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Qualification of Biophysical Methods for the Analysis of Protein Therapeutics

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Biophysics for Therapeutic Protein Development

Part of the book series: Biophysics for the Life Sciences ((BIOPHYS,volume 4))

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Abstract

Biophysical techniques such as analytical ultracentrifugation (AUC), circular dichroism (CD), and differential scanning calorimetry (DSC) have been widely used by the biopharmaceutical industry to study higher-order structure of protein therapeutics. The data generated have generally been included in regulatory filings as part of the elucidation of structure and other characteristics and pharmaceutical development. In recent years, there is increasing scrutiny from the regulatory agencies on the qualification of these techniques. This chapter provides an overview of the biophysical methods used for generating information for regulatory filings during protein therapeutics development, purposes of these analyses, qualification approaches of these methods, any gaps present, and future directions.

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References

  • Affolter S, Ritter A, Schmid M (2001) Interlaboratory tests on polymers by differential scanning calorimetry (DSC): determination of glass transition temperature (Tg). Macromol Mater Eng 286(10):605–610

    Article  CAS  Google Scholar 

  • Alexander DM, Veltman AM (1988) Particulate contamination in solutions of antibiotics packed as dry powders in vials. J Pharm Pharmacol 40(5):358–359

    Article  PubMed  CAS  Google Scholar 

  • Arthur KK et al (2009) Detection of protein aggregates by sedimentation velocity analytical ultracentrifugation (SV-AUC): sources of variability and their relative importance. J Pharm Sci 98(10):3522–3539

    Article  PubMed  CAS  Google Scholar 

  • Berkowitz SA (2006) Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals. AAPS J 8(3):590–605

    Article  Google Scholar 

  • Bruylants G, Wouters J, Michaux C (2005) Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design. Curr Med Chem 12(17):2011–2020

    Article  PubMed  CAS  Google Scholar 

  • Byler DM, Susi H (1986) Examination of the secondary structure of proteins by deconvoluted FTIR spectra. Biopolymers 25:469–487

    Article  PubMed  CAS  Google Scholar 

  • Cao S, Jiao N, Jiang Y, Mire-Sluis A, Narhi LO (2009) Sub-visible particle quantitation in protein therapeutics. Pharmeuropa Bio & Scientific Notes 73–79

    Google Scholar 

  • Cao S, Jiang Y, Narhi LO (2010) A light obscuration method specific for quantifying subvisible particles in protein therapeutics. US Pharmacoepial Forum 36(3):824–834

    Google Scholar 

  • Cao S, Narhi LO, Jiang Y, Rajan RS (2012) Analytical methods to measure sub-visible particulates. In: Mahler HC, Jiskoot W (eds) Analysis of aggregates and particles in protein pharmaceuticals. Wiley, New York

    Google Scholar 

  • Carpenter JF, Prestrelski SJ, Dong A (1998) Application of infrared spectroscopy to development of stable lyophilized protein formulations. Eur J Pharm Biopharm 45(3):231–238

    Article  PubMed  CAS  Google Scholar 

  • Carpenter JF et al (2009) Overlooking subvisible particles in therapeutic protein products: gaps that may compromise product quality. J Pharm Sci 98(4):1201–1205

    Article  PubMed  CAS  Google Scholar 

  • Carpenter JF et al (2010) Potential inaccurate quantitation and sizing of protein aggregates by size exclusion chromatography: essential need to use orthogonal methods to assure the quality of therapeutic protein products. J Pharm Sci 99(5):2200–2208

    Article  PubMed  CAS  Google Scholar 

  • Celej MS, Dassie SA, González M, Bianconi ML, Fidelio GD (2006) Differential scanning calorimetry as a tool to estimate binding parameters in multiligand binding proteins. Anal Biochem 350(2):277–284

    Article  PubMed  CAS  Google Scholar 

  • Chan CC, Lam H, Zhang XM (2011) Practical approaches to method validation and essential instrument qualification. Wiley, New York

