Long Term Stability Analysis of Monoclonal Antibodies
Characterization of biopharmaceuticals during all development phases is critical to the candidate selection process and the ongoing production of the active material. Some recent efforts to achieve patient self-administration has required high API concentrations (100-300 mg/mL). Development concerns for the high concentration formulations are denaturation, aggregation and high viscosity. The primary goal of effective formulation characterization is to rapidly determine the best buffer and excipient conditions that maximize stability and minimize protein aggregation for at least one year at the required high concentrations. Robust, reproducible assays are particularly important as a production process is optimized, and small changes are made in the process that may affect the structure or the function of the product. Isothermal calorimetry (IMC) quantifies the amount and rate of heat release in terms of heat flow, heat and heat capacity and is a non-specific technique, making it ideal for studying almost any kind of physical and chemical processes occurring in biopharmaceutical preparations. Utilizing the TAM IV, the rate of denaturation and aggregation for high concentration biopharmaceuticals can be determined in as little as 3-5 days without having to dilute the original formulation.
About the Speaker
Ernesto Freire is the Henry Walters Professor at the Johns Hopkins University. He has been a member of the Department of Biology and Biophysics since 1986. He also holds a joint appointment in the Department of Biophysics and Biophysical Chemistry at the Johns Hopkins Medical School. Since 2002, Prof. Freire has also been a Scientific Director at the Institute of Biocomputation, BIFI, University of Zaragoza, Spain.
Prof. Freire has pioneered the development of protein stability analysis and drug design strategies using thermodynamics and microcalorimetric techniques. These strategies are aimed at achieving extremely high affinity, high selectivity and superior resistance profiles. The author or co-author of over 230 publications and several patents, Prof. Freire is on the editorial board of Proteins: Structure, Function and Bioinformatics, Current Protein and Peptide Science and Chemical Biology and Drug Design. He has been the recipient of many awards including the Stig Sunner Memorial Award for Outstanding Contributions to Thermochemistry and Thermodynamics, he was awarded a Johnson & Johnson Focused Giving Program Award in 1993. Most recently he was awarded the Hugh Huffman Memorial Award for pioneering contributions at the forefront of structural thermodynamics and development of innovative experimental strategies for drug discovery and optimization at the Calorimetry Conference in 2015. He has served on many scientific advisory committees for the National Institutes of Health and the National Science Foundation. Prof. Freire is an Honor Member of the Spanish Society of Biochemistry and Molecular Biology, and a member of the Academy of Sciences of Latin America.