Dr. Scott Jones has spent more than 35 years advancing assay development and currently leads BioBridge Global’s R&D department. His team works closely with BBG’s subsidiary, BBG Advanced Therapies (BBGAT) to develop and validate rapid, highly sensitive, GMP-compliant potency assays for cell and gene therapy manufacturers.

Potency assays are a quantitative measure of a product’s biological function, from cell killing and immuno-modulation to wound healing, chemotaxis, angiogenesis, or differentiation. They are needed across the entire lifecycle of a product, from initial development and clinical manufacturing to regulatory approval and ongoing commercial supply.

“With cell and gene therapies, it’s important to show that the product still performs the  biological function it’s supposed to do,” says Dr. Jones. “Even though there is a defined manufacturing process, these are living cells subject to numerous variables that can affect potency.”

Dr. Jones explains that potency assays are used across the development process, in product stability evaluations, comparability studies, and manufacturing process studies. During regulatory filings, potency assays must demonstrate that the therapy consistently produces its intended effect, providing regulators with evidence of the product’s strength and functional activity.

During GMP manufacturing, potency assays are an integral aspect of quality control, confirming that each batch retains the intended biological activity before therapies are released. Beyond that, Dr. Jones explains they’re also used to evaluate any impacts of introducing new raw materials, production processes, or facilities.

Matching assay to Mechanisms of Action

“Since potency assays measure the ability of a product to achieve the intended therapeutic effect, they must be product specific,” Dr. Jones says. “At BBG Advanced Therapies, we develop tailored potency assays aligned with the mechanisms of action (MOA) and specific indication for use of the product.”

Dr. Jones explains that cell and gene therapies usually have multiple potency-related Critical Quality Attributes (CQAs), meaning multiple different potency assays are required. If part of a mesenchymal stem cell (MSC) therapy’s function is to modulate the immune system, his team might run a cell-based assay where the MSCs are mixed with immune cells to see how they respond.

“We look at things like cell activation, proliferation, and the release of cytokines or growth factors. We might also test how cells interact with other cell types to show they can activate or suppress specific responses,” he explains.

“Because of this, potency testing usually involves more than one assay,” Dr. Jones reiterates. “Some assays focus on cell-to-cell interactions, others measure released factors in the media, and others look at physical characteristics or surface markers on the cells.”

The exact approach depends on the product, its intended use, and claims being made. The goal is always to connect the assay results to clinical relevance, enabling researchers to prove that the cells are potent and will perform as expected.

Potency assay delays

“While potency assays are essential, they are rarely a priority for cell and gene therapy developers,” says Dr. Jones. “Developers often deprioritise these assays because their focus is on bringing products to market quickly. As a result, potency assays can feel like a looming challenge in the background.” According to Dr. Jones, the hesitation is largely due to the significant time, effort, and expertise required for their development.

As such, potency assays are often addressed too late in the process, which can stall progress and potentially cause approval delays that stretch on for years. According to Dr. Jones, it’s not unusual for the FDA to request additional data and assays, even when biopharma companies feel their existing potency strategy is sufficient.

The challenge could only heighten as regulators tighten the rules for more robust potency strategies. In 2023, the FDA’s latest update to its guidance on potency assays emphasised the importance of a potency assurance strategy which includes the use of multiple complementary assays measuring potency-related CQAs. This draft could become final in coming years, raising the bar for assay development and validation.

Potency risks are already front and centre in regulatory assessments. Former FDA CBER director Peter Marks has noted that potency-related problems are among the most common reasons for delayed approvals in cell and gene therapies[i], while a study in Europe has estimated that almost half of advanced therapy medicinal product (ATMP) applications in the European Medicines Agency database encountered potency-related issues during assessment,[ii] often resulting in substantial delays.

Such challenges underscore the criticality of starting assay development early. “[Biopharmas] should think about these assays from the very beginning, as soon as they know their indication or mechanisms of action,” notes Dr. Jones.

Start early, partner early

Building an assay development strategy into early development can pay dividends, enabling companies to accelerate development and improve product consistency starting from preclinical phase.

This can be challenging, however, especially when a product is subject to formulation changes or when MOAs aren’t yet clear. Nevertheless, starting early builds the foundation for regulatory success, allowing developers to obtain earlier feedback from regulators, adjust their strategy accordingly, and test their potency assays in GMP-compliant conditions. Having a robust and reliable potency strategy during clinical trials also safeguards product quality, ensuring each patient receives an effective dose.

Early and mid-stage biotech companies often lack the in-depth expertise needed to develop their own potency assays effectively, especially since such knowledge is often underutilised outside critical windows. Partnering with specialists gives companies access to the expertise they need when they need it. This allows developers to stay focused on their product, while experts like Dr. Jones leverage decades of experience in potency assay development to design assay strategies that meet rigorous regulatory standards.

BBG Advanced Therapies recognises the urgent need for this expertise as the cell therapy industry expands. Based in San Antonio, Texas, the company offers a dedicated group of experienced assay development scientists that create and validate custom potency assays specific to a cell or gene therapy product. BBGAT is committed to helping innovators confidently accelerate their potency assay programs from early development through regulatory approval and also offers complementary services that support companies with starting material collection and processing, testing, clinical trials, and biomanufacturing.  

 “Working with an experienced potency assay development group like BBG Advanced Therapies will streamline the development process and ensure successful performance of the assays,” says Dr Jones.

“Our team utilises a variety of analytical platforms such as flow cytometry, ELISA, fluorescence imaging, gel electrophoresis, and nucleic acid quantification, to ensure an optimal fit with our client’s technical capabilities, sensitivity requirements, and desired throughput. We have also developed a proprietary, patent-pending analytical platform to further enhance our ability to deliver high-value solutions for our clients.”

Named Premiva, the novel platform offered by BBG Advanced Therapies can demonstrate how a therapy will function in the body against cancer cells. With just a few drops of therapeutic agent, this customisable dynamic flow-based proprietary platform can provide developers a qualified and validated characterisation of auto-/allo- cells including identity, specificity, and potency.

In a world where potency assays loom like a dark raincloud over development, success lies in starting early and partnering early. By crafting a robust, regulator-ready strategy from the outset and working with specialists who understand both the science and regulatory body expectations, developers can replace uncertainty with confidence and regulatory holdups with streamlined approvals.

[i] Solvias. The Potency Puzzle: Overcoming Challenges in Potency Assays for Cell and Gene Therapy Development. [ii] Elsallab, Magdi et al. Mitigating Deficiencies in Evidence during Regulatory Assessments of Advanced Therapies: A Comparative Study with Other Biologicals. Molecular Therapy Methods & Clinical Development, Volume 18, 269 – 279