Cambridge Healthtech Institute’s 3rd Annual
Analytical Characterisation of Biotherapeutics

Harnessing Technologies and Proven Strategies to Improve Analytics

2 - 3 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL

Analytics play an important role throughout a product’s lifecycle, from candidate lead selection, to preparation for IND and characterizing for lot release. This is even more important with today’s diverse and complex molecules, and increasing biosimilar products. The ability to characterize these structures, from sequence to higher structure order, is critical to the understanding of the molecules, its function and behavior, as well as comparability and biosimilarity analysis.

CHI’s 3rd Annual Analytical Characterization of Biotherapeutics conference explores approaches to comparability and biosimilarity assessments; highlights tools and techniques for characterization of ADCs, fusion proteins and bispecific antibodies; discusses strategies for detection of product- and process-related impurities and presents a regulatory perspective on potency assays. 

Final Agenda

Day 1 | Day 2 | Speaker Biographies | Download Brochure

WEDNESDAY 2 NOVEMBER

07:45 Registration and Morning Coffee

BIOSIMILARITY AND COMPARABILITY ASSESSMENT

08:30 Chairperson’s Remarks

Chris Cornell, Ph.D., Research Associate, Analytical Chemistry, Genentech, Inc.

08:35 KEYNOTE PRESENTATION:
High Throughput Assays for the Quantification of the Potency and Comparability of Biosimilars and Innovator Products

Michael Tovey, Ph.D., INSERM Director, Research, Laboratory of Biotechnology & Applied Pharmacology, Ecole Normale Supérieure de Cachan

Successful development of biosimilars is dependent upon direct comparisons of the relative potency and comparability of innovator molecules and biosimilars. A validated standardized high throughput 384 assay platform will be described that is applicable to most biopharmaceuticals and that allows direct comparison of drug potency and comparability of innovator molecules and biosimilars in the same assay. Case studies will be presented for products ranging from Neupogen to Remicade and Enbrel.

09:20 Characterization of Filgrastim Using Intact and Top-Down MS

Urs Lewandrowski, Ph.D., Lab Head, Analytical Characterization, Sandoz

The detailed analytical comparison of Zarxio and the reference product Neupogen provided the foundation for FDA’s approval of Sandoz’s Zarxio as the first biosimilar in the United States. Intact and top-down MS are becoming highly attractive techniques for detailed protein characterization. Using a benchtop Exactive MS, modifications in filgrastim were detected with high sensitivity on the intact level followed by site assignment using all-ion fragmentation mode. Examples of successful top-down MS experiments will be demonstrated.

09:50 Importance of Analytical Characterization for Biosimilar Development - Disulfide Bridging of GP2015/Ezelzi

Fabian Higel, Ph.D., Lab Head PK Profiling, Technical Development Biosimilars, Novartis

Analytical characterization is the foundation of successful biosimilar development. Comprehensive characterization and a deep understanding of the biosimilar candidate and reference product and their variants and modifications can play an important role in different phases of biosimilar development. The unravelling and understanding of disulfide bridging of the biosimilar Erelzi played an important role for the FDA approval and is presented in this talk.

10:20 An Integrated Approach to Managing Immunogenicity Risk and Drug Immune Modulation

Jeremy Fry, D.Phil., Director, Sales, ProImmune

Immunogenicity is one of the most complex issues to address in drug design and development. I will provide an overview of the best tools to mitigate immunogenicity risk, including Mass Spectrometry antigen presentation assays; DC-T and T cell proliferation assays for biologic lead selection/optimization; HLA-peptide binding assays to characterize individual epitopes as well as undiluted whole blood cytokine storm assays.

10:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:30 Overcoming Formulation and Analytical Challenges for Developing Biosimilar Products

Jun Liu, Ph.D., Senior Director, Analytical and Pharmaceutical Science, Coherus Bioscience

Due to the complex nature of biopharmaceuticals, analysis and control of the similarity of biosimilar products to innovators products remains key challenges. Furthermore, critical IP on formulation and process provided additional challenges to introduce biosimilar products into major US and EU markets. In this presentation, we will discuss these challenges on pharmaceutical and analytical development. A case study example will be provided to discuss the strategy to overcome these challenges.

12:00 FTIR Spectroscopy as a Multi-Parameter Analytical Tool for Stability Studies and Batch Consistency Testing of Therapeutic Proteins

Allison Derenne, Ph.D., Researcher, Science-Chemistry, Université libre de Bruxelles

Harnessing the strengths of infrared spectroscopy and recent improvements in chemometric methods, new analytical methods have been developed to study the stability and verify batch-to-batch consistency 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.

12:30 Assessing an Interaction Parameter for Bioformulation Stability in One Measurement, using TDA Concentration Gradients

Markos Trikeriotis, Ph.D., Applications Development Scientist, Malvern Instruments Ltd.

