Assessment of immunogenicity is a real challenge for the biotherapeutics industry. Every year at Immunogenicity at PEGS we present NEW findings and NEW case studies. Furthermore, we encourage NEW speakers to participate; from industry and from academia, including regulatory experts. In this track on Immunogenicity Assessment and Clinical Relevance, we present real examples of immunogenicity assessment in preclinical studies and in the clinic for a range of products, and examine the many challenges encountered and overcome. We also present recommendations for presenting immunogenicity data to the regulatory authorities.


7:00 am Registration and Morning Coffee

Meeting Regulatory Expectations for Innovators and Biosimilars: Strategy and Assay Methodology for Challenging Products

8:00 Chairperson’s Remarks

Boris GorovitsBoris Gorovits, Ph.D., Director, PDM, Pfizer, Inc.



Recommendations for the Assessment and Reporting of Clinical Immunogenicity of Therapeutic Proteins and Peptides

Meena SubramanyamMeena Subramanyam, Ph.D., Vice President, Translational Sciences, Biogen Idec, Inc.

To foster a unified approach to assessing and describing immunogenicity, the AAPS Therapeutic Protein Immunogenicity Focus Group convened a team of experts from the industry and regulatory agencies and tasked them with producing a consensus document comprising best practices and recommendations regarding: standardizing terminology; sampling schema for the assessment of ADA in clinical studies; interpretation and presentation of analytical data; and assessment of clinical impact.

8:40 Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients with Morquio A Syndrome: Results from MOR-004, a Phase 3 Trial

Case Study
Becky Schweighardt
Becky Schweighardt, Ph.D., Director, Immunogenicity Assessment, BioMarin Pharmaceutical, Inc.

Elosulfase alfa is an enzyme replacement therapy (ERT) for the treatment of Morquio A. In a 24-week phase 3 trial, all treated patients developed anti-drug antibodies, and the majority developed neutralizing antibodies (NAb) capable of interfering with cellular receptor binding in vitro. Despite the universal development of anti-drug antibodies, elosulfase alfa treatment was both safe and well tolerated and immunogenicity was not associated with lack of treatment effect.

9:10 Case Study on Characterization of Immunogenicity to Multiple Domain Biotherapeutics

Unpublished Data
Boris Gorovits
Boris Gorovits, Ph.D., Director, PDM, Pfizer, Inc.

An evaluation of an ADA response to an MDB based on drug risk factors, drug MOA, patient population and other parameters could facilitate prediction of safety consequences. This presentation will focus on a strategic approach to evaluation of MDB immunogenicity characteristics based on the program development requirements, including non-clinical and clinical translation. Potential issues and concerns will be discussed based on specific case studies.

9:40 Re-Assessment of Immunogenicity Risk based on Clinical Data: Case Study of a Humanized IgG1 Monoclonal Therapeutic with a Knob-and-Hole Structure

Mauricio MaiaMauricio Maia, Ph.D., Bioanalytical Sciences, Genentech, Inc.

Initial clinical immunogenicity evaluation plans are often based upon an immunogenicity risk assessment that includes a myriad of molecule and patient factors, but prior to attaining clinical experience. Clinical data can and should modify this assessment. This presentation will describe a case study of a structurally novel biotherapeutic whose risk-based assessment was changed following analysis of clinical immunogenicity data derived from early-stage trials.

10:10 Discussion with the Session Speakers   

10:40 Coffee Break in the Exhibit Hall with Poster Viewing

Neutralizing Antibody Assays  

11:25 Development of Neutralizing Antibody Assays for Antibody Therapeutics with Cell Depletion MOA

Shan ChungShan Chung, Ph.D., Senior Scientist, Bioanalytical Sciences, Genentech – A Member of the Roche Group

Monoclonal antibodies with mechanisms of action (MOA) involving cell depletion have been used successfully in treatment of a variety of malignant diseases. This presentation will describe development of a neutralizing antibody (NAb) assay for a humanized therapeutic antibody that depletes target tumor cells via effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated phagocytosis (ADCP). A general guidance on selection of NAb assay format for antibody therapeutics will also be presented.

