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Establishing analytical comparability for “biosimilars”: filgrastim as a case study

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Abstract

Biosimilars are defined as biotherapeutic drugs that have been shown to have comparable quality, safety, and efficacy to the original product. Fuelled by the patent cliff in the next 5 years, the focus of the biopharmaceutical industry is gradually shifting towards production of biosimilars. Scientific and regulatory issues around development and approval of these biosimilars have been a topic of great interest and debate recently. Unlike the conventional small molecular weight drugs, biosimilars exhibit high complexity at the molecular level. Slight variations during the manufacturing of these complex protein molecules may lead to the significant changes in the safety and efficacy profile of the therapeutic product. Establishing comparability to the reference product is essential for successful approval of a biosimilar product. Analytical comparability provides the foundation to this exercise. This paper presents data from such an exercise involving use of several orthogonal analytical tools for establishing analytical comparability. Granulocyte colony-stimulating factor (GCSF/Filgrastim) expressed in Escherichia coli has been selected as the model protein. The approach would be of interest to those engaged in development and commercialization of biosimilars.

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References

  1. Schellekens H (2004) Nat Biotechnol 22:1357–1359

    Article  CAS  Google Scholar 

  2. Belsey MJ, Harris LM, Das RR, Chertkow J (2006) Nat Rev Drug Discov 5:535–536

    Article  CAS  Google Scholar 

  3. Walsh G (2005) Trends Biotechnol 23:553–558

    Article  CAS  Google Scholar 

  4. Rathore AS (2009) Trends Biotechnol 27:698–705

    Article  CAS  Google Scholar 

  5. Weise M, Bielsky M-C, Smet KD, Ehmann F, Ekman N, Narayanan G, Heim H-K, Heinonen E, Ho K, Thorpe R, Vlemickx C, Wadhwa M, Schneider CK (2011) Nat Biotechnol 29:690–693

    Article  CAS  Google Scholar 

  6. Berkowitz SA, Engen JR, Mazzeo JR, Jones GB (2012) Nat Rev Drug Discov 11:527–540

    Article  CAS  Google Scholar 

  7. Chirino AJ, Mire-Sluis A (2004) Nat Biotechnol 22:1383–1389

    Article  CAS  Google Scholar 

  8. Schneider CK, Kalinke U (2008) Nat Biotechnol 26:985–990

    Article  CAS  Google Scholar 

  9. Kresse GB (2009) Eur J Pharm Biopharm 72:479–486

    Article  CAS  Google Scholar 

  10. Skrlin A, Radic I, Vuletic M, Schwinke D, Runac D, Kusalic T, Paskvan I, Krsic M, Bratos M, Marinc S (2010) Biologicals 38:557–566

    Article  CAS  Google Scholar 

  11. Ashton G (2001) Nat Biotechnol 19:307–311

    Article  CAS  Google Scholar 

  12. Rathore AS, Low D (2010) BioPharm Int 23(11):34–40

    Google Scholar 

  13. Hagel L, Jagschies G, Sofer G (2007) Handbook of process chromatography, 2nd edn. Academic, New York

    Google Scholar 

  14. International Conference on Harmonisation Guideline Q8 (R1) (2008) Pharmaceutical Development. Geneva, Switzerland: International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use.

  15. US Food and Drug Administration. FDA guidance concerning demonstration of comparability of human biological products, including therapeutic biotechnology-derived products FDA, Rockville, MD, April 1996. http://www.fda.gov/cder/Guidance/compare.htm

  16. US Food and Drug Administration. Revised guidance for industry: providing regulatory submissions to the Center for Biologics Evaluation and Research (CBER) in electronic format—biologics marketing applications [Biologics License Application (BLA), Product License Application (PLA)/Establishment License Application (ELA) and New Drug Application (NDA)] FDA, Rockville, MD, November 1999. http://www.cfsan.fda.gov/~dms/opaegui3.html

  17. Petit I, Szyper-Karavitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N, Sandbank J, Zipori D, Lapidot T (2002) Nat Immunol 3:687–694

