Analytical Tools for Process and Product Characterization - Select the best approach to determine critical quality attributes. - BioPharm International


Analytical Tools for Process and Product Characterization
Select the best approach to determine critical quality attributes.

BioPharm International
Volume 22, Issue 8


1. Rathore AS, Winkle H. Quality by Design for pharmaceuticals: regulatory perspective and approach. Nature Biotechnol. 2009;27:26–34.

2. Rathore AS, Branning R, Cecchini D. Design space for biotech products. BioPharm Int. 2007;20(4):36–40.

3. Kozlowski S, Swann P. Considerations for biotechnology product Quality by Design. Rathore AS, Mhatre R, editors. In Quality by Design for biopharmaceuticals: Perspectives and case studies. New Jersey: Wiley Interscience; 2009. p. 9–30.

4. Swann PG, Tolnay M, Muthukkumar S, Shapiro MA, Rellahan BL, Clouse KA. Considerations for the development of therapeutic monoclonal antibodies. Curr Opin Immunol. 2008;(42):493–99.

5. Towns J, Webber K. Demonstrating comparability for well-characterized biotechnology products. BioProcess Int. 2008;2:32–43.

6. Schnerman MA, Sunday BR, Kozlowski S, Webber K, Gazzano-Santoro H, Mire-Sluis A. CMC strategy forum report: analysis and structure characterization of monoclonal antibodies. BioProcess Int. 2004;(2):42–52.

7. International Conference on Harmonization. Q6B, Specifications: test procedures and acceptance criteria for biotechnological/biological products. Geneva, Switzerland; 1999.

8. Krull IS, Swartz M. Validation in biotechnology and well-characterized biopharmaceutical product. Pharmaceutical Regulatory Guidance Book. 2006;7:18–23.

9. Apostol I, Kelner D. Managing the analytical lifecycle for biotechnology products. BioProcess Int. Part 1: 2008;9:12–19. Part 2: 2008;(10):12–19.

10. Wu J, Watson JT. Assignment of disulfide bonds in proteins by chemical cleavage and peptide mapping by mass spectrometry. Methods Mol Biol. 2002;194:1–22.

11. Yen T-Y, Yan H, Macher BA. Characterizing closely-spaced, complex disulfide bond patterns in peptides and proteins by liquid chromatography/electrospray ionization tandem mass spectrometry. J Mass Spectrom. 2002;37:15–30.

12. Martinez T, Guo A, Allen MJ, Han M, Pace D, Jones J, et al. Disulfide connectivity of human immunoglobulin G2 structural isoforms. Biochem. 2008;47:7496–508.

13. Zhang W, Marzilli LA, Rouse JC, Czupryn MJ. Complete disulfide bond assignment of a recombinant immunoglobulin G4 monoclonal antibody. Anal Biochem. 2002;311:1–9.

14. Wypych J, Li M, Guo A, Zhang Z, Martinez T, Allen MJ, et al. Human IgG2 antibodies display disulfide-mediated structural isoforms. J Biol Chem. 2008;283:16194–205.

15. Cockrill SL. Complete determination of IgG2 disulfide connectivity: defining an analytical strategy for a new structural paradigm. Invited talk. IBC 12th Annual Well Characterized Biologicals Conference; 2008 Nov 10–12; Reston, VA.

16. European Commission (Enterprise Directorate General). EMEA Guideline on Production and Quality Control of Monoclonal Antibodies and Related Substances (Draft). Brussels, Belgium; 2008 Jul. Available from

17. Anumula KR. High-sensitivity and high resolution methods for glycoprotein analysis. Anal Biochem. 2000;283:17–26.

18. Chen X, Flynn GC, Analysis of N-glycans from recombinant immunoglobulin G by on-line reversed-phase high-performance liquid chromatography/mass spectrometry. Anal Biochem. 2007;370:147–61.

19. Prater BD, Anumula KR, Hutchins JT, Automated sample preparation facilitated by PhyNexus MEA purification system for oligosaccharide mapping of glycoproteins. Anal Biochem. 2007;369:202–09.

20. Prater BD, Connelly HM, Qin Q, Cockrill SL. High-throughput immunoglobulin G N-glycan characterization using rapid resolution reverse-phase chromatography tandem mass spectrometry. Anal Biochem. 2009;385:69–79.

21. Nguyen LT, Wiencek JM, Kirsch LE. Characterization methods for the physical stability of biopharmaceuticals. PDA J Pharm Sci Technol. 2003;57:429–45.

22. Gabrielson JP, et al. 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. 2007;96(2):268–79.

23. Philo JS. Is any measurement method optimal for all aggregate sizes and types? AAPS J. 2006;8(3):E564–E571.

24. Arthur KK, et al. Detection of protein aggregates by sedimentation velocity analytical ultracentrifugation (SV-AUC): Sources of variability and their relative importance (p n/a). J Pharm Sci. 2009;doi 10.1002/jps.21654.

25. Berkowitz SA. Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals. AAPS J. 2006;8(3):E590–605.

26. Liu J, Andya JD, Shire SJ. A critical review of analytical ultracentrifugation and field flow fractionation methods for measuring protein aggregation. AAPS J. 2006;8(3):E580–89.

27. 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;367:225–37.

28. Gabrielson JP, et al. Common excipients impair detection of protein aggregates during sedimentation velocity analytical ultracentrifugation. J Pharm Sci. 2009;98(1):50–62.

29. Schuck P. A model for sedimentation in inhomogeneous media. I. Dynamic density gradients from sedimenting co-solutes. Biophys Chem. 2004;108(1-3):187–200.

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

31. Samavedam R, Morrison R, Kichefski T, Cote S, Rathore AS. Lifetime studies for membrane reuse: principles and case study. BioPharm Int. 2007;20(9):48–54.

32. Rathore AS, Sofer GS. Lifespan studies for chromatography and filtration media. In: Rathore AS, Sofer GS, editors. Process Validation. Marcel Dekker; 2005. p. 169–203.

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