Cambridge Healthtech Institute’s 6th Annual
Characterization of Biotherapeutics
Improving Prediction, Screening, and Characterization of New Biologics
January 20-21, 2020
Part of the Analytics & Impurities pipeline
The popular 6th Annual Characterization of Biotherapeutics conference will bring together leading scientists from the biopharmaceutical industry, academia, and government to discuss case studies, new technologies, assay on analytical development, and
characterization of mAbs, ADCs, bispecifics, novel protein formats, and biosimilars. Some of the hot topics for discussion this year will include regulatory expectations and developability of new product formats, cell and gene therapy products, high-throughput
analytics, multi-attribute methods, glycosylation/post-translational modifications, biophysical assays, and more.
Final Agenda
SUNDAY, JANUARY 19
4:00 - 6:00 pm Pre-Conference Registration
(Sapphire West Foyer)
MONDAY, JANUARY 20
7:00 am Registration (Sapphire West Foyer) and Morning Coffee
(Sapphire West & Aqua West Foyer)
9:00 Organizer’s Welcome Remarks
Nandini Kashyap, Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Suzanne D’Addio, PhD, Principal Scientist - Discovery Pharmaceutical Sciences, Merck & Co., Inc.
FEATURED PRESENTATION
9:10 Developability Assessment to Select Candidates for Clinical Development
Anup Arumughan, PhD, Principal Scientist, Antibody Analytics, Roche
We have developed a highly versatile next-generation biologics platform with a number of candidates in clinical development. During lead identification and optimization of candidates, we typically rank molecules based on their potential for successful
future development. Such developability assessments provide important information about potential liabilities, e.g., chemical degradation of amino acids or unfavorable CMC properties. We have recently expanded our developability concept to systematically
combine
in silico analysis including pharmacokinetics analysis with biophysical and functional testing. In summary, this concept provides a more holistic picture of a candidate’s fitness for future development.
9:50 Analytics in the Development of Biosimilars and Beyond
Robert Mayer, PhD, Senior Fellow, Novartis - Global Drug Development, Technical Research & Development, Sandoz GmbH
Analytical characterization is one of the key pillars for biosimilars development. With the help of case studies, we will demonstrate the powerfulness of analytical methods. In one case study, the elucidation of structure-function relationship will be
addressed. In another case study, an innovative approach for the glycan analysis in PK studies will be shown to evaluate the (possible) impact of individual N-glycan species onto clearance. Furthermore, analytical challenges and requirements for the
development of “fit-for-purpose” analytical methods will be briefly addressed.
10:20 Networking Coffee Break (Sapphire West & Aqua West Foyer)
10:45 Antimicrobial Excipient-Induced Reversible Association of Therapeutic Peptides in Parenteral Formulations
Suzanne D’Addio, PhD, Principal Scientist - Discovery Pharmaceutical Sciences, Merck & Co., Inc.
The high potencies and longer half-lives of therapeutic peptides have given rise to multiuse injectable dosage forms that enable less frequent dosing and patient self-administration, but required antimicrobial preservatives can impact other attributes
of protein and peptide formulations. To understand molecular mechanisms of peptide-preservative interactions influencing solution-phase self-association, we investigated the interactions of commonly used antimicrobial preservatives with an acylated
peptide. We have demonstrated a reversible association phenomenon granting new insights into mechanisms by which peptides can interact with excipients. These findings have practical implications for drug product formulation development.
11:15 Predicting Antibody Affinity Changes upon Mutations by Combining Multiple Predictors
Yoichi Kurumida, PhD, Postdoctoral Fellow, National Institute of Advanced Industrial Science and Technology(AIST).
The prediction of antibody affinity changes upon mutations is important for antibody engineering. Numerous computational methods have been proposed based on different approaches including molecular mechanics and machine learning. However, the prediction
accuracy obtained by each of individual predictors has been limited. In this study, we develop a new prediction method by combining multiple predictors based on machine learning. The method was tested on the SiPMAB database and achieved higher accuracy
than other methods.
11:45 Comparative Evaluation of Chelating Agents to Prevent Polysorbates and API Degradation in Biologic Formulations
Sanket Patke, PhD, Senior Scientist, Biologics Drug Product Development, Sanofi
EDTA and other chelators are used in several products, few of which are biologics. Their need, pros, and cons as excipients are, however, still poorly understood. In this case study, a head-to-head comparison of EDTA with other chelating agents is presented,
including recommendations for their correct use in the formulation of protein-based therapeutics.
