Optimizing Bioassays for Biologics


As the bioassay field continues to move forward, challenges are evolving from new drug formats such as antibody therapies, cell therapy and gene therapy. There are numerous considerations to keep in mind during assay development such as lifecycle management and planning for lot release. At the Fifth Annual Optimizing Bioassays for Biologics, bioassay experts will address the top challenges in bioassay design including novel technologies, increasing complex mechanisms-of-action, regulation and the application of statistics in assay development. Case studies and best practices for handling the most common issues in biological assay design will be presented. Overall, this event will showcase ways to continue moving a biologic forward in the discovery pipeline.

Final Agenda



12:00 pm Registration (Commonwealth Hall)

12:35 Luncheon in the Exhibit Hall with Poster Viewing (Commonwealth Hall)


beacon hill complex

1:40 Chairperson’s Opening Remarks

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

1:50 Statistical Approaches and Considerations for QbD in 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, as discussed in USP <1032>. This presentation will review relevant statistical considerations and approaches when applying QbD principles to method development and will include examples from bioassay development.      

2:20 Optimization of a Complement Dependent Cytotoxicity Assay

Abrams_kristinKristin Abrams, Scientist, Amgen, Inc.

Complement Dependent Cytotoxicity assays are used to measure complement cascade activation for many biopharmaceuticals. These assays can be used for characterization of the ability of the product to activate the complement cascade to avoid undesired safety concerns or these can be used to measure the mechanism of activation of the targeted pathway.  When these assays are used as part of product release, controlling variability is imperative. When run in QC, the CDC assay exhibited a moderate degree of variability. As part of method lifecycle management, the method was closely evaluated, and minor changes were implemented which led to major improvements in assay performance. It has become clear during this assay optimization that the changes will not only significantly improve robustness, precision, and accuracy, but also increase ease of execution.

2:50 Strategic Ways to Meet Bioassay Performance Requirements with Modular Design and Analyses

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

Reportable values (geometric mean) of potency from bioassays of lots are compared to product specifications. Process control limits for log potency are narrower than product specifications. Assay performance requirements and their control limits (on appropriate measures of assay performance) guide assay development and monitoring. Modular design and appropriate analyses support efficient and flexible development and validation as well as alternate assay formats for alternate intended uses.

3:20 Extended Q&A with Session Speaker

3:50 Networking Refreshment Break (Harbor & Mezzanine Level)

4:20 Improving the Robustness of a Bioassay through Outlier ID and Removal

Little_ThomasThomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting

Bioassays are known for being more variable compared to other analytical methods. Variation in the dose response is generally one of the primary root causes. The presentation will discuss within dose and between dose outlier and removal concepts and how it will impact curve fitting, confidence intervals and general bioassay performance. Four Parameter Logistics and Parallel Line Analysis type bioassays will be included in the discussion.

4:50 Strategies and Approaches for Building a Better Bioassay

Alexandra Zakharova, Head, Cell-Based Assay, BIOCAD

This presentation provides an overview of strategies and general considerations for developing MOA reflective, accurate, precise, QC-friendly and phase appropriate potency assays. Potency is a critical quality attribute of biological products. The main problem of bioassays is a very high variability. In the presentation, I will demonstrate approaches that reduce the test variability, increase consistency of analysis and significantly improve the lab efficiency.

5:20 End of Day

5:20 Registration for Dinner Short Courses (Commonwealth Hall)

Recommended Dinner Short Course*

SC13: Bioassay Quality by Design

Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting


*Separate registration required.



8:00 am Morning Coffee (Harbor Level)


beacon hill complex

8:30 Chairperson's Remarks

Perceval Sondag, Senior Manager, Statistics, PharmaLex

8:35 FEATURED POSTER: A Case Study: Addressing Assay Curve Shifts in a Bioassay for a Late Stage Therapeutic Antibody

Tongyun (Tony) Dang, PhD, Senior Scientist, BioTherapeutics Development, Discovery, Product Development, & Supply, Janssen Research & Development

Here we present a case study involving a cell-based bioassay for an IgG1 monoclonal product that had been successfully validated and transferred to multiple testing sites. During late stage development, a shift of the assay curve was identified and investigated, and a root cause was determined. Through review of historical data and evaluation of critical reagents, it was determined that a single critical reagent was responsible for the assay shift. As corrective actions, the method was updated to reduce impact on future assay shifts and the critical reagent qualification procedure was improved. Strategies are discussed to prevent future occurrences of assay curve shifts.

