New therapeutic modalities, including cell & gene therapies, immunotherapies, and antibody therapies, continue to push the limit on bioassay development and implementation. New formats present challenges including determining what reference materials to use and how to validate the assay. Standards are advancing, but questions remain around the regulatory framework for assays. At the 6th Annual Optimizing Bioassays for Biologics, bioassay experts will address the top challenges in bioassay design including lifecycle management, validation, assay bridging, standards, and developing reference materials. Case studies and best practices for handling the most common issues in biological assay design will be presented with a focus on cell & gene therapies.

Final Agenda

Day 1 | Day 2

THURSDAY, MAY 7

12:00 pm Registration

12:35 Luncheon in the Exhibit Hall with Poster Viewing

CELL & GENE THERAPY

1:40 Chairperson’s Opening Remarks

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

1:50 Essentials in Bioassay Design for Gene and Cell Therapy

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

This presentation will cover the unique challenges of evaluating biological activity of genetically modified cells and the specific activity of a viral vector. Novel method for potency and relative potency evaluation will be presented with some case studies. The need for multiple bioassays to explore the elements of activity will also be presented. Potency and relative potency are the most important elements of a drug program.

2:20 From Therapeutic Antibodies to Genomic Medicines: The Challenge of Developing Bioassays Reflecting the Drug’s MOA

Valeria Runza, PhD, Head, Functional Characterization, Large Molecules Research, Pharma Research and Early Development (pRED), Roche Diagnostics GmbH

As the complexity of new drugs increases, the development of mode-of-action reflecting bioassays becomes more challenging. From conventional antibodies to gene therapy, the bioassay strategy has to be carefully designed to balance the efforts and outcomes of phase-appropriate approaches. In this talk, different case-studies covering a wide range of drug complexity and modalities will be presented to set the basis for discussion on what bioassays should reflect and how to overcome case-specific challenges.

2:50 Measurement Assurance, Control Strategies and Documentary Standards for the Development of Bioassays for Cell Therapy

Sumona Sarkar, PhD, Biomedical Engineer, Biosystems and Biomaterials Division, Biomaterials Group, National Institute of Standards and Technology

3:20 Sponsored Presentation (Opportunity Available)

3:50 Networking Refreshment Break

4:20 Strategies, Challenges, and Successes in Optimizing Assays for Cellular Therapies

Jen Fox, PhD, Scientist, Bioassay, Impurities, and Quality, Analytical Sciences, AstraZeneca

4:50 Presentation to be Announced

Lisa Lundberg, Bioassay and Cell Culture Lead, Spark Therapeutics

5:20 End of Day

5:15 Registration for Dinner Short Courses

5:45-8:15 pm Recommended Dinner Short Course*

SC14: USP Standards to Support Quality of Potency Measurements

*Separate registration required.

Day 1 | Day 2

FRIDAY, MAY 8

8:00 am Registration and Morning Coffee

NOVEL ASSAY TYPES

8:30 Chairperson’s Remarks

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

8:35 Bioassay Strategies for Innovative Molecules

Natalia Kozhemyakina, Head, Bioassay Department, BIOCAD

Biological activity is a critical authenticity and quality attribute of biologics. It is extremely important to be sure that we create methods that reflect molecule mode of action, especially in case of multiple MoA, and at the same time is sufficiently precise and accurate. It is well known how potency assay can be variable, laborious, and time consuming with its long multi-stage protocols. The presentation provides case studies of development strategies for innovative molecules and highlights best practices for handling the most common issues in biological assay development.

9:05 Development of a Robust Functional Cell-Based Assay for Replacing the Rabbit Blood Sugar Bioidentity Test of Insulin Analog

Junming Yie, PhD, Principal Scientist, Cell Based Assays, Biologics AR&D, Merck Research Laboratories

A rabbit blood sugar bioidentity assay is required by the FDA to evaluate biological activity for insulin analogs per USP<121> guideline. Not only are a large number of live animals used, but the method is also highly variable and expensive. A reporter cell-based assay was developed by utilizing insulin’s role in regulating hepatic gluconeogenesis pathway. This functional assay was qualified to demonstrate its performance in linearity, accuracy and precision, and was further evaluated on its robustness using design-of-experiment (DoE) approach. Lastly, it was compared with an established insulin receptor phosphorylation assay to demonstrate its superior performance.

