Cambridge Healthtech Institute's 11th Annual

Immunogenicity Assessment and Regulatory Approval of Biologics

( 生物制剂免疫原性评估与主管机构的核可 )

Achieving Assay Quality and Clinical Success of Novel Biologics

2018年5月2-3日 | World Trade Center | 马萨诸塞州波士顿


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 11th 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.

Final Agenda

Recommended Short Course(s)*

SC1: Preclinical and Clinical Assessment of Immunogenicity: Multidomain Therapeutics and New Modalities, Including Gene Therapy and CAR T

SC13: Sub Visible Protein Particles in Immunogenicity: Measurement, Characterization and Impact

*Separate registration required.


7:30 am Registration and Morning Coffee


8:30 Chairperson's Remarks

Shan ChungShan Chung, PhD, Principal Scientist and Group Leader, Genentech, Inc.

8:40 Acid Treatment of Serum Samples in ADA Assays: To Treat or Not to Treat?

Uma Kavita, PhD, Senior Research Investigator, Analytical and Bioanalytical Operations, Bristol-Myers Squibb

Despite the common use of acid treatment to dissociate anti-drug antibody (ADA)-drug complexes, a systematic study of the impact of various acids at different pH levels on ADA of differing affinities and the resulting impact on assay drug tolerance and sensitivity has not been reported. Using a dimeric domain antibody therapeutic and several mouse monoclonal antibodies of well-defined association and dissociation rate constants and differing relative affinities as well as a rabbit pAb as ADA controls, we have addressed several important issues related to acid pre-treatment and impact on ADA assay sensitivity and drug tolerance.

9:10 Sample Pre-Treatment to Resolve Matrix Interference in a Neutralizing Antibody Assay

Lynn KamenLynn Kamen, PhD, Scientist, BioAnalytical Sciences, Genentech

Neutralizing antibody (NAb) assays detect the presence of anti-drug antibodies that neutralize the mechanism of action of a therapeutic. While interference from the drug is a common problem in development of NAb assays, interference from the sample matrix itself can also interfere. This presentation will highlight a case study in which matrix interference in a NAb assay was identified and resolved via sample pre-treatment, allowing the successful detection of NAbs.

9:40 Using ICP-MS to Measure Total Drug Levels and Differentiating between Free Drug and Bound Drug to Anti-Drug Antibodies

Julio DelgadoJulio Delgado, MD, MS, CMO, ARUP Laboratories; Division Chief, Clinical Pathology, University of Utah School of Medicine; Associate Professor, Pathology, University of Utah

Development of anti-drug antibodies (ADA) against biological agents contributes to therapeutic failure. An ICP-MS assay was developed for detection of free Infliximab and Infliximab bound to ADA. The difference in concentrations between free and bound Infliximab indicates presence of ADA. The ICP-MS assay showed high tolerance to residual infliximab, so testing can be performed right after infusion. Early detection of ADA is helpful to optimize treatment in the inpatient setting.

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



Shan ChungShan Chung, PhD, Principal Scientist and Group Leader, Genentech, Inc.


Uma Kavita, PhD, Senior Research Investigator, Analytical and Bioanalytical Operations, Bristol-Myers Squibb

Julio DelgadoJulio Delgado, MD, MS, CMO, ARUP Laboratories; Division Chief, Clinical Pathology, University of Utah School of Medicine; Associate Professor, Pathology, University of Utah

Theo RispensTheo Rispens, PhD, Immunopathology, Sanquin Research, Amsterdam, Netherlands

Steven Bowen, PhD, Immunogenicity Reviewer, OBP/OPQ/CDER, FDA

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

  • Technical considerations for sample pre-treatment methods developed to reduce drug interference
  • Epitope integrity during pre-treatment (e.g. non-denaturing)
  • Subject, patient interfering factors: Cross-reactive antibodies (e.g. rheumatoid factor, allo-antibodies)
  • Applicability of these methods in the clinical laboratory setting
  • Clinical significance/added value of ADA results generated from assays involving sample pre-treatment methods


11:25 The Use of Non-Clinical Assessments in Immunogenicity Risk-Assessment during Drug Development

Zuben SaunaZuben E. Sauna, PhD, Research Biologist & Principal Investigator, Haemostasis Branch, Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, FDA/CBER

Immunogenicity (development of anti-drug antibodies) is an impediment to development and licensure of therapeutic-proteins. There has been significant progress in the development use of non-clinical assessments of immunogenicity-risk. The application of these tools will be illustrated using case studies and examples from our research. I will also present data evaluating different Factor-VIII products in a MHC-Associated-Peptide-Proteomics (MAPPs) assay. These results show that proteins with the identical primary sequence may present differently to the immune system.

11:55 T Cell Response to Biologics: From T Cell Epitope Mapping to Immunomonitoring

Bernard Maillere, PhD, Director, Research and Head of Immunochemistry Laboratory, Institute Frederic Joliot, SIMOPRO, CEA, University Paris-Saclay

As the T cell activation precedes and contributes to antibody response we evaluated the T cell response to biologics in heathy donors and in patients. With the perspective of immunogenicity prediction, we identified T cell epitopes from T cells collected in healthy donors of multiple biologics including infliximab, rituximab, adalimumab, natalizumab, FVIII en IFN-b. T cell epitopes identified from the healthy donors were shown to participate to the T cell response in the treated patients. Using a new triple-cytokine fluorospot assay we revealed a T cell response in multiple ADA- patients qualitatively different from that of ADA+ patients demonstrating that the lack of ADA did not imply an absence of immune response.

