Cambridge Healthtech Institute’s Third Annual
Characterization of Biotherapeutics
Improving Prediction, Screening and Characterization of New Biologics
January 9-10, 2017 | Hilton San Diego Bayfront | San Diego, CA

New biotherapeutics formats are flooding the discovery and development pipelines and with this comes an increasing need for better and faster characterization tools and strategies, and improved biomolecular and biophysical assays for the new biotherapeutics. The Third Annual Characterization of Biotherapeutics conference presents new tools, strategies and case studies on analytical development and characterization of mAbs, ADCs, bispecifics, and other novel protein formats.

We invite you to present a poster and attend to join colleagues in this discussion of the key challenges and solutions improving prediction, screening and characterization of new biologics.

MONDAY, JANUARY 9

7:30 am Conference Registration and Morning Coffee

SCREENING, CHARACTERIZATION AND DEVELOPMENT OF NEW BIOTHERAPEUTICS

9:00 Welcome by Conference Organizer

Nandini Kashyap, Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Shrikant Deshpande, Ph.D., Senior Director, Protein Chemistry, Biologics Discovery California, Bristol-Myers Squibb Co.

Keynote Presentation

9:10 Understanding Chemical Liabilities in Antibody Lead Selection

Shrikant Deshpande, Ph.D., Senior Director, Protein Chemistry, Biologics Discovery California, Bristol-Myers Squibb Co.

Chemical liabilities such as deamidation, and oxidation in an antibody sequence can alter the structure and activity of the lead molecule. So, it is important and necessary to assess and understand the risks they pose in the CMC as well as therapeutic setting. This presentation explores chemical liability risks in lead selection process and provides case studies that provide risk mitigation strategies.

9:50 Biophysical Characterization to Enable the Formulation Development of Multi-Dose Aggregation-Prone Peptide Conjugates

Jingtao Zhang, Ph.D., Principal Scientist, Pharmaceutical Sciences, Merck Research Laboratories

The presentation will focus on the characterization of reversible and irreversible fibril aggregates in peptide formulations, biophysical assays that that guide AME study design, and high resolution biophysical study to enable insights in formulation stabilization mechanism. Overall considerations on the development of multi-dose peptide formulations as well as strategies in overcoming the challenges will also be highlighted.

10:20 Coffee Break

BIOSIMILARITY AND COMPARABILITY

10:45 Biosimilars – The Analytical Challenge

Gerard Powell, Ph.D., Senior Principal Specialist, Product Characterisation, Analytical Sciences, Allergan Biologics Ltd.

An overview of biosimilars and biosimilar development with an emphasis on the unique analytical challenges they present. I will discuss strategies for establishment of analytical similarity and illustrate these with case study data generated on real biosimilar projects.

11:15 Top-Down LC-MS Analysis of Filgrastim and Related Impurities

Dennis Gessmann, Ph.D., Associate Research Scientist, Analytical R&D, Biosimilars Pharmaceutical Sciences, Pfizer, Inc.

Detailed characterization is required to establish biosimilar products are safe and effective. Top-down mass spectrometry was used to identify filgrastim and related impurities that are quantitated by a RP-HPLC assay. Forced degraded samples were used for the analysis. Results are consistent with known filgrastim degradation pathways.

11:45 Analytical Comparability and Characterization of a Non-Covalent Heterodimer Biotherapeutic

Justin Prien, Ph.D., Associate Director, Analytical Development, Shire

This presentation discusses the analytical comparability for a non-covalent heterodimer biotherapeutic performed to facilitate product developmental continuity. The analytical comparability strategy was designed to assess the similarity of the potential critical quality attributes and mitigate false negative results. At the development stage comparability can be challenging due to analytical method immaturity, the extent of process and product knowledge, and a limited number of manufacturing batches from the different processes.

12:15 pm Development of a High-Throughput Formulation Screening Platform for Therapeutic Monoclonal Antibodies

Yunsong (Frank) Li, Principal Scientist, Analytical and Formulation Development, Cook Pharmica

12:45 Session Break 

  1:00 Luncheon Presentation: Making Cancer Go BOOM: Development of Smart Bombs as Potential Cancer Therapeutics using Surface Plasmon Resonance

Paul Belcher, Ph.D., Functional Leader, Biacore™, GE Healthcare

Cytotoxic drugs are broadly used to treat hematological diseases and solid tumors, but often cause adverse events. Efforts at improving the quality of treatment of cancer patients has focused on maintaining the effectiveness of the chemotherapeutic drugs whilst minimizing the cytotoxicity. Antibody drug conjugates (ADC’s) combine the targeting capabilities of the antibody with the cancer killing capabilities of the cytotoxic drug. This presentation will highlight the development of ADC’s for Gynecological Cancer using Biacore™ SPR.

ANALYTICAL DEVELOPMENT: CASE STUDIES AND TOOLS

2:00 Chairperson’s Remarks

Marina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur

 2:05 Characterization of Aluminum Adjuvant and Adsorbed Proteins

Marina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur

This presentation summarizes the characterization of the physicochemical and compositional properties of vaccine components:  aluminum-based adjuvant and adsorbed protein antigens. Particle size distribution was measured by Laser Diffraction, whereas Raman and Fourier Transform Infrared spectroscopies were used to analyze the compositional properties of aluminum-based adjuvant and adsorbed protein antigens.

Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company

Biophysical and analytical measurements are often performed for formulation development and during comparability assessment of protein therapeutics. The roles and relationship of these data and how they relate to method sensitivity, analysis, and interpretation is an im-portant avenue of discussion. This presentation will discuss the utility of these multidimen-sional approaches and the connectivity of these data in terms of thermodynam-ic/conformational stability and kinetic stability of protein.

