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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. 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 its impact on design and further development. Assessment of the critical quality attributes, developability and aggregation propensity, sequence variants, post-translational modifications and higher-order structure hence become a critical component of analytical development.

CHI’s 3rd Annual Analytical Characterization of Biotherapeutics conference arms scientists with the tools that can speed up innovation, and invites scientists with creative strategies and novel techniques to share their ideas, experiences and solutions to support the development of exciting new biotherapeutics.

Final Agenda

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Recommended Short Course*

SC8: Protein Aggregation: Mechanism, Characterisation and Consequences

*Separate registration required


WEDNESDAY 2 NOVEMBER

07:45 Registration and Morning Coffee


BIOSIMILARITY AND COMPARABILITY ASSESSMENT

08:30 Chairperson’s Remarks

Richard Beardsley, Ph.D., Technical Development Senior Scientist, Protein 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 Application of Advanced Methods to Create Analytical Fingerprint of Humira

Czeslaw Radziejewski, Ph.D., Senior Principal Research Scientist, Associate Director Protein Analytics, Process Sciences, AbbVie Bioresearch Center

A comprehensive characterization of Humira® (adalimumab) was performed by using an array of orthogonal analytical methods that measured heterogeneity, structure, stability, and functional aspects of the molecule. The study included multiple batches spanning the product’s history, and by utilizing advanced chromatographic, mass spectrometric and spectroscopic methods, succeeded in establishing a unique analytical fingerprint of the biotherapeutic.

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 Combining Analytical Technologies for the Analysis of Protein Structure and Stability

Stacy Kenyon, Ph.D., Scientist, BioScience Development Initiative, Malvern Instruments Ltd.

The combination of dynamic light scattering (DLS) and Raman spectroscopy increases understanding of protein aggregation and unfolding pathways, and can be applied to high concentration proteins in formulation. Presented here is a case study on the use of combined DLS and Raman spectroscopy to assess the effects of formulation changes on the thermal stability of an innovator product in its original formulation and a biosimilar product in an adjusted formulation, providing information about aggregation pathways.

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

Richard Beardsley, Ph.D., Technical Development Senior Scientist, Protein 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., Research Fellow, Oncology Research Unit, Pfizer-Rinat

This talk will describe methods used to explore the epitope diversity observed across panels of monoclonal antibodies generated by different I 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.

17:15 Problem-Solving Breakout Discussions

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

19:15 End of Day

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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 Stable Formulation Development of Peptides – Interpretation of Ordered Peptide Aggregation

Adrian Podmore, Ph.D., Formulation Scientist, MedImmune

The current understanding of ordered peptide aggregation will be discussed in formulation development, and approaches used to mitigate physical instability. Application of techniques such as field flow fractionation with light scattering, batch method dynamic light scattering, and nanoparticle tracking analysis to investigate ordered aggregation in the context of defining a ‘stable’ formulation. A new strategy of stable peptide formulation development will be suggested.

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 Sponsored Presentation (Opportunity Available)

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 (Invited)

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

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

13:30 End of Analytical Characterisation of Biotherapeutics



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