Bioassays are a critical component of biologics drug discovery and development. However, ever-changing technology, approaches, and regulatory requirements make it difficult to keep projects on track and on budget. Cambridge Healthtech Institute's inaugural Bioassays for Biologics will showcase strategies for assay selection, validation, transfer, and maintenance with an emphasis on molecules with multiple mechanisms. Special focus will be given to the development and validation of potency assays, developing bioassays for multi-domain proteins, and establishing a standard for using cell-based vs. non-cell-based assays. Finally, new technologies and bioassay formats will be presented along with recommendations for implementation to ensure a steady drug development pipeline.



12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

1:40 Chairperson’s Remarks

Liz England, Scientist, Antibody Discovery and Protein Engineering, MedImmune

1:50 Assessment of Neutralizing Anti-Drug Antibodies for Multi-Domain Biologics

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

A growing number of research labs are now working on multi domain biologics (MDB) with a complex and multistep mode of action. As with any biotherapeutic, MDBs present a risk of immune response that could result in various types of clinical sequelae. This presentation will focus on risk-based considerations related to evaluation of neutralizing anti-MDB antibodies, the need and benefits of NAB domain specificity evaluation. Case studies will be presented to support proposed ideas.

2:20 Development and Validation of Novel SPR-Based Assays for Bispecific Molecules

JoelMoellekenJoerg Moelleken, Ph.D., Senior Scientist, Roche Pharmaceutical Research and Early Development, Large Molecule Research, Roche Innovation Center GmbH

Increasing complexity of novel biotherapeutics like bispecific antibodies or fusion proteins raises new challenges for functional characterization as compared to standard antibodies, since two individual interactions and the inter-dependency of binding events needs to be considered. Novel SPR-based binding assays allow parallel assessment of additional information and therefore can lead to a “total” description of the molecule. These assays be validated and enable fast development.

2:50 Bioassays for Antibody Maytansinoid Conjugates (AMCs) Having Multiple Activities

GillianPayneGillian Payne, Senior Director, Bioanalytical Science, ImmunoGen, Inc.

All AMCs have potent maytansinoid-directed anti-tumor activity. Some AMCs also have additional antibody-directed anti-tumor activity. A control strategy for such AMCs will be presented.

3:20 iLite Reporter Gene Technology: Assay Sensitivity & Specificity Throughout The Drug Development Life Cycle

Tovey_MichaelMichael G. Tovey, Ph.D, Managing Director, Biomonitor SAS

Innovative, engineered reporter gene cell lines have been developed with a high degree of specificity, and sensitivity for the quantification of the activity of a diverse range of biopharmaceuticals. The same cell line in which drug-induced activity is normalized relative to the expression of an internal standard can be used in drug discovery, for the quantification of drug potency, and for the analysis of functional drug levels and anti-drug neutralizing antibodies in both pre-clinical, and clinical studies and post-market commitments without drug interference or serum matrix effects within 2 to 5 hours. A common normalized assay read-out also allows direct comparisons of the relative activity & immunogenicity of innovator molecules and biosimilars. The iLite technology has been used to develop highly sensitive and specific assays for critical targets including Her2, VEGF2, CD20, FGF21, IL-23, TNF and to quantify ADCC activity.

3:50 Refreshment Break

4:20 Problem-Solving Breakout Discussions

Implementation of USP1032-33-34 Approach for Relative Potency Assay Development and Validation

Moderator: Gaël Debauve, Analytical Sciences for Biologicals, Bioassay Development Laboratory, UCB Pharma S.A., Braine-L’Alleud, Belgium

  • Added value of the USP approach
  • Challenges associated to the similarity assessment
  • Challenges associated to equivalence limit definition
  • Definition of sample specifications across drug development phases

Strategies for Bioassays with Multiple Mechanisms

Moderator: Gillian Payne, Senior Director, Bioanalytical Science, ImmunoGen, Inc.

  • Aligning industry standards for MDB evaluation
  • Control strategies for molecules with multiple activities
  • Which bioassays are most effective?

5:20 End of Day

5:15 Registration for Dinner Short Courses


8:00 am Morning Coffee

Assay Comparability Case Studies

8:30 Chairperson’s Remarks

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

Unpublished Data

8:35 Bridging Discovery to Development, Leveraging Technology for Accelerated Bioassay Development

HanLiHan Li, Ph.D., Senior Research Investigator II, Lead Discovery and Optimization, Bristol Myers Squibb

To support the fast expanding biologics portfolio in BMS, a bioassay core team has been built in the Cellular Resource Group of Lead Discovery and Optimization department for bridging discovery and development. Our core team is to leveraging the discovery assay experiences, cell line development capacity, extensive cell line inventory and state of art technology platforms.

9:05 Application of Cell-Based Assays in Biologics Drug Discovery

LizEnglandLiz England, Scientist, Antibody Discovery and Protein Engineering, MedImmune

The use of cell-based assays for primary HTS for identification of therapeutic biologics presents a number of extra challenges, due to sample tolerance and assay sensitivity, and therefore have primarily been used for hit to lead evaluation. We will discuss recent advances in high-throughput sample expression techniques that have opened up new possibilities for cell-based HTS within the biologics industry.

9:35 Improved Efficiency and Better Consistency by Applying Ready-to-Plate Cells in a Neutralizing Antibody Bioassay

JennyHuJenny Hu, MSc, Scientist, Bioanalytical Science, PKDM, Amgen, Inc.

A cell-based bioassay, often used in detecting neutralizing antibodies (NAb) against protein therapeutics, can not only produce inconsistent response due to cell age and culture conditions, but also is labor intensive in maintaining a continuous culture. Here we describe using ready-to-plate cryopreserve cells as a reagent to develop and optimize a NAb assay. A comparison of assay performance overtime with regard to the continuous culture was also provided.

