Optimizing Bioassays for Biologics

Case Studies Demonstrating Success in an Era of Emerging Modalities including Cell & Gene Therapy

October 5 - 6, 2022 ALL TIMES EDT

More and more products have emerged including cell & gene therapies and other novel therapeutic modalities. This continues to push the need for better testing and improved bioassay development. Many of these new formats present challenges. For ten years, Cambridge Healthtech Institutes, Optimizing Bioassays for Biologics have brought together speakers from industry and academia working in bioassay development, bioprocessing and bioanalytical. Here the aim has been, educating newer and up-and-coming scientists entering this field in large numbers, showcasing cutting edge and case studies from their work and discussing how agencies in the US and in Europe are viewing testing with emerging modalities, especially with cell and gene therapy. Participate to hear from innovative speakers, especially those with a product coming to market, on best practices for handling the most common challenges in biological assay development, validation, transfer, and maintenance. How did they get a product to market in the face of challenges like creating a standard, how did they deal with potency calculations and beyond.

Wednesday, October 5

Registration Open (Arlington Registration)12:00 pm


ROOM LOCATION: Arlington Salon VI

12:45 pm

Chairperson's Opening Remarks

Ravindra Kumar, PhD, Director, Bioassay Lead, Analytical Sciences, Spark Therapeutics, Inc.

12:50 pm

Trimming the Fat from Your Bioassay – Ways to Make the Most of Your Plate Real Estate

Ann Yellowlees, PhD, Director of Statistics, Quantics Consulting Ltd.

Manufacturing is about “Lean” (i.e. efficient): How do we apply the same disciplines to bioassay? During development, many assays evolve in a complex way that is not necessarily “Lean”. It doesn’t have to stay that way! Once the biology is stable and well-characterized we can re-evaluate the design, before validation, to increase throughput (efficiency) whilst retaining precision (effectiveness). We’ll discuss case studies showing improved outcomes by embracing “Lean” principles.

1:20 pm

Change of Drug Product Formulation-Mediated Innovation for Potency Development and Calculation

Jan Amstrup, PhD, Principal Scientist, Chemistry, Manufacturing & Controls BioAnalysis, Novo Nordisk AS

A potency assay used for several years showed not to be sensitive to low-affinity insulin analogs as well as impacted by the Drug Product matrix. A story regarding implementation of two new potency assays as well as the learnings will be described.

1:50 pm

Selecting the Dilution Levels and Dealing with Outliers

Perceval Sondag, Senior Director of Data Science, Head of Scientific Analytics, Novo Nordisk

This talk will address two common challenges faced by bioassay scientists. The first challenge is the selection of the proper dilution levels in relative potency assays, to observe the most precise and accurate estimates of both relative potency and similarity metrics. Common optimizers are challenging to use for nonlinear models and require the help of highly experienced statisticians. This talk will present a simple alternative that is easy to implement by non-statisticians. The second challenge addressed is the presence of outliers in bioassay data. This talk will present the different types of outliers in such data, and give pointers on how to detect, and deal with them.


Immunogenicity Challenges in Bioanalytical Development of Cell and Gene Therapy Products


Stephanie Pasas-Farmer, PhD, President and Founder, Ariadne Software LLC

  • Unwanted immunogenicity assessment for classical modalities vs ATMPs
  • Immunogenicity assessment strategies for autologous vs. allogenic cell therapies
  • Innate immunity and its impact on cell and gene therapy products
  • NAb vs. Tab response or cellular response to capsid proteins
  • Importance of biomarkers/PD for programs with expected complex immunogenicity profile​

Boris Gorovits, PhD, Vice President, Bioanalytical & Non-Clinical Biomarkers, Sana Biotechnology

Priya S. Chockalingam, PhD, Vice President & Head, Clinical Bioanalytics & Translational Sciences, Beam Therapeutics

Cheikh Kane, PhD, Senior Director Biopharma, KCAS Bioanalytical & Biomarker Services

John Farmer, PhD, Director, Immunology & Large Molecule Bioanalysis, Lovelace Biomedical

Richard Snyder, Senior Medical & Scientific Advisor, Q2 Solutions

Refreshment Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)2:50 pm

3:30 pm

An Overview of Bioassays Development and Validation for Biologic, Vaccine, and Gene Therapy Modalities

Ravindra Kumar, PhD, Director, Bioassay Lead, Analytical Sciences, Spark Therapeutics, Inc.

Biomolecules are highly complex, physiochemical information alone is not sufficient to confirm high-order structure. Therefore, biological activity needs to be demonstrated for biomolecules. Biological activity is measured in bioassay to determine potency which is a critical attribute that measures the ability of drugs to elicit their function. Basic methodology of bioassay development and validation is the same for biologic, vaccine, and gene therapy modalities. However, the mechanism of action, variability, and challenges are drastically different. The talk will be focused on providing an overview of bioassay challenges and best practices for biologic, vaccine, and gene therapy products.