    Google Scholar 

  • Chiu MH, Prenner EJ (2011) Differential scanning calorimetry: an invaluable tool for a detailed thermodynamic characterization of macromolecules and their interactions. J Pharm Bioallied Sci 3(1):39–59

    Article  PubMed  CAS  Google Scholar 

  • Coligan JE et al (2001) Measuring protein thermostability by differential scanning calorimetry. In: Makhatadze GI (ed) Current protocols in protein science/editorial board. Wiley, New York

    Chapter  Google Scholar 

  • Council of Europe (2007) Particulate contamination: sub-visible particles, general chapter 2.9.19. Council of Europe, Strasbourg

    Google Scholar 

  • Cover TM, Hart PE (1967) Nearest neighbor pattern classification. IEEE Trans Inf Theory IT-13(1):21–27

    Article  Google Scholar 

  • D’antonio J, Murphy BM, Manning MC, Al-Azzam WA (2012) Comparability of protein therapeutics: quantitative comparison of second-derivative amide I infrared spectra. J Pharm Sci. doi:10.1002/jps.23133

  • Dam J et al (2004) Calculating sedimentation coefficient distributions by direct modeling of sedimentation velocity concentration profiles. In: Methods in enzymology. Academic. pp 185–212

    Google Scholar 

  • Drechsler A, Miles AJ, Norton RC, Wallace BA, Separovic F (2009) Effect of lipid on the conformation of the n-terminal region of equinatoxin II: a synchrotron radiation CD study. Eur Biophys J 39:121–127

    Article  PubMed  CAS  Google Scholar 

  • Driscoll DF (2004) Examination of selection of light-scattering and light-obscuration acceptance criteria for lipid injectable emulsions. Pharm Forum 30:2244–2253

    Google Scholar 

  • Fu K, Griebenow K, Hsieh L, Klibanov AM, Langer R (1999) FTIR characterization of the secondary structure of proteins encapsulated within PLGA microspheres. J Controlled Release 58:357–366

    Article  CAS  Google Scholar 

  • Gabrielson JP, Arthur KK (2011) Measuring low levels of protein aggregation by sedimentation velocity. Methods 54(1):83–91

    Article  PubMed  CAS  Google Scholar 

  • Gabrielson JP et al (2007a) Quantitation of aggregate levels in a recombinant humanized monoclonal antibody formulation by size-exclusion chromatography, asymmetrical flow field flow fractionation, and sedimentation velocity. J Pharm Sci 96(2):268–279

    Article  PubMed  CAS  Google Scholar 

  • Gabrielson JP et al (2007b) Sedimentation velocity analytical ultracentrifugation and SEDFIT/c(s): limits of quantitation for a monoclonal antibody system. Anal Biochem 361:24–30

    Article  PubMed  CAS  Google Scholar 

  • Gabrielson JP, Arthur KK, Stoner MR et al (2010) Precision of protein aggregation measurements by sedimentation velocity analytical ultracentrifugation in biopharmaceutical applications. Anal Biochem 396(2):231–241

    Article  PubMed  CAS  Google Scholar 

  • Gmelin E, Sarge St.M (1995) Calibration of differential scanning calorimeters. IUPAC, Pure Appl Chem 67:1789–1800

    Google Scholar 

  • Greenfield NJ (1996) Methods to estimate conformation of proteins and polypeptides from CD data. Anal Biochem 235(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Greenfield NJ, Fasman GD (1969) Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry 8:4108–4116

    Article  PubMed  CAS  Google Scholar 

  • Gross PC, Zeppezauer M (2010) Infrared spectroscopy for biopharmaceutical protein analysis. J Pharm Biomed Anal 53:29–36

    Article  PubMed  CAS  Google Scholar 

  • Haines-Nutt RF, Munton TJ (1984) Particle size measurement in intravenous fluids. J Pharm Pharmacol 36(8):534–536

