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 (Commonwealth Hall) and Morning Coffee (Harbor Level)

7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided) (Waterfront 1&2)


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, Vice President, Platform Technologies, AdaptImmune

Charlotte A. RussellCharlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience

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

Kristi SarnoKristi Sarno, Senior Director, Business Development, Pfenex


beacon hill complex

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

Kamerud_JohnJohn 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 (Commonwealth Hall)

10:15 Women in Science Speed Networking in the Exhibit Hall (Commonwealth Hall)


beacon hill complex

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

NEW: Daniela Verthelyi, MD,  PhD, Chief, Immunology Lab, Therapeutic Proteins, 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 Towards a fit for purpose approach for evaluating relevant immunogenicity of mAbs in oncology human clinical trials

Hassanein_MohamedMohamed Hassanein, PhD, Staff scientist, Bioanalytical, Regeneron Pharmaceuticals.  

Recent data from oncology trials indicated that human mAbs (h-mAbs) elicit low treatment-emergent immunogenicity. In this presentation, we will provide a tailored approach for assessing immunogenicity of therapeutic mAbs in oncology trails that factors in both the low risk profile of h-mAbs as well as the immunity status of the target population. The goal of this “fit-for-purpose” approach is to provide immunogenicity data that is relevant to health-care providers and patients.

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.

Lonza-tagline-stacked 12:25 pm The Role of Product and Process-Related Impurities in the Innate Immune Response to Biotherapeutic Proteins

Noel Smith, PhD, Principal Group Leader, Lonza Pharma & Biotech

Immunogenicity is a common problem for biotherapeutic proteins and can impact both efficacy and safety. Human in vitro assays are now routinely used during early development to assess the risk of a biotherapeutic protein inducing both an innate and adaptive immune response. This presentation will focus on the use of highly sensitive human primary cell assays for the assessment of product and process-related impurities that may contribute to driving an unwanted immune response.

12:55 Enjoy Lunch on Your Own

1:55 Session Break


beacon hill complex

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 Attend Concurrent Track

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

4:45 Problem-Solving Breakout Discussions - Click here for details (Commonwealth Hall)

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

7:00 End of Day


8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)


beacon hill complex

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 (Commonwealth Hall)

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

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