4:00 pm

Approaches to Overcome Unique Challenges in Bioassay Development for Gene Therapy

Elena Balkanska-Sinclair, Senior Research Associate II, Analytical Development, Ultragenyx Pharmaceutical

The gene therapy field is one of the fastest growing modalities in the pharmaceutical development realm. Potency assays are an essential regulatory aspect of the gene therapy field. The development and validation of these assays are paramount in licensing, but often pose time-consuming, multifaceted, and expensive challenges. This talk will explore effective optimization methodologies to overcome some of the more significant challenges that arise during the development process.

ROOM LOCATION: Arlington Salon V


Immunogenicity Assessment of Gene Therapy Products


Michael Partridge, PhD, Director, Bioanalytical Sciences, Regeneron

  • Assessment of pre-existing antibodies to gene therapy vectors and the potential impact of these antibodies on the therapy
  • Discussion around T cells: An important issue for many gene therapy products
  • Assays: Is the protein therapeutics paradigm applicable? Tiered assessment; Binding ADA and NAb (inhibitor); Conservative 5%/1% false positive concept; Cut point determination. E.g. Hemophilia GTx Guidance and recommendations for assessment of inhibitors. Is assessment of binding antibodies recommended as well?
  • Are these elements needed for assessment of immunogenicity to the components of the GTx and the transgene?
  • Is an integrated summary of immunogenicity recommended? 
  • Is an immunogenicity risk assessment recommended?

Andrew Byrnes, PhD, Chief, Gene Transfer and Immunogenicity Branch, CBER, FDA

Brian Long, PhD, Principal Scientist, Clinical Immunology, BioMarin Pharmaceutical, Inc.

Klaudia Kuranda, PhD, Head of Immunology, Spark Therapeutics, Inc.

Close of Day5:00 pm

Thursday, October 6

Registration and Morning Coffee ( Arlington Foyer)7:30 am


ROOM LOCATION: Arlington Salon V

7:55 am

Chairperson's Remarks

Steven Walfish, Statistics Lead, GSK

8:00 am

Advances in Co-Formulation Biologic Therapeutics – A Bioassay Perspective

Uchechukwu Okorji-Obike, PhD, Scientist, Bioassay, Biosafety and Impurities (BB&I), AstraZeneca

Combination therapy can significantly increase the impact of biologics as therapeutics. Patient-friendly delivery methods are essential for improved clinical outcomes. Factors like patient compliance, therapeutic efficacy, pharmacological specificity, and concordance could be addressed by co-formulation; making this approach a sought after outcome where possible.  Development of analytical methods including bioassay within CMC is crucial for delivery of co-formulation therapeutics. This presentation will explore the technical challenges and considerations for developing co-formulation biologics from a bioassay perspective. A case study will look at potential pinpoints to be examined and activities leveraged on for delivering bioassays to support a combination therapy.

8:30 am

Principles and Practices for Reference Standards

Tim Schofield, Owner & Consultant, CMC Sciences LLC

Reference standards are essential to the development and control of biological products. USP recommends reporting potency of test articles relative to a reference standard, while some laboratories use these also or instead as a control. Considering their importance, however, there is no consensus on the source of a reference standard, the basis, and means of reference standard qualification and stability evaluation, or the use of a primary standard. This talk will discuss principles and practices related to reference standards used to report potency of biological products and propose strategies for their acquisition and evaluation. Those proposals will borrow from practices related to quality by design for analytical methods, highlighting fitness-for-use of a references standard as well as reduction of uncertainty and the decision risks associated with their uses during development and quality control.

9:00 am Development of an iLite Reporter Cell Platform for the Quantification of Anti-AAV Neutralizing Antibodies

Jordi Rodó Morera, PhD, R&D, Svar Life science

The efficacy of gene therapies using recombinant AAV can be limited by an antibody-mediated immunity against the virus. AAV infections, potentially occurring in early childhood, may result in a pre-existing immunity to one or more AAV serotypes. Here we present a novel two-component iLite reporter cell system for the detection and quantification of neutralizing antibodies against AAV vectors. This assay allows for reliable assessment of anti-AAV antibodies in clinical applications.  

Breakout Discussions9:30 am

Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit the breakout discussions page on the conference website for a complete listing of topics and descriptions.

