CONFERENCE SERIES: Bioprocess and Manufacturing
Recorded at: Immunogenicity Summit
About this Product:
A 3 ½ hour digital course containing highlights from the conference on Immunogenicity Assessment and Clinical Relevance at the Immunogenicity Summit in Bethesda in November 2011. This includes
- Regulatory guidance from the FDA
- Updates from the EMEA on unwanted immunogenicity of innovators and biosimilars
- Case studies on the key challenges of immunogenicity assays: Methodology for neutralizing antibody assays, ligand-binding assays, and acid dissociation studies
- Advice from the experts on carrying out clinical immunogenicity studies: a practical road map and means of characterizing and dealing with pre-existing anti-drug antibodies.
About this Product:
7 Presentations
233 Slides
Over 207 Minutes
Individual: $345
Site License: $1380
Agenda At A Glance:
Improved Methods for More Accurate Detection of Neutralizing Antibodies
Michael Tovey, Ph.D., Director, Research, Laboratory of Biotechnology & Applied Pharmacology, ENS Cachan
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.
Biography: Michael G. TOVEY, Ph.D, is INSERM Director of Research, Laboratory of Biotechnology and Applied Pharmacology at the Ecole Normale Supérieure de Cachan, Cachan, France. He is the author of more than 200 articles on interferon, cytokines, biotechnology, and immunogenicity. He is a member of numerous scientific boards and is French representative for the ISICR International Council. He is chair of the International Cytokine Standards Committee, a member of the ISICR Meetings Committee, and a member of the European Adjuvant Advisory Committee. He is editor-in-chief of Detection and Quantification of Antibodies to Biopharmaceuticals:Practical and Applied Considerations, and Associate Editor of the Journal of Interferon and Cytokine Research.
Perspectives on Ligand Binding Assays for Immunogenicity Assessment
Marie T. Rock, Ph.D., Vice President, Protein Bioanalysis, Midwest BioResearch LLC, a Wil Research Company
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.
Biography: Over 30 years experience in all phases of drug development, specialized knowledge of clinical pathology and immunochemistry, biomarker development and protein therapeutics. Authored over 75 publications, two books, drug metabolism sections of IND and NDA and analytical methods sections of BLA regulatory documents, speaker at numerous national and international meetings. She now serves on the Editorial Board of the Journal of Immunoassay and Immunochemistry, is an active member of AAPS, currently serving as Chairman of the Ligand Binding Assay Focus Group Steering Committee, is involved in training programs and collaborative activities with the regulatory agencies.
The Pros and Cons of Acid Dissociation
Albert Torri, Ph.D., Senior Director, Bioanalytical Sciences, Regeneron Pharmaceuticals, Inc.
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.
Biography: Albert Torri is a Senior Director of Bioanalytical Sciences at Regeneron Pharmaceuticals in Tarrytown, NY. He received his Ph.D. in Biochemistry from the University of Alabama at Birmingham and conducted his post-doctoral studies at Johns Hopkins University. He then joined the Bristol-Myers Squibb Company where he served as a Senior Research Investigator and member of the Discovery Working Group. In his current position at Regeneron Pharmaceuticals, he directs assay development and sample analysis efforts. Responsibilities include the development, validation and automation of PK, PD and immunogenicity assays to support preclinical and clinical studies of biologics, as well as the analysis of all clinical samples.
IMMUNOGENICITY IN THE CLINIC AND RELATION TO PRE-CLINICAL PREDICTIVE STUDIES
Clinical Immunogenicity Testing Road Map: What We've Learned from Clinical Studies
Sue Richards, Ph.D., Group Vice President, Clinical Laboratory Sciences, Genzyme Corp.
The ability of a drug to elicit an immune response is routinely evaluated as a component of clinical development for biotherapeutics. However, immunogenicity assessment often does not end with just testing drug-specific antibodies and neutralizing antibodies. Additional characterization is often necessary in the context of safety or efficacy evaluations. A number of factors can be considered when implementing further in-depth analyses. Case examples will be presented to demonstrate approaches taken to support clinical programs and lessons learned.
Biography: Sue Richards heads the Clinical Laboratory Sciences Department at Genzyme where she has been extensively involved in the development of biologics for the past twenty-five years. Her responsibilities span four functional areas: Clinical Assay Development, CLIA-certified Clinical Specialty Lab, CLS Quality Systems, and Investigative Clinical Immunology. The department has in-depth experience developing and validating bioanalytical methods for immunogenicity, biomarkers, pharmacokinetics, genotyping, and flow cytometry. Our clinical lab supports Phase 1-4 clinical studies, postmarketing commitments and Genzyme’s Registry programs. Current research activities involve investigating immune tolerance induction for therapeutic proteins. Dr. Richards received her Ph.D. in Microbiology from SUNY at Buffalo. She has co-authored over 50 scientific publications including several focused on immunogenicity and immune mitigation of therapeutic proteins. Dr. Richards has been actively involved in the AAPS as a Steering Committee member of the Ligand Binding Assay Bioanalytical Focus Group (LBABFG) and currently is a Steering Committee member of the Therapeutic Immunogenicity Focus Group (TIFG) where she is serving as the Immunogenicity Mitigation APA lead.