The self-association characteristics of molecules in dilute solutions can provide an assessment of stability at an early stage. The diffusion interaction parameter (kD) is a measure of the propensity for self-association, but the determination of this parameter using existing methodologies requires several measurements over a concentration series. Here, we show how Taylor Dispersion Analysis can be used to generate a concentration gradient from which the kD can be extracted in a single, low volume measurement.

13:00 Luncheon Presentation: In silico Approaches for Early Assessment of Immunogenicity

Speaker to be Announced

Unexpected adverse events are reasons of drug development failures that contribute to the attrition rate in the pharmaceutical industry. A possible cause specifically associated to Biotherapeutics (peptides/proteins) is immunogenicity: the ability of some biotherapeutics to trigger immune responses that conduct to the generation of antibodies specifically directed against the drug. This immune response can possibly reduce the treatment efficacy and provoke adverse effects. Predicting immunogenicity is proving difficult because of the complexity of the underlying biological processes. We present here an informatics application based on modeling and simulation approaches that can help pharmaceutical R&D to prioritize promising drugs with respect to the immunogenicity risk.

13:30 Session Break

TOOLS AND TECHNIQUES FOR PRODUCT CHARACTERISATION

14:00 Chairperson’s Remarks

Peter M. Ihnat, Ph.D., Principal Research Scientist, Drug Product Development Pre-Formulation, AbbVie Bioresearch Center

14:05 Analytical Characterization of Conjugation-Related Events in the Manufacture of ADCs

Chris Cornell, Ph.D., Research Associate, Analytical Chemistry, Genentech, Inc.

The manufacture of cysteine-linked antibody-drug conjugates (ADCs) involves the partial reduction of inter-chain disulfide bonds, and subsequent conjugation of the reduced cysteine residues to a maleimide-containing drug-linker. This presentation will focus on the LC-MS characterization of the products of the conjugation reaction, with an emphasis on how various conjugation process parameters may impact reaction specificity.

14:35 Product Characterization and Control Strategy

Ping Feng, MSc., Director, Analytical Sciences and Operation, Teva Pharmaceuticals

Product characterization should be planned based on knowledge of protein sequence and manufacturing process impact. The level of characterization should be phase-appropriate for an adequate balance between risk and benefit. A well-designed characterization study can be very valuable to support commercial specification with reduced release testing or more robust range of a criterion allowed. Two case studies will be presented: antibody glycan analysis and product variant characterization of a HAS fusion protein.

15:05 Advances in Epitope Characterization Using Label-Free Biosensors

Yasmina Abdiche, Ph.D., CSO, Wasatch Microfluidics

This talk will describe methods used to explore the epitope diversity observed across panels of monoclonal antibodies generated by different in vitro and in vivo platforms, including chicken immunizations. High throughput epitope binning experiments on label-free biosensors were used to merge large panels of antibodies and compare their epitope outputs. Data will be presented for both, wild-type and transgenic chickens, highlighting the therapeutic potential of chicken-derived antibodies.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

16:15 Investigating the Interaction between FcRn and IgG Variants by Hydrogen/Deuterium Exchange Mass Spectrometry

Maximiliane Hilger, Ph.D., Senior Scientist, Mass Spectrometry, Large Molecule Research, Pharma Research and Early Development, Roche Innovation Center Munich

The recycling of IgGs by FcRn regulates antibody plasma levels and half-life. Here we study the IgG1–FcRn interaction by HDX-MS to gain deeper molecular understanding that will ultimately allow us to optimize antibody pharmacokinetics, efficacy and safety. Interestingly, our data demonstrate a conformational interplay between the Fab and Fc regions of the antibodies upon FcRn binding and suggest the presence of direct FcRn interaction sites in the Fab region.

16:45 Using Viscosity-Derived Parameters and Thermal Analysis to Evaluate the Solution Properties of Bispecific Dual Variable Domain Immunoglobulins

Peter M. Ihnat, Ph.D., Principal Research Scientist, Drug Product Development Pre-Formulation, AbbVie Bioresearch Center

The Fab regions of dual variable domain immunoglobulins (DVD-Ig) consist of outer and inner complementarity determining regions (CDR) that confer bivalent antigen specificity. The protein – protein interactions (PPI) and protein – solvent interactions (PSI) of DVD-Ig solutions were studied by light scattering and rheological techniques to identify the factors that contribute to achieving stable high concentrations.

18:15 Networking Reception in the Exhibit Hall with Poster Viewing

19:15 End of Day

Day 1 | Day 2 | Speaker Biographies | Download Brochure

THURSDAY 3 NOVEMBER

08:00 Registration and Morning Coffee

CHARACTERISING PRODUCT- AND PROCESS-RELATED IMPURITIES

08:30 Chairperson’s Remarks

Jihong Yang, Ph.D., Senior Scientist, Bioanalytical Sciences, Genentech

08:35 Enhanced Detection of Product-Related Variants and Impurities in Recombinant Glycoproteins

Francois Griaud, Ph.D., Functional Lead Analytics, Biologics Process Development/Late Phase Analytical Development, Novartis Pharma AG

Monitoring and controlling post-translational modifications (PTMs) in recombinant glycoproteins is a requirement to ensure manufacturing process consistency and product quality. Aside from the example of glycosylation, the analyst may face the challenging task of detecting less predictable post-translational modifications, product-related variants and impurities. This presentation will focus on different mass spectrometry and data analysis approaches to enable the semi-automated detection of such species during technical development.

