2013 Archived Content

Safety Stream

6th Annual
Immunogenicity for Regulatory Success

Regulatory Guidance, Risk Assessment , Preclinical and Clinical Assays, and Strategy

April 29-30, 2013

Industry research reveals an increasing concern about immunogenicity as more innovator and biosimilar biotherapeutics approach the clinic. Following year-on-year success with Immunogenicity at PEGS, CHI is introducing a double Immunogenicity track. Immunogenicity for Regulatory Success will present high level science and expert advice on preclinical and clinical testing strategies, risk assessment and regulatory guidance to ensure your product gains regulatory approval without delay.

Day 1 | Day 2 | Download Brochure 



7:00 am Conference Registration and Morning Coffee

Experiences with Risk Assessment and Working the Regulatory Authorities 

8:30 Chairperson’s Opening Remarks

George R. Gunn, III, Ph.D., Associate Scientific Director, Biologics Clinical Pharmacology, Janssen Research & Development, LLC.

8:40 Immunogenicity Risk Assessment and the Impact on Biological Drug Development

Holly W. Smith, B.A., Principal Research Scientist, Toxicology, Eli Lilly & Co.

This presentation discusses factors considered in an Immunogenicity Risk Assessment, how the outcome affects decisions through all phases of drug development, and the importance of communication of the risk decision across internal components and external regulators to ensure a cohesive strategy for immunogenicity characterization and mitigation.

9:10 Performing Timely Risk Assessment and Deploying Phase-Appropriate Risk Management Strategies for Immunogenicity

Renuka PellutlaRenuka C. Pillutla, Ph.D., Director, Immunochemistry & Biomarker Development, Bristol-Myers Squibb

Immunogenicity risk assessment must be performed early in the development of a biotherapeutic.  However, as the molecule progresses through development and additional data is collected, the risk should be re-evaluated periodically.  Thus, immunogenicity risk assessment is an iterative process.  There are various factors to consider with regards to the assessment of immunogenicity risk.  Based on careful consideration of the risk factors, a program-specific risk mitigation and / or risk management strategy needs to be defined.  These factors and strategies can be categorized into three areas – clinical, CMC-related and bioanalytical.  Examples of some factors and potential mitigation strategies will be discussed in the context of the phase of development. Phase-appropriate risk management strategies are critical to minimize immunogenicity-related concerns from regulatory agencies.

9:40 Evaluating the Relationship between Immunogenicity Assay Results and PK in Clinical Studies on Human Monoclonal Antibodies

Albert TorriAlbert Torri, Ph.D., Senior Director, Bioanalytical Sciences, Regeneron Pharmaceuticals, Inc.

Anti-Drug Antibody (ADA) responses occur even when patients are administered biotherapeutics which are fully human monoclonal antibodies. Evaluating the impact of these ADA on the efficacy of the biotherapeutics can be challenging, particularly if observed drug and biomarker levels in the ADA negative patients are variable. A case study highlighting this issue will be presented.

10:10 Grand Opening Coffee Break in Exhibit Hall with Poster Viewing

Regulatory Guidance and Expectations 


11:10 Immunogenicity Considerations for Novel Antibody Products

Laurie Graham, Product Quality Reviewer, Division of Monoclonal Antibodies FDA/CDER


11:40 Strategies for Managing Drug Interference in Neutralizing Antibody Assays

Marie T. Rock, Ph.D., Vice President, Protein Bioanalysis, Midwest BioResearch LLC, a Wil Research Company

ProImmune12:10 pm Tools and Technologies for Comprehensive Immunogenicity Risk Management

Nikolai Schwabe, Ph.D., CEO, ProImmune Inc

ProImmune has developed a comprehensive suite of in vitro assays that characterize DC, T cell, B cell and innate immune responses.  Antigen presentation assays using mass spectrometry, dendritic cell - T cell assays and physical HLA-peptide binding assay can be combined to provide a broad picture of protein antigenicity.  Data from these assays can help inform improved drug design and lead selection through a clearer understanding of the mechanisms that drive immune responses.

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

Development, Validation and Interpretation of Assays 

2:00 Chairperson’s Remarks

Renuka C. Pillutla, Ph.D., Director, Immunochemistry & Biomarker Development, Bristol-Myers Squibb

2:05 Rationalized Design and Validation of a Cell-Based Luciferase Assay for Detection of Neutralizing Antibodies to rhGM-CSF and Demonstration of Advantages over the Cell Proliferation-Based Method

Yuanxin XuYuanxin Xu, Ph.D., Senior Scientific Director, Clinical Assay Development, Clinical Laboratory Sciences, Genzyme, a Sanofi Company

A robust assay is essential for monitoring neutralizing antibody (NAb) in rhGM-CSF treated patients. In collaboration with Michael Tovey (Institute Andre Lwoff, France), a GM-CSF specific luciferase reporter-gene cell line was generated. The 1-day luciferase NAb assay showed significant improvement over the 4-day cell-proliferation based methodin assay performance and meets the current standard.

