Potency assays play a vital role in biopharmaceutical development by measuring a drug candidate’s biological activity against a reference standard — offering essential insights into product quality and its potential clinical success.
From early research through commercial release, the development and validation of these assays help confirm a therapy’s functional performance and batch-to-batch consistency. By accounting for biological variability, complex mechanisms of action (MoAs) and evolving regulatory expectations, potency assays provide the data needed to avoid setbacks and support informed decision-making across the drug development lifecycle.
In this Xtalks Spotlight interview, two experts from Abzena, Dr. Erika Kovacs, Senior Director of Bioassay, and Rekha Patel, Global Vice President of Analytical Services, shared how potency assays guide chemistry, manufacturing and control (CMC) strategies, meet regulatory expectations and mitigate downstream risks.
The Role of Potency Assays in Drug Development
In biopharmaceutical drug development, potency assays are not just another analytical requirement — they are central to ensuring the safety, efficacy and consistency of a therapeutic product.
Because they reflect the MoA and therapeutic potential of a drug, potency assays are indispensable across the product lifecycle. In early development, they support candidate selection and help optimize formulations. As programs advance, these assays become critical to establishing batch release criteria, demonstrating stability over time and supporting comparability assessments — all key components of a robust CMC strategy.
“Potency assays practically measure the functionality of a test molecule,” said Dr. Kovacs. “That involves any type of drug under development — biologics, [Antibody-drug conjugates] ADCs — and throughout the drug development process… it’s really important that we are able to measure that functionality, how that drug works and how that’s impacting the cells.”
Unlike many other analytical methods, potency assays often involve live cells or biological systems, introducing inherent complexity and variability. As such, their design, qualification and validation require a deep understanding of both the molecule and its biological context.
With the increasing complexity of therapeutic modalities — from biologics to bioconjugates and bispecifics — the role of potency assays is only growing in importance.
A well-designed potency assay not only satisfies regulatory expectations but also reduces the risk of late stage delays and helps streamline the path to commercialization.
Why Using Potency Assays in Early Development Is Essential
Potency assays are often viewed as a late-stage requirement, but waiting too long to develop them can jeopardize timelines and regulatory success. In reality, assay development should begin as early as possible, ideally just after a lead candidate is selected or immediately after an Investigational New Drug (IND) application.
Early investment in potency assay design pays off by enabling developers to gather critical performance data over time. This not only strengthens the assay’s robustness but also ensures it’s suitable for later qualification and validation, including use in batch release, stability testing and regulatory submissions.
“The more data you gather, the more opportunity you have to have the right robustness in your assay, the right throughput of your assay and then also the best design for that assay,” explained Patel.
Early development also gives teams the time to address one of the most challenging aspects of potency assays — biological variability. Unlike physicochemical assays, cell-based potency assays are highly sensitive to conditions and require substantial optimization to ensure reproducibility and regulatory compliance. By beginning assay development in parallel with early characterization work, sponsors are better positioned to avoid delays at critical junctures such as Biologics License Application (BLA) filing.
Starting early turns the potency assay from a regulatory hurdle into a strategic asset — one that not only reduces development risk but also facilitates smoother transitions from clinical to commercial stages.
The Attributes of a Successful Potency Assay
A well-designed potency assay does more than measure biological activity — it offers regulators, developers and manufacturers confidence that the product will perform consistently and predictably from batch to batch. But achieving that level of reliability requires an approach grounded in both biological relevance and practical assay performance.
Cell-based potency assays, in particular, pose unique challenges. Unlike biochemical or biophysical methods, they rely on living systems, which introduce inherent variability and require careful optimization of assay conditions. Selecting the right cell line and readout system — one that reflects the drug’s MoA — is foundational to success.
“What is key is that from very early on, we select the most suitable cell line as well as the most suitable readout to assess a particular drug’s potency,” said Dr. Kovacs. “That includes thinking about aspects such as MoA. We need to make sure that it is MoA reflective. However, at the same time, we balance that with simplicity that is required to make a good potency assay.”
Simplicity, in this case, refers to minimizing complexity in ways that improve assay reproducibility, accuracy and precision, which are critical parameters for method validation. A wide assay window, high sensitivity and low variability all contribute to an assay’s ability to meet regulatory expectations and stand up to real-world use.
Ultimately, a successful potency assay must balance scientific relevance with operational robustness. This ensures the delivery of reliable, actionable data that supports product quality and builds regulatory confidence.
What Regulators Expect from Potency Assay Data
Among the various analytical methods used in drug development, potency assays are considered by regulators to be among the most critical, particularly for biologics and complex modalities like ADCs.
These assays serve as a direct measure of a drug’s functional activity, making them essential not only for batch release and stability testing but also for demonstrating product consistency, safety and efficacy.
“The regulators do find the potency assay data to be one of the most critical assays,” said Patel. “The consistency of your batch, making sure the drug is effective, is so critical for the final strategy of any drug.”
Because of their central role in the CMC package, regulatory agencies such as the FDA and EMA place significant emphasis on how potency assays are designed, qualified and validated. They expect the assay to reflect the drug’s MoA, demonstrate appropriate sensitivity and specificity, and remain robust across multiple manufacturing lots and time points.
“With Abzena working with a lot of new types of modalities, especially in the bioconjugate space, we really have to work even more diligently around these assays,” Patel added. The goal is to ensure that any variability is well understood and scientifically justified — not a consequence of assay design flaws or inadequate development timelines.
Moreover, regulators expect developers to show that the assay has undergone thorough stress testing and risk assessment. If there are limitations or known challenges, those must be addressed with supporting data and rationale.
“Even if there is some robustness gap, did we do the due diligence to make sure that’s justifiable?” Patel emphasized. That level of transparency and scientific rigor is key to gaining regulatory trust.
In the end, potency assay data must do more than check a box. It must tell a clear, scientifically sound story of product performance — one that supports patient safety, regulatory approval and long-term commercial success.
With increasing complexity in therapeutic modalities, including ADCs and next-generation biologics, robust potency assay development is more important than ever.
Watch the full interview here:
