Comparability & Biosimilarity3rd Annual

Comparability & Biosimilarity

Ensuring Regulatory Compliance and Commercialization Succes

March 23-24, 2017 | Hyatt Regency | Bethesda, MD

Due to a protein molecule’s structural complexity, it is often challenging to preserve the molecule’s bioactivity, potency and stability throughout its lifecycle from development to scale up to storage and delivery. Regulators demand scientifically tested data to ascertain that the product is consistent and comparable between batches, between process and site changes, and between new and old analytical methods. This is compounded if you work with biosimilars, which requires proof of highly similar or finger-print similarity in terms of safety, efficacy and potency between your molecule and the originator’s in order to demonstrate biosimilarity.

The 3rd Annual Comparability and Biosimilarity conference delves into the regulatory requirements and guidelines, the analytical strategies, risk-based approaches, as well as higher order structure analysis to support comparability and demonstrate biosimilarity. 

Final Agenda

Thursday, March 23, 2017

7:30 am Registration & Morning Coffee

8:30 Chairperson’s Opening Remarks

Hans-Martin Mueller, Ph.D., Director, Bioprocess Development, Biologics & Vaccines, MSD Merck


8:40 Featured Presentation: An FDA Perspective on Demonstrating Analytical Similarity

Marjorie ShapiroMarjorie Shapiro, Ph.D., Chief, Laboratory of Molecular and Developmental Immunology, CDER, FDA

This presentation will focus on the FDA’s expectations regarding analytical similarity data that should be submitted during clinical development and with a BLA submission, as well as analytical bridging studies to leverage non-clinical and clinical data using a non-US approved comparator product.

9:20 Update on FDA Expectations for Characterization, Manufacture and Control of Protein Drugs and Biosimilars

Emily Shacter, Ph.D., Independent Consultant, ThinkFDA

9:50 Analytical Strategies to Satisfy Regulatory Requirements for Biotech and Biosimilar Products

Nadine M. Ritter, Ph.D., President and Analytical Advisor, Global Biotech Experts, LLC.

When developing a biotech or biosimilar product, it can appear that regulatory authorities require innumerable analytical studies that generate overwhelming amounts of data. This presentation will provide an overview of which regulations are applicable to the analytics of biotech/biosimilar products, what studies are defined, when they should be conducted, and how to know which analytical methods are appropriate. It will also highlight the most common deficiencies seen in analytical sciences for biopharma product development activities.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing


10:50 Limits of Detection for Altered Structure in Comparability Studies with Hydrogen Exchange Mass Spectrometry

David_WeisDavid Weis, Ph.D., Associate Professor, Chemistry and Pharmaceutical Chemistry, University of Kansas

Recently, there has been considerable interest in the use of hydrogen exchange mass spectrometry (HX-MS) as an analytical tool to demonstrate comparability of higher order structure in therapeutic proteins. This talk will present recent work aimed at exploring the limits of this approach. The detection of small changes in higher-order structure in model systems will be presented. In addition, this talk will advance a general methodology for establishing the limit of detection and suitable statistics for establishment of similarity.

11:20 Application of a A Risk-Based Comparability Approach and Advanced Analytical Technologies to Support Late Stage Process Changes

Valerie_TsangValerie Liu Tsang, Ph.D., Technical Development Program Lead, Biogen

With a growing repertoire of advanced analytical capabilities available for evaluating biochemical, physicochemical, and biological attributes of proteins, the increased level of product understanding provides more confidence in the use of these techniques for comprehensive comparability assessments following major process changes. This talk will illustrate Biogen’s approach to assessing comparability including risk assessment, extensive product characterization including structure activity relationships and in vivo CQA studies, and the use of statistics for determining comparability criteria following process changes. An example of Biogen’s risk-based approach to comparability for a late stage clinical program will be described, including advice received from health authorities on applicability of this approach.

GE Healthcare logo small 11:50 Similar or Not? Innovative Methods for Active Concentration and Similarity Determination of Proteins and Biological Products.

