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MONDAY, AUGUST 20
Determining the biomolecular structure of proteins is of high importance in drug development. Biophysical properties such as protein dynamics, conformation, self-association, aggregation and particulate formation affect the quality attributes of protein therapeutics. Detailed knowledge and characterization of the underlying proteins and their behavior thus enables assessment of how protein structure is affected by manufacturing, storage, handling and delivery; and, in turn, allows researchers to better determine the impact on safety and efficacy. Presenters will share case studies and stories on the use of the appropriate biophysical method, method development and qualification to characterize the quality attributes at different stages of the product lifecycle.
8:00 am Pre-Conference Registration and Morning Coffee
11:30 am - 5:30 pm Main Conference Registration
1:00 pm Chairperson’s Opening Remarks
Bruce Kerwin, Ph.D., Scientific Director, Drug Product Development, Amgen - Biography
» 1:10 Opening Keynote Presentation:
Higher-Order Structure of Protein Products – Who Needs It?
Emily Shacter, Ph.D., Former Chief, Laboratory of Biochemistry, Division of Therapeutic Proteins, Office of Biotechnology Products, CDER/OPS, FDA - Biography
Proteins are defined by their amino acid sequence and higher-order structures. The bioactivities, biodistribution, immunogenicity, and clinical safety and efficacy profiles of proteins depend on proper synthesis and folding; transcriptional, translational, and post-translational modifications; and exposure to external stresses during manufacture and storage. The FDA’s regulatory expectations for evaluation of protein higher-order structure are evolving as advanced analytical tools become more available. This talk evaluates why and when protein higher-order structure should be analyzed.
1:45 Differential Scanning Calorimetry (DSC) for Biopharmaceutical Development: Versatility and Thermodynamic Power at Work
Sorina Morar-Mitrica, Ph.D., Investigator, Biopharmaceutical Technologies, GlaxoSmithKline R&D - Biography
This talk focuses on the use and application of DSC for structure and stability investigations of biopharmaceuticals, with an emphasis on monoclonal antibodies, in both early development and late stage products. Case studies presented will show how DSC analysis is used in formulation development, forced degradation, or comparability studies. From thermogram shape to identification of structural transitions, from melting temperatures (Tm) to Tm-based stability ranking, DSC allows for more confident biopharmaceutical development at a faster development pace.
2:15 Hydrogen Exchange Mass Spectrometry (HDX) for Studying Protein Structure and Dynamics
Erik Fernandez. Ph.D., Professor, Chemical Engineering, University of Virginia - Biography
Aggregate structures are difficult to characterize because of their heterogeneity, large size, and sometimes multiphase nature. Hydrogen-deuterium exchange detected by mass spectrometry (HDX) is emerging as a new approach that can provide relatively high-resolution structural information, even in complex environments. In this talk, an overview of the physical basis and experimental methods for HDX will be given. Examples of the different kinds of information that can be obtained from aggregating protein systems will be provided.
2:45 Sponsored Presentation (Opportunity Available)
3:00 Refreshment Break
» 3:15 Featured Presentation:
Influence of Electrostatics on Higher-Order Structure and Assembly
Christopher Roberts, Ph.D., Associate Professor, Department of Chemical Engineering, University of Delaware - Biography
This talk focuses on experimental characterization of the effects of pH and salt concentration on the formation of a range of aggregate sizes, morphology, and structure (local to larger scale). Examples include monoclonal antibodies and smaller, model proteins. The conditions are typical of therapeutic protein formulations, and highlight the importance of electrostatic inter- and intra-protein interactions, as well as more traditional views that emphasize hydrophobic and hydrogen bonding interactions. Phenomenological models also help to guide formulation design to account for these features.
3:45 Implementation of Sub-Visible Particle Analysis in Developmental Stability Studies
Nicholas Guziewicz, Ph.D., Scientist, Bioformulations Development, Genzyme - Biography
4:15 Small-Group Breakout Discussions
This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.
Use of Differential Scanning Calorimetry (or Other Thermal Analysis Techniques) in Higher-Order Structure Characterization and Prediction
Moderator: Jie Wen, Ph.D., Senior Scientist, Global Cellular & Analytical Resources, Amgen
• We often use Tm as one of parameters in higher-order structure characterization and prediction. What are the limitations of this method?
• In addition to Tm, has anyone used any other parameters in higher-order structure characterization and prediction?
• Besides DSC, are there any other thermal analysis techniques used in higher-order structure characterization and prediction? What are the advantage and disadvantages among these techniques?
Defining Optimal Charge Landscape of a Protein Using High-Throughput Analytical Tools
Moderator: Henryk Mach, Ph.D., Research Fellow, Bioprocess Analytical and Formulation Sciences, Merck Research Laboratories
• Do we need to adjust the concentration of ions to equalize ionic strength across pH range?
• Working at the low limits of buffering capacity and ionic strength, is the DOE approach appropriate for early pre-formulation work?
• What are the approaches for minimizing the amount of sample and time, while assuring effective analysis of data sets from HTS?
Relative Advantages and Disadvantages of Different Techniques for Characterizing Protein-Protein Interaction in Concentrated Protein Solutions
Moderator: Allen Minton, Ph.D., Senior Investigator, Physical Biochemistry, NIH
Impact of High-Concentrations on Downstream Processing
Moderator: Andrew Zydney, Ph.D., Department Head and Walter L. Robb Family Endowed Chair, Department of Chemical Engineering, The Pennsylvania State University; Editor-in-Chief, Journal of Membrane Science (Tentative)
• Ultrafiltration — process modifications and/or new modules
• Sterile filtration — challenges to throughput and capacity
• Alternate unit operations to meet new challenges
Characterization of Heterogeneous Particles
Moderator: Dean Ripple, Ph.D., Leader, Bioprocess Measurements Group, National Institute of Standards and Technology
• Recent research has demonstrated that therapeutic proteins can adsorb on to a non-protein nucleus, resulting in a chemically heterogeneous particle. What methods are suitable for identification and compositional characterization of heterogeneous particles?
• Nuclei composition depends on manufacturing and storage conditions; possible nuclei include glass, metal, or ceramic particles, or silicon oil droplets. What methods are suitable for studying protein conformation of adsorbed proteins?
• Should forced-degradation studies include seeding therapeutic proteins with potential particle nuclei?
Compatibility of Historical Practices with High Concentration Biologics
Moderator: Erinc Sahin, Ph.D., Research Investigator, Biopharmaceutics, Drug Product Science & Technology, Bristol-Myers Squibb
• At high protein concentrations, deviations from linear profiles may be observed on various properties (a large change in a given property due to a small change in concentration/pH/temperature/...).
• These non-linear dependencies may not be compatible with utilization of historical workflows and specifications.
o Can/should we target tighter specifications?
o Quality by design: efforts vs. benefits
o Experimental design (e.g. formulation robustness) in complex systems with multiple dependencies between parameters
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5:15 Breakout Group Summaries
5:30 Welcome Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
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