Immunogenicity Assessment and Regulatory Approval of Biologics



Immunogenicity has always been a critical safety concern, especially when many biotherapeutics are becoming increasingly complex. Understanding and controlling immunogenicity-related risks are essential in the development of biotherapeutics to ensure meeting the regulatory requirements. The 12th Annual Immunogenicity Assessment and Regulatory Approval of Biologics conference brings industry, regulatory and scientific experts together to share best practices in assessing immunogenicity of novel biologics along with biosimilar products. The session will also discuss the challenges and solutions for addressing new regulatory guidelines in assay development and validation for cell and gene therapies.

Final Agenda


Recommended Short Course*

SC11: Developability of Bispecific Antibodies: Formats and Applications

Nimish Gera, PhD, Director, Research and Development, Mythic Therapeutics


*Separate registration required.


7:15 am Registration and Morning Coffee

7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided)


Jennifer-ChadwickJennifer S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter


Joanna BrewerJoanna Brewer, PhD, VP, Platform Technologies, AdaptImmune

Charlotte A. RussellCharlotte A. Russell, MD, DMSc, Chief Medical Officer, Alligator Bioscience

Susan RichardsSusan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D

Kristi SarnoKristi Sarno, Senior Director Business Development, Pfenex


8:30 Chairperson’s Opening Remarks

Zhandong Don Zhong, PhD, Associate Director, Specialty Bioanalytics, Teva Pharmaceuticals

8:40 Novel, Simplified Approaches to ADA Cut Point Calculation

John Kamerud, PhD, AR Fellow, Director, Bioanalytical, Pfizer

Investigators across the industry indicate problems with very low ADA cut point factors, which can lead to elevated rates of reported positives, many of which are not biologically relevant. This talk will describe approaches to cut point calculation in which pre-existing positive samples are identified and removed, while forgoing any additional outlier analysis to retain natural variability. The resulting cut points should better reflect meaningful immunogenicity.

9:10 Strategies for Setting Cut-Points for ADA Assays in Multi-Tier vs Single-Tier Testing in a Routine Clinical Setting

Theo_RispensTheo Rispens, PhD, Principle Investigator, Antibody structure and function, Sanquin

Immunogenicity testing may be a useful tool to assess reasons for non-response during e.g. anti-TNF therapy. Current guidelines for ADA assays focus on early stages of testing new (or biosimilar) drugs in the clinic, but may not be optimally tailored towards practical implementation of ADA testing in the context of routine care. This presentation will address different strategies for calculating cut-points in relation to single vs multi-tier assay strategies and discuss case studies comparing these different approaches

9:40 Orthogonal Approaches and Utility of ADA Assays

Gupta_soumiSoumi Gupta, PhD, Director, Immunogenicity Assessment, BioMarin Pharmaceutical Inc.

We will demonstrate using Pegvaliase (a PEGylated bacterially derived enzyme substitution therapeutic) as a case study, how to evaluate appropriateness of the ADA assays based on integrated analysis of immunological laboratory data generated by orthogonal approaches as well as clinical safety data. We will present data generated from two different ADA assays developed against Pegvaliase, one for the detection of drug-specific IgE and the other for the detection of anti-PEG IgG/IgM antibodies, alongside laboratory and clinical safety data.

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:15 Women in Science Speed Networking in the Exhibit Hall


10:55 Chairperson’s Remarks

Kay Stubenrauch, PhD, Expert Scientist, Pharma Research & Early Development pRED, Pharmaceutical Sciences, Large Molecule Bioanalytical R&D, Roche Innovation Center Munich

10:55 FEATURED PRESENTATION: FDA’s Current Thinking on Immunogenicity Assessment of Biosimilars

Hallett_WilliamWilliam Hallett, PhD, Biologist, OPQ/OBP, CDER, FDA

An overview of immunogenicity assessment of biosimilars will be presented: current landscape of biosimilar products, success rate versus failure rate and best practices to improve the quality of immunogenicity assessment for biosimilars from an FDA’s perspective.

11:25 Challenges of Immunogenicity Prediction

Grzegorz Terszowski, PhD, Lab Head, PK/PD Bioanalytics Drug Metabolism and Pharmacokinetics Biologics, Novartis Institutes for BioMedical Research

In my presentation I will describe current methods used to assess a risk of development of immune reaction against therapeutic. I will also focus on challenges of used assays and strategies to minimize possibility of false results.

11:55 Application of Mechanistic Modelling to Prediction of Immunogenicity

Hickling_TimTimothy Hickling, PhD, Immunogenicity Sciences Lead, Biomedicine Design, Pfizer, Inc.

This presentation will introduce an immunogenicity consortium that coordinates vitro data to predict immunogenicity in the clinic. The wide range of data is integrated into mechanistic models for prediction, PK and ADA characterization which then allows for better decision-making when translating to the clinic.

12:25 pm Presentation to be Announced

Abzena12:55 Luncheon Presentation to be Announced

1:55 Session Break


2:10 Chairperson’s Remarks

Kay Stubenrauch, PhD, Expert Scientist, Pharma Research & Early Development pRED, Pharmaceutical Sciences, Large Molecule Bioanalytical R&D, Roche Innovation Center Munich

2:15 Development and Clinical Utility of a Novel Drug-Specific IgE Assay

Zhong_ZhandongZhandong Don Zhong, PhD, Associate Director, Specialty Bioanalytics, Teva Pharmaceuticals

Evaluation of drug-specific IgE is important during biotherapeutic development, as anti-drug IgE formation has been reported to potentially correlate with hypersensitivity events (anaphylaxis). Nevertheless, detection of drug-specific IgE remains challenging due to its low levels in circulation, numerous potential interfering endogenous substances, and difficulty in generating a surrogate positive control. The purpose of this presentation is to demonstrate the development and clinical utility of a novel anti-drug IgE assay platform.

