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Stability Testing Considerations for Biologicals and Biotechnology Products

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Methods for Stability Testing of Pharmaceuticals

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

This chapter discusses common issues and general approaches to studying the stability of biologicals for product development, covering key required studies for product registration and post-approval process changes. Several commonly used stability-indicating test methods for proteins are discussed with procedural details. Design considerations of accelerated stability and forced degradation (stress testing) studies for support of manufacturing operations and comparability demonstrations are outlined.

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References

  1. Pharmaceutical Research and Manufacturers of America Report (2013) Medicines in development biologics. www.phrma.org/sites/default/files/pdf/biologics2013.pdf

  2. Liu H, Ponniah G, Zhang HM et al (2014) In vitro and in vivo modifications of recombinant and human IgG antibodies. MAbs 6(5):1145–1154

    Article  PubMed  PubMed Central  Google Scholar 

  3. Dill KA (1990) Dominant forces in protein folding. Biochemistry 29:7133–7155

    Article  CAS  Google Scholar 

  4. Manning MC, Chou DK, Murphy BM et al (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27:544–575

    Article  CAS  PubMed  Google Scholar 

  5. Liu D, Ren D, Huang H et al (2008) Structure and stability of human IgG1 Fc as a consequence of methionine oxidation. Biochemistry 47:5088–5100

    Article  CAS  PubMed  Google Scholar 

  6. Gao SX, Zhang Y, Stansberry-Perkins K et al (2011) Fragmentation of a highly purified monoclonal antibody attributed to residual CHO cell protease activity. Biotechnol Prog 108:977–982

    CAS  Google Scholar 

  7. Dixit N, Salamaat-Miller N, Salinas PA, Taylor KD, Basu SK (2016) Residual host cell protein promotes polysorbate 20 degradation in a sulfatase drug product leading to free fatty acid particles. J Pharm Sci 105:1657–1666

    Article  CAS  PubMed  Google Scholar 

  8. Wang W, Ignatius AA, Thakkar SV (2014) Impact of residual impurities and contaminants on protein stability. J Pharm Sci 103:1315–1330

    Article  CAS  PubMed  Google Scholar 

  9. Wurth C, Demeule B, Mahler HC, Adler M (2016) Quality by design approaches to formulation robustness—an antibody case study. J Pharm Sci 105:1667–1675

    Article  CAS  PubMed  Google Scholar 

  10. ICH Q1A(R2) (2003) Stability testing of new drug substances and products. Fed Regis 68(225):65717–65718

    Google Scholar 

  11. ICH Q5C (1996) Quality of biotechnological products: stability testing of biotechnological/biological products. Fed Regis 61:36466–36474

    Google Scholar 

  12. Yang X et al (2013) Developability studies before initiation of process development. Improving manufacturability of monoclonal antibodies. MAbs 5(5):787–794

    Article  PubMed  PubMed Central  Google Scholar 

  13. Brader ML et al (2015) Examination of thermal unfolding and aggregation profiles of a series of developable therapeutic monoclonal antibodies. Mol Pharm 12:1005–1017

    Article  CAS  PubMed  Google Scholar 

  14. Thiagarajan G, Semple A, James JK, Cheung JK, Shameem M (2016) A comparison of biophysical characterization techniques in predicting monoclonal antibody stability. MAbs 8(6):71088–71097

    Article  CAS  Google Scholar 

  15. Wang W, Roberts CJ (2013) Non-Arrhenius protein aggregation. AAPS J 15:840–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Drenski MF, Brader ML, Alston RW, Reed WF (2013) Monitoring protein aggregation kinetics with simultaneous multiple sample light scattering. Anal Biochem 437:185–197

    Article  CAS  PubMed  Google Scholar 

  17. Maity H, Lai Y, Srivastava A et al (2012) Principles and applications of selective biophysical methods for characterization and comparability assessment of a monoclonal antibody. Curr Pharm Biotechnol 13:2078–2101

    Article  CAS  PubMed  Google Scholar 

  18. Mazzeo A, Carpenter P (2009) Stability studies for biologics. In: Huynh-Ba K (ed) Handbook of stability testing in pharmaceutical development. Springer Science+Business Media, LLC, New York. https://doi.org/10.1007/978-0-387-85627-8. 17

    Chapter  Google Scholar 

  19. Bhatnagar BS, Bogner RH, Pikal MJ (2007) Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol 12:505–523

    Article  CAS  PubMed  Google Scholar 

  20. Singh SK, Kolhe P, Mehta AP, Chico SC, Lary AL, Huang M (2011) Frozen state storage instability of a monoclonal antibody: aggregation as a consequence of trehalose crystallization and protein unfolding. Pharm Res 28:873–885

