As the biopharmaceutical industry continues to evolve, so must its analytical techniques. Protein characterization plays a
critical role in determining the safety and efficacy of biological products, and as such there is a need to continue to improve
the accuracy, sensitivity, specificity, and robustness of protein assays, and to develop novel assays that target specific
areas of concern. Biomanufacturers must leverage their experience and knowledge to determine which methods to apply at each
stage of the drug development process, and use a risk-based approach to guide their selection. Collaboration between manufacturers
and regulatory agencies is critical in the ongoing search for an answer to the question—How well characterized is well characterized
Lisa Crossley, PhD, the founder and principal of BioVentures, Ontario, Canada, 888.405.9549, email@example.com
1. Morrow KJ. Tools for protein structure characterization. Gen Eng Biotech News. May 2008;28(9).
2. Magil S. Biopharmaceutical characterization techniques for early phase development of proteins. BioPharm Int. Guide to
Bioanalytical Advances. Sept 2005; p. 34–42.
3. Towns J, Webber K. Demonstrating comparability for well-characterized biotechnology products: Early phase, late phase,
and post-approval. BioProcess Int. Feb 2008:6(2):32–43.
4. Krishnamurthy R, Sukumar M, Das T, Lacher N. Emerging analytical technologies for biotherapeutics development. BioProcess
Int. May 2008;6(5):32–42.
5. US Food and Drug Adminsitration. Guidance for Industry. Q6B specifications: Test procedures and acceptance criteria for
biotechnological/biological products. Rockville, MD; Aug 1999.
6. Dougherty J, et al. Postapproval changes for large-scale biopharmaceutical manufacturing: Global regulatory issues. Langer
ES, ed. In: Advances in large-scale biopharmaceutical manufacturing. ASM Press: Washington, DC, 2004; pp. 555–91.
7. Patten PA, Schellekens H. The immunogenicity of biopharmaceuticals: lessons learned and consequences for protein drug
development. Brown F, Mire-Sluis AR, editors. Immunogen Therapeutic Bio Prod.
8. Aldridge S. Next-generation protein characterization. Gen Eng Biotech News. Apr 2006;26(7).
9. Lipp, E. Characterizing Proteins to Bolster Pipelines. Genetic Eng Biotech News. June 2010; 30(12).
10. Vivian JT, Callis PR. Mechanisms of tryptophan fluorescence shifts in proteins. Biophys J. 2001;80(5):2093–109.
11. Wales TE, Engen JR. Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom Rev. 2006;25(1):158–70.
12. Berkowitz SA. Role of analytical ultracentrifugation in assessing the aggregation of protein biopharmaceuticals. AAPS
13. 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;96:268–79.