Day One: Immunogenicity Assessment and Clinical Relevance
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WEDNESDAY, NOVEMBER 16
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Stephen Keller, Ph.D., Associate Director, Pre-Clinical and Clinical Development Sciences, Abbott Biotherapeutics Corp.
8:35 Improved Methods for More Accurate Detection of Neutralizing Antibodies
Michael Tovey, Ph.D., Director, Research, Laboratory of Biotechnology & Applied Pharmacology, ENS Cachan - Biography
Conventional cell-based assays are sensitive to serum-matrix effects, have low drug tolerance, and are unsuitable for detection of NADAs against therapeutic monoclonal antibodies dosed at high concentrations and with prolonged washout rates. Case studies in RA and Crohn’s disease show that both circulating levels of functional infliximab, adalimumab, and etanercept and NADAs can be quantified rapidly with the elimination of serum matrix effects using a standardized validated assay based on an engineered cell line.
9:05 Perspectives on Ligand Binding Assays for Immunogenicity Assessment
Marie T. Rock, Ph.D., Vice President, Protein Bioanalysis, Midwest BioResearch LLC, a Wil Research Company - Biography
This presentation will provide a perspective on using ligand binding assays for immunogenicity assessment and includes approaches and insights of the AAPS Ligand Binding Assay Focus Group Steering Committee. In addition, the difficulties and challenges encountered (reagents, patient population, controls, cut-point) will be discussed with approaches for successfully overcoming those difficulties and challenges using case studies.
9:35 A High-throughput Approach to Overcome High Levels of Drug Endogenous Counterpart in ADA
Screening Assays
Sam Song, M.D., Senior Scientist, Immunoassay Development, Merrimack Pharmaceuticals, Inc. - Biography
When a drug is a counterpart of a major endogenous protein, often present in extremely high levels in the blood circulation, it is almost impossible to detect ADAs, even with acid dissociation because the ADA re-associates with the endogenous protein during the neutralization step after acid dissociation. This presentation will introduce a novel approach to detect ADAs in the presence of extremely high level of endogenous protein counterpart of drug.
Sponsored by
10:05 How to Benefit from a Diagnostic Partner in the Assay Development
Speaker to be Announced, Pharmaceutical and Healthcare Collaborations, Thermo Fisher Scientific
With more than 40 years of expertise in the area of immunoassay development meeting clinical demands, Thermo Fisher Scientific can be a perfect match in your assay development. The expertise, experience and assay platforms are now accessible for you to develop R&D assays and/or clinical tests. Working with Thermo Fisher Scientific reduces assay development times and ensure high performance and if/when needed, world-wide supply.
10:20 Networking Coffee Break in the Exhibit Hall with Poster Viewing
11:00 The Pros and Cons of Acid Dissociation
Albert Torri, Ph.D., Senior Director, Bioanalytical Sciences, Regeneron Pharmaceuticals, Inc. - Biography
The drug tolerance of an immunogenicity assay determines the ability of the assay to detect ADA responses in the presence of drug in the sample. If drug levels in study samples are expected to be relatively high, incorporating an acid dissociation step into the assay may improve the detection of ADA. The use and issues associated with acid dissociation will be discussed.
11:30 Translation of Pre-Clinical Cytokine Assessments to Cytokine Release and Cytokine Release Syndrome in Humans Following MAb Treatment
Tobias Manigold, M.D., Lab Head, Immunosafety, Hoffmann-La Roche - Biography
Among IRRs, cytokine release syndrome (CRS) can cause major harm to patients and innovative drugs if encountered unexpectedly and without appropriate mitigation strategies. This presentation will provide insight to the value of pre-clinical in vivo and in vitro cytokine testing for the translation of CR(S) in humans. Moreover, the need for further validation of in vitro prediction systems to allow individualized prediction of CRS within the clinic will be discussed.
12:00 Impact of Assay Method Selection on ATA Data
Melissa Cheu, M.S., Principal Research Associate, BioAnalytical Assays, Genentech, Inc. - Biography
Immunogenicity data can be impacted by the methodology and format of the assay used to detect anti-therapeutic antibodies (ATAs). The use of different methodologies (ELISA, RIP, ECLA) for detection of ATAs to the same molecule can affect ATA data due to differences in relative sensitivity and drug tolerance between methods. Case studies of several assays will be presented.
12:30 Luncheon Presentation
(Sponsorship opportunity available, please contact Katelin Fitzgerald, kfitzgerald@healthtech.com) or Lunch on Your Own
1:55 Chairperson’s Remarks
Michael Tovey, Ph.D., Director, Research, Laboratory of Biotechnology & Applied Pharmacology, ENS Cachan
» FEATURED PRESENTATION
2:00 Mice with a Human Immune System: Applicability and Use for Immunogenicity Studies
Kristina Howard, D.V.M., Ph.D., FDA Commissioner’s Fellow, Therapeutic Proteins, Pharmaceutical Sciences, CDER, FDA
Humanized mouse models now permit assessment of antigen specific adaptive immune responses made in the context of human HLA. A variety of models will be reviewed including the benefits and limitations inherent with each model. Discussion will focus on the use of humanized mice in immunogenicity testing and drug development for a range of pharmaceutical products including biologics, drugs and devices.