    Article  CAS  Google Scholar 

  18. Aritomi M, Kunishima N, Okamoto T, Kuroki R, Ota Y, Morikawa K (1999) Nature 401:713–717

    Article  CAS  Google Scholar 

  19. Chu JW, Yin J, Wang DI, Trout BL (2004) Biochemistry 43:1019–1029

    Article  CAS  Google Scholar 

  20. Chu JW, Brooks BR, Trout BL (2004) J Am Chem Soc 126:16601–16607

    Article  CAS  Google Scholar 

  21. Lu HS, Fausset PR, Sotos LS, Clogston CL, Rohde MF, Stoney KS, Herman AC (1993) Protein Expr Purif 4:465–472

    Article  CAS  Google Scholar 

  22. Guillon JM, Mechulam Y, Schmitter JM, Blanquet S, Fayat G (1992) J Bacteriol 174:4294

    CAS  Google Scholar 

  23. Schenauer MR, Flynn GC, Goetze AM (2012) Anal Biochem 428:150–157

    Article  CAS  Google Scholar 

  24. Wang X, Junter AK, Mozier NM (2009) Biotechnol Bioeng 103:446–458

    Article  CAS  Google Scholar 

  25. Valente KN, Schaefer AK, Kempton HR, Lenhoff AM, Lee KH (2014) Biotechnol J 9:87–99

    Article  CAS  Google Scholar 

  26. Xie H, Chakraborty A, Ahn J, Yu YQ, Dakshinamoorthy DP, Chen W, Skilton J, Mazzeo J (2010) mAbs 2:379–394

    Article  Google Scholar 

  27. Doneanu CE, Xenopoulos A, Fadgen K, Murphy J, Skilton SJ, Prentice H, Stapels M, Chen W (2012) mAbs 41:24–44

    Article  Google Scholar 

  28. Gilar M, Xie H, Chakraborty A, Ahn J, Yu YQ, Chen W, Skilton J, Mazzeo J, Dakshinamoorthy DP (2010) Biopharm Int 2010:1–4

    Google Scholar 

  29. Bhambure R, Gupta D, Rathore AS (2013) J Chromatogr A 1314:188–198

    Article  CAS  Google Scholar 

  30. Bhambure R, Sharma R, Gupta D, Rathore AS (2013) J Chromatogr A 1307:49–57

    Article  CAS  Google Scholar 

  31. Bade P, Kotu SP, Rathore AS (2012) J Sep Sci 35:3160–3169

    Article  CAS  Google Scholar 

  32. Filgrastim concentrated solution: European Pharmacopoeia Monograph 7:2015–2018

  33. Cygnus application notes. http://cygnustechnologies.com/product_detail/bacterial/e-coli-hcp-elisa-kit.html

  34. Invitrogen application notes. http://www.invitrogen.com/site/us/en/home/brands/Product-Brand/Quant-iT.html

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Acknowledgments

Financial assistance from the Department of Biotechnology, Government of India, New Delhi, India is gratefully acknowledged. We are thankful to Waters Corporation, USA, for their help with analytical characterization of GCSF and to the National Institute of Biologicals, India, for performing the bioassay. We are also thankful to the High Impact Research Proposal Grant from IIT Delhi that contributed towards this project.

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Authors and Affiliations

  1. Department of Chemical Engineering, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India

    Anurag S. Rathore & Rahul Bhambure

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  1. Anurag S. Rathore
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  2. Rahul Bhambure
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Correspondence to Anurag S. Rathore.

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Published in the topical collection Analysis of Biological Therapeutic Agents and Biosimilars with guest editor Karen Phinney.

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Rathore, A.S., Bhambure, R. Establishing analytical comparability for “biosimilars”: filgrastim as a case study. Anal Bioanal Chem 406, 6569–6576 (2014). https://doi.org/10.1007/s00216-014-7887-4

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  • DOI: https://doi.org/10.1007/s00216-014-7887-4

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