The amount, type, and size of the aggregates in biopharmaceuticals can have important consequences for the safety and efficacy of biopharmaceuticals. Alliance Protein Laboratories has extensive experience in aggregation issues and analysis of aggregation in proteins and other macromolecules.
Our scientists are widely recognized experts in this area and have published several major review articles. They have also pioneered new analytical approaches for aggregation analysis that are now widely used in the biotechnology industry. Over the last 10 years, APL has completed hundreds of aggregation-related projects on over 250 proteins, peptides, nucleic acids, and other molecules.
The primary tools we use for aggregation analysis are:
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analytical ultracentrifugation (AUC), including both sedimentation velocity and sedimentation equilibrium
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both static light scattering (SEC-MALS and/or CG-MALS) and dynamic light scattering (DLS)
We also have extensive experience at using these technologies to cross-validate SEC or other assays that companies are using for routine aggregation analysis or lot release, and in using these technologies to demonstrate comparability of aggregation for biosimilars, between different manufacturing processes or sites, etc.
Our understanding of aggregation mechanisms and world-class expertise on how solvent composition affects protein conformation and influences aggregation during chromatographic purification means we may also be able to help you to prevent aggregation during manufacturing.
Below are downloadable versions of a few of our publications and presentations about aggregation (more can be found on the Resources page):
Philo, J. S., and Arakawa, T. (2009). Mechanisms of protein aggregation. Curr. Pharm. Biotechnol. 10, 348-351. [A PDF file is available but by request only (use the Contact Form, and be specific about which article you want).]
Philo, J. S. (2009). A critical review of methods for size characterization of non-particulate protein aggregates. Curr. Pharm. Biotechnol. 10, 359-372. [A PDF file is available but by request only (use the Contact Form , and be specific about which article you want).]
"Aggregation analysis of therapeutic proteins, part 1: General aspects and techniques for assessment". Arakawa, T., Philo, J. S., Ejima, D., Tsumoto, K., and Arisaka, F. (2006). Bioprocess International 4 (10), 42-49.
"Aggregation analysis of therapeutic proteins, part 2: Analytical ultracentrifugation and dynamic light scattering". Arakawa, T., Philo, J. S., Ejima, D., Tsumoto, K., and Arisaka, F. (2007). Bioprocess International 5 (4), 36-47.
"Aggregation analysis of therapeutic proteins, part 3: Principles and optimization of field-flow fractionation (FFF)". Arakawa, T., Philo, J. S., Ejima, D., Sato, H., and Tsumoto, K. (2007). Bioprocess International 5 (10), 52-70
"Focus on aggregation: types, causes, characterization, and impact", invited talk, Comparability for Biotherapeutics, Berlin June 2007
"Sensitivity and Reproducibility of Protein Aggregate Analysis by Sedimentation Velocity", poster, WCBP 2005
