Biophysical and structural analysis are now playing increasingly important roles in the discovery and development of next generation biotherapeutics. Developability assessment is now standard practice across the industry, and understandings gained at
this step are now being applied in the optimization of candidates at early stages of the pipeline. Higher resolution tools are enabling better understandings of how to characterize and control aggregation and particulates and are increasingly allowing
these methods to be used in a quantitative, rather than qualitative way. The PEGS “Biophysical and Structural Analysis” conference brings together an international audience of protein scientists and analytical specialists to explore the
latest technologies and methods for problem solving in this dynamic field and identify ways of optimizing the studies performed in support of regulatory filings and manufacturing.
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TUESDAY, APRIL 9
Recommended Short Course*
SC9: Introduction to Biophysical Analysis for Biotherapeutics: Development Applications - Detailed Agenda
Christine P. Chan, PhD, Principal Scientist, Global Manufacturing Science & Technology, Sanofi
*Separate registration required.
WEDNESDAY, APRIL 10
7:15 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided) (Waterfront 1&2)
Jennifer S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-Chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter
Joanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune
Charlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience
Susan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D
Kristi Sarno, Senior Director, Business Development, Pfenex
8:30 Chairperson’s Opening Remarks
Jessy Fan, PhD, Scientist, Amgen
8:40 Characterization of Therapeutic Proteins by Circular Dichroism Spectroscopy: Application to Process Comparability and Establishment of Critical Quality Attributes
Gurusamy Balakrishnan, PhD, Scientist, Bristol-Myers Squibb
Circular dichroism (CD) spectroscopy is a widely used technique for assessing protein higher order structure (HOS) but remains difficult to assess HOS with high fidelity due to lack of sensitivity towards subtle structural perturbations. This presentation
will discuss these challenges and an effective experimental method for CD measurements with the relevant examples from analytical comparability for process change and forced degradation studies for establishing critical quality attributes.
9:10 Ion Mobility Spectrometry Mass Spectrometry (IMS-MS) for HOS Characterization
Brandon Ruotolo, PhD,
Professor, Chemistry, University of Michigan
The next generation of medicines will rely heavily upon our ability to quickly assess the structures and stabilities of large, complex macromolecular machines, as well as the influence of large libraries of conformationally-selective small molecule binders
and protein-based biotherapeutics. Such endeavors are nearly insurmountable with current tools. In this presentation, I will discuss recent developments in ion mobility-mass spectrometry (IM-MS) technology that seek to bridge this gap.
9:40 Keynote Presentation: The Underestimated Power of Well-Established Methods to Assess Protein Higher Order Structure
Alejandro Carpy, PhD, Head, Senior Scientist, Large Molecule Research, Roche Innovation Center Munich, Germany
Proper higher order structure (HOS) is essential for the function and stability of biologics. A large number of biochemical or biophysical methods are available to assess HOS, which differ in sensitivity and specificity. We will show that approaches based
on combination of conventional methods such as bioassays or liquid chromatography, which are used for batch release, are well-suited and sufficient to assess HOS, especially during early clinical development.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:15 Women in Science Speed Networking in the Exhibit Hall (Commonwealth Hall)
10:55 MAM Method Development and Qualification
Jihong Wang, PhD, Principal Scientist,
Several multi-attribute monitoring methods (MAM) have been developed in the biopharmaceutical industry in recent years. We reported MAM method based on Quadrupole Dalton (QDa) mass detector to selectively monitor and quantitate PTMs in a therapeutic monoclonal
antibody. In this talk, case studies will be presented on applications and implementation of QDa-based QC friendly MAM methods from supporting process characterization to product release.
11:25 Implementing the Multi-Attribute Method in a Multi-Site Analytical Development Organization: Successes and Challenges
Kristin Boggio, PhD., Senior
Scientist, Protein Mass Spectrometry, Pfizer
Biotherapeutics development requires thorough understanding of product quality attributes (PQAs) to ensure that clinical materials meet the desired safety/efficacy profile. Numerous routine assays are used to characterize and monitor PQAs; however, execution
of multiple methods becomes time and resource intensive, often providing indirect measurements of biologically-relevant PQAs. We have incorporated the mass spectrometry-based multi-attribute method at various stages in non-GMP product development
to monitor multiple PQAs within a single experiment.