    Article  PubMed  CAS  Google Scholar 

  • Haris PI, Chapman D (1995) The conformational analysis of peptides using Fourier transform IR spectroscopy. Biopolym (Pept Sci) 37:251–263

    Article  CAS  Google Scholar 

  • Huang CT, Sharma D, Oma P, Krishnamurthy R (2009) Quantitation of protein particles in parenteral solutions using micro-flow imaging. J Pharm Sci 98(9):3058–3071

    Article  PubMed  CAS  Google Scholar 

  • ICH M4Q (2001) The common technical document for the registration of pharmaceuticals for human use: quality. US Department of Health and Services, FDA, CDER

    Google Scholar 

  • ICH Q2(R1) (2005) Validation of analytical procedures: test and methodology. In: ICH Harmonised Tripartite guideline in international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use

    Google Scholar 

  • ICH Q5E (2005) Comparability of biotechnological/biological products subject to changes in their manufacturing process. US Department of Health and Services, FDA, CDER & CBER

    Google Scholar 

  • ICH Q6B (1999) Test procedures and acceptance criteria for biotechnological and biological products

    Google Scholar 

  • Jiang Y, Narhi LO (2006) Applying selective biophysical techniques in assessing the comparability of protein therapeutics – case studies. J Am Pharm Rev 9(5):34–43

    CAS  Google Scholar 

  • Jiang Y, Li C, Ramachander R, Wen J, Narhi LO (2008) Meeting new regulatory expectations of ­characterization methods-Qualification of biophysical analyses. J Am Pharm Rev February, online issue, Russell Publishing. http://pharmoutsourcing.com/ViewArticle.aspx?ContentID=2221. Accessed 7 Feb 2012

  • Jiang Y, Li C, Nguyen X, Muzammil S, Towers E, Gabrielson JP, Narhi LO (2011) Qualification of FTIR spectroscopic method for protein secondary structural analysis. J Pharm Sci 100(11):4631–4641

    Article  PubMed  CAS  Google Scholar 

  • Johnson WC Jr (1988) Secondary structure of proteins through circular dichroism spectroscopy. Annu Rev Biophys Biophys Chem 17:145–166

    Article  PubMed  CAS  Google Scholar 

  • Johnson WC Jr (1999a) Analyzing protein circular dichroism spectra for accurate secondary structures. Proteins 35(3):307–312

    Article  PubMed  CAS  Google Scholar 

  • Johnson WC (1999b) Analysing protein circular dichroism spectra for accurate secondary structures. Proteins 35(3):307–312

    Article  PubMed  CAS  Google Scholar 

  • Johnson CR, Morin PE, Arrowsmith CH, Freire E (1995) Thermodynamic analysis of the structural stability of the tetrameric oligomerization domain of p53 tumor suppressor. Biochemistry 34(16):5309–5316

    Article  PubMed  CAS  Google Scholar 

  • Johnston MJW, Frahm G, Li X, Durocher Y, Hefford MA (2011) O-linked glycosylation leads to decreased thermal stability of interferon alpha 2b as measured by two orthogonal techniques. Pharm Res 28(7):1661–1667

    Article  PubMed  CAS  Google Scholar 

  • Jones C et al (2004) Val-CiD Best Practice Guide: CD spectroscopy for the quality control of biopharmaceuticals. National Physical Laboratory. DQL-AS 008 ISSN: 1744–0602. British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire, LS23 7BQ

    Google Scholar 

  • Kelly SM, Jess TJ, Price NC (2005) How to study proteins by circular dichroism. Biochim Biophys Acta 1751:119–139

    Article  PubMed  CAS  Google Scholar 

  • Kendrick BS, Dong A, Allison SD, Manning MC, Carpenter JF (1996) Quantitation of overlap of infrared second derivative spectra to determine structural similarity between proteins. J Pharm Sci 85:155–158