09:05 Identification and Monitoring of HCPs by Mass Spectrometry in Bioprocess Development

Yan-Hui Liu, Ph.D., Senior Principal Scientist, Merck Research Lab

09:35 Pyrogen Detection by Monocyte Activation Test in Antibody Formulations

Anya Fritsch, Ph.D., CSO, Confarma France SAS

Detection of pyrogens - fever inducing substances - relies predominantly on the rabbit pyrogen test. In preparations where endotoxin is the only potential contaminant, the rabbit test can be replaced by a specific endotoxin test. The Monocyte Activation Test provides a sensitive, reliable alternative for those cases, where potential contaminants other than endotoxin might be present. It monitors the release of cytokines induced by pyrogens present in the sample using human cells as test system.

10:05 Simultaneous Detection of Protein Aggregation and Affinity Measurements in a Single SPR Experiment

Eric Reese, Ph.D., Vice President, Sales and Marketing, SensiQ Technologies, Inc.

SensiQ presents data from a Genentech collaboration highlighting the simultaneous detection of protein aggregation and affinity determination in a single experiment as enabled by Pioneer FE SPR instrumentation with diSPR® injection technology. This is the first presentation of an SPR biosensor capable of both key measurements in a single experiment.

10:20 Semi-Automated, Mass Spectrometric Determination and Evaluation of Glycosylation CQAs at the Bioreactor Level

Catherine Evans, Ph.D., Business Development Manager – Biopharma, Bruker Daltonics

Mass spectrometry is a powerful tool for monitoring CQAs related to bioproduction, providing insights into the design-space and its impact on the product specification. We present here a standalone analytical platform developed for the direct connection of bioreactors to an MS system for real time at-line monitoring of mAb CQAs.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

CHARACTERISATION OF POTENCY ASSAYS AND ASSAY REAGENTS

11:15 Potency Assays for Biopharmaceuticals: A Regulatory Perspective

Baolin Zhang, Ph.D., Senior Investigator & Product Quality Reviewer, Office of Biotechnology Products, CDER, FDA

Because of the complex nature of biopharmaceuticals, it can be scientifically challenging to develop appropriate potency assays for each product. A regulatory evaluation of adequacy of potency assays is made on a case-by-case basis, taking into account multiple factors including, but not limited to, product type, MoA, associated risk, and phases of development. This presentation provides an overview of regulatory expectations regarding potency assays and discusses several case studies that highlight some of the relevant issues commonly seen in the regulatory submissions.

11:45 Robust Characterization Methods to Ensure Quality Bioanalytical Assay Reagents

Jihong Yang, Ph.D., Senior Scientist, Bioanalytical Sciences, Genentech

Bioanalytical assays are critical for the assessment of the exposure-response relationship, safety, and efficacy of biotherapeutics. Robust biophysical and bioanalytical methods can be used to generate important characterization data for critical assay reagents. The talk will highlight some of the emerging analytical and bioanalytical technologies that can be used to characterize assay reagents and describe case studies to demonstrate the application of these methods to support biotherapeutic development.

12:15 Luncheon Presentation: How Similar is My Biosimilar? A LC and MS Prospective

John C. Gebler, Ph.D., Director, Biopharma Business Development, Waters Corporation

Additional incentive has come from reducing the cost and increasing global access to life-saving therapies for patents.Biologic drugs are inherently homogeneous and innovator products are often a composite of similar species manufactured within a specific range of variability.Drug manufactures and regulators want to reduce risks to patients and ensure that biologics and safe and efficacies.The presentation will report on the use of LC/MS for in-depth, reproducible, and meaningful characterization/comparability between an innovator and biosimilar.

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 End of Analytical Characterisation of Biotherapeutics

Day 1 | Day 2 | Speaker Biographies | Download Brochure

Conference Programs

• Display of Biologics
• Engineering Antibodies
• Machine Learning - Part 2

• Antibody-Based Therapies
• Emerging Targets & Approaches
• Membrane Protein Targets

• Safety & Efficacy
• Advancing Bispecifics
• Engineering Bispecifics

• Modulating the TME
• Innovative CAR T Therapy
• Next-Gen Immunotherapies

• Optimisation & Developability
• Analytical Characterisation
• Protein Stability & Formulation

• Data Science & Engineering
• Optimising Expression
• Process Development

• Intro to Machine Learning
• Machine Learning - Part 1
• Machine Learning - Part 2

• Antibody-based Therapies
• Engineering Conjugates
• Next-Gen Immunotherapies