3:05 Get the Full Picture and Predict Biotherapeutics Stability with nanoDSF

Charles Heffern, Application Specialist, NanoTemper Technologies

To support scientists on their cumbersome way to the perfect biotherapeutics product in terms of developability and long-term stability, we designed the Prometheus instruments for rapid and precise high-throughput stability screenings using nanoDSF. Get introduced to case studies with major biopharmaceutical companies and learn how they revolutionized development of biotherapeutics.

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Comprehensive Characterization of Product Variants and Higher-Order Structure of Monoclonal Antibodies with Case Studies

Renata Varga, Ph.D., Characterization Scientist, Analytical Sciences, Global

Biological CMC, Teva Pharmaceuticals

Characterization of monoclonal antibodies under development is a key step to better understand the properties and behavior of that new mAb, especially for product variants. After a critical quality attribute assessment, the anticipated variants can be thoroughly characterized based on a well-designed plan. Characterization data on mAb size variants, aglycosylated species, and isoforms (charge, disulfide) by several analytical methodologies will be presented.

4:30 Therapeutic Protein Characterization for Process Development – a Case Study

Quanzhou Luo, Ph.D., Senior Scientist, Process Development, Amgen

Although therapeutic proteins are relatively stable, they can undergo a variety of degradations during manufacturing, formulation and storage. It is, therefore, very important to characterize the biophysical and biochemical properties of the degradations to better assess their safety and efficacy. With the implementation of the quality by design (QbD) concept to drug devel-opment, monitoring product quality attributes (PQAs) during process development has be-come increasingly critical.

5:00 PANEL DISCUSSION: Challenges in Implementing New Assays, Automation and Miniaturized Assay 

Moderator: 

Marina Kirkitadze, Ph.D., MBA, Deputy Director, Analytical R&D Biochemistry, Sanofi Pasteur 

Panelists: 

Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company 

Stefan Duhr, Ph.D., CEO, NanoTemper Technologies 

Renata Varga, Ph.D., Characterization Scientist, Analytical Sciences, Global 

Quanzhou Luo, Ph.D., Senior Scientist, Process Development, Amgen

6:20-7:30 Welcome Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

TUESDAY, JANUARY 10

8:00 am Conference Registration and Morning Coffee

APPLICATION OF MASS SPECTROSCOPY AND OTHER ANALYTICAL TECHNIQUES

8:30 Chairperson’s Remarks

Audrey Hanard, MSc., Spin-off Developer, Structure and Function of Biological Membranes, Université libre de Bruxelles

8:35 Assessing the Higher-Order Structure of Therapeutic Monoclonal Antibodies by NMR Spectroscopy

Yves Aubin, Ph.D., Research Scientist, Regulatory Research Division, Health Canada

Monoclonal antibodies (mAbs) are the fastest growing class of therapeutic protein. In addition, a number of mAb products have lost or will lose patent protection. Here we will present our latest efforts in applying NMR spectroscopy to obtain high-resolution structural information to facilitate the assessment of this critical quality attribute. The approach is applicable in the context of a comparability exercise, whether it is for innovator or biosimilar products alike.

9:05 Use of Steady-State and Time-Resolved Fluorescence Spectroscopy for Higher-Order Structure Characterization

Michael Ignatov, Ph.D., Senior Scientist, Biologics Development Analytical Sciences, Allergan, Plc

Intrinsic tryptophan fluorescence serves as a highly sensitive indicator of the higher-order structure of proteins. Tryptophan fluorescence properties are extremely sensitive to the local environment around tryptophan and solvent accessibility. Differences in the fluorescence properties of proteins are measured to monitor the changes in the higher-order structure. Effect of chemical modifications, chemical unfolding, thermal unfolding, etc. on the spectral properties and fluorescence lifetimes is assessed using several model proteins.

9:35 Antibody Protein De Novo Sequencing with LC-MS/MS

Mingjie Xie, Co-founder, CEO, Rapid Novor Inc

Many applications in antibody engineering require the direct sequencing of antibody proteins. At Rapid Novor (rapidnovor.com) we have developed a robust workflow and routinely sequenced antibody proteins. Here we share the success experiences, examine common mistakes novices make, and present our practices to ensure the correctness of every amino acid.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 FTIR Spectroscopy as a Multi-Parameter Analytical Tool for Comparability Testing and Stability Studies of Therapeutic Proteins 

Audrey Hanard, MSc., Spin-off Developer, Structure and Function of Biological Membranes, Université libre de Bruxelles

Harnessing the strengths of infrared spectroscopy and recent improvements in chemometrics, new analytical methods have been developed to study the stability and perform comparability studies of therapeutic proteins. The presentation will demonstrate the feasibility, through one quick and direct measurement, to simultaneously obtain information concerning four key characteristics of therapeutic proteins: (i) structural integrity, (ii) quantification of post-translational modifications, (iii) overall protein concentration and (iv) quantification of key excipients.

  

11:30 Software Platform for Therapeutic Protein Characterization with LC-MS

Lin He, Ph.D., Senior Application Scientist, Bioinformatics Solutions, Inc.

Advancements in mass spectrometry have given us the capability to well-characterize therapeutic proteins. The challenge, however, is the ability to process combined-datasets which are derived by various methods, and efficiently report this information. In this study, we will look the software platform, PEAKS AB, which presents the following functions for protein characterization: (1) Protein de novo sequencing with LC-MS/MS of multiple-enzyme digestion; (2) PTM quantification with label-free approach; (3) Protein sequence confirmation with peptide mapping and intact protein analysis.

12:00 pm Title to be Announced 
Satish Singh, Ph.D., Head, Drug Product Process Development, Lonza AG

12:30 Enjoy Lunch on Your Own

1:15 Close of Conference