BEBPA Blog
Tech Briefing: The Wonderful World of Potency Assays: Look at me now Ma!
The concept of potency assays came into being specifically for biopharmaceutical products. Originally these products were complex mixtures, produced in a natural system (Like a horse!). They were often ill-defined and rarely purified to any extent. Because of these characteristics, these products were defined as a manufacturing process. The mantra “the product is the process” was a well-known and guiding concept for regulation and oversight for decades. Vaccine products were some of these earliest approved biologicals.
Originally, these products were regulated merely to ensure safety. At that time, the turn of the 19th century, this type of oversight was a game-changing event as there was virtually no oversight of biopharma manufacturers.
Vaccines were thus manufactured for several decades, assuring the safety of the product, but with little knowledge of the potency/efficacy of the batches being released to the public. Eventually, it was noticed that different batches of vaccine had varying efficacy in the field. In the 1940s, Dr. Margaret Pittman in the Biologics Control Laboratory (now CBER) developed the first assay for a pertussis vaccine to assess potency. By 1949, manufacturers were able to sell whooping cough vaccine approved on potency as well as on safety and sterility.
Fast forward to today where the potency bioassay is required for all biopharmaceutical therapeutics and is considered a key quality assay. In fact, many clinical holds and product development delays are due to insufficiently developed potency assays.
At BEBPA conferences, we have been focusing on Bioassays for over 17 years. During this time, we have seen a movement away from in-vivo to invitro assays, with a focus on cell-based assays. Frozen-ready-to use cells have become a major game changer for easing these assays into commercial quality control labs. Assays utilizing primary cells have almost become a thing of the past because of modern cloning techniques being used to make custom cells. Readouts have gone from simple proliferation assays to looking at specific upregulation of critical intermediate proteins.
However, don’t think that the challenges of developing an acceptable potency assay have disappeared. In fact, the bioassay is still quoted as the most variable and most time-consuming assay to develop. At the upcoming BEBPA US Bioassay Conference we will be discussing the following topics:
- Phase-appropriate assays for Gene Therapy Products
- How to ensure the transferability of a potency assay
- Development of high-throughput assays for CAR-T cell therapies
- Development of frozen-ready-to use assay cell banks
- Regulatory perspective and requirements for biosimilar potency assays
- Potency assays for gene editing therapeutics
- Improving operational efficiency of potency assays
- Reference material for CAR-T lentiviral vector integration copy number
- Reference material for CAR-T cells
- Bridging mAb reference standards for potency assays
- Use of potency assay to enhance final product design
- Co-validation and technology transfer of automated assays
- Engineering cell lines for development of cell-based assays
Additionally, we have workshops about:
- How to Design Comparability Studies – a statistical heads-up
- Modern Data Analysis, with talks about:
- Partial dose response curves
- Dealing with replicate
- Defining total analytical error during validation
- Modern approaches to assessing similarity
- And much more!
Interest Group 1: Data Analysis
Using Equivalence Testing to Define Lot Release Limits for Product Potency
Nancy Sajjadi, Founder and Principal Consultant, Sajjadi Consulting
All You Ever Wanted to Know About Target Measurement Uncertainty and Total Analytical Error for Analytical Validation
Pierre Lebrun, Director Statistics, Pharmalex Belgium SA
Limiting Potency Bias From Allowed Non-Similarity While Protecting The Similarity Pass Rate
David Lansky, President, Precision Bioassay Inc
Interest Group 2: Assuring Potency for Cell and Gene Therapy Products
The FDA now has two guidances about the potency of Cell and Gene Therapies (CGT). The most recent was released December 2023 entitled “Potency Assurance for Cellular and Gene Therapy Products Draft Guidance for Industry”. The older guidance entitled “Guidance for Industry Potency Tests for Cellular and Gene Therapy Products” has been around since 2011. These two guidances will be discussed in this interest group
Mike Sadick, Imugene and Laureen Little, BEBPA
Interest Group 3: Handling Dose-Response Curves
Partial Dose-Response Curves – Contributions To The Discussion On “Allowed” Non-Similarity In Biological Assays
Ralf Stegmann, CEO, Stegmann Systems
Replicates: Should They Be Averaged Before Modelling?
