.org/10.1016/j.jbiotec.2016.08.015 CrossRefGoogle Scholar
  32. Fish B, Williams R (2007) Avoiding pitfalls in scaling up biopharmaceutical production. Pharm Technol Eur 19(10):29. doi: not availableGoogle Scholar
  33. Frenzel A, Bergemann C, Kohl G, Reinard T (2003) Novel purification system for 6xHis-tagged proteins by magnetic affinity separation. J Chromatogr A 793:325–329.  https://doi.org/10.1016/S1570-0232(03)00332-5 CrossRefGoogle Scholar
  34. Frost, Sullivan (2004) Strategic analysis of downstream processing. In: Biopharmaceutical productionGoogle Scholar
  35. Gagnon P (2006) Polishing methods for monoclonal IgG purification. In: Shukla AA, Etzel MR, Gadam S (eds) Process scale bioseparations for the biopharmaceutical industry. Taylor & Francis, New York, pp 491–505CrossRefGoogle Scholar
  36. Gagnon P (2012) Technology trends in antibody purification. J Chromatogr A 1221:57–70.  https://doi.org/10.1016/j.chroma.2011.10.034 CrossRefGoogle Scholar
  37. Gary W (2000) Biopharmaceutical benchmarks. Nat Biotechnol 18:832–833.  https://doi.org/10.1038/nbt.3040 CrossRefGoogle Scholar
  38. Gary W (2003) Biopharmaceutical and pharmaceutical biotechnology. In: Biopharmaceuticals: biochemistry and biotechnology, 2nd edn. Wiley, ChichesterGoogle Scholar
  39. Ghose S, Hubbard B, Cramer SM (2006) Evaluation and comparison of alternatives to Protein A chromatography: mimetic and hydrophobic charge induction chromatographic stationary phases. J Chromatogr A 1122(1-2):144–152.  https://doi.org/10.1016/j.chroma.2006.04.083 CrossRefGoogle Scholar
  40. Ghose S, Jin M, Liu J, Hickey J (2009) Integrated polishing steps for monoclonal antibody purification. In: Gottschalk U (ed) Process scale purification of antibodies. Wiley, New York, pp 145–141CrossRefGoogle Scholar
  41. Giovannini R, Freitag R (2001) Isolation of a recombinant antibody from cell culture supernatant: continuous annular versus batch and expanded-bed chromatography. Biotechnol Bioeng 73(6):522–529.  https://doi.org/10.1002/bit.1087 CrossRefGoogle Scholar
  42. Goeddel DV, Heyneker HL, Hozumi T, Arentzon R, Itakura K, Yansura DG, Ross MJ, Miozzari G, Crea R, Seeburg P (1979a) Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature 281(5732):544–548.  https://doi.org/10.1038/281544a0 CrossRefGoogle Scholar
  43. Goeddel DV, Kleid DG, Bolivar F, Heyneker HL, Yansura DG, Crea R, Hirose T, Kraszewski A, Itakura K, Riggs AD (1979b) Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA 76(1):106–110. doi: not availableCrossRefGoogle Scholar
  44. Gözke G, Kirschhöfer F, Heissler S, Trutnau M, Brenner-Weiss G, Ondruschka J, Obst U, Posten C (2012) Filtration kinetics of chitosan separation by electrofiltration. Biotechnol J 7(2):262–274.  https://doi.org/10.1002/biot.201000466 CrossRefGoogle Scholar
  45. Gronemeyer P, Ditz R, Strube J (2014) Trends in upstream and downstream process development for antibody manufacturing. Bioengineering 1(4):188–212.  https://doi.org/10.3390/bioengineering1040188 CrossRefGoogle Scholar
  46. Gueorguieva L, Palani S, Rinas U, Jayaraman G, Seidel-Morgenstern A (2011) Recombinant protein purification using gradient assisted simulated moving bed hydrophobic interaction chromatography. Part II: process design and experimental validation. J Chromatogr A 1218(37):6402–6411.  https://doi.org/10.1016/j.chroma.2011.07.008 CrossRefGoogle Scholar
  47. Hanke AT, Ottens M (2014) Purifying biopharmaceuticals: knowledge-based chromatographic process development. Trends Biotechnol 32(4):210–220.  https://doi.org/10.1016/j.tibtech.2014.02.001 CrossRefGoogle Scholar
  48. Harrison STL (2011) Cell disruption. In: Comprehensive biotechnology, 2nd edn. Elsevier, Oxford, pp 619–639CrossRefGoogle Scholar