Robert_KarlssonRobert Karlsson, Ph.D., Staff Scientist, GE Healthcare

Critical Quality Attributes(CQA) are important for the safety and efficacy of biotherapeutic drugs and CQA’s are particularly important in the assessment of comparability and biosimilars. In this presentation, we will highlight the use of BiacoreTM SPR for performing comparability and biosimilar studies using both Kinetic and Calibration Free Concentration Analysis in applications including antibody screening, Fc-receptor binding, characterization of ADCs and the use of protein probes for detection of stress-induced conformational change.


12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

1:20 Chairperson’s Remarks

David Weis, Ph.D., Associate Professor, Chemistry and Pharmaceutical Chemistry, University of Kansas


1:30 Challenges and Regulatory Requirements for Comparability Assessment of Biotech Products

Joana Qing Zhou, Product Quality Team Leader, Division of Biotechnology Review and Research I (DBRR I), OBP, CDER, FDA

With the increasing complexity of biotechnology products, improvements in analytical methods, and accelerated product development, performing appropriate studies and analyses to demonstrate comparability can be challenging. This talk will discuss regulatory requirements for comparability assessments of biotechnology products at different stages of product development and highlight new challenges emerging from modern biotechnology and bioprocessing.

2:00 Biophysical Methods for Higher Order Structure and Comparability Analysis of Antibody-Drug Conjugates

Brianna_CassidyBrianna Cassidy, Ph.D., Scientist I, Analytical & Pharmaceutical Sciences, ImmunoGen

An important aspect of antibody-drug conjugate (ADC) characterization is protein higher order structure (HOS) assessment. Multiple analytical approaches were employed to identify HOS changes between native and stressed versions of an ADC. Datasets from each assay were analyzed statistically to determine the potential of each analytical approach to differentiate between native and stressed ADC samples.

2:30 Roundtable Breakout Session


    Table 1: Empirical Phase Diagrams, Radar Charts, and Other Multidimensional Data Visualization Techniques for Protein Higher Order Structure (HOS) Characterization

    Moderator: Brianna Cassidy, Ph.D., Scientist I, Analytical & Pharmaceutical Sciences, ImmunoGen

    • Implementation and utility of multidimensional data visualization techniques for protein HOS exploration in industrial and regulatory environments.
    • Considerations when designing experiments for inclusion in multidimensional data visualization plots.
    • Considerations when choosing analytical techniques for inclusion in multidimensional data visualization plots.
    • Data processing techniques for multidimensional data visualization plots and their effects on interpretation.
    • Software options for creating multidimensional data visualization plots and their pros and cons.

    Table 2: Biological LC-MS Is Being Used in QC Lab Widely. Ionization Efficiency Can Be Variable. Is There A Standardized Approach To Control Robustness And Reproducibility?

    Moderator: Jane Xiao, Ph.D., Director, Biophysical Characterization, Oncobiologics

    Table 3: Comparability Strategies for Late Stage Process Changes

    Moderator: Valerie Liu Tsang, Ph.D., Technical Development Program Lead, Biogen


    3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

    4:10 Comparative Analysis of Novel Non-Platform Protein Products

    Sophia_LevitskayaSophia Levitskaya, Ph.D., Scientist, Analytical Biotechnology, MedImmune

    Structural characterization and comparability assessment of non-platform proteins are challenging due to limited product and process knowledge, and high molecular complexity. Case study describes comparative analysis of non-platform biotherapeutics based on thorough pCQA evaluation, characterization of a higher order structure, and application of complementary orthogonal techniques.

    4:40 Development of Platform ADCP and ADCC Reporter Bioassays for Assessing Antibody Effector Function

    Arturo Orjalo, Jr., Ph.D., Scientist, ADQC-Biological Technologies, Genentech, a Member of the Roche Group

    Antibody-dependent cell-mediated phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity (ADCC) are important mechanisms of action of therapeutic antibodies. We have developed reporter-based bioassays for ADCP and ADCC, and the bioassay work flows for these assays are fast and simple and amenable for measuring the potency and stability of antibodies in a quality-controlled setting. These bioassays are mechanism of action (MOA)-based and have the potential for being platform assays.