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2:30 Efficient Immunogenicity: Can We Streamline
Non-Clinical Immunogenicity Assessment?
Holly W. Smith, B.A., Senior Research Scientist, Investigative Toxicology, Eli Lilly and Company
Recent white paper and guidance documents are triggering thought-provoking process change considerations. After years of discussing approaches to measure, confirm, and characterize anti-drug antibodies, is it possible that we may not need to perform these activities in most non-clinical studies? Is a weight of evidence approach a sufficient assessment? Is it appropriate to lengthen a study specifically for drug wash-out for ADA measurements? Case studies will be presented to discuss these questions, the issues that arise, and the impact on drug development from a non-clinical perspective.
Sponsored by
3:00 Clinically Relevant Immunogenicity Testing from R&D to Clinic
Jörgen Dahlström, Ph.D., M.B.A., Senior Manager Marketing & Scientific Support, Phadia, now Thermo Fisher Scientific
Immunogenicity assessment of a biopharmaceutical drug’s immunogenic potential is a challenging task. It involves developing a range of assays specific for the biological -a long, tedious and labour intense process, as these tests must be designed for transfer to CROs and eventually made available for companion diagnostics. Phadia, now thermo Fisher Scientific, has more than 40 years of expertise in the area of immunoassay development that meets clinical demands. We now offer access to both expertise and platforms, for you to develop R&D assays and/or clinical tests.
3:30 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Results from a Toxicokinetic Study of a Novel Protein
Matthias Hofmann, Ph.D., Senior Investigator, Bioanalytics, Novartis Institutes for Biomedical Research - Biography
A novel protein was tested in a TK-study. Validation of assays developed to analyze PK, immunogenicity, and bioactive PK will be presented, as well as an integrated picture of the study results. Although anti-drug antibodies seem to target the Ag-binding site of the drug, neutralizing effects were not detected.
4:30 Drug-induced Immune Complex-Mediated Hypersensitivity Reactions in the Non-Human Primate (NHP)
Daniel T. Mytych, Ph.D., Principal Scientist, Clinical Immunology, Amgen, Inc.
5:00 Report from Clinical and Laboratory Standards Institute on Design and Validation of Immunoassays for Assessment of Human Allergenicity of New Biotherapeutic Drugs
Robert G. Hamilton, Ph.D., D. ABMLI, Professor, Medicine and Pathology, Clinical Immunology and Allergy, Johns Hopkins University School of Medicine; Director, John Hopkins Dermatology, Allergy & Clinical Immunology Reference Laboratory
The CLSI I/LA34-P document provides a framework for the design and validation of a qualitative immunoassay that detects human IgE antibody to new drugs in various body fluids and tissue extracts. Unique challenges are discussed involving validation of a drug-specific IgE antibody assay in the absence of a positive IgE antibody control serum, minimization of interference by microgram/ml levels of IgG antibody in the detection of nanogram/ml levels of IgE antibody, and the potential for high non-specific binding when human test specimens are analyzed undiluted.
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Table 1: Challenges in Developing Neutralizing Antibody Assays
Moderator: Michael Tovey, Ph.D., Director, Research, Laboratory of Biotechnology & Applied Pharmacology, ENS Cachan - Biography
Table 2: Benefits and Risks of the Competitive Ligand Biding Assays for Neutralizing Antibodies
Moderator: Marie T. Rock, Ph.D., Vice President, Immunoassays, Midwest BioResearch, a Wil Research Company - Biography
Table 3: Dealing with Pre-Existing Positive ADA Activity in Study Patients
Moderator: Stephen Keller, Ph.D., Associate Director, Pre-Clinical and Clinical Development Sciences, Abbott Biotherapeutics Corp. - Biography
Table 4: Practical Application of Immunogenicity Pre-Clinical Risk Assessment
Moderator: Holly W. Smith, B.A., Senior Research Scientist, Investigative Toxicology, Eli Lilly and Company
Table 5: Immunogenicity Testing During Clinical Trials
Moderator: Meena Subramanyam, Ph.D., Vice President, Translational Sciences & Technology, Biogen Idec, Inc. - Biography
Table 6: CLSI ILA-34 Guideline on IgE Anti-drug Assay Development and Validation
Moderator: Robert G. Hamilton, Ph.D., D. ABMLI, Professor, Medicine and Pathology, Clinical Immunology and Allergy, Johns Hopkins University School of Medicine, and Director, John Hopkins Dermatology, Allergy & Clinical Immunology Reference Laboratory
Table 7: What Does the FDA Expect From an Immunogenicity Program?
Moderator: Susan Kirshner, Ph.D., Associate Chief, Laboratory of Immunology, Office of Biotechnology, FDA
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6:30 Networking Reception in the Exhibit Hall with Poster Viewing
7:30 End of Day One of Immunogenicity Assessment and Clinical Relevance
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