    Article  PubMed  CAS  Google Scholar 

  • Kendrick BS et al (2001) Online size-exclusion high-performance liquid chromatography light scattering and differential refractometry methods to determine degree of polymer conjugation to proteins and protein–protein or protein–ligand association states. Anal Biochem 299(2):136–146

    Article  PubMed  CAS  Google Scholar 

  • King SM, Johnson WC (1999) Assigning secondary structure from protein coordinate data. Proteins 35:313–320

    Article  PubMed  CAS  Google Scholar 

  • Kong J, Yu S (2007) Fourier transform infrared spectroscopic analysis of protein secondary structures. Acta Biochim Biophys Sin 39(8):549–559

    Article  PubMed  CAS  Google Scholar 

  • Laue TM et al (1992) Computer-aided interpretation of analytical sedimentation data for proteins. In: Harding SE, Rowe AJ, Horton JC (eds) Analytical ultracentrifugation in biochemistry and polymer science. Royal Society of Chemistry, Cambridge, pp 90–125

    Google Scholar 

  • Lebowitz J, Lewis MS, Schuck P (2002) Modern analytical ultracentrifugation in protein science: a tutorial review. Protein Sci 11(9):2067–2079

    Article  PubMed  CAS  Google Scholar 

  • Lees JG, Wallace BA (2002) Synchrotron radiation circular dichroism and conventional circular dichroism spectroscopy: a Comparison. Spectroscopy 16:121–125

    Article  CAS  Google Scholar 

  • Lees JG, Miles AJ, Wien F, Wallace BA (2006) A reference database for circular dichroism spectroscopy covering fold and secondary structure space. Bioinformatics 22:1955–1962

    Article  PubMed  CAS  Google Scholar 

  • Li C, Nguyen X, Narhi LO, Chemmalil L, Towers E, Muzammil S, Gabrielson JP, Jiang Y (2011) Applications of circular dichroism for structural analysis of proteins: qualification of near- and far-UV CD for protein higher order structural analysis. J Pharm Sci 100(11):4642–4654

    Article  PubMed  CAS  Google Scholar 

  • Lopez MO, Freire E (1987) Dynamic analysis of differential scanning calorimetry data. Biophys Chem 27(1):87–96

    Article  Google Scholar 

  • Mahler HC, Friess W, Grauschopf U, Kies S (2009) Protein aggregation: pathways, induction factors and analysis. J Pharm Sci 98:2909–2934

    Article  PubMed  CAS  Google Scholar 

  • Manning MC, Woody RW (1989) Theoretical study of the contribution of aromatic side chains to the circular dichroism of basic bovine pancreatic trypsin inhibitor. Biochemistry 28:8609–8613

    Article  PubMed  CAS  Google Scholar 

  • Meersman F, Atilgan C, Miles AJ, Bader R, Shang W, Matagne A, Wallace BA, Koch MHJ (2010) Consistent picture of the reversible thermal unfolding of hen egg-white lysozyme from experiment and molecular dynamics. Biophysical J 99:2255–2263

    Article  CAS  Google Scholar 

  • Miles AJ, Wallace BA (2006) Synchrotron radiation circular dichroism spectroscopy of proteins and applications in structural and functional genomics. Chem Soc Reviews 35:39–51

    Article  CAS  Google Scholar 

  • Miles AJ, Wien F, Lees JG, Rodger A, Janes RW, Wallace BA (2003) Calibration and standardisation of synchrotron radiation circular dichroism (SRCD) amplitudes and conventional circular dichroism (CD) spectrophotometers. Spectroscopy 17:653–661

    Article  CAS  Google Scholar 

  • Miles AJ, Wien F, Wallace BA (2004) Redetermination of the extinction coefficient of camphor-b-sulfonic acid, A calibration standard for circular dichroism spectroscopy. Anal Biochem 335:338–339