    5:10 End of Day/Short Course Registration

    6:00 – 8:30 Dinner Short Courses*

    *Separate Registration Required.

    Friday, March 24, 2017

    8:00 am Morning Coffee


    8:30 Chairperson’s Opening Remarks

    David Wylie, Ph.D., Principal Scientist, Sterile Process and Analytical Development, Merck Research Labs

    8:40 Preparation of a Strong and Convincing Biosimilar File Supported by Sophisticated Analytical Characterization

    Hans-Martin Mueller, Ph.D., Director, Bioprocess Development, Biologics & Vaccines, MSD Merck

    Demonstrating comparability for a commercial biosimilar product may present the greatest challenge of an analytical scientist’s career. This presentation will talk about the preparation of a robust analytical package for US and EU health authorities; in particular, how to be successful with demonstrating comparability through batch testing, extended characterization, stability studies and forced degradation.

    9:10 Analytical Biosimilarity of GP2015 (Erelzi™) to US-Licensed Enbrel®

    Urs_LewandrowskiUrs Lohrig, Ph.D., Lab Head, Phys-Chem-Characterisation Biosimilars, Biologics Tech Development and Manufacturing, Sandoz GmbH

    In August 2016, the Food and Drug Administration (FDA) approved Sandoz’s Erelzi™ as a biosimilar to the reference product Enbrel® (etanercept) in the United States. This talk summarizes the analytical similarity assessment leading to the successful approval of Erelzi™ and exemplifies results as well as analytical challenges faced during the exercise.

    9:40 Poster Presentation: A Better Fingerprint of Therapeutic Protein Higher Order Structure: The Electrospray Ion Mobility Analysis of Intact NISTmAb

    Michael Bogan, Ph.D., Director, Development, IonDx, Inc.

    Electrospray ion mobility without mass spectrometry has been used as a medical diagnostic for a decade (lipoprotein testing). Here we discuss data from its application to higher order structure characterization of singly-charged intact biotherapeutic protein ions. Use of singly-charged ions simplifies data analysis (no charge-state deconvolution) and generates collision cross-sectional area fingerprints for antibodies, nanoparticle-conjugates, or even exosomes. Continued advancement in standalone electrospray ion mobility instrumentation by IonDx offers a new paradigm for biosimilar comparability studies and innovator drug development.

    10:10 Networking Coffee Break

    10:40 Application of PTMs for Comparability and Biosimilarity Assessment

    Jane_XiaoJane Xiao, Ph.D., Director, Biophysical Characterization, Oncobiologics

    Post-translational modifications (PTMs) analysis plays a key role for biosimilar development. High resolution mass spectrometer-based multi attribute peptide mapping technology is used in initiating reference product quality assessment, providing quality range for clone selection, process development, and assessing analytical similarity. The presentation will review the PTMs that may be important in order to align critical quality attributes into quality ranges and minimize batch to batch variation.

    11:10 Near UV Circular Dichroism as a Tool for Detecting Higher Order Structure Changes in Innovative/Biosimilar Product Development and Process Comparability of Biotherapeutic Products

    Christopher_ShawChristopher Shaw, Scientist I, Manufacturing Sciences and Technology, AstraZeneca

    We have characterized a partially-degraded mAb by biochemical (SEC, CE, peptide mapping, etc.), as well as biophysical (NUV CD and DSC), techniques. The results suggest that these biophysical methods are suitable orthogonal approaches for detecting or confirming protein structural modifications. In this study we describe the sensitivity of a Near UV Circular Dichroism method for detecting such modifications. This method is a useful tool for determining similarity during product development or process comparability of biotherapeutic products.

    11:40 End of Biotherapeutics Analytical Summit