Abstract: This talk will illustrate how a combination of biophysics, simulations and analytical tools can be employed for understanding the molecular basis for the purification of biological products from process and product related impurities. We will discuss how high throughput protein surface footprinting using covalent labeling followed by LC/MS analysis can be employed to identify preferred binding domains for several classes of biotherapeutics in several chromatographic systems and conditions. We will then examine this data set using a variety of simulation tools including dewetting calculations of protein and chromatographic surfaces to shed light on the nature of selectivity and peak shape in these complex bioseparation systems. In addition, the development of expedited process development workflows will be discussed for bioprocess development. This will include the use of high throughput screening, QSAR and mechanistic/hybrid modeling for process development.
Bio: Professor Steven Cramer is an Institute Professor at Rensselaer Polytechnic Institute, Troy, New York. The Cramer lab’s research over the past 38 years has helped to improve the state of the art of downstream bioprocessing and its successful implementation for the biomanufacturing of biological products. Current research in the Cramer lab using a combination of biophysics, molecular dynamics simulations and chromatography with ligand protein libraries has provided insights into the design of novel multimodal chromatographic systems. Recent work on integrated biomanufacturing and expedited process development is having an impact on how bioprocess development is carried out in the industry. The Cramer lab is now actively involved in gene therapy downstream biomanufacturing projects, continuous mRNA processing, and several big data modeling efforts. Professor Cramer has won numerous awards including the ACS National Award in Separations Science and Technology, the ACS BIOT Division’s Michaels Award in the Recovery of Biological Products, the Gaden award from the Biotechnology and Bioengineering Journal, and several awards from RPI including the Wiley Distinguished Faculty Award and the School of Engineering Outstanding Professor and Research Excellence Award. Cramer has been elected a member of the National Academy of Engineering and U.T. Austin’s Academy of Distinguished Chemical Engineers. He is also an elected fellow of the American Association for the Advancement of Science, American Institute of Chemical Engineers, the American Chemical Society, and the American Institute for Medical and Biological Engineering. He has published extensively in the field with 250 publications, and the 60 Ph.D. graduates from the Cramer lab have had a significant impact with many of his former students now playing key leadership roles in the state of the art of industrial bioprocessing at most of the major biopharmaceutical and bioseparations companies worldwide as well as academia.