11:55 Driving Factors for Choice of Immunogenicity/NAb Strategy

Unpublished Data
Shalini Gupta
Shalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

Currently a clear strategy for choosing a cell-based or non cell-based assay for the detection of anti-drug neutralizing antibodies is not available. This talk will provide an overview of an AAPS white paper currently being compiled that provides three rationales for selecting the NAb assay format. These include (i) the mechanism of action of the drug; (ii) the risk of NAbs on patient safety and (iii) assay characteristics of the NAb assay. When applied together these 3 aspects can guide the strategy of NAb assay format selection in a consistent manner for the vast majority of biological therapeutics.

12:25 pm ImmunoCAP® ADA Bridging Assay – a Comparison of Different Immunoassay Formats

DeWitt_AsaÅsa Marknell DeWitt, Ph.D., Senior Scientist, Diagnostic Partnering, Thermo Fisher Scientific

The ImmunoCAP ADA bridging assay is an anti-drug-antibody assay based on an IVD platform. In this pilot study we have compared technical and inter assay performance of the ImmunoCAP ADA bridging assay with ELISAs to evaluate the robustness of the assays for global transferability. Customized assays are developed for the automated Phadia system, using standardized reagents. The features of the ImmunoCAP solid phase enables further characterization on the same platform, e.g. measurement of specific IgE and specific IgG4.

12:55 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:55 Session Break

Overcoming Target Interference

2:10 Chairperson’s Remarks

Meena SubramanyamMeena Subramanyam. Ph.D., Vice President, Translational Sciences, Biogen Idec, Inc.


2:15 Case Studies on Troubleshooting Soluble Target Interference in Immunogenicity Assays in the Clinical Space

Case Study
Qiang Qu
Qiang Qu, M.S., Senior Scientist, PDM, Pfizer, Inc.

Soluble targets that form multimers can result in false positive signals in bridging assays. This presentation will focus on troubleshooting clinical immunogenicity assays with interference from the soluble target multimers found in the circulation of the intended population. Two case studies will be presented with their own distinctive approaches to overcome the target interference, and a general mitigation strategy will be discussed for clinical immunogenicity assay development.

2:45 Strategy for Overcoming Target Interference throughout Development

Olivier PetricoulOlivier Petricoul, Ph.D., Senior Investigator II, DMPK-PK/PD, Novartis Institutes for Biomedical Research

While drug interference is a well-known phenomenon for immunogenicity assays and is routinely characterized and optimized during the development and validation of the assays, interference by the pharmacological target occurs only under particular circumstances and is assessed on a case by case basis. This presentation will review different strategies for overcoming target interference, and case studies will be shown to illustrate how an integrated PK/PD/IG assessment can help to assess the clinical relevance of the immunogenicity assay.

3:15 Meeting or Exceeding Regulatory Expectations for Anti-Drug Antibody Assays

 Jim McNally, Ph.D., Associate Research Fellow, Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc. 

 The goal of this talk will be to host an interactive session with the audience to discuss and to share our collective experiences with anti-drug antibody (ADA) assays and to ask the question “Should we meet or exceed expectations?”  Are there examples where the pursuit of increased drug tolerance, improved sensitivity and greater characterization of the ADA response results in significant expenditures of time and effort without adding value to the project?  

Potential discussion topics:

Sensitivity of ADA assay vs. biological relevance

Increased drug tolerance vs. process controls for sample collection

Clinical impact of pre-existing reactivity



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


4:45 Problem-Solving Breakout Discussions

1. Presentation of Immunogenicity Data to the Regulatory Authorities

Meena SubramanyamMeena Subramanyam. Ph.D., Vice President, Translational Sciences, Biogen Idec, Inc.

  • Recommendations on making the clinical correlation with PK
  • Advice on analysis of data
  • What sort of data is required and how is it presented?
  • Planning from the start with the BLA submission in mind
  • How to study the impact of immunogenicity

2. Immunogenicity Considerations for Biosimilars

Shefali KakarShefali Kakar, Ph.D., Senior Director, Clinical Pharmacology, Novartis Oncology Business Unit

  • Important features of regulatory guidances on immunogenicity for biosimilars
  • Experiences with working with the regulatory authorities
  • Strategies for Biosimilar immunogenicity testing assay formats
  • The most challenging issues

3. Challenges of Neutralizing Antibodies Assays

Shalini GuptaShalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.


Deborah FincoDeborah Finco, Ph.D., Senior Principal Scientist, Drug Safety R&D, Pfizer, Inc.