Matthew Stephenson, Director of Statistics, Quantics Biostatistics
Poster Presentation: Outlier Analysis for Relative Potency Assays Using SoftMax Pro Function for Rosner Extreme Studentized Deviate Test
Alena Nikolskaya, Associate Director, Abzena
Interest Group 3: Development, Care and Handling of Analytical Cell Banks for Potency Assays
You will certainly agree that cell culture is essential to invitro potency assays. Sure, but everyone knows how to cultivate cells. That’s not a big deal and not a hot topic anymore. Is that really true? Do I exactly know how culture conditions impact cell response? Do I want to replace serum but don’t know how or even why? How many cells do I need to support my product’s life cycle? What’s the best cell banking strategy, how do I qualify and where do I store them. If you have an opinion or even the only valid answer to any of the questions, please join the discussion, to get cell culture to the next level of standardization.
Oliver Wehmeier, aCELLerate
Join us in March for BEBPA’s 2024 Hybrid US Bioassay Conference. It will ensure that you are meeting current standards for developing your potency assays. Don’t let your bioassay be the basis for a clinical hold! Register through the link below.
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[/vc_column_text][/vc_column][/vc_row][vc_row margin_top=”40″][vc_column][vc_row_inner][vc_column_inner][vc_column_text]Tech Briefing: The Wonderful World of Potency Assays: Look at me now Ma!
[/vc_column_text][vc_separator align=”align_left”][vc_column_text]The concept of potency assays came into being specifically for biopharmaceutical products. Originally these products were complex mixtures, produced in a natural system (Like a horse!). They were often ill-defined and rarely purified to any extent. Because of these characteristics, these products were defined as a manufacturing process. The mantra “the product is the process” was a well-known and guiding concept for regulation and oversight for decades. Vaccine products were some of these earliest approved biologicals. Originally, these products were regulated merely to ensure safety. At that time, the turn of the 19th century, this type of oversight was a game-changing event as there was virtually no oversight of biopharma manufacturers. Vaccines were thus manufactured for several decades, assuring the safety of the product, but with little knowledge of the potency/efficacy of the batches being released to the public. Eventually, it was noticed that different batches of vaccine had varying efficacy in the field. In the 1940s, Dr. Margaret Pittman in the Biologics Control Laboratory (now CBER) developed the first assay for a pertussis vaccine to assess potency. By 1949, manufacturers were able to sell whooping cough vaccine approved on potency as well as on safety and sterility. Fast forward to today where the potency bioassay is required for all biopharmaceutical therapeutics and is considered a key quality assay. In fact, many clinical holds and product development delays are due to insufficiently developed potency assays. At BEBPA conferences, we have been focusing on Bioassays for over 17 years. During this time, we have seen a movement away from in-vivo to invitro assays, with a focus on cell-based assays. Frozen-ready-to use cells have become a major game changer for easing these assays into commercial quality control labs. Assays utilizing primary cells have almost become a thing of the past because of modern cloning techniques being used to make custom cells. Readouts have gone from simple proliferation assays to looking at specific upregulation of critical intermediate proteins. However, don’t think that the challenges of developing an acceptable potency assay have disappeared. In fact, the bioassay is still quoted as the most variable and most time-consuming assay to develop. At the upcoming BEBPA US Bioassay Conference we will be discussing the following topics:- Phase-appropriate assays for Gene Therapy Products
- How to ensure the transferability of a potency assay
- Development of high-throughput assays for CAR-T cell therapies
- Development of frozen-ready-to use assay cell banks
- Regulatory perspective and requirements for biosimilar potency assays
- Potency assays for gene editing therapeutics
- Improving operational efficiency of potency assays
- Reference material for CAR-T lentiviral vector integration copy number
- Reference material for CAR-T cells
- Bridging mAb reference standards for potency assays
- Use of potency assay to enhance final product design
- Co-validation and technology transfer of automated assays
- Engineering cell lines for development of cell-based assays
- How to Design Comparability Studies – a statistical heads-up
- Modern Data Analysis, with talks about:
- Partial dose response curves
- Dealing with replicate
- Defining total analytical error during validation
- Modern approaches to assessing similarity
- And much more!