  49. Himeji D, Horiuchi T, Tsukamoto H, Hayashi K, Watanabe T, Harada M (2002) Characterization of caspase-8L: a novel isoform of caspase- 8 that behaves as an inhibitor of the caspase cascade. Blood 99:4070–4078.  https://doi.org/10.1182/blood.V99.11.4070 CrossRefGoogle Scholar
  50. Hodge G (2005) Media development for mammalian cell culture. Biopharm Int 18:54Google Scholar
  51. Hofmann I, Schnolzer M, Kaufmann I, Franke WW (2002) Symplekin, a constitutive protein of karyo- and cytoplasmic particles involved in mRNA biogenesis in Xenopus laevis oocytes. Mol Biol Cell 13(5):1665–1676.  https://doi.org/10.1091/mbc.01-12-0567 CrossRefGoogle Scholar
  52. Hossler P, Khattak SF, Li ZJ (2009) Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 19(9):936–949.  https://doi.org/10.1093/glycob/cwp079 CrossRefGoogle Scholar
  53. Huddleston J, Veide A, Köhler K, Flanagan J, Enfors SO, Lyddiatt A (1991) The molecular basis of partitioning in aqueous two-phase systems. Trends Biotechnol 9(11):381–388.  https://doi.org/10.1016/0167-7799(91)90130-A CrossRefGoogle Scholar
  54. Huettmann H, Berkemeyer M, Buchinger W, Jungbauer A (2014) Preparative crystallization of a single chain antibody using an aqueous two-phase system. Biotechnol Bioeng 111(11):2192–2199.  https://doi.org/10.1002/bit.25287 CrossRefGoogle Scholar
  55. Iberer G, Schwinn H, Josic D, Jungbauer A, Buchacher A (2002) Continuous purification of a clotting factor IX concentrate and continuous regeneration by preparative annular chromatography. J Chromatogr 972(1):115–129.  https://doi.org/10.1016/S0021-9673(02)01074-9 CrossRefGoogle Scholar
  56. Itakura K, Hiroso T, Crea R, Riggs AD, Heyneker HL, Bolivar F, Boyer HW (1977) Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. Science 198(4321):1056–1063.  https://doi.org/10.1126/science.412251 CrossRefGoogle Scholar
  57. Ivory CF, Gilmartin M, Gobie WA, McDonald CA, Zollars RL (1995) A hybrid centrifuge rotor for continuous bioprocessing. Biotechnol Prog 11(1):21–32.  https://doi.org/10.1021/bp00031a003 CrossRefGoogle Scholar
  58. Jayapal KP, Wlaschin KF, Hu WS, Yap MGS (2007) Recombinant protein therapeutics from CHO cells – 20 years and counting. Chem Eng Prog 103(10):40–47. doi: not availableGoogle Scholar
  59. Jozala AF, Geraldes DC, Tundisi LL, Feitosa VA, Breyer CA, Cardoso SL, Mazzola PG, Oliveira-Nascimento L, Rangel-Yagui CO, Magalhães PO, Oliveira MA, Pessoa A Jr (2016) Biopharmaceuticals from microorganisms: from production to purification. Braz J Microbiol 47(1):51–63.  https://doi.org/10.1016/j.bjm.2016.10.007 CrossRefGoogle Scholar
  60. Jungbauer A (2013) Continuous downstream processing of biopharmaceuticals. Trends Biotechnol 31(8):479–492.  https://doi.org/10.1016/j.tibtech.2013.05.011 CrossRefGoogle Scholar
  61. Jungbauer A, Kaar W (2007) Current status of technical protein refolding. J Biotechnol 128(3):587–596.  https://doi.org/10.1016/j.jbiotec.2006.12.004 CrossRefGoogle Scholar
  62. Kato Y, Nakamura K, Kitamura T, Hasegawa M, Sasaki H (2004) Hydrophobic interaction chromatography at low salt concentration for the capture of monoclonal antibodies. J Chromatogr A 1036(1):45–50.  https://doi.org/10.1016/j.chroma.2004.02.009 CrossRefGoogle Scholar
  63. Kennedy RM (2005) Expanded-bed adsorption chromatography. Curr Protoc Protein Sci Jun; Chapter 8: Unit 8:8.  https://doi.org/10.1002/0471140864.ps0808s40 CrossRefGoogle Scholar
  64. Kramberger P, Urbas L, Štrancar A (2015) Downstream processing and chromatography based analytical methods for production of vaccines, gene therapy vectors, and bacteriophages. Hum Vaccin Immunother 11(4):1010–1021.  https://doi.org/10.1080/21645515.2015.1009817 CrossRefGoogle Scholar