    Article  PubMed  CAS  Google Scholar 

  • Miles AJ, Wien F, Lees JG, Wallace BA (2005) Calibration and standardisation of synchrotron radiation and conventional circular dichroism spectrometers. Part 2: factors affecting magnitude and wavelength. Spectroscopy 19:43–51

    Article  CAS  Google Scholar 

  • Miles AJ, Hoffman SV, Tao Y, Janes RW, Wallace BA (2007) Synchrotron radiation circular dichroism (SRCD) spectroscopy: new beamlines and new applications in biology. Spectroscopy 21:245–255

    Article  CAS  Google Scholar 

  • Narhi LO, Jiang Y, Cao S, Benedek K, Shnek D (2009) A critical review of analytical methods for subvisible and visible particles. Curr Pharm Biotechnol 10(4):373–381

    Article  PubMed  CAS  Google Scholar 

  • Pekar A, Sukumar M (2007) Quantitation of aggregates in therapeutic proteins using sedimentation velocity analytical ultracentrifugation: practical considerations that affect precision and accuracy. Anal Biochem 367:225–237

    Article  PubMed  CAS  Google Scholar 

  • Perczel A, Fasman GD (1993) Effect of spectral window size on circular dichroism spectra deconvolution of proteins. Biophys Chem 48:19–29

    Article  CAS  Google Scholar 

  • Perczel A, Hollosi M, Tusnady G, Fasman GD (1991) Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins. Protein Eng 4:669–679

    Article  PubMed  CAS  Google Scholar 

  • Philo JS (2006) Is any measurement method optimal for all aggregate sizes and types? AAPS J 8(3):564–571

    Article  Google Scholar 

  • Powl AM, O'Reilly AO, Miles AM, Wallace BA (2010) Synchrotron radiation circular dichroism spectroscopy-defined structure of the C-terminal domain of NaChBac and its role in channel assembly. Proc Natl Acad Sci 107:14064–14069

    Article  PubMed  CAS  Google Scholar 

  • Prestrelski S, Tedeschi N, Arakawa T, Carpenter J (1993) Biophys J 65(2):661–671

    Article  PubMed  CAS  Google Scholar 

  • Protasevich I, Yang Z, Wang C, Atwell S, Zhao X, Emtage S, Wetmore D, Hunt JF, Brouillette CG (2010) Thermal unfolding studies show the disease causing F508del mutation in CFTR thermodynamically destabilizes nucleotide-binding domain 1. Protein Sci 19(10):1917–1931

    Article  PubMed  CAS  Google Scholar 

  • Pyrpassopoulos S, Vlassi M, Tsortos A, Papanikolau Y, Petratos K, Vorgias CE, Nounesis G (2006) Equilibrium heat-induced denaturation of chitinase 40 from Streptomyces thermoviolaceus. Proteins 64(2):513–523

    Article  PubMed  CAS  Google Scholar 

  • Ravi J, Rakowska PD, Garfagnini T et al (2010) International comparability in spectroscopic measurements of protein structure by circular dichroism: CCQM-P59.1, Metrologia 47(6):631–641

    Google Scholar 

  • Ravi J, Schiffmann D, Tantra R et al (2010) International comparability in spectroscopic measurements of protein structure by circular dichroism: CCQM P59, Metrologia 47:1A

    Google Scholar 

  • Schiffmann D, Butterfield DM, Yardley RE, Knight A, Windsor SA, Jones C (2004) Val-CiD Appendix A: CD spectroscopy: an inter-laboratory study. DQL-AS 009 ISSN: 1744–0602

    Google Scholar 

  • Schmid M (2012) Precision of DSC measurements: results of interlaboratory tests. http://www.eurostar-science.org/MAP1/Schmid.pdf. Accessed 7 Feb 2012

  • Schuck P et al (2002) Size-distribution analysis of proteins by analytical ultracentrifugation: strategies and application to model systems. Biophys J 82(2):1096–1111

