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Day: January 13, 2026

Potency assays in cell therapies: A look behind the challenges

Posted on by Brooklyn Wilkinson

Potency assays are a cornerstone of effective cell therapies, but they can also be a source of delay during development. We spoke with Scott Jones, PhD, Senior Vice President and Chief Scientific Officer at BioBridge Global (BBG) to understand the challenges of product-specific potency assays and the solutions for streamlined success.

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.

Download the official whitepaper Here.

We’ll Flex, If You Get Serious

Posted on by Brooklyn Wilkinson

Blueprint for Breakthroughs is a LinkedIn newsletter published by Adrienne B. Mendoza, MHA, SVP BioBridge Global and Chief Operating Officer (COO), BBG Advanced Therapies

Originally published on LinkedIn on January 13, 2026

Where FDA Is Coming From

The Center for Biologics Evaluation and Research (CBER) has always had one of the hardest jobs in the agency: regulating blood, tissues, vaccines—and now cell and gene therapies—under the same statutory mandate to assure safety, purity, and potency, without choking off innovation. Over the past decade, FDA has approved nearly 50 CGTs, largely by applying a regulatory framework built for conventional biologics. That framework assumed large, repeatable lots and mature manufacturing systems. CGTs, by contrast, are often small-batch, patient-specific, and time-sensitive.

Historically, FDA tried to square this circle through risk-based judgment and case-by-case flexibility. Concepts like minimal manipulation, homologous use, and enforcement discretion allowed lower-risk products to move forward with lighter oversight, while higher-risk therapies underwent full premarket review. That approach worked—until CGTs stretched it to the breaking point.

The result was a gray zone. Some sponsors received flexibility on specifications, lot history, or trial design; others did not. Expectations lived more in reviewers’ experience than in written guidance. Feedback during the review process and interpretation of CFRs appeared subjective and inconsistent. Predictability suffered.

This January, the FDA made this flexibility explicit.

What FDA Just Said—Out Loud

On January 11, the FDA announced it is “sharing information about the agency’s flexible approach to overseeing CMC requirements for cell and gene therapies.” That phrasing matters. Several signals stand out:

  • CBER acknowledged reality. Applying largely uniform CMC expectations to individualized, small-batch CGTs is not sustainable.
  • Flexibility is now intentional. FDA explicitly calls this “regulatory flexibility tailored for cell and gene therapies”—common-sense adjustments to address CGT-specific challenges without compromising safety, purity, or potency
  • Consistency is the goal. Flexibilities that used to be applied case by case are now being communicated broadly, so sponsors are not dependent on which review team they happen to draw

CMC is also being reinforced, not loosened, by what sits around it. The 2025 trio of draft guidances—on innovative trial designs for small populations, expanded use of expedited programs for regenerative medicines, earlier opportunities for FDA feedback on CMC and clinical plans, and post-approval methods to capture safety and efficacy—provide the clinical and post-market scaffolding for this shift.

In August 2025, FDA added PreCheck, a voluntary program to de‑risk and accelerate U.S. manufacturing by assessing facilities and CMC elements earlier and more predictably in the lifecycle, with an emphasis on onshoring and modernization. For CGT developers, PreCheck is about getting facility and CMC readiness right up front—streamlining inspections, clarifying expectations, and enabling platform-level efficiencies so there are not surprises.

This is not FDA “getting soft.” It is FDA aligning the rulebook with how CGTs actually behave in the real world, while keeping the core obligation to assure safety, purity, and potency firmly in place.

The Practical Moves: Where Flexibility Shows Up

1. CMC Expectations That Can Evolve

FDA now says clearly that for CGTs:

  • Pre-approval expectations for lot history and specifications may be more flexible—particularly in rare diseases and small populations—provided sponsors have a credible plan to refine and tighten those specifications as manufacturing experience grows.
  • CBER has identified regulatory flexibilities already available under existing regulations to accommodate CGT complexity and time constraints, while preserving control strategies that protect safety, purity, and potency.
  • CMC is explicitly framed as lifecycle work, not a single gate before BLA.

2. Trial Designs That Fit Tiny Populations

The draft guidance on innovative designs for small populations is FDA’s clearest acknowledgment yet that traditional randomized trials often do not fit CGTs.

FDA now explicitly encourages:

  • Adaptive designs and Bayesian or other advanced methods that extract more information from small N.
  • Thoughtful use of external or natural-history controls when randomization is not feasible.
  • Trial designs that transition cleanly into long-term postapproval follow-up, rather than stopping at first approval.

This marks a departure from the era when “gold standard” implicitly meant large, simple randomized trials—an approach many CGTs cannot realistically execute.

3. Expedited Pathways and Postapproval Data—Together

The updated expedited programs guidance for regenerative medicines, paired with the new postapproval methods guidance, makes FDA’s expectations unmistakable.