  65. Kwon JS-II, Nayhouse M, Christofides PD, Orkoulas G (2014) Modeling and control of crystal shape in continuous protein crystallization. Chem Eng Sci 107:47–57.  https://doi.org/10.1016/j.ces.2013.12.005 CrossRefGoogle Scholar
  66. Lain B, Cacciuttolo MA, Zarbis-Papastoitsis G (2009) Development of a high-capacity Mab capture step based on cation-exchange chromatography. BioProcess Int 7(5):26–34Google Scholar
  67. Lander R, Daniels C, Meacle F (2005) Efficient, scalable clarification of diverse bioprocess streams. Bioprocess Int 11:32–40Google Scholar
  68. Langer ES (2011) Trends in perfusion bioreactors: will perfusion be the next revolution in bioprocessing? BioProcess Int. 9(10):18–22Google Scholar
  69. Larsson PO (1994) Magnetically enhanced phase separation. Methods Enzymol 228:112–117. doi: not availableCrossRefGoogle Scholar
  70. Lebreton B, Brown A, van Reis R (2008) Application of high-performance tangential flow filtration (HPTFF) to the purification of a human pharmaceutical antibody fragment expressed in Escherichia coli. Biotechnol Bioeng 100(5):964–974.  https://doi.org/10.1002/bit.21842 CrossRefGoogle Scholar
  71. Li F, Vijayasankaran N, Shen AY, Kiss R, Amanullah A (2010) Cell culture processes for monoclonal antibody production. MAbs 2(5):466–479.  https://doi.org/10.4161/mabs.2.5.12720 CrossRefGoogle Scholar
  72. Lin N, Mascarenhas J, Sealover NR, George HJ, Brooks J, Kayser KJ, Gau B, Yasa I, Azadi P, Archer-Hartmann S (2015) Chinese hamster ovary (CHO) host cell engineering to increase sialylation of recombinant therapeutic proteins by modulating sialyltransferase expression. Biotechnol Prog 31(2):334–346.  https://doi.org/10.1002/btpr.2038 CrossRefGoogle Scholar
  73. Liu HF, Ma J, Winter C, Bayer R (2010) Recovery and purification process development for monoclonal antibody production. MAbs 2(5):480–499.  https://doi.org/10.4161/mabs.2.5.12645 CrossRefGoogle Scholar
  74. Liu Z, Wickramasinghe SR, Qian X (2017) Membrane chromatography for protein purifications from ligand design to functionalization. Sep Sci Technol 52:299–319.  https://doi.org/10.1080/01496395.2016.1223133 CrossRefGoogle Scholar
  75. Lowe CR (2001) Combinatorial approaches to affinity chromatography. Curr Opin Chem Biol 5(3):248–256.  https://doi.org/10.1016/S1367-5931(00)00199-X CrossRefGoogle Scholar
  76. Machold C, Schlegl R, Buchinger W, Jungbauer A (2005) Continuous matrix assisted refolding of a-lactalbumin by ion exchange chromatography with recycling of aggregates combined with ultradiafiltration. J Chromatogr A 1080(1):29–42.  https://doi.org/10.1016/j.chroma.2005.03.018 CrossRefGoogle Scholar
  77. Mahajan E, George A, Wolk B (2012) Improving affinity chromatography resin efficiency using semi-continuous chromatography. J Chromatogr A 1227:154–162.  https://doi.org/10.1016/j.chroma.2011.12.106 CrossRefGoogle Scholar
  78. Martinez Cristancho CA, David F, Franco-Lara E, Seidel-Morgenstern A (2013) Discontinuous and continuous purification of single-chain antibody fragments using immobilized metal ion affinity chromatography. J Biotechnol 163(2):233–242.  https://doi.org/10.1016/j.jbiotec.2012.08.022 CrossRefGoogle Scholar
  79. Middelberg A (1995) Process-scale disruption of microorganisms. Biotechnol Adv 13(3):491–551.  https://doi.org/10.1016/0734-9750(95)02007-P CrossRefGoogle Scholar
  80. Mitragotri S, Burke PA, Langer R (2014) Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev Drug Discov 13(9):655–652.  https://doi.org/10.1038/nrd4363 CrossRefGoogle Scholar
  81. Mun S, Yi X, Kim JH, Wang NHL (2003) Optimal design of a size-exclusion tandem simulated moving bed for insulin purification. Ind Eng Chem Res 42(9):1977–1993.  https://doi.org/10.1021/ie020680+ CrossRefGoogle Scholar