    Article  PubMed  CAS  Google Scholar 

  • Sharma DK, King D, Oma P, Merchant C (2010a) Micro-flow imaging: flow microscopy applied to sub-visible particulate analysis in protein formulations. AAPS J 12(3):455–464

    Article  PubMed  CAS  Google Scholar 

  • Sharma DK, Peter O, Pollo MJ, Sukumar M (2010b) Quantification and characterization of subvisible proteinaceous particles in opalescent mab formulations using micro-flow imaging. J Pharm Sci 99(6):2628–2642

    PubMed  CAS  Google Scholar 

  • Sharma DK, King D, Merchant C (2011) Reference material development for calibration and verification of image-based particle analyzers. Int J Pharm 416(1):293–295

    Article  PubMed  CAS  Google Scholar 

  • Shire SJ (1994) Analytical ultracentrifugation and its use in biotechnology. In: Schuster TM, Laue TM (eds) Modern analytical ultracentrifugation. Birkhauser, Boston

    Google Scholar 

  • Surewicz WK, Mantsch HH (1988) New insight into protein conformation from infrared spectroscopy. Biochim Biophys Acta 952:115–130

    Article  PubMed  CAS  Google Scholar 

  • Susi H, Byler M (1986) Resolution enhanced fourier transform infrared spectroscopy of enzymes. Meth Enzymol 130:290–311

    Article  PubMed  CAS  Google Scholar 

  • Susi H, Byler M (1987) Fourier transform infrared study of proteins with parallel b-chains. Arch Biochem Biophys 258(2):465–469

    Article  PubMed  CAS  Google Scholar 

  • Taylor JR (1997) An introduction to error analysis: the study of uncertainties in physical measurements, 2nd edn. University Science Books, Sausalito

    Google Scholar 

  • Taylor SA, Spence J (1983) Particles in small volume injections. J Pharm Pharmacol 35(12):769–773

    Article  PubMed  CAS  Google Scholar 

  • TQ Analyst Algorithm (2007–2010) Thermo OMNIC software manual, Thermo Electron Scientific Instruments, LLC., Madison, WI, USA (part of Thermo Fisher Scientific Inc.)

    Google Scholar 

  • United States Pharmacopeial Convention, Inc (2009) Particular matter in injections, general chapter <788>, USP 32, NF 27. United States Pharmacopeial Convention, Inc., Rockville

    Google Scholar 

  • Van Stokkum IHM, Spoelder HJW, Bloemendal M, Van Grondelle R, Groen FCA (1990) Estimation of protein secondary structure and error analysis from CD spectra. Anal Biochem 191:110–118

    Article  PubMed  Google Scholar 

  • Vedantham G, Sparks G, Sane SU, Tzannis S, Przybycien TM (2000) A holistic approach for protein secondary structure estimation from infrared spectra in H2O solutions. Anal Biochem 285:33–49

    Article  PubMed  CAS  Google Scholar 

  • Venyaminov SW, Baikalov I, Chuen-Shang C, Yang JT (1991) Some problems of CD analysis of protein conformation. Anal Biochem 198:250–255

    Article  PubMed  CAS  Google Scholar 

  • Vonhoffa S, Condliffeb J, Schiffterb H (2010) Implementation of an FTIR calibration curve for fast and objective determination of changes in protein secondary structure during formulation development. J Pharm Biomed Anal 51(1):39–45

    Article  Google Scholar 

  • Wallace BA (2005) Shining new light on protein structure and function thru synchrotron radiation circular dichroism (SRCD) spectroscopy. Australian Biochemist 36:47–50

    Google Scholar 

  • Wallace BA, Janes RW (2010) Synchrotron radiation circular dichroism (SRCD) spectroscopy: an enhanced method for examining protein conformations and protein interactions. Biochem Soc Trans 38:861–873

    Article  PubMed  CAS  Google Scholar 

  • Wallace BA, Whitmore L, Janes RW (2006) The protein circular dichroism data bank (PCDDB): a bioinformatics and spectroscopic resource. Proteins 62:1–3