    Article  CAS  PubMed  Google Scholar 

  21. Bond MD et al (2010) Evaluation of a dual-wavelength size exclusion HPLC method with improved sensitivity to detect protein aggregates and its use to better characterize degradation pathways of an IgG1 monoclonal antibody. J Pharm Sci 99:2582–2597

    Article  CAS  PubMed  Google Scholar 

  22. Philo JS (2006) Is any measurement method optimal for all aggregate sizes and types? AAPS J 8:E564–E571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fekete S, Beck A, Veuthey JL, Guillarme D (2014) Theory and practice of size exclusion chromatography for the analysis of protein aggregates. J Pharm Biomed Anal 101:161–172

    Article  CAS  PubMed  Google Scholar 

  24. Salas-Solano O, Tomlinson B, Du S, Parker M, Strahan A, Ma S (2006) Optimization and validation of a quantitative capillary electrophoresis sodium dodecyl sulfate method for quality control and stability monitoring of monoclonal antibodies. Anal Chem 78:6583–6594

    Article  CAS  PubMed  Google Scholar 

  25. Nunnally B et al (2006) A series of collaborations between various pharmaceutical companies and regulatory authorities concerning the analysis of biomolecules using capillary electrophoresis. Chromatographia 64:359–368

    Article  CAS  Google Scholar 

  26. Zhang J, Burman S, Gunturi S, Foley JP (2010) Method development and validation of capillary sodium dodecyl sulfate gel electrophoresis for the characterization of a monoclonal antibody. J Pharm Biomed Anal 53:1236–1243

    Article  CAS  PubMed  Google Scholar 

  27. Guo A, Camblin G, Han M, Meert C, Park S (2008) Role of CE in biopharmaceutical development and quality control. Separation Sci Tech 9:357–399

    CAS  Google Scholar 

  28. Rustandi RR, Peklansky B, Anderson CL (2014) Use of imaged capillary isoelectric focusing technique in development of diphtheria toxin mutant CRM197. Electrophoresis 35:1065–1071

    Article  CAS  PubMed  Google Scholar 

  29. Salas-Solano O et al (2012) Robustness of iCIEF methodology for the analysis of monoclonal antibodies: an interlaboratory study. J Sep Sci 35:3124–3129

    Article  CAS  PubMed  Google Scholar 

  30. ICH Q6B (1999) Specifications: test procedures and acceptance criteria for biotechnological/biological products. Fed Regis 64 (159):44928–44935

    Google Scholar 

  31. ICH Q1E (2004) Evaluation for stability data. Fed Regis 69(110):32010–32011

    Google Scholar 

  32. Schofield TL (2009) Vaccine stability study design and analysis to support product licensure. Biologicals 37:387–396

    Article  CAS  PubMed  Google Scholar 

  33. Capen R et al (2012) On the shelf-life of pharmaceutical products. AAPS Pharm Sci Tech 13:911–918

    Article  Google Scholar 

  34. ICH Q5E (2005) Comparability of biotechnological/biological products subject to changes in their manufacturing process. Food Drug Administration 70(125):37861–37862

    Google Scholar 

  35. Chan CP (2016 July/August) Analytical strategies for comparability in bioprocess development. BioPharma Asia, p 26–33

    Google Scholar 

  36. ICH Q1B (1997) Stability testing: photostability testing of new drug substances and products. Fed Regis 62(95):27115–27122

    Google Scholar 

  37. Tamizi E, Jouyban A (2016) Forced degradation studies of biopharmaceuticals: selection of stress conditions. Eur J Pharm Biopharm 98:26–46

    Article  CAS  PubMed  Google Scholar 

  38. Chan CP (2016) Forced degradation studies: current trends and future perspectives for protein-based therapeutics. Expert Rev Proteomics 13:651–658

    Article  CAS  PubMed  Google Scholar 

  39. Burdick RK, Sidor L (2013) Establishment of an equivalence acceptance criterion for accelerated stability studies. J Biopharm Stat 23:730–743

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Global Manufacturing Science & Technology, Specialty Care Operations, Sanofi, Framingham, MA, USA

    Christine P. Chan

Authors
  1. Christine P. Chan
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Corresponding author

Correspondence to Christine P. Chan .

Editor information

Editors and Affiliations

  1. Select Biosciences India Private Limited, Chandigarh, India

    Sanjay Bajaj

  2. Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India

    Saranjit Singh

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© 2018 Springer Science+Business Media, LLC, part of Springer Nature

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Chan, C.P. (2018). Stability Testing Considerations for Biologicals and Biotechnology Products. In: Bajaj, S., Singh, S. (eds) Methods for Stability Testing of Pharmaceuticals. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7686-7_15

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  • DOI: https://doi.org/10.1007/978-1-4939-7686-7_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7685-0

  • Online ISBN: 978-1-4939-7686-7

  • eBook Packages: Springer Protocols

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