  82. Ngantung FA, Miller PG, Brushett FR, Tang GL, Wang DI (2006) RNA interference of sialidase improves glycoprotein sialic acid content consistency. Biotechnol Bioeng 95(1):106–119.  https://doi.org/10.1002/bit.20997 CrossRefGoogle Scholar
  83. Nishiya Y, Hibi T, Oda JL (2002) A purification method of the diagnostic enzyme Bacillus uricase using magnetic beads and nonspecific protease. Protein Expr Purif 25:426–429.  https://doi.org/10.1016/S1046-5928(02)00022-0 CrossRefGoogle Scholar
  84. Odabasi M, Denizli A (2004) Cibacron Blue F3GA-attached magnetic poly(2-hydroxyethyl methacrylate) beads for human serum albumin adsorption. Polym Int 53:332–338.  https://doi.org/10.1002/pi.1305 CrossRefGoogle Scholar
  85. Ozdural AR et al (2007) A novel technology for virus vaccine purification: modeling and operation of continuous annular chromatography unit. In: AIChE annual meeting: 2007 Spring meeting and 3rd global congress on process safety. American Institute of Chemical Engineers, p 18Google Scholar
  86. Peeva L, da Silva Burgal J, Valtcheva I, Livingston AG (2014) Continuous purification of active pharmaceutical ingredients using multistage organic solvent nanofiltration membrane cascade. Chem Eng Sci 116:183–194.  https://doi.org/10.1016/j.ces.2014.04.022 CrossRefGoogle Scholar
  87. Pennica D, Hayflick JS, Bringman TS, Palladina MA, Goeddel DV (1985) Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci U S A 82:6060–6064. doi:not availableCrossRefGoogle Scholar
  88. Pirrung SM, van der Wielen LAM, van Beckhoven RFWC, van de Sandt EJAX, Eppink MHM, Ottens M (2017) Optimization of biopharmaceutical downstream processes supported by mechanistic models and artificial neural networks. Biotechnol Prog 33(3):696–707.  https://doi.org/10.1002/btpr.2435 CrossRefGoogle Scholar
  89. Rajendran A, Paredes G, Mazzotti M (2009) Simulated moving bed chromatography for the separation of enantiomers. J Chromatog A 1216(4):709–738.  https://doi.org/10.1016/j.chroma.2008.10.075 CrossRefGoogle Scholar
  90. Rathore AS, Agarwal H, Sharma AK, Pathak M, Muthukumar S (2015) Continuous processing for production of biopharmaceuticals. Prep Biochem Biotechnol 45(8):836–849.  https://doi.org/10.1080/10826068.2014.985834 CrossRefGoogle Scholar
  91. Rathore AS, Kumar D, Kateja N (2018) Recent developments in chromatographic purification of biopharmaceuticals. Biotechnol Lett 40(6):1–11.  https://doi.org/10.1007/s10529-018-2552-1 CrossRefGoogle Scholar
  92. Roque AC, Lowe CR, Taipa MA (2004) Antibodies and genetically engineered related molecules: production and purification. Biotechnol Prog 20(3):639–654.  https://doi.org/10.1021/bp030070k CrossRefGoogle Scholar
  93. Ruanjaikaen K, Zydney AL (2011) Purification of singly-pegylated α-lactalbumin using charged ultrafiltration membranes. Biotechnol Bioeng 108:822–829.  https://doi.org/10.1002/bit.22991 CrossRefGoogle Scholar
  94. Saboya LV, Maillard MB, Lortal S (2003) Efficient mechanical disruption of Lactobacillus helveticus, Lactococcus lactis and Propionibacterium freudenreichii by a new high-pressure homogenizer and recovery of intracellular aminotransferase activity. J Ind Microbiol Biotechnol 30(1):1–5.  https://doi.org/10.1007/s10295-002-0011-3 CrossRefGoogle Scholar
  95. Safarik I, Safarikova M (1993) Batch isolation of hen egg white lysozyme with magnetic chitin. J Biochem Biophys Methods 27:327–330.  https://doi.org/10.1016/0165-022X(93)90013-E CrossRefGoogle Scholar
  96. Saraswat M, Musante L, Ravidá A, Shortt B, Byrne B, Holthofer H (2013) Preparative purification of recombinant proteins: current status and future trends. Biomed Res Int 2013:312709.  https://doi.org/10.1155/2013/312709 CrossRefGoogle Scholar
  97. Schafer F, Romer U, Emmerlich M, Blumer J, Lubenow H, Steinert K (2002) Automated high-throughput purification of 6xHis-tagged proteins. J Biomol Tech 13:131–142. doi:not availableGoogle Scholar