  • Factors for selection of cell-based Nab vs. non-cell-based Nab assays
  • New technologies
  • How you deal with poor drug tolerance, lack of sensitivity and matrix interference
  • Challenges for Nab validation
  • Interpretation of the results and implications for risk assessment

Immunogenicity Strategy for Overcoming Target Interference

Olivier PetricoulOlivier Petricoul, Ph.D., Senior Investigator II, DMPK-PK/PD, Novartis Institutes for Biomedical Research

  • Important points to consider when developing your strategy to ensure you get good assay results for the BLA and NDA: what needs to be included?
  • Challenges experienced with target interference and strategies for overcoming this
  • Which clinical relevance
  • Sharing of experiences

4. Evaluation of Pre-Existing Antibodies, and their Relevance and Impact

Jim McNally, Ph.D., Senior Principal Scientist, Biotherapeutics Research, Pfizer, Inc.

  • Potential complications with pre-existing antibodies
  • How to distinguish between pre-existing antibodies and potential immune responses to the drug
  • Sharing of examples seen in the clinic and their relevance
  • Implications for humanized antibodies and novel humanized antibody products


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

7:00 End of Day


8:00 am Morning Coffee

Immunogenicity Assessment Challenges in the Clinic

8:30 Chairperson’s Remarks

Shalini GuptaShalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

8:35 Immunogenicity and Biosimilars

Bonnie Rup, Ph.D., Independent Consultant

9:05 Using Statistical Design of Experiment (DOE) in Assay Development to Reduce Drug Interference in Immunogenicity Assays 

Christopher Ehlinger, Ph.D., Senior Associate Scientist, Biologics Clinical Pharmacology, Janssen Research & Development, LLC

An acid dissociation approach is often used to overcome drug interference in immunogenicity assays for anti-drug antibody (ADA) detection.  We utilize a statistical design of experiment (DOE) concept with nonhierarchical 4-Factor Split Plot design to thoroughly evaluate the effects of acid types, acid concentrations, temperature and duration of acidification of acid treatment conditions in the acid dissociation step of immunogenicity assays to improve drug tolerance and more accurately detect ADAs. 


9:35 Advances in Improving Drug Tolerance of NAb assays

Christian VettermannChristian Vettermann, Ph.D., Scientist, Clinical Immunology, Bioanalytical Sciences/PKDM, Amgen, Inc.

To achieve maximal sensitivity, NAb assays utilize a very low concentration of drug that can be easily neutralized by anti-drug antibodies. Therefore, exogenous drug contained in study samples is one of the most critical interference factors that can preclude NAb detection during the dosing phase. This presentation will focus on current approaches to improve drug tolerance of NAb assays through sample pretreatment and their limitations. The relevance of drug tolerance for the interpretation of study data will be discussed, and a novel strategy for detecting clinically impactful NAbs in the presence of high amounts of drug will be presented.

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

NAbs /  Safety of IgE Adas / Immune Complex Disease 

11:05   Challenges Encountered for Cell-based Neutralizing Antibodies Assays

Weifeng Xu, Ph.D., Senior Research Investigator, Bioanalytical Sciences, BMS

11:35 Evaluation of Antibodies of IgE Isotype to Omalizumab and their Potential Correlation to Anaphylaxis

Case Study
Sally Fischer
Sally Fischer, Ph.D., Senior Scientist and Group Leader, Assay Development and Technology, Genentech, Inc.

To better understand the risk of anaphylaxis in patients with allergic asthma receiving regulatory-approved omalizumab, a recombinant humanized monoclonal antibody, a post-marketing pharmacosurveillance study was initiated in March, 2009. As part of this study, an assay was developed to detect antibody of IgE isotype to omalizumab. This presentation will discuss the challenges and approaches in development of this assay as well as the outcome of this post-marketing commitment.

12:05 Cynomolgus Monkey Case Study of Immune Complex Disease

Deborah FincoDeborah Finco, Ph.D., Senior Principal Scientist, Drug Safety R&D, Pfizer, Inc.

We developed a method to induce immune complex glomerulopathy (ICG) in non human primaytes (NHPs) using BGG as the immunogen. The goal was to evaluate possible immune related biomarkers to detect early glomerular injury in non-human primates. We investigated: complement receptor 1 levels on erythrocytes; levels of circulating immune complexes complement split products, macrophage chemotactic protein 1, and anti- BGG antibodies. BGG dosing was associated with changes in CR1, CIC, anti-BGG titers and serum complement split products. The utility as biomarkers will be further discussed during the presentation.

12:35 End of Conference

5:15 Registration for Dinner Short Courses

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