2022 FDA Updates:


11:10 am  FEATURED PRESENTATION: Simultaneously Engineering Protein Molecules for Increased Efficacy and Lower Immunogenicity
Wojciech JankowskiWojciech Jankowski, PhD, Commissioner’s Fellow, CBER, FDA
Engineering therapeutic proteins for improved clinical outcomes is now routine. Introduction of neo-sequences can however elicit immune response to the engineered protein-therapeutic (immunogenicity), which is an important safety concern. The potential consequences of immunogenicity range from loss in quality life to a life-threatening situation. In my talk I will discuss emerging trends in protein engineering that can allow the design of proteins with improved efficacy and lower immunogenicity.


12:00 pm FEATURED PRESENTATION: Innate Immune Response Modulating Impurities Testing for Biosimilars: Where we are and What we are Missing
daniela_verthelyiDaniela Verthelyi, MD, PhD, Chief, Laboratory of Immunology, CDER, FDA
Comparative in vitro analytical methods to characterize innate immune response modulating impurities could potentially provide a more robust understanding of immunogenicity risk for biosimilars and help streamline their development. This talk will discuss the risk posed by innate immune response modulating impurities, available assays and data interpretation, as well as common pitfalls and remaining knowledge gaps.

12:50 pm  KEYNOTE PRESENTATION: Differential Immune Responses to Deamidated Adeno-Associated Virus Vector
Ronit MazorRonit Mazor, PhD, Principal Investigator, CBER, FDA
Adeno-associated viruses (AAV) are potent vectors used for gene therapy, but recent clinical findings have revealed immunogenicity-related challenges, including formation of a cytotoxic immune response against AAV capsid protein in transfected cells. We report that deamidation, a spontaneous post-translational modification that occurs in multiple AAV serotypes, can result in formation of CD4 T cell epitopes with a Th1 cytokine pattern in donor samples with specific HLA backgrounds.

3:30 pm  KEYNOTE PRESENTATION: Understanding and Navigating Immune Responses to Proteins Used as Therapeutics and in Novel Modalities Like Gene Editing
Zuben SaunaZuben Sauna, PhD, Research Biologist, CBER, FDA
Immunogenicity refers to immune responses to proteins used in therapeutic applications. Immunogenicity is of concern during drug development and licensure as it can affect the safety and/or efficacy of drug products. The presentation will provide: (1) An overview of tools available for immunogenicity risk assessment during drug development and licensure. (2) Specific examples that illustrate the use of in silico, in vitro, and ex vivo methods for immunogenicity risk assessment of proteins used therapeutically and those used in emerging technologies such as gene editing. Judicious application of tools available for immunogenicity risk assessment can permit better decision-making and potentially safer drugs.

4:30 pm PANEL DISCUSSION: Immunogenicity Assessment of Gene Therapy Products
byrnes_andrewAndrew Byrnes, PhD, Chief, Gene Transfer and Immunogenicity Branch, CBER, FDA

  • Assessment of pre-existing antibodies to gene therapy vectors and the potential impact of these antibodies on the therapy
  • Discussion around T cells: An important issue for many gene therapy products
  • Assays: Is the protein therapeutics paradigm applicable? Tiered assessment; Binding ADA and NAb (inhibitor); Conservative 5%/1% false positive concept; Cut point determination. E.g. Hemophilia GTx Guidance and recommendations for assessment of inhibitors. Is assessment of binding antibodies recommended as well?
  • Are these elements needed for assessment of immunogenicity to the components of the GTx and the transgene?
  • Is an integrated summary of immunogenicity recommended? 
  • Is an immunogenicity risk assessment recommended?


8:30 am  FEATURED PRESENTATION: Understanding and Circumventing the Immune Responses to Approved Protein Therapeutics
Daniel LaGasseDaniel LaGasse, PhD, Research Regulator, CBER, FDA
Immunogenicity can compromise the safety and/or efficacy of therapeutic protein products. Due to the serious conditions they treat and lack of alternatives many protein therapeutics are approved even if they elicit immune responses. In the clinic, in addition to poor patient outcomes, the social and economic costs associated with neutralizing antibodies are considerable. In this presentation, I survey the immunogenicity of approved therapeutic proteins, discuss strategies for clinical management of immunogenicity, and identify challenges associated with circumventing the immune responses to approved protein therapeutics.