11:55 Development of MS-Based Multi-Attribute Methods for ADC Process Support
Lintao Wang, Ph.D., Associate Director,
Analytical and Pharmaceutical Development, ImmunoGen, Inc.
Antibody-drug conjugates (ADCs) are complex anti-cancer biomolecules that have multiple quality attributes. A mass spectrometry based multi-attribute method (MAM) was developed for monitoring quality attributes (such as deamidation, oxidation, glycosylation,
disulfide mispairing, etc.) to support process development of an ADC with engineered cysteine linkage.
12:25 pm A Three-Pronged Characterization Tool That Makes Unstable Proteins Cry “Uncle”
Kevin Lance, PhD, Product Manager, Marketing, Unchained Labs
Optimizing protein stability and developing the best formulations for avoiding aggregation is important throughout the biologics development pathway. Uncle’s unique combination of static light scattering, dynamic light scattering, and fluorescence
gives you the flexibility needed to tease out the right answers and understand the whole story.
12:55 Luncheon Presentation I: The Perfect Recipe for Protein Characterization Starts with Tycho and Knowing Protein Quality
Peter A. Fung, Senior Manager Product Marketing, NanoTemper Technologies
Starting with material of questionable quality for protein purification and characterization leads to irreproducible or ambiguous results. Tycho tells you so much about the quality of your protein—its presence, purity, concentration, functionality
and similarity — in a single experiment. These can all be measured simply by determining whether your protein is structurally intact or properly folded. Tycho fits into any step of a purification or characterization workflow to easily monitor
protein quality and help researchers to get more consistent results.
1:25 Luncheon Presentation II: High Throughput Low Volume Subvisible Particle Analysis
John Proctor, PhD, Vice President, Marketing, Halo Labs
Subvisible particle analysis is a key predictor of protein drug stability and an essential drug product quality metric. Currently it is almost impossible to obtain this vital info during early stage formulation development. Come see how the new
HORIZON system from Halo Labs uses Backgrounded Membrane Imaging (BMI) to measure subvisible particles, including translucent protein aggregates. The measurement is fully automated for up to 96 samples and uses 1/10th the volume of other techniques.
1:55 Session Break
2:10 Chairperson’s Remarks
Brandon Ruotolo, PhD, Professor, Chemistry, University of Michigan
2:15 Leveraging Force Degraded Material to Increase the Throughput of Peptide Map Characterization
Romesh Rao, Research Associate, Analytical
Sciences, Seattle Genetics
Appropriately degraded samples can increase the throughput of peptide map characterization by facilitating data analysis. Post-translational modifications (PTMs) in a highly degraded sample were identified and site localized, enabling rapid, site-specific
assignments of PTMs during subsequent analysis of nominal samples by comparison. This approach can also support lower resolution, higher throughput workflows.
2:45 PULSE-SPR and its Applications in Developability Assessment
Li Zhou, PhD, Senior Scientist, Global Biologics,
Downstream purification of therapeutic antibodies requires candidates to be stable under various stress conditions such as low pH. Here we report a high throughput method that measures protonation induced unfolding of ligand binding sites for stability
evaluation by surface plasmon resonance, or PULSE SPR.
3:15 Advances in High-Throughput Screening for Development and Formulation of Biologics
PhD, Senior Applications Scientist, Northeast Regional Manager, Sales, Wyatt Technology
Light scattering addresses many key analytical challenges in drug nanoparticle R&D, including accurate size distributions, conformation, payload, and formulation. We review light scattering fundamentals and then present examples illustrating how.
