2014 Archived Content

Immunogenicity for Regulatory Success

Assessment of immunogenicity for many types of biotherapeutics continues to challenge the industry. Investigators need to know how to develop and validate assays, when to perform them, and how to interpret the results as a meaningful risk assessment before moving into the clinic. The FDA requirement for neutralizing antibody assays is a particular hurdle. In the clinic, investigators need to work out how to deal with interfering drugs and to understand the significance of pre-existing antibodies. This conference will enable the investigator to work out an immunogenicity testing strategy for regulatory success and to ensure that their drug is both safe and efficacious.

Day 1 | Day 2Download Safety Stream Brochure | Download Overall Event Brochure | Speaker Bios 

Recommended Pre-Conference Short Course* 

Overcoming the Challenges of Immunogenicity Assessment - View Detailed Agenda 

*Separate registration required.  


7:00 am Registration and Morning Coffee

Assays, Interpretation and Standards 

8:00 Chairperson's Opening Remarks

MeenaSubramanyamMeena Subramanyam, Ph.D., Vice President, Translational Medicine, Biogen Idec, Inc.


8:10 Latest Trends in Neutralizing Antibody Detection and the Clinical Relevance of Immunogenicity Assessment

Shalini GuptaShalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

This talk will provide a summary of an AAPS white paper currently being compiled that focuses on NAb assay strategy selection for biologicals with varied mechanisms of action. In addition, the clinical relevance of immunogenicity assessment will be presented via case studies.


8:40 International Bioassay Standardization for the Quantification of Neutralizing Antibodies

Michael ToveyMichael G. Tovey, Ph.D., INSERM Director, Research, Laboratory of Biotechnology and Applied Pharmacology, ENS-Cachan

Validated standardized assays are key to obtaining reliable data and regulatory approval, in particular for cell-based assays recommend by regulatory authorities for the detection of neutralizing anti-drug antibodies. The EMA initiative to establish a common assay and the E.U. initiative ABIRISK to develop common validated cell-based assays for the quantification of immunogenicity will be presented.

9:10 Interference from Fc-Fc Interactions in Bridging Immunogenicity Assays for IgG4 Monoclonal Antibody Therapeutics

MichaelPartridge Michael Partridge, Ph.D., Staff Scientist, Bioanalytical Sciences,Regeneron Pharmaceuticals, Inc.

Human IgG4 antibodies are known to interact with other IgG4s via their Fc. In bridging immunogenicity assays, IgG4 Fc-Fc contacts generate increasing signal over time for the negative control, reducing assay sensitivity and complicating confirmation cut point determination. Increasing background signal over time is especially problematic for automated analysis, as reagents are prepared in advance and used over several hours during a run.  This presentation will discuss these interactions and the impact they have on immunogenicity assays for IgG4 drugs.;

9:40 Evaluation of Immunogenicity for Enzyme Replacement Biotherapeutics

Yongchang QiuYongchang Qiu, Ph.D., Group Director and Head, Bioanalytical and Biomarker Development, Shire

Replacement enzymes are a special class of protein therapeutics that often need to be taken up by the target cells for efficacy. In addition, they have endogenous counterparts and are highly glycosylated. Several marketed enzyme replacement therapies serve as treatment for critically ill patients, many of whom are children. This talk will outline the unique challenges in the assessment of immunogenicity of replacement enzymes including cross-reactive immunologic materials (CRIM) testing.

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

 Immune Complexes and Hypersensitivity 

11:10 Case Study on Identification and Potential Impact of Immune Complexes

BinodhDesilvaBinodh Desilva, Ph.D., Executive Director, Bioanalytical Sciences & Biologics, Bristol-Myers Squibb

This presentation will describe immune complexes that have been observed regarding their frequency and where they form, and attempt to provide an explanation for their occurrence. It will discuss methodologies for identifying and characterizing them, their relationship with tox results and their long term impact with complement deposition in the issues.

11:40 Assessment of Biotherapeutic Drug Allergenicity

RobertHamiltonRobert G. Hamilton, Ph.D., D.ABMLI, F.AAAAI, Professor of Medicine and Pathology, Johns Hopkins University School of Medicine

This lecture will overview the basic pathophysiology at the basis of the immediate type hypersensitivity response and methods for assessing the presence and relative level of drug specific IgE antibody. Recent consensus guidelines will be overviewed that suggest an approach for validation of the IgE antibody assay in the absence of a positive drug-specific human IgE antibody serum.