    Article  PubMed  CAS  Google Scholar 

  • Weissburg RP, Burris FE, Ferrell TK, Montgomery ER (2002) Validation of DSC and TGA for pharmaceutical analysis under current good Manufacturing Practices (cGMP). Am Pharm Rev 5(2):76–81

    Google Scholar 

  • Wen J, Arakawa T, Philo JS (1996) Size-exclusion chromatography with on-line light-scattering, absorbance, and refractive index detectors for studying proteins and their interactions. Anal Biochem 240(2):155–166

    Article  PubMed  CAS  Google Scholar 

  • Wen J, Jiang Y, Narhi LO (2008) Effect of carbohydrate on thermal stability of antibodies. Am Pharm Rev 11:98–104

    Article  CAS  Google Scholar 

  • Wen J, Arthur K, Chemmalil L, Muzammil S, Gabrielson JP, Jiang Y (2011) Applications of differential scanning calorimetry for thermal stability analysis of proteins: qualification of DSC. J Pharm Sci. doi:10.1002/jps.22820

  • Whitmore L, Wallace BA (2004) DICHROWEB, An online server for protein secondary structure analyses from circular dichroism spectroscopic data. Nucleic Acids Res 32:668–673

    Article  Google Scholar 

  • Whitmore L, Wallace BA (2008) Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. Biopolymers 89:392–400

    Article  PubMed  CAS  Google Scholar 

  • Woody RW (1994) Contributions of tryptophan side chains to the far-ultraviolet circular dichroism of proteins. Eur Biophys J 23:253–262

    Article  PubMed  CAS  Google Scholar 

  • Woody RW (1996) Theory of circular dichroism of proteins, circular dichroism and the conformational analysis of biomolecules. In: Fasman GD (ed) Circular dichroism and the conformational analysis of biomolecules. Plenum, New York

    Google Scholar 

  • Wuchner K, Büchler J, Spycher R, Dalmonte P, Volkin DB (2010) Development of a microflow digital imaging assay to characterize protein particulates during storage of a high concentration IgG1 monoclonal antibody formulation. J Pharm Sci 99(8):3343–3361

    Article  PubMed  CAS  Google Scholar 

  • Wyatt PJ (1993) Light scattering and the absolute characterization of macromolecules. Anal Chim Acta 272:1–40

    Article  CAS  Google Scholar 

  • Yang JT, Wu CSC, Martinez HM (1986) Calculation of protein conformation from circular dichroism. Methods Enzymol 130:208–269

    Article  PubMed  CAS  Google Scholar 

  • Yoshii K (1997) Application of differential scanning calorimetry to the estimation of drug purity: various problems and their solutions in purity analysis. Chem Pharm Bull 45(2):338–343

    Article  CAS  Google Scholar 

  • Zölls S, Tantipolphan R, Wiggenhorn M, Winter G, Jiskoot W, Friess W, Hawe A (2011) Particles in therapeutic protein formulations, Part 1: overview of analytical methods. J Pharm Sci. doi:10.1002/jps.23001

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Authors and Affiliations

  1. Process and Product Development, Amgen Inc., One Amgen Center Drive, 30E-1-C, Thousand Oaks, CA, 91320, USA

    Yijia Jiang

  2. Process and Product Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA

    Cynthia Li

  3. Analytical Sciences, Amgen Inc., 4000 Nelson Road, Longmont, CO, 80503, USA

    John Gabrielson

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  1. Yijia Jiang
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  2. Cynthia Li
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  3. John Gabrielson
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Correspondence to Yijia Jiang .

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  1. , Research & Development, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, 91320, California, USA

    Linda O. Narhi

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Jiang, Y., Li, C., Gabrielson, J. (2013). Qualification of Biophysical Methods for the Analysis of Protein Therapeutics. In: Narhi, L. (eds) Biophysics for Therapeutic Protein Development. Biophysics for the Life Sciences, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4316-2_5

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