  98. Schoemaker JM, Brasnett AH, Marston FA (1985) Examination of calf prochymosin accumulation in Escherichia coli: disulphide linkages are a structural component of prochymosin-containing inclusion bodies. EMBO J 4(3):775–780. doi:not availableCrossRefGoogle Scholar
  99. Schoner RG, Ellis LF, Schoner BE (1985) Isolation and purification of protein granules from Escherichia coli cells overproducing bovine growth hormone. Bio Technol 3:151–154.  https://doi.org/10.1038/nbt0285-151 CrossRefGoogle Scholar
  100. Schuster M, Wasserbauer E, Ortner C, Graumann K, Jungbauer A, Hammerschmid F, Werner G (2000) Short cut of protein purification by integration of cell-disrupture and affinity extraction. Bioseparation 9(2):59–67.  https://doi.org/10.1023/A:100813591 CrossRefGoogle Scholar
  101. Scott JH, Schekman R (1980) Lyticase: endoglucanase and protease activities that act together in yeast cell lysis. J Bacteriol 142(2):414–423. doi:not availableGoogle Scholar
  102. Shao S, Gross V, Yan W, Guo T, Lazarev A, Abersold R (2015) Hands-free sample homogenisation and protein extraction from small tissue biopsy samples using pressure cycling technology and PCT micropestle (poster). In: US HUPO 2015 Conference, Tempe, AZ. http://www.pressurebiosciences.com/documents?task=document.viewdoc&id=64
  103. Shinkai M, Kamihira M, Honda H, Kobayashi T (1992) Rapid purification of monoclonal antibody with functional magnetite particles. Kag Kog Ronbunshu 18:256–259.  https://doi.org/10.1252/kakoronbunshu.18.256 CrossRefGoogle Scholar
  104. Shukla AA, Hinckley P (2008) Host cell protein clearance during protein A chromatography: Development of an improved column wash step. Biotechnol Prog 24(5):1115–1121.  https://doi.org/10.1002/btpr.50 CrossRefGoogle Scholar
  105. Shukla AA, Thömmes J (2010) Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 28(5):253–261.  https://doi.org/10.1016/j.tibtech.2010.02.001 CrossRefGoogle Scholar
  106. Shukla AA, Hubbard B, Tressel T, Guhan S, Low D (2007) Downstream processing of monoclonal antibodies – application of platform approaches. J Chromatogr B Anal Technol Biomed Life Sci 848(1):28–39.  https://doi.org/10.1016/jchromb.2006.09.026 CrossRefGoogle Scholar
  107. Siew WE, Livingston AG, Ates C, Merschaert A (2013) Continuous solute fractionation with membrane cascades – a high productivity alternative to diafiltration. Sep Purif Technol 102:1–14.  https://doi.org/10.1016/j.seppur.2012.09.017 CrossRefGoogle Scholar
  108. Strohl WR (2015) Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs 29(4):215–239.  https://doi.org/10.1007/s40259-015-0133-6 CrossRefGoogle Scholar
  109. Szoka PR, Schreiber AB, Chan H, Murthy J (1986) A general method for retrieving the components of a genetically engineered fusion protein. DNA 5(1):11–20.  https://doi.org/10.1089/dna.1986.5.11 CrossRefGoogle Scholar
  110. 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.  https://doi.org/10.1002/btpr.1581 CrossRefGoogle Scholar
  111. Top drugs by sales revenue in 2015: Who sold the biggest blockbuster drugs? (2016) The PharmaCompass Newsletter. http://www.pharmacompass.com/radiocompass-blog/top-drugs-by-sales-revenue-in-2015-whosold-thebiggest-blockbuster-drugs
  112. Tsumoto K, Ejima D, Nagase K, Arakawa T (2007) Arginine improves protein elution in hydrophobic interaction chromatography. The cases of human interleukin-6 and activin-A. J Chromatogr A 1154(1–2):81–86.  https://doi.org/10.1016/j.chroma.2007.02.061 CrossRefGoogle Scholar
  113. van Reis R, Zydney A (2007) Bioprocess membrane technology. J Membr Sci 297:16–50.  https://doi.org/10.1016/j.memsci.2007.02.045 CrossRefGoogle Scholar
