Cambridge Healthtech Institute’s 7th Annual

Optimizing Bioassays for Biologics  

Case Studies Demonstrating Successful Bioassay Development

October 17-18, 2019


As the bioassay field continues to move forward, new technologies and software are changing the way scientists view experimental design and data analysis. The health authorities and USP have provided guidance for the design and validation of a bioassay; however, they do not discuss solutions to common problems springing from this revolution in technology. At Cambridge Healthtech Institute's Seventh Annual Optimizing Bioassays for Biologics, leaders working in bioanalytical and bioassay development will come together to provide case studies and best practices for handling the most common issues in biological assay development, validation, transfer, and maintenance. There will also be a focus on new modalities including cell therapies (encompassing immunotherapies), gene therapies and antibodies. In addition, new technologies and bioassay formats will be presented along with recommendations for implementation to ensure a steady drug development pipeline.

Final Agenda

Thursday, October 17

1:00 pm Conference Registration


1:40 Chairperson’s Opening Remarks

Nancy Sajjadi, MSc, Independent Quality Consultant

1:45 Ensuring Biosimilar Monoclonal Antibody Product Consistency through New Publicly Available Bioassay Standards

Prior_SandraSandra Prior, PhD, Senior Scientist, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC)

The increasingly complex product landscape for biotherapeutic monoclonal antibodies and their biosimilars highlights the need for publicly available bioassay International Standards. These preparations are intended for the calibration of bioassays and local standards, allowing harmonization of bioassay data across products and jurisdictions. International Standards for monoclonal antibodies support a knowledge-based approach to addressing future challenges of potential drifts and divergence in the bioactivities over the lifecycle of these products and will contribute to long-term product consistency.

2:15 Making USP Bioassay Chapters Fit the New Assay Paradigm

Walfish_StevenSteven Walfish, MBA, Principal Scientific Liaison, USP

Laboratory automation, gene therapy assays, and new assay formats are challenging the USP Bioassay Chapter paradigm. During the initial development of the USP Bioassay chapters, the focus was on relative potency assays using a standard. This talk will focus on changes proposed to USP Bioassay Chapters to address the new challenges from our stakeholders to ensure that the Bioassay Chapters stay relevant.

2:45 Current Efforts in Standardization for Bioassays

Dawn Henke, PhD, Senior Technical Program Manager, Standards Coordinating Body


BioAgilytix 3:15 A Platform Assay for Detection of Anti-PEG Antibodies in Patient Serum

Lindley_KathrynKathryn Lindley, Vice President, Operations, BioAgilytix

Modification of bioactive molecules with PEG is commonly used to reduce immunogenicity. However, induction of anti-PEG antibodies in patients has undesirable clinical consequences, including loss of therapeutic efficacy and increase in adverse effects. Here we describe development of a platform assay to detect anti-PEG antibodies in human serum with high specificity and sensitivity. With this assay, we have detected anti-PEG antibodies in serum of patients treated with therapeutics containing 5kDa, 20kDa and 40kDa PEG molecules.

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


4:25 Functional Bioassays for Immune Check Point Inhibitor Screening and I/O Selection

Pattijn_SofieSofie Pattijn, CTO, ImmunXperts

Early evaluation of the effectiveness of candidate therapeutics and combination therapies can be done using in vitro bioassays with primary mouse or human immune cells. Mixed lymphocyte reaction assays using both innate cells and lymphoid cells mimic a physiological T cell response and are widely used for the potency screening of candidate therapeutics. The use of different allogeneic donor combinations can provide additional information on the profile of the responding population. An important factor for sensitive assays and consistent results is the quality of the primary immune cells.

4:55 Harnessing Biolayer Interferometry to Overcome Aggregates Interference in the FcγRIIa Binding Assay

Bajardi-Taccioli_AdrianaAdriana Bajardi-Taccioli, Scientist II, Analytical Development, Biogen

FcγRIIa receptor binding is a part of the mechanism of action for many therapeutic antibodies. The presence of aggregates can impact the binding of Fc-containing molecules to FcRn and FcR, masking actual changes in Fc activity. This presentation will describe a FcγRIIa binding assay based on Biolayer Interferometry, suitable for testing samples with moderate levels of aggregates, and capable of detecting differences in Fc binding due to various glycosylation patterns.

5:25 PANEL DISCUSSION: Emerging Standards for Bioassays

Moderator: Nancy Sajjadi, MSc, Independent Quality Consultant

Panelists: Steven Walfish, MBA, Principal Scientific Liaison, USP

Sandra Prior, PhD, Senior Scientist, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC)

Dawn Henke, PhD, Senior Technical Program Manager, Standards Coordinating Body

Friday, October 18

7:30 am Problem Solving Roundtable Discussions

Please join us for a moderated round table discussion with brainstorming and interactive problem solving. These sessions bring together attendees from diverse backgrounds to exchange ideas and develop future collaborations around a focused topic, in an informal environment.

What is Parallelism, and Why is it so Important?

