Strategies for the Assessment of Protein Aggregates in Pharmaceutical Biotech Product Development

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2010 Oct 26

PMID 20972611

Citations 86

Authors

John den Engelsman

Patrick Garidel

Ronald Smulders

Hans Koll

Bryan Smith

Stefan Bassarab

Andreas Seidl

Otmar Hainzl

Wim Jiskoot

Affiliations

Soon will be listed here.

Abstract

Within the European Immunogenicity Platform (EIP) ( http://www.e-i-p.eu ), the Protein Characterization Subcommittee (EIP-PCS) has been established to discuss and exchange experience of protein characterization in relation to unwanted immunogenicity. In this commentary, we, as representatives of EIP-PCS, review the current state of methods for analysis of protein aggregates. Moreover, we elaborate on why these methods should be used during product development and make recommendations to the biotech community with regard to strategies for their application during the development of protein therapeutics.

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References

Huang C, Sharma D, Oma P, Krishnamurthy R . Quantitation of protein particles in parenteral solutions using micro-flow imaging. J Pharm Sci. 2008; 98(9):3058-71. DOI: 10.1002/jps.21575. View

Chi E, Krishnan S, Randolph T, Carpenter J . Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation. Pharm Res. 2003; 20(9):1325-36. DOI: 10.1023/a:1025771421906. View

Ye H . Simultaneous determination of protein aggregation, degradation, and absolute molecular weight by size exclusion chromatography-multiangle laser light scattering. Anal Biochem. 2006; 356(1):76-85. DOI: 10.1016/j.ab.2006.05.025. View

Horneman D, Ottens M, Keurentjes J, van der Wielen L . Surfactant-aided size-exclusion chromatography for the purification of immunoglobulin G. J Chromatogr A. 2007; 1157(1-2):237-45. DOI: 10.1016/j.chroma.2007.05.014. View

Hermeling S, Crommelin D, Schellekens H, Jiskoot W . Structure-immunogenicity relationships of therapeutic proteins. Pharm Res. 2004; 21(6):897-903. DOI: 10.1023/b:pham.0000029275.41323.a6. View

Singh S, Afonina N, Awwad M, Bechtold-Peters K, Blue J, Chou D . An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics. J Pharm Sci. 2010; 99(8):3302-21. DOI: 10.1002/jps.22097. View

Wen J, Arakawa T, Philo J . Size-exclusion chromatography with on-line light-scattering, absorbance, and refractive index detectors for studying proteins and their interactions. Anal Biochem. 1996; 240(2):155-66. DOI: 10.1006/abio.1996.0345. View

Arakawa T, Ejima D, Li T, Philo J . The critical role of mobile phase composition in size exclusion chromatography of protein pharmaceuticals. J Pharm Sci. 2009; 99(4):1674-92. DOI: 10.1002/jps.21974. View

Mirzaei H, Regnier F . Protein:protein aggregation induced by protein oxidation. J Chromatogr B Analyt Technol Biomed Life Sci. 2008; 873(1):8-14. DOI: 10.1016/j.jchromb.2008.04.025. View

10.

Philo J . A critical review of methods for size characterization of non-particulate protein aggregates. Curr Pharm Biotechnol. 2009; 10(4):359-72. DOI: 10.2174/138920109788488815. View

11.

Jones L, Kaufmann A, Middaugh C . Silicone oil induced aggregation of proteins. J Pharm Sci. 2005; 94(4):918-27. DOI: 10.1002/jps.20321. View

12.

Fraunhofer W, Winter G . The use of asymmetrical flow field-flow fractionation in pharmaceutics and biopharmaceutics. Eur J Pharm Biopharm. 2004; 58(2):369-83. DOI: 10.1016/j.ejpb.2004.03.034. View

13.

Gabrielson J, Arthur K, Stoner M, Winn B, Kendrick B, Razinkov V . Precision of protein aggregation measurements by sedimentation velocity analytical ultracentrifugation in biopharmaceutical applications. Anal Biochem. 2009; 396(2):231-41. DOI: 10.1016/j.ab.2009.09.036. View

14.

Carpenter J, Randolph T, Jiskoot W, Crommelin D, Middaugh C, Winter G . 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. 2009; 99(5):2200-8. DOI: 10.1002/jps.21989. View

15.

Bhatnagar B, Bogner R, Pikal M . Protein stability during freezing: separation of stresses and mechanisms of protein stabilization. Pharm Dev Technol. 2007; 12(5):505-23. DOI: 10.1080/10837450701481157. View

16.

Chi E, Weickmann J, Carpenter J, Manning M, Randolph T . Heterogeneous nucleation-controlled particulate formation of recombinant human platelet-activating factor acetylhydrolase in pharmaceutical formulation. J Pharm Sci. 2004; 94(2):256-74. DOI: 10.1002/jps.20237. View

17.

Yumioka R, Sato H, Tomizawa H, Yamasaki Y, Ejima D . Mobile phase containing arginine provides more reliable SEC condition for aggregation analysis. J Pharm Sci. 2009; 99(2):618-20. DOI: 10.1002/jps.21857. View

18.

Pekar A, Sukumar M . Quantitation of aggregates in therapeutic proteins using sedimentation velocity analytical ultracentrifugation: practical considerations that affect precision and accuracy. Anal Biochem. 2007; 367(2):225-37. DOI: 10.1016/j.ab.2007.04.035. View

19.

Liu J, Andya J, Shire S . A critical review of analytical ultracentrifugation and field flow fractionation methods for measuring protein aggregation. AAPS J. 2006; 8(3):E580-9. PMC: 2761065. DOI: 10.1208/aapsj080367. View

20.

Mahler H, Friess W, Grauschopf U, Kiese S . Protein aggregation: pathways, induction factors and analysis. J Pharm Sci. 2008; 98(9):2909-34. DOI: 10.1002/jps.21566. View