9:35 Metabolic Functional Bioassay Development for Monoclonal Antibodies and Insulins

Carole Sourbier, PhD, Principal Investigator, Office of Biotechnology Products, US FDA

The Biologics Price Competition and Innovation Act was passed as part of the Affordable Care Act and under that law, insulins will be regulated as biologics in March 2020. Under the regulations for Biologics License Application review, it is expected that the potency of the insulins and of their associated biosimilars will be assessed quantitatively in a cell-based assay or bioassay that, ideally, represents the product mechanism of action. Currently, the USP is recommending an in vivo rabbit bioidentity test for the assessment of the biological activity of insulins. However, reduction in animal experiments is a worldwide goal for many and it is likely that in vitro bioassays will be submitted for assessing the potency of insulins products. This research talk will highlight some of the aspects of metabolic functional assays to think about during development and product characterization for insulin products and for antibodies that target metabolic pathways.

10:05 Networking Coffee Break

STANDARDS AND REGULATORY CONSIDERATIONS

10:35 Principles and Practices for Bioassay Standards

Timothy Schofield, Owner and Consultant, CMC Sciences, LLC

Standards are essential to the development and control of biological products. Considering their importance, there is no consensus on the source of a standard, the basis and means of standard qualification, and stability evaluation. This talk will discuss principles and practices related to standards used to report potency of biological products and propose strategies. Those proposals will borrow from practices related to quality by design, highlighting fitness-for-use of a standard.

11:05 Current Efforts in Bioassay Standardization

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

This discussion will cover standards for regenerative medicine products. Discussion will focus on standards for bioassays. Published standards and how to implement these standards be addressed. An overview of current standards under development and how to get involved, as well as a forum for questions will be provided.

11:35 PANEL DISCUSSION: Standards and Regulatory

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

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

Timothy Schofield, Owner and Consultant, CMC Sciences, LLC

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

• Setting standards for new bioassay modalities including cell & gene therapies and immunotherapies
• Developing standards and using already-established standards
• Getting involved with standard-setting organizations
• Qualification of standards
• Correction of relative potency when changing standards

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

1:05 Networking Refreshment Break

CASE STUDIES IN BIOASSAY DEVELOPMENT

1:35 Chairperson’s Remarks

Steven Walfish, MBA, Principal Scientific Liaison, USP

1:40 Statistical Model Selection Using USP <1034>

Steven Walfish, MBA, Principal Scientific Liaison, USP

Relative potency is a measure obtained from the comparison of a test sample to a standard based on the capacity to produce the expected biological activity. USP <1034> presents several different models and suitability criteria to determine the reliability of the estimate. This talk will cover traditional linear and non-linear bioassay models with an emphasis on model suitability including parallelism.

2:10 KEYNOTE PRESENTATION: Best Practices in Bioassay Development to Support Registration of Biopharmaceuticals

Marla Abodeely, PhD, Director, Bioassay, Global MSAT Analytical Science and Technology, Sanofi

Biological activity is a critical quality attribute for biopharmaceuticals which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address a number of challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle.

2:40 Uh-Oh, Our Primary Standard Isn’t Stable: What Do We Do Now?

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

Setting: a product with primary standard nearing expiry (pivotal clinical lots and the original standard have expired). Problem: recent confirmation that the primary standard is not stable. How to assign potency to new primary standard? Solution: model potency of all samples in all assays allowing for variation within assay, between assay, between lots, and among degradation rates for lots; use this model to assign the potency of the new standard.

3:10 Critical Reagents Characterization Strategy to Support Biologics/Vaccines Projects at Regulated Bioanalysis

Kun Yang, PhD, Associate Principal Scientist, PPDM, Merck

At the heart of bioassays for biologics are critical reagents used to directly or indirectly measure biologic markers or signals. A comprehensive analytical toolbox of biochemical, functional and biophysical methods (UPLC-SEC, IEX, RP, HIC, CE, icIEF, Octet, and HRMS) has been developed to evaluate the quality of critical reagents. Several case studies, including reagents, troubleshooting and comparison of small scale hybridoma and large-scale recombinant protein, lifecycle management of biologics, developing reference material, emerging standards and regulatory frameworks, will be presented.

3:40 End of Conference

Day 1 | Day 2

* The program is subject to change without notice, due to unforeseen reason.