9:05 PANEL DISCUSSION: Best Practices to Overcome Bioassay Development Challenges

Moderator: Perceval Sondag, Senior Manager, Statistics, PharmaLex

Panelists: Gaël Debauve, PhD, Head, Bioassay Development, Analytical Sciences for Biologics, UCB

Steven Walfish, MBA, Principal Scientific Liaison, USP

Alexandra Zakharova, Head, Cell-Based Assay, BIOCAD Statistical considerations at each stage of bioassay development

  • Challenges presented by new modalities and emerging therapies
  • Best practices in ensuring quality control, lot management, and release
  • Implementing new technologies and techniques in assay design and validation

10:05 Networking Coffee Break (Harbor & Mezzanine Level)

10:35 KEYNOTE PRESENTATION: Demystifying USP Bioassay Chapters

Steven Walfish, MBA, Principal Scientific Liaison, USP

Many companies do not have access to statistical support for bioassay design and development relying on USP General Chapters for guidance. This talk gives insights into the chapters and explains some common misconceptions with them. The importance of dilutional similarity and bioassay analysis will be highlighted.


Beacon Hill Complex

11:05 Statistical Approaches for Successful Assay Bridging

Sondag_PercevalPerceval Sondag, Senior Manager, Statistics, PharmaLex

To calculate a relative potency of a vaccine batch, a reference batch is needed. The problem is that the reference batch has a life span of 3-4 years (before running out of stock, for example), and a vaccine has a commercial life of about 30 years. Bridging studies are used to estimate a correction factor between a new and an old reference batch. Statistical methodologies for a successful bridging are widely misunderstood. This talk presents an overview of the statistical methods applied to assay bridging.

11:35 Analytical Bridging: How to Cross on the Wire Stretched Between Two Bioassay Methods? A Case Study

Debauve_GaelGaël Debauve, PhD, Head, Bioassay Development, Analytical Sciences for Biologics, UCB

Biological products rely on a wide range of analytical methods for lot release and stability testing. As method improvement is a continued effort during lifecycle management of biopharmaceuticals, bridging studies are key to demonstrate comparability between old and new methods. Through case studies, we will attempt to clear the way, sometimes complex, allowing to conclude to method equivalence.

12:05 pm Statistical Considerations for Design and Analysis of Assay Bridging Studies

Yang_HarryHarry Yang, Ph.D., Senior Director, Statistical Sciences, AstraZeneca

Biological products rely on a wide array of analytical methods for product characterization, lot release, and stability testing. As method improvement is a continued effort during the lifecycle of a biopharmaceutical product, bridging studies are often conducted to demonstrate comparability of the old and new methods. In this presentation, we discuss statistical considerations in the design and analysis of bridging studies for analytical methods.

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Networking Refreshment Break (Harbor & Mezzanine Level)


beacon hill complex

1:35 NEW: Chairperson’s Remarks

Craig Kaftan, Senior Scientist, Analytical Development, Pharmaceutical Sciences, Shire HGT, a Member of the Takeda Group of Companies

1:40 Identifying and Controlling Sources of Variation in Cell-Based Potency Assays

lowe_emilyEmily Lowe, PhD, Senior Scientist, Analytical Sciences, Kite Pharma, a Gilead Company

Cell-based potency assays are essential for engineered cell therapy products to demonstrate that drug product activity is linked to biological critical quality attributes. One of the biggest challenges in designing and executing cell-based potency assays is identifying and controlling variability. A poorly controlled and highly variable potency assay can increase invalid and re-test rates, or worse, cause a manufacturing process to appear out of control or a drug product to appear unstable. Identifying and mitigating sources of variability begins during initial assay design, as part of QbD for method development, and should continue to be a focus through life cycle management. Here, we will discuss expected and unexpected sources of variability and control strategies through presentative case studies.

2:10 NEW: Challenges in Developing Bioassays for Novel Therapeutics: Focus on Antibody Drug Conjugates

Luu ly Le, Immunogen


2:40 Cytotoxicity Assay Development for CAR-T

Mullan_ashleyAshley Mullan, Scientist, Development, Analytical Sciences, AstraZeneca

3:10 NEW: The Rare Case: Bioassay Method Development and Two Happy Customers, PD and Quality

Kaftan_CraigCraig Kaftan, Senior Scientist, Analytical Development, Pharmaceutical Sciences, Shire HGT, a Member of the Takeda Group of Companies

The goal of cell-based potency methods is to provide meaningful insights into a therapeutic’s structural integrity and intended physiological role. Both development and implementation come with challenges inherent when working with living organisms. Additionally, potency methods need to satisfy two very different customers, PD and Quality. For product development, the methods need to be specific, precise, robust and sensitive to be effective tools to support Process and Formulation Development and Regulatory Filings while concurrently simple in execution and management to support routine GMP lot release. However, when successful, it may come with great reward such as more comprehensive product and process understanding improving the likelihood of successful, expedient new product development.

3:40 End of Conference

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