Detecting, Characterizing, and Dealing with Pre-Existing ADA in Clinical Studies
Stephen Keller, Ph.D., Associate Director, Pre-Clinical and Clinical Development Sciences, Abbott Biotherapeutics Corp.
ADA methods are becoming increasingly effective at identifying subjects that develop post-treatment antibody responses to biotherapeutics. Occasionally, however, very high assay signals are seen in samples from drug-naïve populations, raising the questions of what's being detected and what to do about it? This presentation will use case studies to illustrate this phenomenon and offer some perspective on what should be done to follow up such observations.
Biography: Stephen Keller, Ph.D. is Head of Preclinical and Clinical Development Sciences at Abbott Biotherapeutics in Redwood City, CA (ABR). After receiving his B.S. in Physiology at U.C. Davis, Dr. Keller spent 4 years developing diagnostic assays for Baxter Healthcare in Seattle. He then went on to complete his Ph.D. in Human Genetics at the University of Utah, where he studied gene expression involved in leukemic cell transformation. Following graduate school, Dr. Keller began his biotech career at Protein Design Labs which, after several name changes, was eventually bought by Abbott Laboratories. His group is responsible for Toxicology, Bioanalytical Sciences, and PK/PD support for all biotherapeutic drug candidate programs at ABR. He is a member of the American Association for Pharmaceutical Scientists (AAPS), active in the LBABFG, and enjoys a game of catch.
GLOBAL REGULATORY CONCERNS
FDA Guidance on Immunogenicity Testing
Susan Kirshner, Ph.D., Associate Chief, Laboratory of Immunology, Therapeutic Proteins, Biotechnology, FDA
The US FDA published its Draft Guidance for Industry: Assay development for immunogenicity testing of therapeutic proteins in December 2009. The Draft Guidance provides FDA recommendations for the development and validation of assays to test for anti-therapeutic antibodies to protein therapeutics. The Guidance has undergone a period of public comment and the Agency is currently assessing the comments provided by the public with the aim of revising the Draft Guidance. This talk will highlight aspects of the Draft Guidance.
Biography: Dr. Susan Kirshner received an M.Sc. from University of North Carolina School of Public Health in the field of environmental toxicology. She received a Ph.D. in Immunology from the Weizmann Institute of Science, where she worked on the development of a biological therapeutic. Dr. Kirshner’s post-doctoral training was at the National Cancer Institute in the area of transcriptional regulation of MHC class I genes. Dr. Kirshner worked both in the government and industry before joining the Division of Therapeutic Proteins in the Office of Biotechnology Products at the US FDA over 8 years ago. She is currently the Associate Chief of the Laboratory of Immunology at the FDA.
European Update on Unwanted Immunogenicity of Biologicals and Biosimilars
Robin Thorpe, Ph.D., FRCPath, Head, Biotherapeutics Group, National Institute for Biological Standards and Control, UK
The Biosimilars Working Party of the CHMP has drafted a guideline on unwanted Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins, and a new guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use is being drafted. This presentation will provide an update on unwanted immunogenicity and the status and interpretation of existing EU guidelines. Considerations relevant to the immunogenicity assessment of biosimilars will also be included.
Biography: Robin Thorpe PhD, FRCPath, is Head of the Biotherapeutics Group at the National Institute for Biological Standards and Control (NIBSC). Recent interests include the unwanted immunogenicity of biologicals, development of improved bioassays for cytokines, the immunology of monoclonal antibodies and cytokine contamination of biological products. He attends meetings of the Biologicals Working Party & Biosimilars Working Party of the CHMP at the EMEA. He is a member of the British Pharmacopoeia Commission (MHRA) Expert Advisory Group NOM, the British Pharmacopoeia Panel of Experts on Biological and Biotechnological Products and chairman of the Working Group on Monoclonal Antibodies of the European Pharmacopoeia. Dr Thorpe is a member of the Biologicals & Vaccines Expert Advisory Group of the CHM. He is the Chairman of the IUIS nomenclature subcommittee for chemokines and the standardisation and nomenclature committee of the International Cytokine Society. He is a biologicals advisor to the WHO INN program. Dr Thorpe is an author on over 200 publications in scientific journals and books. He is an associate editor for the journal Cytokine, Biotherapeutics section editor for Biologicals and editorial board member of the Journal of Immunological Methods & Current Analytical Chemistry.
About the Conference:
A 2-day conference with record breaking attendance that covered all important aspects of immunogenicity for biotherapeutics: Assay Developments; PK/PD Case Studies; Relationship between Hypersensitivity and Immunogenicity; Immunogenicity in the Clinic, and Global Regulatory Concerns.
A few quotes about the event:
"A very comprehensive program with industry and regulators", Dan Mytych, Amgen
"It was so well organized and the topics were timely. This must be one of the best conferences on immunogenicity so far."Marie T. Rock, Ph.D., Vice President, Protein Bioanalysis, Midwest BioResearch LLC, a Wil Research Company