3:25 pm  Talk Title to be Announced
Kristina-HowardKristina E. Howard, Staff Fellow, Division of Drug Safety Research, FDA


Andrew Byrnes, PhD, Chief, Gene Transfer and Immunogenicity Branch, CBER, FDA
Andrew P. Byrnes, PhD, is Chief of the Gene Transfer and Immunogenicity Branch, which is in the Division of Cellular and Gene Therapies at FDA’s Center for Biologics Evaluation and Research. He has over 20 years of experience at FDA in reviewing the manufacturing of gene therapies, cell therapies and other products for clinical use. The Gene Transfer and Immunogenicity branch is a group of six laboratories that perform research to improve the safety and efficacy of cell and gene therapies, and members of the Branch also review manufacturing of investigational and licensed cell and gene therapy products. Dr. Byrnes has a background in virology and gene therapy. Dr. Byrnes received his undergraduate degree from Yale University, earned his Ph.D. from the University of Oxford, and then conducted postdoctoral research at Johns Hopkins University before joining FDA in 2000.

Kristina E. Howard, PhD, Staff Fellow, Division of Drug Safety Research, FDA
No bio available

Wojciech Jankowski, PhD, Commissioner’s Fellow, CBER, FDA
Dr. Jankowski is a research reviewer with the US Food and Drug Administration in the Office of Tissues and Advanced Therapies. He is part of an active research laboratory and his research interests lie in the regulatory-science associated with the licensure of the next generation of therapeutic proteins. A key focus of his research activities has been to understand the immune response to protein therapeutics, which can significantly affect the efficacy and safety of these drugs. He uses a combination of computational, in vitro and ex vivo approaches in his work. Dr. Jankowski received his Ph.D. from Rutgers University, NJ and was subsequently selected for the highly competitive Commissioner’s Fellowship program at the FDA. His research has been published in high impact journals such as Nature and Nature Chemical Biology.

Daniel LaGasse, PhD, Research Regulator, CBER, FDA
Daniel Lagassé conducts research and CMC review as a Biologist in the Division of Plasma Protein Therapeutics within the Center of Biologics Evaluation and Research at the U.S. Food and Drug Administration. Dr. Lagassé received his PhD in Molecular Microbiology and Immunology from Johns Hopkins Bloomberg School of Public Health.

Ronit Mazor, PhD, Principal Investigator, CBER, FDA
Ronit Mazor did her undergraduate studies in Tel Aviv University in Israel. She performed her PhD in the NIH’s International Graduate Partnership Program, in collaboration with Tel Aviv University. Ronit continued her Post doctoral training in the national cancel institute working on the immunogenicity of recombinant immunotoxins for cancer therapy with Ira Pastan. She then joined the antibody discovery and protein engineering in Medimmune/AstraZeneca in Gaithersburg where she established their cellular and in silico pre-clinical immunogenicity prediction platform. In 2019, Ronit joined the Gene Transfer and Immunogenicity Branch in the FDA as a principal investigator. She is leading a research group studying the interaction between the immune system and gene therapy viral vectors.

Zuben Sauna, PhD, Research Biologist, CBER, FDA
Zuben E. Sauna is a Principal Investigator and also a CMC Reviewer at the US Food and Drug Administration. His research interests lie in understanding the pharmacogenetic basis of the immune response to proteins used in therapeutic interventions as these affect efficacy and safety. His laboratory exploits a combination of computational, in vitro and ex vivo approaches to understand why some individuals and/or sub-populations develop immune responses while others do not. Work from his laboratory has been published in high impact journals such as Nature Biotechnology, Nature Medicine, Science, Science Translational Medicine and Nature Reviews Genetics. He received his Ph.D. from Poona University, India with subsequent training at the National Cancer Institute, Bethesda, USA.

Daniela Verthelyi, MD, PhD, Chief, Laboratory of Immunology, CDER, FDA
Dr. Verthelyi directs a lab focused on understanding innate immunity and inflammation and applying the information to address regulatory problems. Her group develops new methods and models to understand the role of product and process related impurities on product immunogenicity, as well as animal models to assess the safety and efficacy of innate immune response modulators and other therapeutics to respond to infectious diseases. Dr. Verthelyi trained in medicine at the University of Buenos Aires and then obtained a PhD in Immunology from Virginia Tech in USA. She has authored over 100 peer-reviewed articles, is the inventor in several patents, and has received FDA's, CBER’s, and CDER’s “Excellence in Laboratory Sciences” awards, among other honors. In addition to her position at FDA, she has Chaired the FDA-NIH Immunology Interest Group, the NIH-FDA Cytokine Interest Group, and served on the Advisory Boards for the NIH Human Immunology Group.

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