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 13th Annual Immunogenicity Assessment and Regulatory Approval of Biologics conference brings industry, regulatory and scientific experts together to share the best practices in assessing immunogenicity of novel biologics along with biosimilar products. The sessions will also discuss the challenges and solutions for addressing new regulatory guidelines in assay development and validation for cell and gene therapies and other platforms.

Final Agenda


Recommended Short Course*

SC9: Introduction to Biophysical Analysis for Biotherapeutics: Development Applications

*Separate registration required.


7:15 am Registration and Morning Coffee

7:25 Women in Science Panel Discussion with Continental Breakfast

Rochard_LucieLucie Rochard, PhD, Liaison, Scientific & Entrepreneurial Initiatives; Director, Innovation Services, Massachusetts Biotechnology Council

Nora MinevaNora Mineva, PhD, CSO, Adecto Pharmaceuticals

Liu_TinaTina Liu, MBA, Co-Founder and CEO, Ally Therapeutics

Chadwich_JenniferJennifer Chadwich, PhD, Vice President, Biologic Development, BioAnalytix, Inc.



8:40 Chairperson’s Opening Remarks

Boris Gorovits, PhD, Senior Director, Pharmacokinetics, Dynamics & Metabolism, Pfizer Inc.

8:50 What Is the Best Approach to Overcoming Drug Interference in Immunogenicity Assays, BEAD, SPEAD, or Maybe LCMS?

Hao Jiang, PhD, Principal Scientist, Bioanalytical Sciences, Bristol-Myers Squibb

In our assay, a larger amount of capture drug than that in LBA format can be used in the assay to outcompete the drug-ADA complex and no detection drug is needed, but LCMS direct detection of ADA molecules, either total ADA or individual immunoglobulin isotopes. In this presentation, I will give an overview of several effective approaches (with case studies) to overcome the drug interference in ADA assays using different assay formats and detection tools.

9:20 Fully Automated Cell-Based Binding Neutralizing Antibody Assay on MSD Platform

Weifeng Xu, PhD, Principal Scientist, PPDM, Regulated Immunogenicity and Molecule, Merck

The newest FDA Immunogenicity Testing Guidance mentioned that LBA could be developed for antagonistic mAb NAb assay. However, in the case of dual-receptors drug target or hard-to-express drug target/ligand, it is also very challenging to have LBA NAb assay. Here, we share a case study of fully automated NAb assay development and validation using a MSD-based cell binding assay.

9:50 ADA Analysis Demonstrates the Potential Impact of Insufficient Drug Tolerance

Kelli Phillips, PhD, MBA, Laboratory Manager, PPD® Laboratories

An ELISA method with Acid Dissociation was developed for the detection of ADA against a biosimilar therapeutic at PPD (2015). Pre-validation data indicated that the method was able to detect up to 100 ng/mL of the positive control in the presence of 43.3 mcg/mL drug. This degree of drug tolerance was predicted to be fit-for-purpose for sample analysis; measured serum concentrations of the innovator drug during Phase III trials ranged from 0.50 to 6.00 mcg/mL. An alternate dosing strategy for a biosimilar drug was also tested. As a result, serum drug concentrations surpassed the drug tolerance of the originally validated assay. An improved ECL-Bead ADA method with increased drug tolerance was developed at PPD (2019) and the impact of the improved drug tolerance was evaluated using a subset of study samples.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Women in Science Speed Networking in the Exhibit Hall


11:05 FDA Regulatory Perspective on the Harmonized ADA Validation Testing and Reporting

Zhenzhen Liu, PhD, FDA/CDER/OPQ/Office of Biotechnology Products, FDA

11:35 Immunogenicity Risk Factors Associated with Multi-Domain Biotherapeutics

Boris Gorovits, PhD, Senior Director, Pharmacokinetics, Dynamics & Metabolism, Pfizer Inc.

Compounds containing two or more structural domains with a distinct mode of action-relevant functionality have been defined as multi-domain biotherapeutics (MDB). Several modalities, including endogenous protein fusions with Fc fragment or another polypeptide, bispecific antibodies, antibody-drug conjugates, as well as polyethylene glycol conjugates, have been viewed as examples of MDB type. Similar to other biotherapeutics, MDB compounds have a potential to induce host immune response, commonly detected in a form of anti-drug antibodies (ADA). The need to characterize ADA specificity to a particular domain of MDB has been identified as a potential requirement based on the compound nature and associated immunogenicity risk factors. MDB-related immunogenicity risk factors and related strategy of ADA specificity evaluation will be discussed.

12:05 pm Evaluation of Statistical Approaches for the Monitoring of Anti-Drug Antibody (ADA) Assay Performance during Clinical Development

Ching-Ha (Vicky) Lai, PhD, Senior Staff Scientist, Bioanalytical Sciences, Regeneron Pharmaceuticals, Inc.

It is expected that immunogenicity will be monitored throughout the clinical development program of a biotherapeutic. The ADA assay used to monitor immunogenicity is needed to support multiple clinical studies through different development phases, over several years. Thus, it is important to have an assay life cycle management process in place, which monitors assay performance over time and in different clinical indications. In this presentation, case studies will be used to discuss and compare approaches for monitoring quality control (QC) performance of ADA assays, to study the factors that may potentially influence assay performance, and to address potential assay drifts during clinical bioanalysis.

12:35 Presentation to be Announced

1:05 Session Break

1:10 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

2:10 Session Break


2:25 Chairperson’s Remarks

Zhenzhen Liu, PhD, FDA/CDER/OPQ/Office of Biotechnology Products, FDA

2:30 FDA Guidance on Bi- and Tri-Platforms

Mark Ma, PhD, Executive Director, Bioanalytical Development, Alexion Pharmaceuticals Inc.