2:35 Neutralizing Antibody Assay Challenges:  Cell-Based vs. Ligand Binding Assay Format Feasibility vs. Utility in a Clinical Program

Lakshmi Amaravadi, Ph.D., Director, Translational Medicine, Biogen Idec, Inc. and Chair, Ligand Binding Assay Focus Group-AAPS

This presentation will discuss a case study on developing a cell-based assay for detection of neutralizing antibodies and will discuss challenges related to inherent sensitivity, drug interference and clinical study design that limit the utility of the assay in a clinical program. Alternative approaches to address these issues will be presented.

3:05 Humanized Mouse Models, Part One: Model Development and Challenges in Assessing Immunogenicity

Kristina E. Howard, DVM, Ph.D., Staff Fellow, Division of Drug Safety Research, FDA, CDER

Humanized mice represent a new animal model that may benefit pre-clinical and drug discovery research. This presentation will review of a variety of humanized mouse models with discussion of the applicability, advantages and disadvantages of each. Examples of the challenges encountered employing this animal model for immunogenicity drug testing will be presented.

3:35 Increasing ADA Method Drug Tolerance: Does it Really Tell Us More?

George GunnGeorge R. Gunn, III, Ph.D., Associate Scientific Director, Biologics Clinical Pharmacology, Janssen Research & Development, LLC

This presentation discusses the recent push by regulatory agencies to address ADA method drug tolerance limitations and explores whether improved drug tolerance actually leads to a better understanding of the clinical impact of ADA on safety and efficacy.

4:05 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem Solving Breakout Discussions

Concurrent problem solving breakout discussions, open to all attendees, speakers, sponsors, and exhibitors, provide a forum for discussing key issues and meeting potential collaborators. Plan to take part and explore these topics in-depth. Please pick a topic of your choice, find your table and join in.

Dealing with Pre-existing Positive ADA Activity in Study Patients

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

• If pre-dose samples with high levels of reactivity are identified, should we care?  If so, what are the appropriate follow up activities?
• Open exchange - what have you seen when characterizing pre-existing ADA and their impact?
• What are the regulatory expectations for characterizing pre-existing ADA?

Evaluation of Immunogenicity in Novel Products / Non MAB Products

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

• How this differs for each product
• Complex components to consider
• Experiences with evaluating epitope binding
• Regulatory requirements and experiences
• How this is part of a risk-based approach

Detection of Immune Complexes (ICs) and Their Impact on Immunogenicity Assessment

Moderator: Daniel T.  Mytych, Ph.D., Principal Scientist, Clinical Immunology, Amgen, Inc.

• What methods/reagents are used for detecting human antibody drug/ADA ICs in NHP? Rat?
• When to use the CIC assays in GLP studies?
• How do we detect small protein drug/ADA ICs?
• Is qualitative detection of ICs enough? Is quantitation required?
• How do we differentiate CIC-related toxicity from other adverse events? 
• IC+ animals do not always developing Type III hypersensitivity.  How do we address/explain?
• Has anyone developed a drug-specific IC assay in humans?
• Sharing of experiences

Implementation of Ligand-Binding Neutralizing Antibody Assays

Moderator: Lakshmi Amaravadi, Ph.D., Director, Translational Medicine, Biogen Idec, Inc. and Chair, Ligand Binding Assay Focus Group-AAPS

• When to implement Ligand Binding Nab assays as opposed to cell based assays?
• Choice of assay depends on product, MOA and how to draw  from potency assays
• Challenges regarding reagents, patient population, controls and cut-points
• Sensitivity and drug interference and implications for Nabs assays
• Regulatory perspective on ligand-binding assays and other experiences

Regulatory Expectations Regarding Immunogenicity Assessment

Albert Torri, Ph.D., Senior Director, Bioanalytical Sciences, Regeneron Pharmaceuticals, Inc.

• How and when to approach the regulators: Benefits of discussion with the regulatory authorities
• Proper validation and characterization of assays
• Neutralizing antibody assays: When should they be carried out and why?
• The case for binding assays versus cell-based for NABs
• Novel Products and Biosimilars: what challengers is the FDA seeing and anticipating?

Long-Term Immunogenicity Assay Support

Moderator: Yuanxin Xu, Ph.D., Senior Scientific Director, Clinical Assay Development, Clinical Laboratory Sciences, Genzyme, a Sanofi Company

• Are assay controls and established assay pass/fail criteria appropriate?  If not, what is the moving forward plan?
• Is assay performance (such as precision) acceptable?  If not, what is the moving forward plan?
• Is assay cut-point appropriate? If not, what is the moving forward plan?
• What is the practice to demonstrate critical reagent comparability if a new reagent is needed?
• Is sample minimal dilution appropriate and dilution scheme suitable?
• How is sample long term stability established to support batch testing/incurred sample analysis?

5:45 - 6:45 Welcoming Reception in the Exhibit Hall with Poster Viewing

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