Wyatt’s unique light scattering instrumentation facilitates rapid and effective development of controlled release vehicles including liposomes, VLPs, polymer-encapsulated nanoparticles, and nanogels.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:45 Problem-Solving Breakout Discussions - Click here for details (Commonwealth Hall)
5:45 Networking Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:00 End of Day
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THURSDAY, APRIL 11
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Iain D. G. Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen
8:35 Cutting-Edge Chromatographic, Electrophoretic and Mass Spectrometry of mAbs, Fc-Fusion Proteins and ADCs
Alain Beck, PhD, Senior Director,
Biologics CMC and Developability, Pierre Fabre Laboratories, France
Developability and comparability assessment of current and next generation of biologics such as engineered mAbs, Fc-fusion proteins, BsAbs and 2 or 3G-ADCs requires state-of-the-art analytical and structural methods. Case studies will be presented
based on native and ion mobility MS, multi-level 2- to 4 LC-MS, multiplexed Top and Middle-Down MS, multiple fragmentation techniques, comprising high energy collisional-, electron-transfer and ultraviolet photo-dissociation (HCD, ETD and UVPD)
9:05 The Application of Fourier Transform Ion Cyclotron Resonance MS and Spectral Deconvolution Algorithms within Biopharma Research
Iain D. G.
Campuzano, Principal Scientist, Discovery Attribute Sciences, Amgen
Native-MS analyses for accurate antibody, protein and nanodisc MW and DAR confirmation have traditionally been performed using oa-ToF instrumentation and more recently the extended mass range Orbitrap analyzer with incremental improvements in data
quality. Analysis of mAbs, ADCs, nanodiscs and a PEGylated biotherapeutics used FT-ICR MS under both native and denaturing LC-MS conditions. Also demonstrated is the use of a new parsimonious deconvolution algorithm that can efficiently deconvolve
highly polydisperse MS spectra.
9:35 Considerations of the Use of Analytical Ultracentrifugation for Characterization of AAV Gene Delivery Vectors
Christopher Sucato, PhD, Senior Scientist, Biophysical Characterization, Charles River
Analytical Ultracentrifugation (AUC) in the biopharmaceutical industry has traditionally been employed in the analysis of aggregation and higher order structure
in protein drug products, where monomeric or dimeric protein is commonly the analyte. More recently, the rise of gene delivery vectors as a means to treat a number of conditions has opened new avenues for AUC-based characterization and QC lot
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
11:05 Ultrafast High-Resolution Protein Analysis Unconventional Devices
Raja Ghosh, PhD, Professor, Chemical
Engineering, McMaster University, Canada
High-speed, high-resolution analytical separation is one of the current needs with biopharmaceuticals. Separations using ultrafine particulate chromatographic media require ultra-high pressures which could have detrimental effects on the molecules
being analyzed. In this presentation, membrane-based devices suitable for rapid, high-resolution analytical protein separation are discussed. Using these devices, high-resolution separation of proteins could be carried out in minutes at less than
1 MPa backpressure.
11:35 Effect of L-proline, L-arginine.HCl and NaCl on the Aggregation and Viscosity Behavior of High-Concentration Antibody Formulations
PhD, Postdoctoral Associate, Molecular Engineering, Massachusetts Institute of Technology
Development of subcutaneous formulations for monoclonal antibodies is hindered by several physical instabilities. In this study, we compare preferential interactions of L-proline, L-arginine.HCl and NaCl with the native state of three IgG1 mAbs that
differ in their physical stability attributes. We also highlight differences amongst the excipients in terms of their effect on the aggregation and viscosity of these antibodies at high protein concentration.
12:05 pm Impact of Non-Ideal Analyte Behavior on the Separation of Protein Aggregates by Asymmetric Flow Field-Flow Fractionation
Björn Boll, Ph.D.,
Head, Particle Lab and Higher Order Structure Protein Analytics, Novartis Pharma AG, Switzerland
Asymmetric flow field-flow fractionation (AF4) is a valuable tool for the characterization of protein aggregates owing to its broad size range and unique separation principle. In practice, AF4 is non-trivial to use due to deviations from theory. This
presentation gives an overview about non-ideal effects that influence AF4 separation including new approaches to minimize non-ideal behavior and drastically improving AF4 resolution by adjusting the mobile phase.
12:35 End of Biophysical and Structural Analysis
Recommended Short Course*
SC14: Subvisible Protein Particles in Immunogenicity: Measurement, Characterization and Impact - Detailed Agenda
Björn Boll, PhD, Head, Particle Lab and Higher Order Structure Protein Analytics, Physical Chemical Analytics, Novartis Pharma AG
Antonio Iglesias, PhD, Expert Scientist, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd. Basel
*Separate registration required.
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