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 Dr. Daniela Verthelyi
Former Chief, Laboratory of Immunology, Office of Biotechnology Products
Food and Drug Administration
United States of America |
Keynote Speech
Technical and regulatory considerations regarding the assessment immunogenicity risk for new and follow-on peptide and nucleic acid therapeutics
Abstract (1):
For therapeutic proteins, peptides, and oligonucleotides, the measurement of anti-drug antibody responses during clinical trials is currently used to identify potential immunogenicity-related adverse outcomes. However, this approach is not suitable for all products or development programs including those for follow-on products. To address these gaps, immunogenicity risk assessment is pivoting towards the use of new analytical, in silico, in vitro, and ex vivo tools. This talk will focus on the information needed to construct an informative risk assessment using the new analytical approaches, describe the possibilities and limitations of these approaches, and discuss how they are being used in regulatory strategies.
Title:
Multiplexed Immunophenotyping for Innate Activation Assessment Detects Single-Cell Responses to Immunomodulatory Nucleic Acid Impurities in Therapeutics
Abstract (2):
Comparative in vitro analytical methods to characterize innate immune response modulating impurities can inform the immunogenicity risk and help streamline the development of generic peptides and biosimilar proteins. This talk will describe a new Multiplexed Immunophenotyping for Innate Activation Assessment (MIIAA) assay that utilizes single-cell spectral flow cytometry to capture innate responses by APCs, like cDC, pDC, and other cell types that are critical in initiating immune and inflammatory responses but are at low frequency in peripheral blood. MIIAA offers a powerful immunophenotyping tool to characterize single-cell responses to drug products and potential immunomodulatory impurities that may find utility in drug pipelines to characterize the impact of therapeutics on specific immune cells and to interrogate immunogenic or immunomodulatory risk in comparisons between reference and follow-on products.
Biography:
Daniela Verthelyi, MD/PhD, is a science-driven regulatory leader with 25+ years at FDA leading research and review teams and has been a key contributor to developing FDA’s strategy to assess the immunogenicity risk of a variety of therapeutics, including low molecular weight heparins, peptides, oligonucleotides, and proteins. At FDA she served as Division Director in the Office of Product Quality, Chief of the Laboratory of Immunology, and Director of the Center for Excellence in Infectious Diseases and Inflammation. She has chaired the NIH-FDA Immunology, the NIH-FDA Cytokine Interest Groups, and served on the Advisory Board of the NIH Human Immunology Group. Her core expertise is in innate immunity, inflammation, and product immunogenicity risk assessment and she has led efforts to develop methods to identify product- or process- related impurities in therapeutic products that can foster unwanted immune responses to self-proteins or enhance the immunogenicity of critical therapeutic proteins and thus impacting their safety and efficacy. The methods and data derived from those studies have supported multiple FDA guidance documents, licenses, and approvals, and are frequently cited by sponsors. Daniela Verthelyi holds an MD from the University of Buenos Aires and an PhD in Immunology from Virginia Tech. She has authored over 100 peer-reviewed articles, is the inventor in several patents, and has received “Excellence in Laboratory Sciences” awards from FDA’s, CBER’s, and CDER’s, among other honors.
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