BREAKOUT DISCUSSION: Defining a “Phase Appropriate” Bioassay – IN-PERSON ONLY

Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

  • What does it mean to adopt a lifecycle approach to bioassay development and validation? 
  • What matters most to regulators at Phase I, II and III when it comes to measuring potency?
  • How to choose an Interim reference standard(s) and transition to a Primary reference standard and a Working standard?​

BREAKOUT DISCUSSION: Collaboration with Your Statistician – IN-PERSON ONLY

Tim Schofield, Owner & Consultant, CMC Sciences LLC

  • When should bioassay scientists require help from a statistician?
  • What can bioassay scientists learn to do themselves?
  • When should bioassay scientists perform Design of Experiments?
  • Should bioassay scientists use Statistical Process Control for their assays?

Coffee Break in the Exhibit Hall with Poster Viewing (Arlington Salon IV)10:20 am

ROOM LOCATION: Arlington Salon VI

11:00 am

Recent Advances in WHO International Standards for Biotherapeutics

Sandra Prior, PhD, Senior Scientist, National Institute for Biological Standards and Control (NIBSC, a Centre of The Medicines and Healthcare products Regulatory Agency)

International standards have a long history supporting biological medicines. They are essential to the assignment of biological potency to many biological products and are responsible to maintain a global network of secondary standards. In the era of recombinant products, biosimilars, and other novel therapeutic modalities, the need for public standard preparations contributing to harmonization in the evaluation of biologicals is increasingly important. Recent data from international collaborative studies illustrate their role.

11:30 am

Steps toward Strategic Control of Potency Bias Caused by Allowed Non-Similarity 

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

Small amounts of some types of non-similarity cause appreciable potency bias. Precision, sample size, and power considerations (or more simply the typical width of similarity confidence intervals) lead to a strategic approach: equivalence bounds based on bias limits with assay size based on precision and power needs for similarity. This approach has important implications for assay design and analysis. This talk will illustrate these issues with examples. 

12:00 pm

Current State of Artificial Intelligence in Drug Discovery and Development

Stephanie Pasas-Farmer, PhD, President and Founder, Ariadne Software LLC

Artificial Intelligence (AI) is increasing efficiencies in drug discovery and development by automating human tasks that are repetitive, demand accuracy, and/or require immense resources. Using some case studies, we will highlight the benefits of AI solutions, as well as discuss challenges that the industry faces in the adoption of AI solutions, such as:

  • Regulatory: lack of guidance for low-risk AI tools; use of existing approval pathways for high-risk AI solutions without addressing some major issues
  • Data: inaccessibility to large amounts of quality training data
  • Awareness: limited understanding of AI
  • Cognitive biases that shape erroneous and biased models
  • Implementation challenges
12:30 pmEnjoy Lunch on Your Own


2:00 pm

Co-Chairperson's Remarks

Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

Steven Walfish, Statistics Lead, GSK

2:05 pm

Statistical Methods for Bioassay Equivalence Testing

Steven Walfish, Statistics Lead, GSK

USP <1033> discusses methods for the suitability of a bioassay for its intended use. This talk will cover the relationship between Cpm and the probability of being out of specification. Focus on the two terms related to assay in the denominator and a discussion of relative bias and intermediate precision.

  • Discussion of relative bias and intermediate precision
  • How does bioassay performance impact the probability of out of specification
  • Is total error models better than Cpm?
2:25 pm

Evaluating Robustness: Defining and Demonstrating "Lack of Effect" as Maximum Allowable Inherent Variability

Janice Callahan, Consulting Statistician, Callahan Associates, Inc.

Robustness variables are studied to optimize and evaluate bioassays. Experimental design is a technique to gain efficiency in this process. Response variables include system suitability parameters and relative potency (RP) measures. When assay development is complete, experimental design and RP variabilities are used to prove the assay is robust.

2:45 pm

Lifecycle of Product Reference Standards: Statistical Considerations for the Scientist with a Bridging Case Study

Brian R. Peterson, President & CSO, Bioassay Solutions LLC

Development and characterization of product reference standards present a number of challenges that many fast become acquainted with and others perhaps years after commercialization. This talk will discuss briefly what a number of these challenges can be and how to first be aware and then possibly avoid them. A case study will be presented with actual data (masked/confidential) to demonstrate how to bridge to a new reference standard.


  • Representativeness in the context of Reference Standard (connection to clinical material)?
  • Reference Standard selection and bridging
  • Reference Standard Lifecycle

Statistics & Bioassays, from FAQs to Facts


Nancy Sajjadi, Independent Quality Consultant, Sajjadi Consulting

Steven Walfish, Statistics Lead, GSK

  • Statistically, what does it mean for an assay to be "fit-for-purpose"?
  • What bioassay precision metric(s) should be reported in regulatory submissions to justify specifications?
  • How is the maximum tolerated "variability" of a bioassay established?
  • How does a shift in reference material impact the relative bias limit for a bioassay?​

Janice Callahan, Consulting Statistician, Callahan Associates, Inc.

Brian R. Peterson, President & CSO, Bioassay Solutions LLC

Close of Conference3:35 pm