Institute for International Research

Description

In this course, you will learn the fundamentals of protein structural analysis using modern analytical technologies. We will review the post-translational modifications commonly observed on recombinant proteins produced from manufacturing cell lines and discuss the potential impact of the structural heterogeneities on biological activity. In addition, biophysical methods used for characterization of aggregates and application of target binding and cell-based functional assays will be discussed. We will review application examples on characterization of recombinant proteins including monoclonal antibodies and evaluate the use of key orthogonal techniques. We will discuss the impact of cell line selection and process parameters on product quality profile as well as considerations of effects of sample preparation, storage and handling of process intermediates. The objective is to provide participants with key technical information along with perspectives to enable them to apply the technologies to their own projects and evolve their own analytical strategy to support the various stages of product development.

Instructor

Christine P. Chan, Ph.D., Senior Manager, Technology Development, Genzyme Corporation
Christine Chan is a protein biochemist with broad experience in the biopharmaceutical industry, including prior experience at Sandoz Pharmaceuticals and Merck & Co., Inc. She specializes in the analysis of recombinant products produced from mammalian cells for vaccines and biologics development. She has extensive hands-on experience with classical protein chemistry methods including Edman sequencing, amino acid analysis and protein purification, as well as capillary electrophoresis and mass spectrometry. She is experienced in high-throughput screening using plate-based assays as well as cell-based assays. Dr. Chan obtained her Ph.D. from the University of California-Davis and did postdoctoral work at the Howard Hughes Medical Institute at the University of Washington on growth factor signal transduction and protein phosphorylation.

Course Agenda

• Introduction to protein structure and post-translational modifications
• Protein Chemistry Techniques: capillary electrophoresis and HPLC, enzymatic methods and peptide mapping, mass spectrometry, amino acid analysis and protein sequencing, sample treatment, preparation & work flow
• Biophysical Characterization: spectral methods, light scattering, calorimetry, analytical ultracentrifugation, and field flow fractionation; aggregation and particle size analysis
• Characterization of recombinant protein products: glycosylation analysis; monoclonal antibody structure and subclasses, additional recombinant proteins, product heterogeneity analysis
• Quality control of biotechnology products: guidance documents
• Bioprocess impact on product quality: cell line selection, upstream process variables, downstream process impact, formulation and storage
• Selecting characterization methods to support various stages of product development