Understanding and Overcoming Immunogenicity of Protein Therapeutics

» Opening Keynote Presentations 

1:40 Understanding the Impact of Aggregates on Immunogenicity 

 Jack Ragheb, Ph.D., Senior Regulatory Research Officer and Principal Investigator, Division of Therapeutic Proteins, FDA 

Large protein aggregates are known to be produced during the pharmaceutical manufacturing of therapeutic protein products. However, our understanding of how protein aggregate attributes such as size contribute to this immunogenicity is very limited. This talk will focus on subvisible protein aggregates, how they may interact with the immune system, and the potential impact these particles could have on a product’s safety and efficacy profile. 

 

2:10 Protein Aggregation and Immunogenicity: The Formulation Matters 

 Wim Jiskoot, Ph.D., Professor, Drug Delivery Technology, Leiden University 

In this talk I will present product-related risk factors for protein immunogenicity, with a focus on aggregation. Clinical case studies illustrating the importance of the formulation in relation to protein immunogenicity will be presented. Moreover, theoretical considerations and pre-clinical studies pointing to which types of aggregates (including subvisible particles) may serve as a risk factor will be discussed. 

4:00 Problem Solving Breakout Sessions 

Concurrent Problem Solving Breakouts are interactive sessions hosted by a moderator to discuss a topic in depth. They are open to all attendees, sponsors, exhibitors, and speakers and provide a forum for discussing key issues and meeting potential partners. Please pick a topic of your choice and join in. 

TABLE 7: Understanding the Role of Aggregates in Immunogenicity 

Moderator: Wim Jiskoot, Ph.D., Professor, Drug Delivery Technology, Leiden University 

Moderator: Melody Sauerborn, Ph.D., Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutics, Utrecht University 

• Why aggregates are immunogenic from a theoretical point of view
• How can we verify the theory
• Risk factors for immunogenicity - beyond aggregates 

TABLE 8:  Immunogenicity Risks and Prediction Approaches 

Moderator: Li Xue, Ph.D., Senior Research Scientist II, Immunogenicity Sciences, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc.   

• What are the high risk factors that impose immunogenicity response in humans?
• How to deal with high prevalence of pre-existing antibodies seen in clinical studies?
• Approaches to immunogenicity prediction: strategy, assays and interpretation 

TABLE 9:   Strategies to Address Drug Interference 

Moderator:  Maria Barbosa, Ph.D., Senior Principal Scientist, Bristol-Myers Squibb
Moderator:  Darshana Jani, Ph.D., Scientific Manager, Clinical Science & Technology, Biogen IDEC 

• Pre-clinical and clinical immunogenicity assessment of biotherapeutics: drug interference
• Selecting the time for sample collection
• Anti-drug antibody (ADA) assays suitable for the intended purpose 
       - Choice of assay platform
• ADA assay validation: drug tolerance
• Improving drug tolerance of ADA assays
       - Sample pre-treatment 

TABLE 10: Pre-Existing Drug-Reactive Antibodies in Human Serum Specific to Afucosylated Therapeutic Antibodies 

Moderator: Shan Chung, Ph.D., Scientist, Bioanalytical Technologies and Strategies, Genentech 

• Characterization of pre-existing drug-reactive antibodies in humans.
• Overcoming pre-existing drug-reactive antibodies in immunogenicity assays.
• Potential impact of pre-existing drug-reactive antibodies on immunogenicity risk. 

TABLE 11: Immunoassays and Risk-based Approaches to Immunogenicity 

Moderator: Jack Ragheb, Ph.D., Senior Regulatory Research Officer and Principal Investigator, Division of Therapeutic Proteins, FDA 

• What constitutes an appropriate positive control in your immunoassay?
• IgE assays: issues of sensitivity and interference
• Risk based approaches to immunogenicity 

Recommended Short Courses 

SC8 – Changing Guidances and Regulatory Expectations for Biologics 

SC9 – Characterization Techniques for Protein Therapeutics – Orthogonal vs. Complimentary