The FDA has licensed two bispecific antibodies (BsAbs) and the number in clinical development has steadily increased in recent years. I will discuss the current expectation and guideline from the FDA for novel modalities with a focus on bi- and tri-specific antibodies.

3:00 Tales from the Vault: Case Studies of Immunogenicity Assay Validation from the FDA’s Office of Biotechnology Products

Leopold Kong, PhD, Chemist, Product Quality Reviewer, Biotechnology Review & Research IV, Office of Biotechnology Products, OPQ, CDER, FDA

Anti-drug antibody (ADA) assays should be sufficiently sensitive to detect ADA before they reach levels associated with altered pharmacokinetic, pharmacodynamic, safety, or efficacy profiles. We will discuss case studies illustrating key points and considerations in determining assay suitability in the context of product immunogenicity risk and clinical experience.

3:30 Talk Title to be Announced

Corinna Fiorotti, PhD, Scientific Officer, BioAgilytix

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

TABLE: Strategies and Considerations for Developing Immunogenicity Assays for Novel Modalities

Moderator: Hao Jiang, PhD, Principal Scientist, Bioanalytical Sciences, Bristol-Myers Squibb

  • Novel modalities such as bispecific Abs, probodies and lipid nanoparticle siRNA pose lots of challenges in clinical immunogenicity assay development
  • What are the major considerations for developing ADA and NAb assays, such as assay formats and cell lines?
  • What are the potential risks from regulatory perspective?

TABLE: Fully Automated Cell-Based Binding Neutralizing Antibody Assay on MSD Platform

Moderator: Weifeng Xu, PhD, Principal Scientist, PPDM, Regulated Immunogenicity and Molecule, Merck

  • NAb assay development: when to have an assay, which format: cell or non-cell?
  • How to overcome drug interference;
  • Interpretation of new 2019 Jan FDA Immunogenicity guidance

6:00 Taste of New England Networking Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day


8:00 am Registration and Morning Coffee


8:30 Chairperson’s Remarks

Timothy Hickling, PhD, Immunogenicity Sciences Lead, Pfizer Inc.

8:35 Current Practice in Predicting Immunogenicity of Biopharmaceuticals for Candidate Selection and Risk Management

Timothy Hickling, PhD, Immunogenicity Sciences Lead, Pfizer Inc.

Immunogenicity prediction through in silico and in vitro assays is widely employed for screening and selection of candidate biopharmaceuticals across our industry. During clinical development, these techniques, together with mathematical modeling and simulation, can help to understand the overall immunogenicity risk, pointing towards immunogenicity risk management strategies. I will review current practice and provide examples across the drug discovery and development pipeline.

9:05 A Case Study on Prediction of Immunogenicity Potential of Therapeutic Proteins

Sivan Cohen, PhD, Scientist, BioAnalytical Sciences, Genentech

Immunogenic response, such as generation of anti-drug antibodies (ADA), against biotherapeutic products can have detrimental effects on drug safety, efficacy, and pharmacokinetics. Therefore, prediction and quantification of the risk for immunogenicity of therapeutic protein drugs before clinical trials is a crucial need. This presentation will describe state-of-the-art in silico analyses and in vitro assays for characterization of the immunogenic potential of a panel of biotherapeutic proteins and their correlation to the clinically observed immunogenicity outcome. A novel T cell assay with shortened turnaround time, improved efficiency, and robustness will also be discussed.

ProImmune 9:35 Mastering Immunogenicity in Biologics Development

Jeremy Fry, DPhil, Director of Sales, ProImmune

Immunogenicity is one of the most complex issues to address in drug design and development and requires intelligent application of integrated platforms to mitigate the risk to your biologic. In this talk I will present case studies to illustrate the range of solutions that ProImmune provides including DC-T/T cell proliferation assays for lead selection/optimization, MAPPS assays 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 and Poster Award

11:05 Benchmarking Predictions and Experimental Data for HLA Class II Binding, Eluted Ligands, and Immunogenicity

Alessandro Sette, Dr. Biol. Sci., Professor, Head and Member, La Jolla Institute for Immunology

11:35 New Technologies and Approaches to Assess and Circumvent Immunogenicity

Wojciech Jankowski, PhD, Biologist, Center for Biologics, Evaluation and Research / Office of Tissues and Advanced Therapies, FDA

We will describe examples of the use of novel assays to assess immunogenicity and use the information to de-immunize therapeutic-proteins. I will give examples how we: evaluated and re-designed immunogenic rFVIIa analog (Vatreptacog Alfa); redesigned variants exhibiting both desired functional activity and reduced immunogenicity-risk; evaluated plasma-derived FVIII vs. recombinant FVIII using the MAPPs assay; and gave the explanation for clinical findings. We have been developing new approaches and assays for immunogenicity assessments and applying these to specific proteins and immunogenicity issues. Thus, my talk will not only lay out the broad principles, but also provide specific examples where our approaches have been useful.

12:05 pm Case Study for In-Study Cut Point Evaluations According to the 2019 FDA Guidance

Megan Wiberg, Laboratory Manager, PPD® Laboratories

Validation of immunogenicity assays results in cut points that may or may not be relevant when applied to the study population once the method is implemented for clinical study support. The potential for the validated cut point to be unsuitable during sample analysis should be considered when determining cut point strategies during method validation. This talk will address approaches for choosing the population used to establish cut points during pre-study validation, evaluating the suitability of validated cut points during sample analysis, and highlight strategies for in-study cut point determination and implementation when the validated cut point is deemed unsuitable.

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

Recommended Short Course*

SC15: Introduction to Gene Therapy Products Manufacturing and Analytics

*Separate registration required.

* The program is subject to change without notice, due to unforeseen reason.

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