10:05 Coffee Break

Technologies and Tools for Bioanalytical Method Development

10:35 Targeted & Functional Proteomics Approaches for High-Throughput Assays

ManuelFuentesManuel Fuentes, Ph.D., Scientist, Medicine, Proteomics Unit, Cancer Research Center, University of Salamanca-CSIC

Targeted proteomics is a powerful approach that enables quantitative analysis of peptides from complex biological samples with high sensitivity and specificity. We report a method for high-throughput, cost-efficient empirical discovery of optimal proteotypic peptides and fragment ions for targeted proteomics applications using in vitro-synthesized proteins. We demonstrate that low-abundance targets and empirically derived proteotypic peptides for 98% of the target proteins. We show that targeted proteomic assays developed using our approach facilitate robust in vivo quantification of clinically relevant human proteins.

Case Study

11:05 Acoustic Membrane Micro-Particle: An Emerging Technology in the Ligand Binding Assay Space

ShannonChilewskiShannon D. Chilewski, Research Scientist II, Analytical & Bioanalytical Development, Bristol-Myers Squibb

This presentation will share a case study addressing key points on how we approached the evaluation of the Acoustic Membrane Micro Particle (AMMP) technology. The instrument has an oscillating membrane where an immunocomplex containing the analyte is captured for detection. The membrane is sensitive to mass changes that affect its vibrating frequency in a manner proportional to the analyte’s concentration. The main potential advantages over established platforms were sensitivity and throughput. The evaluation focused of 4 main points, which will be reviewed as part of this talk.

Case Study

11:35 Optimization of a Bioassay for a Multi Component Immunomodulator using Design of Experiment

Jasmin Barbara Hebeis, Ph.D., Principal Scientist, CMC Bioassay and Genomics, NDA Analytics

We have developed a potency assay for a multi peptide immunoregulator using an IL-2 ELISpot read-out. This was then optimised using Design of Experiment (DoE). As a result, the assay window and net response were improved considerably, with limited effect on the inter-replicate variability. The method was validated to ICH guidelines and is currently in use for cGMP compliant potency testing for clinical release and stability.

12:05 pm FEATURED POSTER PRESENTATION: Method Establishment for Characterization of Anti-Drug Antibody Responses against a Pegylated-G-CSF Drug in Human Patients with Breast Cancer

Mathilde Yu, Ph.D., Director, Research & Development Unit, CIRION Clinical Trial Services, Inc.

12:35 Enjoy Lunch on Your Own

1:05 Refreshment Break

Working with Different Assay Types  

1:35 Chairperson’s Remarks

Susan E. Rutberg, Ph.D., Senior Scientist, Analytical Development, Genzyme

1:40 Strategy for the Use of Orthogonal Methods to Characterize New CHO Host Cell Protein Reagents

Carl Co, Ph.D., Scientist, Analytical Development, Biogen Idec

This presentation describes a strategy used to generate new HCP reagents. Multiple orthogonal techniques including 2D-DIGE, 2D Western Blot and sandwich immunoassays are utilized to characterize different antigens and antibodies. Case studies are presented which highlight different challenges in the generation of new HCP reagents.

Unpublished Data

2:10 A High Performance Non-Radioactive Potency Assay for Measuring Cytotoxicity: A Full Substitute of Chromium-Release Assay Targeting the Regulatory-Compliance Objective

AlexisRossignolAlexis Rossignol, Ph.D., R&D Project Manager, Bioassays, Clean Cells

A novel cytotoxicity potency assay will be described, combining all the advantages of the chromium-release assay with a non-radioactive read-out method. Unlike existent non-radioactive assays (LDH release, CD16 engagement, etc.), the new assay specifically measures the lysis of target cells while exhibiting similar performances (sensitivity, accuracy, precision) to the chromium method, revealing great potentialities for standardized ADCC, CDC or apoptosis activity measurement on a fully regulatory-compliant basis.

2:40 Implementation of Statistical Methods during Method Development for a Cell-Based Potency Assay

SusanRutbergSusan E. Rutberg, Ph.D., Senior Scientist, Analytical Development, Genzyme

Potency testing for biological therapeutics often relies on a measurement of the relative potency of a test sample compared with a reference standard. A method for accurately comparing the dose response curves that considers parallelism of the data must be selected. The USP guidelines promote following an equivalence testing approach for parallelism testing of bioassay data. A case history demonstrating the adoption of the USP guidelines for the determination of relative potency values will be presented.

Case Study

3:10 Why Do We Need Dedicated Guidelines to Develop and Validate Relative Potency Assays? Implementation of USP Approach on Binding and Cell-Based Assays

Gaël Debauve, Analytical Sciences for Biologicals, Bioassay Development Laboratory, UCB Pharma S.A., Braine-L’Alleud, Belgium

We will review the limitations of classical development/validation approaches (i.e. ICHQ2R1) when applied to relative potency assays and how the USP chapters (1032, 1033 and 1034) were successfully implemented on binding and cell-based assays. Through case studies, we will present how fitting model and equivalence limits were defined and how validation characteristics can support the choice of the assay format.

3:40 Potency Assay Strategies for Accelerated Program Timelines 

Zulfia Babadjanova, Associate Principal Scientist, Biologics Analytical Testing, Merck

Potency assays are some of the most technically challenging analytical assays to develop. They often require long lead times and may require specialized reagents or cell lines. However data generated from these assays are critical to understanding a product’s stability profile, the impact of manufacturing changes, and for supporting formulation decisions. The challenges of developing high quality potency assays are even more acute when faced with an accelerated program timeline. In this talk, I will discuss potency assay strategies for a biologic on an accelerated timeline. 

4:10 End of Conference

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