CBER Expertise
Analytical proteomics as a tool for the characterization of biologic products and discovery and validation of biomarkers
Principal Investigator: Michail A. Alterman, PhD
Office / Division / Lab: OCTGT / DCGT / TVBB
Overview
Public Health Issue: CBER evaluates cellular, tissue and gene therapy products that have the ability to regenerate, repair and cure genetic and acquired disorders. To accurately evaluate these 21st century products, state-of-the-art analytical tools are needed to assess product quality, safety, and efficacy. However, the ability to perform rapid evaluation of product quality creates a major regulatory challenge that must be addressed.
Regulatory Contribution: Biologic products are derived from living sources and represent mixtures of proteins, carbohydrates, lipids and other biomolecules of enormous analytical complexity. The major physical-chemical feature that can be measured for all components of biological mixtures and uniquely identify and distinguish them is molecular mass. Mass-spectrometry-based proteomics is the leading technology for the rapid analysis of complex protein mixtures. This technology provides means for concomitant analysis of all components of biological products. The goal of this research project is to develop and adapt mass-spectrometry-based and protein array-based proteomic techniques for qualitative and quantitative analytical testing of cells, cell-derived products and tissues. A new direction in our research is application of mass spectrometry-based proteomics approach for evaluation of influenza vaccine potency and purity.
Research Approach: Proteomic characterization (profiling) of cell substrate, such as human embryonic kidney 293 cells, PICM-19 liver stem cell line, MRC-S cells, and dendritic cells is being studied. The ultimate goal of this project is to develop a reliable proteomics approach to qualitatively and quantitatively analyze changes in protein expression levels caused either by different types of stimulation (like stimulation with cytokines) or some pathological changes (cancer). The data obtained would contribute to the development of new analytical techniques aimed at the characterization of the product identity and potency. We will explore the possible use of differential cytochrome P450 isozyme expression as biomarker of cancer development.
Mission Relevance and Outcomes: These studies will provide unique ability to apply cutting edge analytical tools in the evaluation of safety and efficacy of cellular products and an opportunity to develop effective tools used in manufacturing process controls. Fast, reliable, and precise evaluation of protein biomarkers will allow identification of product characteristics including potency, safety, and efficacy. The resulting information will enhance our ability to adopt latest techniques in regulatory decision making and facilitate development of complex biologic products.
Publications
Chem Res Toxicol 2007 Mar;20(3):511-9
A proteomic analysis of bromobenzene reactive metabolite targets in rat liver cytosol in vivo.
Koen YM, Gogichaeva NV, Alterman MA, Hanzlik RP