12:15 pm Selected Poster Presentation I: Development of Standards for Cation exchange chromatography Column Qualification
Jie (Amy) Liu, Scientist IV, Biologics & Biotechnology Laboratory Global Biologics, United States Pharmacopeia
USP has sponsored several roundtables with stakeholders to identify challenges in biologics development that could be alleviated with standards. Standards for qualification of cation exchange columns were ranked as high priority. We evaluated three new
USP monoclonal antibody standards under development using pH gradient and salt gradient CEX methods on columns from different vendors to support selection of a candidate for further development of the CEX column qualification standard.
12:30 NEW Selected Poster Presentation II:Utilizing Alginate Beads as a Protein Capturing Resin
Jamie Song, Postgraduate Researcher, Chemical and Structural Biology Laboratory, School of Biological an Health Sciences, Technological University Dublin City Campus, Ireland
12:45 Session Break
12:55 LUNCHEON PRESENTATION I: High-Resolution Charge Variant Analysis for a Variety of Therapeutic Proteins in as Little as 5 Minutes
Peter Holper, Applications Scientist, CE & BioPharma, SCIEX
In this study, we present a native state charge variant analysis that delivers high resolution results in as little as 5 minutes. Using a technique that requires little to no method development, a simple sample preparation and a higher analytical throughput
and wider sample concentration range than icIEF, this platform method can easily be applied to a wide array of therapeutic proteins such as: antibody drug conjugates (ADCs), mono- and multi-specific antibodies, and fusion proteins.
2:00 Chairperson’s Remarks
Elizabeth M. Topp, PhD, Dane O. Kildsig Chair and Department Head, Department of Industrial and Physical Pharmacy, Purdue University
2:05 Diverse Samples, Fast Turnaround: Providing Meaningful Data in Biotherapeutic Early Discovery
Alayna George Thompson, PhD, Senior Scientist I, Drug Discovery Science & Technology, AbbVie
Characterizing early discovery biologics presents challenges related to the diversity of molecules and formats coupled with the need for quick data turnaround. To address these challenges, we expanded a walk-up mass spectrometry analysis workflow for
purified proteins to include characterization (protein identification, post-translation modifications, and proteolysis) of proteins during transient cell expression. These analyses provide business impact by empowering data-driven decisions for biologics
production.
KEYNOTE PRESENTATION
2:35 Solid-State Hydrogen Deuterium Exchange (ssHDX-MS): High-Resolution Characterization of Lyophilized Biotherapeutics
Elizabeth M. Topp, PhD, Dane O. Kildsig Chair and Department Head, Department of Industrial and Physical Pharmacy, Purdue University
More than 40% of biologics approved in the last ten years are marketed in lyophilized form, but the factors controlling stability in these amorphous powders are poorly understood. ssHDX-MS is a novel analytical method that characterizes protein structure
and matrix interactions in the solid state with peptide level resolution. Results of ssHDX-MS analysis have been shown to be highly correlated with protein stability on long-term storage. This presentation reviews the ssHDX-MS method and presents
new results from ongoing studies of exchange kinetics and mechanisms.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments
Join your peers and colleagues for interactive roundtable discussions.
Click here for more details
4:30 Characterization of Glycan Heterogeneity for mAb based molecules using High Resolution and Single Ion Monitoring Mass Spectrometry Techniques
Sheila Mugabe, MSc, Scientist, MacroGenics, Inc.
Monoclonal antibodies and novel bispecific DART® molecules are being developed for a variety of indications including immune-oncology. This presentation discusses the analysis of glycan heterogeneity profiles for such molecules using High Resolution and Single Ion monitoring mass spectrometry techniques. High throughput characterization approach during process development will be discussed.
5:00 Computational Methods for Cell Culture Media Optimization and Product Quality Control
Gaurav Chauhan, MS, Associate Principal Scientist, Biologics Process Research and Development, Merck & Co., Inc.
Biologics development leading to approval can take decades. Acceleration is desired to bring safe and efficacious drugs to patients as early as possible. One research focus is to reduce development time for cell culture process development and optimization.
Strategies will be shared that cover optimizing cell culture media using Orthogonal-Partial Least Squares (OPLS) regression and modulating glycosylation by altering small molecule compound concentrations based on the Concentration Impact Factor.
5:30 Risk Assessment of Formulation Attributes and Feasibility for Alternative Routes of Administration of Biologics during the Developability Stage
Yingkai Liang, PhD, Senior Scientist, Discovery Pharmaceutical Sciences, Merck & Co., Inc.