  114. van Reis R, Gadam S, Frautschy LN, Orlando S, Goodrich EM, Saksena S, Kuriyel R, Simpson CM, Pearl S, Zydney AL (1997) High performance tangential flow filtration. Biotechnol Bioeng 56(1):71–82. https://doi.org/10.1002/(SICI)1097-0290(19971005)56:1<71::AID-BIT8>3.0.CO;2-SGoogle Scholar
  115. Varma SK (2009) An overview of biopharmaceutical industry in India. Pharmabiz Chronicle Specials. http://saffron.pharmabiz.com/article/detnews.asp?articleid=53092&sectionid=50
  116. Wang X, Rivière I (2016) Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolyt 3:16015.  https://doi.org/10.1038/mto.2016.15 CrossRefGoogle Scholar
  117. Warikoo V, Godawat R, Brower K, Jain S, Cummings D, Simons E, Johnson T, Walther J, Yu M, Wright B, McLarty J, Karey KP, Hwang C, Zhou W, Riske F, Konstantinov K (2012) Integrated continuous production of recombinant therapeutic proteins. Biotechnol Bioeng 109(12):3018–3029.  https://doi.org/10.1002/bit.24584 CrossRefGoogle Scholar
  118. Watt JG (1970) Automatically controlled continuous recovery of plasma protein fractions for clinical use. A preliminary report. Vox Sang 18(1):42–61.  https://doi.org/10.1111/j.1423-0410.1970.tb01428x CrossRefGoogle Scholar
  119. Wellhoefer M, Sprinzl W, Hahn R, Jungbauer A (2013) Continuous processing of recombinant proteins: integration of inclusion body solubilization and refolding using simulated moving bed size exclusion chromatography with buffer recycling. J Chromatogr A 1319:107–117.  https://doi.org/10.1016/j.chroma.2013.10.039 CrossRefGoogle Scholar
  120. Wikstrom P, Flygare S, Grondalen A, Larsson PO (1987) Magnetic aqueous two-phase separation: a new technique to increase rate of phase-separation, using dextran-ferrofluid or larger iron oxide particles. Anal Biochem 1(2):331–339.  https://doi.org/10.1016/0003-2697(87)90173-4s CrossRefGoogle Scholar
  121. Wilson AW, Neumann PJ (2012) The cost-effectiveness of biopharmaceuticals: a look at the evidence. MAbs 4(2):281–288.  https://doi.org/10.4161/mabs.4.2.18812 CrossRefGoogle Scholar
  122. Winkler ME, Blaber M, Bennett GL, Holmes W, Vehar GA (1985) Purification and characterization of recombinant urokinase from Escherichia coli. Bio Technol 3:990–1000.  https://doi.org/10.1038/nbt1185-990 CrossRefGoogle Scholar
  123. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Iida S, Nakano R, Wakitani M, Niwa R, Sakurada M, Uchida K, Shitara K, Satoh M (2004) Establishment of FUT8 knockout Chinese Hamster Ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibody dependent cellular cytotoxicity. Biotechnol Bioeng 87(5):614–622.  https://doi.org/10.1002/bit.20151 CrossRefGoogle Scholar
  124. Zang Y, Kammerer B, Eisenkolb M, Lohr K, Kiefer H (2011) Towards protein crystallization as a process step in downstream processing of therapeutic antibodies: screening and optimization at microbatch scale. PLoS One 6(9):1–8.  https://doi.org/10.1371/journal.pone.0025282 CrossRefGoogle Scholar
  125. Zhou JX, Tressel T (2006) Basic concepts in Q membrane chromatography for large-scale antibody production. Biotechnol Prog 22(2):341–349.  https://doi.org/10.1021/bp050425v CrossRefGoogle Scholar
  126. Zhu J (2012) Mammalian cell protein expression for biopharmaceutical production. Biotechnol Adv 30(5):1158–1170.  https://doi.org/10.1016/j.biotechadv.2011.08.022 CrossRefGoogle Scholar
  127. Zydney AL (2015) Continuous downstream processing for high value biological products: a review. Biotechnol Bioeng 113(3):465–475.  https://doi.org/10.1002/bit.25695 CrossRefGoogle Scholar
  128. Zydney AL, van Reis R (2001) High performance tangential flow filtration. In: Wang WK (ed) Membrane separations in biotechnology, 2nd edn. Marcel Dekker, New York, pp 277–298Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of BiochemistryKurukshetra UniversityKurukshetraIndia

Personalised recommendations