12:10 pm Tools and Technologies for Comprehensive Immunogenicity Risk Management

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

Immunogenicity is one of the most complex and difficult issues to address in drug design and development. I will provide an overview of the best tools for immunogenicity risk management, including Mass Spectrometry antigen presentation assays, Dendritic cell - T cell assays to measure responses to fully formulated biologics, HLA-peptide Binding Assays, and naïve T cell Proliferation Assays to characterize individual epitopes. I will also discuss how the potential risk of first infusion reactions can be mitigated using whole-blood cytokine release assays.

12:40 Luncheon Presentations (Sponsorship Opportunities Available) on Lunch on Your Own 

1:40 Session Break


2:00 Chairperson's Remarks

Shalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

2:05 The Evaluation of Immunogenicity in Remsima Clinical Studies: From Development to Global Regulatory Approval

Alex KudrinAlex Kudrin, M.D., MBA, MRCP, MFPM, Vice President & Head,Global Development, Celltrion, Inc.

The presentation will cover the data generated to support recent EU approval of the biosimilar infliximab and challenges that needed to be addressed throughout the development of the product. In addition, some switch-related immunogenicity and safety data will be presented.


2:35 Pre-Existing Antibodies

Mary BirchlerMary Birchler, Investigator, Clinical Immunology, GlaxoSmithKline, Inc.

Pre-existing antibodies in treatment-naïve subjects have been often detected during clinical ADA assessments. However, limited information on prevalence, physiological effect, and impact on post treatment ADA induction is available. This talk will address pre-existing antibody characterization and implications for immunogenicity management and strategies during clinical studies.

3:05 Case Study on Pre-Existing Reactivity and Risk Mitigation

Jim McNallyJim McNally, Ph.D., Senior Principal Scientist, Biotherapeutics Research, Pfizer, Inc.

Pre-existing reactivity to biotherapeutics can result in extensive bioanalytical investigations and delays for clinical sample testing.  An increase in the frequency of observations of pre-existing reactivity led us to implement a plan to identify this reactivity as early as possible in the drug development process.  Our goal is tomitigate risk indrug candidate selection and to inform the development of clinical bioanalytical assays for a proactive testing strategy.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing


4:20 Problem Solving Breakout Discussions

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Table: Challenges in Developing Neutralizing Antibody Assays

Shalini GuptaModerator: Shalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

  • Factors for selection of cell-based Nab vs. non-cell-based Nab assays
  • Bioanalytical challenges
  • Challenges for Nab validation
  • New technologies
  • Interpretation of the results and implications for risk assessment

Table: Practical Application of Immunogenicity Risk Assessment

Moderator: Eric Wakshull, Ph.D., Senior Scientist and Group Leader, Bioanalytical Sciences, Genentech, Inc.

  • Relevant risk factors
  • Potential of emerging antibody products for greater immunogenicity
  • How attempts to increase half-life may render the product more immunogenic
  • Risk assessment at different stages of development
  • How to translate the identified risk into a testing strategy
  • Experiences with reporting findings to the regulatory authorities

Table: Regulatory Expectations Regarding Immunogenicity Assessment

Meena SubramanyamModerator: Meena Subramanyam, Ph.D., Vice President, Translational Medicine, Biogen Idec, Inc.

  • How and when to approach the regulators: Benefits of discussion with the regulators
  • How much assessment is necessary? How much is too much? What is the essential strategy?
  • Proper validation and characterization of assays
  • Neutralizing antibody assays: When should they be carried out and why?
  • Ligand binding assays. Can they be used instead of cell-based assays?
  • Pitfalls to avoid

Table: Dealing with Pre-Existing Positive ADA Activity in Study Patients

Mary Birchler

Moderator: Mary Birchler, Investigator, Clinical Immunology, GlaxoSmithKline, Inc.

  • Potential complications with pre-existing antibodies
  • How to distinguish between pre-existing antibodies and potential immune responses to the drug and to determine a meaningful drug-induced response
  • Examples seen in the clinic and their relevance
  • Implications for humanized antibodies and novel humanized antibody products
  • Implications regarding PK/PD safety and efficacy

Table: Perspectives on Immunogenicity Studies for a Biosimilar

Alex KudrinModerator: Alex Kudrin, MD, MBA, MRCP, MFPM, Vice President & Head, Global Development, Celltrion, Inc.

  • Clinical relevance of immunogenicity: do we always need to be concerned?
  • Regulatory requirements for immunogenicity: FDA and EMA perspectives and differences in view points
  • Immunogenicity assessment for different classes of biologics and biosimilars
  • The future of immunogenicity applications in clinical management of patients

5:20 Networking Reception in the Exhibit Hall with Poster Viewing

6:30 End of Day


Day 1 | Day 2 | Download Safety Stream Brochure | Download Overall Event Brochure| Speaker Bios 

Immunogenicity Prediction and Mitigation 

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