LONZA tagline12:25 pm Presentation to be Announced

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

1:55 Session Break


2:10 Chairperson's Remarks

Marisa JoubertMarisa K. Joubert, PhD, Principal Scientist, Process Development, Amgen, Inc.

2:15 Updates on FDA Guidelines for Novel Biologics: Interpretation and Implementation

William HallettWilliam Hallett, PhD, Product Quality & Immunogenicity Reviewer, CDER/OPQ/OBP, FDA

Assessment of immunogenicity as well as appropriate interpretation of immunogenicity data is of critical importance for defining safety profile of therapeutic protein products for licensure. An understanding of the kinetics of anti-drug antibody development and how it relates to clinical impact is important. This talk will compile FDA's current thinking on assay development in assessing immunogenicity and provide recommendations to improve the integration of immunogenicity data in submissions.

2:45 Mitigation of Low Cut-Point for Immunogenicity Evaluation

Zhandong ZhongZhandong Don Zhong, PhD, Associate Director, Teva Pharmaceuticals

Cut point (CP) is a fundamental assay criterion in immunogenicity assessment. It is therefore critical to determine a robust assay CP that is statistically sound and relevant to the population under evaluation. Various assay factors and donor characteristics may contribute to low assay background, lack of assay variability, and unnecessary outlier removal, leading to an extremely low CP. This talk will discuss strategies to effectively mitigate such a low CP.

3:15 Sponsored Presentation (Opportunity Available)

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

4:45 Problem-Solving Breakout Discussions

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

7:00 End of Day


8:00 am Morning Coffee


8:30 Chairperson's Remarks

Marisa JoubertMarisa K. Joubert, PhD, Principal Scientist, Process Development, Amgen, Inc.

8:35 Innate Immune Response Modulating Impurities: Impact, Detection, and Interplay with Aggregates

Daniela VerthelyiDaniela Verthelyi, PhD, Chief, Laboratory of Immunology, Office of Biotechnology Products, Office of Pharmaceutical Quality, CDER

This talk will discuss the impact of innate immune response modulating impurities and aggregates on the immunogenicity risk assessment for therapeutic peptides and proteins with a particular focus on how they can modulate the local innate immune and inflammatory responses.

9:05 Impact of Chemical Modifications on the Immunogenicity of IgG Subvisible Particles

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

The theoretical concerns regarding the potential immunogenicity of proteinaceous aggregates and subvisible particles in protein therapeutics have been widely debated. This talk will present the detailed mechanistic studies on the biological impact of aggregates and sub-visible proteinaceous particles in a hIgG1 transgenic mouse model. The results are discussed within the current status of related literature of in vivo and in vitro studies.

9:35 Sponsored Presentation (Opportunity Available)

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

11:05 Case Studies Assessing the Impact of Key Product Quality Attributes on Safety of Biotherapeutics

Marisa JoubertMarisa K. Joubert, PhD, Principal Scientist, Process Development, Amgen, Inc.

11:35 Complexity of Phenomena and Factors that Influence the Aggregation of Biopharmaceuticals in Human Plasma Revealed by New Case Studies

Tudor ArvinteTudor Arvinte, PhD, Professor, Biopharmaceutics, School of Pharmacy Geneva-Lausanne, University of Geneva and Therapeomic, Inc.

Biopharmaceutical formulations, despite successful release for particulates according to regulatory requirements, may aggregate during in vivo administration. New in vitro studies of the aggregation of biopharmaceuticals in plasma show that: i) plasma aggregation occurs in many types of biopharmaceuticals, ii) can be different in plasma from patients and healthy donors, iii) there are donor-to-donor and patient-to-patient variations, iv) aggregation in animal model plasma can be different from human plasma, v) plasma aggregation may depend on the manufacturing clone, vi) stable formulations that do not aggregate in plasma can be developed.

12:05 pm Immunomodulatory Effects of Host Cell Impurities in Biotherapeutic Monoclonal Antibodies

Shraddha RaneShraddha Rane, PhD, Postdoctoral Research Associate, Infection Immunity and Respiratory Diseases, The University of Manchester

The ability of monoclonal antibodies to induce immune responses in patients, and the production of anti-drug antibodies (ADA), can reduce efficacy and provoke adverse health effects. There is increasing evidences that aggregation and presence of host cell impurities (even at very low levels) can enhance and modify the immunogenic potential of monoclonal antibodies (mAb) and other protein therapeutics. Here we examined the ability of low levels of a common host cell impurity to modulate the immune responses to aggregates of two mAbs. The fact that HCP preferentially binds to mAb aggregates suggests that HCP impurities, although low, could be selectively concentrated by aggregate formation and thus contribute to an adjuvant-like stimulation of the immune responses.

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

* 活动内容有可能不事先告知作更动及调整。

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