Moderator: Steven Walfish, MBA, Principal Scientific Liaison, USP

  • Is this the same as dilutional similarity?
  • Why is the F-test outdated?
  • What happens if my curves are not parallel?
  • Discuss your experience with parallelism testing

NEW: Validity Criteria Selection for a Bioassay

Moderators: James Little, Vice President Business Development, Thomas A. Little Consulting, BioAssay Sciences
Daniel Harding, Principal Consultant, Bioassay Sciences


  • Selection of Systems Suitability and alternatives
  • Validity Criteria and Limits
    • Positive Control
    • Negative Control
    • Curve Parameters
    • R2, RMSE
    • RP Delta
    • Curve Parameter Ratios
    • Equivalence Tests
    • F-Tests



8:30 Chairperson’s Opening Remarks

Sandra Prior, PhD, Senior Scientist, Biotherapeutics, National Institute for Biological Standards and Control (NIBSC)

8:35 Method Validation Based on Total Error

Yang_HarryHarry Yang, PhD, Senior Director, Statistical Sciences, AstraZeneca

9:05 Establishing Validity Criteria for Bioassays

Harding_DanielDaniel Harding, Principal Consultant, Bioassay Sciences

Presentation will cover validity and systems suitability alternatives, best practice, and regulatory requirements. It will discuss the rationale and justification for selection of criteria for both 4PL and PLA type bioassays. Statistical and practical risk-based method of setting the limits will be presented with associated recommendations and templates to set limits.

9:35 Roundtable Report Outs

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

10:45 Strategies and Adaptations of Automated Workflows for Cell-based Assays

Villareal-Kinney_JeanetteJeanette Villarreal-Kinney, Senior Research Associate, Technical Development, Biological Technologies, Genentech, Inc.

Cell-based assays have emerged in recent years, as an effective and robust addition to the suite of assay technologies available for validating potency methods. Previously, biochemical target-based assays have been the technology of choice. With the emergence of automation and other ergonomic friendly technologies, it is important to keep in mind the lessons that have been learned from the adaptation of these technologies, with special consideration being given to reporter cell lines, liquid handling complications and instrument-introduced artifacts. We present an overview of the problems encountered and effective solutions to these problems.

11:15 The Analytical Target Profile and Bioassay Development

Ryan Yamagata, US Function Head, CMC Statistical Sciences, Vaccines Technical Research & Development, GSK

ICH Q8(R2) does not explicitly refer to analytical method development. However, a Quality by Design (QbD) approach can also be applied to bioassay development, driven by the Analytical Target Profile (ATP). This talk will present how the ATP can be used as a guide for bioassay development and assess the fitness for use of a bioassay.

11:45 Statistical Approach to Reference Material Bridging

Lui_JiaJia Liu, PhD, Manager, Pharm Science & PGS Statistics, Pfizer Inc.

Reference materials play a significant role in calibrating and trending the performance of some analytical assays, including bioassays. These analytical assays are used to assess the product quality in a number of activities, such as characterization, comparability, lot release, and stability. However, the guidelines for bridging a new reference material to a current one are general and there is not a clear best practice across industry. To assess the suitability of the new reference material, including full characterization of the material, a powered statistical assessment is proposed to ascertain that the new reference material is equivalent to the existing reference material. Statistical approaches based on different phases of product development will be presented and discussed herein.

12:20 pm Session Break

GeNovu 12:30 LUNCHEON CO-PRESENTATION: Data-Driven Methods Development – Using GeNovu’s ADA MultiParameter Modules to Develop Methods More Efficiently

Kyle Cook, CEO, CTO,  GeNovu

Alex Gurka, Scientist III,  DMPK, Boeringer Ingelheim

Using Design of Experiments (DOE) during clinical ADA methods development allows for numerous assay parameters to be tested simultaneously.  Executing these highly complex designs manually can be challenging and subject to human error.  By integrating automation and DOE using GeNovu’s MultiParameter Modules, method optimization can be executed more efficiently while also producing a wealth of data, providing confidence that the most appropriate assay has been developed for the program.

1:15 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing


1:55 Chairperson’s Remarks

Walter W. Hauck, PhD, Former Senior Scientific Fellow, USP

2:10 Recent Results on Equivalence Test Bounds to Limit Non-Similarity Induced Bias in Potency, with Additional Discussion about Power

Lansky_davidDavid Lansky, PhD, President, Precision Bioassay, Inc.

Minimizing bias of potency is a major goal of bioassay design, development, validation, and monitoring. Sensitivity analyses show that non-similarity causes appreciable bias. Similarity equivalence bounds (for scaled shifts) can be set to limit bias in potency due to non-similarity; these results are robust to both the design and properties of assays. Additionally, power analyses for similarity assessment are not routine; we show why they are important.

2:40 PANEL DISCUSSION: Methods for Setting Equivalence Bounds

Moderator: Walter W. Hauck, PhD, Former Senior Scientific Fellow, USP

Panelists: Ryan Yamagata, US Function Head, CMC Statistical Sciences, Vaccines Technical Research & Development, GSK

Harry Yang, PhD, Senior Director, Statistical Sciences, AstraZeneca

3:30 Close of Optimizing Bioassays for Biologics