In drug development, one question sits quietly at the core of everything: Does the therapy actually do what it promises to do? It sounds straightforward. It isn’t.
When it comes to biologics, the solution is a potency assay that determines the efficacy and potency of drug candidates. These assays inform decisions starting from discovery to regulatory approval and continuous quality control. Yet for a long time, many of these assays measured something close to the signal/ output of interest rather than the actual output of interest.
Conventional assays primarily measured signals from surrogate targets, i.e., downstream markers indicating activity rather than measuring directly the target/ signal of interest. To an extent, they were effective. However, these assays do not measure the intended mechanism-of-action (MOA) of the drug in vivo. This made the interpretation of results ambiguous. A true MOA reflective assay enables rank ordering of the potency of drug candidates, which is crucial in the immunotherapy and metabolic diseases drug discovery and development domain, where precision is important.
Changing this narrative meant asking a different question, not how to improve existing assays, but what they should have been measuring all along.
Addressing this gap required a shift from measurement of surrogate signals to systems that could capture biological function directly. Within this effort, Debatri Chatterjee led the innovation to commercialization of a series of first-to-market cell-based potency assays designed to reflect the mechanism-of-action of biologic drugs. At the time, standard approaches leaned heavily on reporter-gene assays, and no broadly usable platform existed that could directly measure functional biological outcomes aligned with in vivo activity.
Her work shifted the focus from inference to observation.
Traditional assays for mechanisms like antibody-dependent cellular cytotoxicity (ADCC) often depended on surrogate markers. These approaches captured fragments of the biological response, but not the response itself. Quantifying ADCC potential of an antibody therapeutic being evaluated relies on employing assays that include either radiolabeling (posing safety challenges), dye-based assays (risking
the spontaneous release of dyes from the cells), or reporter gene assays (indirect MOA (mechanism-of-action)-reflective downstream detection only), all of which compromise the quality of the final data or provide non-functional output. This creates the need for a secondary bridging ADCC assay that measures direct target cell death by immune effector cells.
Under Debatri’s direction, a different approach was implemented. This approach used a cell-based assay platform that directly quantified target tumor cell death driven by immune effector mechanisms methods. This cell-based assay format, also known as the KILR® cytotoxicity assay platform, provides robustness, precision, and accuracy. It demonstrates its fit-for-purpose nature from screening therapeutic antibody candidates in early drug development to characterization and potency testing in QC lot-release programs. Rather than interpreting signals, the system measured the outcome itself. Developed as part of the KILR® cytotoxicity platform, it allowed researchers to observe, in real time, what the drug was actually doing.
That differentiation between measuring a signal and measuring an effect transformed the way the data could be utilized. It made the data more trustworthy and less ambiguous. It also allowed one assay format to measure the direct killing of the target tumor cells. This measurement is very effective and can be used to evaluate the efficacy of drugs from discovery through development to lot-release testing.
This was not just a scientific adjustment; it was an operational one. Under her technical direction, these assays were developed as ready-to-use formats, removing the need for extensive in-house assay development by drug discovery and development companies. Scientists and laboratories could deploy them directly, reducing setup time and variability across environments.
A similar pattern emerged in metabolic disease research.
For targets such as glucagon-like peptide-1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP), existing assays often measured downstream activity rather than direct signaling. Debatri led the launch of thaw-and-use cell-based potency assays that directly measured intracellular responses like cAMP accumulation. At the time, few systems combined direct mechanism-of-action measurement with immediate usability in this way.
The benefit was not just technical accuracy, but time. Researchers could move from assay setup to drug MOA evaluation without rebuilding assay systems for drug MOA evaluation from scratch.
Another extension of this work involved bringing to market ready-to-use cell-based potency assays qualified with reference drug molecules. According to internal validation data, these systems reduced drug development timelines by eliminating iterative assay design and optimization phases that could span for 9-12 months or longer. In practice, this meant faster transitions from lab research to clinical evaluation, particularly in biosimilar programs where functional comparison and speed to market are critical.
What connects these contributions is a shift in mindset. Assay development had long been treated as a bespoke process, slow, variable, and dependent on local expertise. The approach here treated it instead as infrastructure: standardized, mechanism-aligned, and deployable across organizations.
That shift has had visible effects.
Global pharmaceutical and biosimilar developers operating in regulated environments have implemented these assays to streamline development workflows. By removing the need for repeated assay design and optimization as well as enabling consistent measurement of drug function, these qualified cell-based potency assays have supported faster progression from discovery to clinical stages. Their role does not end there.
“The challenge wasn’t detecting activity; it was ensuring that what we measured actually reflected how the drug functions in a biological system,” Debatri notes. The implication is straightforward: if the measurement is wrong, everything that follows is built on unstable ground.
In regulated manufacturing, this matters even more. Potency assays remain in use long after a drug is approved, forming the backbone of lot-release testing and long-term quality assurance. Using mechanism-of-action reflective assays in these programs ensures continuity, not just in process, but consistency in the drug product itself.
The broader field has taken note. Following the introduction of these first-to-market assays, competing solutions began to emerge, though many continued to rely on indirect measurement approaches. Even so, the conversation shifted. What had once been considered sufficient began to look incomplete.
And that is often how change happens in complex systems, not through sudden disruption, but through a quiet redefinition of what counts as adequate.
There is a tendency in scientific practice to optimize within constraints rather than question them. Indirect measurement worked well enough, so it persisted. But once a more direct, scalable alternative exists, the old approach begins to reveal its limitations.
As biologics and biosimilars expand into more complex therapeutic areas, the demand for precision will only increase. Measurement, in that context, is not just a technical step; it is a foundational one.
Seen this way, this work is not simply about better assays. It is about aligning measurement with reality. And once that alignment becomes possible, it is difficult to justify anything less.