While intravenous administration is a generally well-accepted route of administration for biologicals, increasing market competition and desire for local therapy have renewed interest in the delivery of proteins by alternative routes of administration.
This presentation will cover the assessment of formulation parameters in the context of optimizing developability properties of proteins intended for administration by alternate routes of delivery.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster
Viewing (Sapphire Ballroom)
7:15 Close of Day
TUESDAY, JANUARY 21
8:15 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:45 Chairperson’s Remarks
Peter Schurtenberger, PhD, Professor, Department of Chemistry, Lund University
8:50 Size and Weight Are Two Related but Different Fundamental Measurables
David Hayes, PhD, Biophysics Consultant, International Solidarity of Scientists
Analytical methods and assays seldom measure product quality attributes directly, but they quantitate attribute levels through a related signal. Speaking of the various methods that quantitate aggregation, the terms such as size, weight, and molecular
weight are conflated to mean the same thing. Understanding the strengths and weaknesses of aggregation assays requires more rigorous mathematical definition of measurables.
9:20 Biopharm Critical Quality Attributes (CQAs): It is When Product Analytics, Process, and Clinical Outcomes Connect
Wasfi AlAzzam, PhD, Chief Scientific Officer, TechnoPharmaSphere LLC
Analytical methods have been playing a major role in creating in vitro and in vivo biopharm product characterization packages. Compiling both sets of data helps in-depth understanding of product’s quality attributes (QA) and filters some
to figure the product’s CQAs. It is proven that some CQAs have impact on the product’s biological and clinical profiles. Biopharm industry is now revising their CMC strategy to accelerate product development. This talk will connect
analytical, CQAs, and clinical outcomes.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 High-Throughput Biophysical Characterization of New Classes of Antibodies
Mitra Mosharraf, PhD, HTD Biosystems, Inc.
In this talk, characterization of various biomolecules such as mAb, fusion proteins, Fab and bispecifc antibodies will be discussed. We will showcase use of high-throughput technologies such as nDSF, MST, DLS, and protein chip bioanalyzer in characterization
of the conformational and colloidal stability of these molecular entities alone and in combination.
11:30 Characterizing Protein Interactions and Solution Viscosities Using Advanced Scattering Tools
Peter Schurtenberger, PhD, Professor, Department of Chemistry, Lund University
Measuring and predicting solution viscosity is essential in formulating biopharmaceuticals. We show how we can use a combination of advanced characterization techniques, such as small-angle neutron (SANS) and X-ray scattering (SAXS) to characterize
protein interactions and microrheology experiments to assess and predict solution viscosity in concentrated solutions
of biopharmaceuticals. We will discuss recent advances in protein microrheology using either optical or microfluidics approaches.
12:00 pm Influences of Sample Preparation and Data Evaluation on CE-SDS and SDS-PAGE
Rebeca Wiesner, PhD, Scientist, Technische Universität Braunschweig, Institute of Medicinal and Pharmaceutical Chemistry
Gel electrophoresis (SDS-PAGE) is the most common approach for molecular mass determination (MW) of proteins. Results are compared to CE-SDS (Maurice, ProteinSimple) and Simple Western (WES, ProteinSimple) concerning precision and accuracy of
MW using nine typical model proteins (7-180 kDa) and Matuzumab (IgG antibody). Various conditions of sample preparation e.g. different temperature conditions and reducing agents and the influence of data evaluation by comparison of different
molecular weight markers were investigated.
12:30 Session Break
12:40 LUNCHEON PRESENTATION: Improve the Characterization of New Biologics by Knowing Protein Stability First with Prometheus
Peter Fung, PhD, Senior Product Marketing Manager, NanoTemper Technologies
1:10 Close of Characterization of Biotherapeutics Conference
5:45 - 8:45 Recommended Dinner Short Courses*
SC3: Structure-Based Optimization of Antibodies - Detailed Agenda
Instructor:
Traian Sulea, PhD, Principal Research Officer, Human Health Therapeutics, Biotechnology Research Institute, National Research Council Canada
SC4: Asset Reacquisition: Planning before Out-Licensing - Detailed Agenda
Instructor:
Deb Harris, Managing Director, Industry Special Services, BDO USA LLP
SC5: Protein Aggregation: Mechanism, Characterization, and Consequences - Detailed Agenda
Instructors:
Thomas Laue, PhD, Professor Emeritus, Biochemistry and Molecular Biology; Director, Biomolecular Interaction Technologies Center (BITC), University of New Hampshire
Kevin Mattison, PhD, Principal Scientist, Malvern Pananalytical, Inc.
*Separate registration required