2:45 Detection of Drug-Specific IgE Antibodies to Biotherapeutics: Challenges and Advances

Richards_Susan_SPBSusan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D

Most focus on immunogenicity has been on the development of IgG/IgM ADA. However, a more challenging assessment is the detection of drug specific IgE antibodies. When IgE specific ADA present on the surface of mast cells or basophils is cross-linked by binding specific antigen, a series of events unfolds including the release of pharmacologic mediators leading to the symptoms experienced by patients. This can result in hypersensitivity reactions and at an extreme anaphylaxis. Sensitive and highly specific assays are needed to detect low levels of drug specific IgE ADA in the presence of total IgE and also presence of any drug specific IgG antibodies. This presentation will discuss the challenges and progress made in detecting specific IgE ADA.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions - Click here for details

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day


8:00 am Registration and Morning Coffee


8:30 Chairperson’s Remarks

Theo Rispens, PhD, Principle Investigator, Antibody structure and function, Sanquin

8:35 Impact of Impurities on Bioactivity Assays

verthelyi_danielaDaniela Verthelyi, MD, PhD, Chief, Immunology Lab, Therapeutic Proteins, CDER, FDA

Product immunogenicity has emerged as one of the critical roadblocks in the development of biologics, complex generics and biosimilars. This talk will focus on the impact of process-related innate immune response modulating impurities and aggregates on the milieu where the products are delivered highlighting the complex interplay of different impurities on product immunogenicity risk.

9:05 Streamlining Preclinical and Clinical Assessment for Immunogenicity

Dellatore_SharaShara M. Dellatore, PhD, Director, Regulated Immunogenicity and Molecular Biology Bioanalytics, Merck & Co., Inc.

The titer method has been widely used for reporting immunogenicity magnitude as part of a three tiered strategy for immunogenicity assay development and validation. Through multiple case studies, we compared traditional titer to a streamlined strategy using signal-to-noise (S/N). Overall there was a strong correlation between titer and S/N methods and proved comparable for interpretation of relevant impact. The S/N approach has multiple advantages of reduced sample volume, time, resource, cost and may be a future alternative to titer-based method.

9:35 An Integrated Approach to Managing Immunogenicity Risk and Optimum Protein Design

Knowlton_Emilee_AGI_CAR_SPBEmilee Knowlton, PhD, Immunology, Sales Specialist, Sales, ProImmune Inc.

Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages. ProImmune offers mutational activity mapping for optimal protein design, DC-T/T cell proliferation assays for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

11:05 Assay Strategies to Monitor Immunogenicity of New Antibody Therapeutics in Preclinical and Clinical Studies

Stubenrauch_kayKay Stubenrauch, PhD, Expert Scientist, Pharma Research & Early Development pRED, Pharmaceutical Sciences, Large Molecule Bioanalytical R&D, Roche Innovation Center Munich

Bridging immunoassays are currently the predominant assay format for immunogenicity assessment. The assay allows for high throughput testing and simple implementation. However, the reliability of bridging assays can suffer in the presence of i) an oligomeric target reducing specificity or ii) residual drug reducing sensitivity. Thus, there is a need for alternative assay formats or approaches that can overcome these inherent weaknesses. In addition, some methods are introduced to further characterize ADA responses.

11:35 Characterization of Critical Reagents Using LBA, LCMS, and Chromatography for Use in Regulated Bioanalysis

Kernstock_RobertRobert Kernstock, PhD, Senior Group Leader, R&D, Immunochemistry, PPD® Laboratories

According to the new bioanalytical guidance released by the FDA in 2018, there is an expectation to characterize critical reagents for use in regulated bioanalysis. According to the guidance, characterization includes: Identity, Purity, and Stability. We have developed a menu of services to provide reagent characterization using various analytical tools such as ligand binding assays, mass spectroscopy and protein purification to provide address the guidance recommendations.

12:05 pm Preclinical Immunogenicity Assessment of Therapeutic Protein and Antibody: Applications of a Novel ADA Assay Platform Based on Capillary Electrophoresis and Immunodetection

Zhang_ShuliShuli Zhang, PhD, Principal Scientist, PPDM Global Bioanalytics, Merck Research Laboratories

Peggy Sue is a capillary-based western/immunoassay platform that can separate proteins by size or charge. It uses a HRP-conjugated secondary antibody for detection and quantitation. In his work, this platform provides comparable ADA results to traditional bridging assays with distinct advantages. These include no requirement for labeled capture and detection reagents, reduced sample volume, and valuable charge/size characterization of the immunogenic agent. Most importantly, Peggy Sue is an ideal platform for characterization of ADA specificity against complex biologics such as bispecific or multi-specific biotherapeutics.

12:35 End of Immunogenicity Assessment and Regulatory Approval of Biologics

Recommended Short Course*

SC14: Subvisible Protein Particles in Immunogenicity: Measurement, Characterization and Impact

Björn Boll, PhD, Head, Particle Lab and Higher Order Structure Protein Analytics, Physical Chemical Analytics, Novartis Pharma AG

Antonio Iglesias, PhD, Expert Scientist, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd. Basel


*Separate registration required.

* 活动内容有可能不事先告知作更动及调整。

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