FDA is prepared to use RMAT and other expedited pathways for serious conditions—and expects sponsors to repay that flexibility with disciplined commitments for post-approval evidence generation.

That trade looks like:

  • Greater latitude in early trial design and endpoints, including surrogate markers, functional outcomes, and staged benefit–risk assessments.
  • Stronger expectations for registries, long-term follow-up, and real-world data systems purpose-built for CGTs.
  • A direct link between how much FDA flexes pre-approval and how robust the postapproval evidence plan is.

Flexibility is not a shortcut. It is an exchange

What Hasn’t Changed—and Where FDA Will Not Bend

Despite the new openness, several lines remain firm:

  • The obligation to demonstrate safety, purity, and potency is unchanged. FDA is explicit that flexibility will not “compromise or undermine” its ability to assure these attributes.
  • For higher-risk products—particularly complex gene therapies or novel indications— FDA still expects strong mechanistic rationale, adequate preclinical support, and rigorous long-term safety monitoring.
  • FDA’s posture toward unsanctioned stem cell clinics and unapproved products has not softened. Risk-based enforcement, including warning letters, seizures, and injunctions, remains very much in play.

The takeaway is straightforward: FDA is flexible on how you get to robust evidence—not on whether that evidence exists.

What This Means in Practice

For teams developing, supplying, or enabling CGTs/ATMPs, this guidance should directly inform strategy.

1. Treat CMC as a Living Program

  • Build a lifecycle CMC plan that shows how specifications, assays, and processes will mature from early clinical phases through postapproval, instead of presenting everything as final at BLA.
  • Design analytical methods—and partnerships with testing labs—that allow for method evolution and comparability, rather than locking the program into today’s assays indefinitely.
  • Document your control strategy so reviewers can easily follow the logic of risk management over time.

2. Make Starting Materials Central to Your Regulatory Story

This is where starting-material strategy becomes a regulatory lever, rather than just an operational detail.

  • Donor and patient material quality, including leukapheresis/apheresis, should be treated as CMC variables. Consistent, standardized collection supports tighter specifications as programs mature.
  • If decentralized or mobile collection is part of the model to create tighter control of SOPs, data capture, and chain-of-identity/custody, then work with partners that are robust enough to demonstrate risk reduction—not added variability.
  • Align starting-material strategy with access strategy. FDA flexibility does not solve geographic gaps; it simply gives sponsors more room to design around them.

3. Build Trials That Feed Long-Term Evidence Systems

  • Use innovative and adaptive designs that respect small populations while generating data that can flow directly into registries and long-term follow-up.
  • Plan postapproval evidence infrastructure from the outset—registries, PROs, and RWE pipelines are part of how sponsors “pay back” regulatory flexibility.

4. Choose Partners Who Can Operate in a Flexible World

  • Choose Partners Who Can Operate in a Flexible World
  • Prioritize apheresis, testing, and manufacturing partners who are comfortable with lifecycle evolution and design phase-appropriate controls—lean but safe in early development, then progressively more robust as you move toward and beyond BLA, instead of freezing an overbuilt Phase 1 process.
  • Look for teams that understand the financial dimension: they should be technically strong and cost-effective, able to scale requirements and infrastructure with the program so you can conserve cash for trials, evidence generation, and market access work.
  • Favor integrated partners who can help you tell one coherent, phase-appropriate story—from starting material and access, through CMC, into real-world performance and postapproval commitments—rather than isolated vendors that only see one slice of the lifecycle.

One Lens Worth Keeping

The cleanest way to interpret FDA’s message is this:

The agency is aligning expectations with how CGTs are actually made and used. Flexibility is real—but it belongs to teams that can demonstrate discipline across the full product lifecycle.

For those who have lived inside quality systems for cell therapy, this feels less like a revolution than a long-overdue catch-up. FDA is effectively saying: We’ll meet you where you are—if you can show us how you’ll protect patients as you scale.

That is where the next decade of CGT success will be written—not only in breakthrough data, but in the quieter, harder work of building systems, partnerships, and infrastructure that can thrive in a flexible, risk-based regulatory world.

A Final Note on Support

If you’re working to translate FDA’s new flexibility into real-world CMC, starting material, and postapproval decisions, you don’t have to do it alone. At BBG Advanced Therapies, the Quality & Regulatory team operates in this space every day—connecting leukapheresis and starting materials, manufacturing strategy, potency testing, safety studies, and long-term evidence generation into a single, coherent, inspection-ready story.

This article was informed by their practical experience. Leaders like Valery Freeman-Allen, Joe Higdon, and the broader BioBridge Global team work side by side with sponsors to turn FDA’s “we’ll flex if you get serious” message into disciplined, defensible lifecycle strategies for advanced therapies.