Potency Assay Development Starts With the Cell Line
FDA reopened the potency conversation this summer. Consequently, potency assay development is back on many CMC timelines. On August 20, 2026, the agency published a draft guidance, Potency Assessment of Active Immunotherapy Products, under docket FDA-2026-D-8561. Comments close November 18, 2026. The draft addresses active immunotherapy products, not every biologic. However, its logic travels well.
Why Potency Assay Development Is Drawing Attention
FDA frames potency as a strategy rather than a single assay. Additionally, the draft supplements the agency’s 2023 potency assurance guidance for cellular and gene therapy products. Therefore, the direction looks consistent across product classes. Regulation defines potency at 21 CFR 600.3(s) as a product’s specific ability to effect a given result. For protein and antibody programs, one lesson stands out. Assay design cannot outrun the material it measures.
The Cell Line Sets the Assay Baseline
Every potency number traces back to a cell line. If expression drifts, the result drifts too. For example, clonal heterogeneity can shift glycosylation, and glycosylation can shift biological activity. Meanwhile, transgene copy-number loss across passages lowers titer and alters the impurity background. As a result, an assay qualified on early material may behave differently at scale. Good cell line characterization catches these shifts before they reach a potency dataset.
Reference material deserves equal care. A potency assay needs a stable comparator, and that comparator usually comes from banked cells. Therefore, reserve enough vials at the outset. Otherwise, a later bank change forces bridging studies. Data from cell line stability work also helps justify the passage limits you set.
Potency Assay Development Needs a Stable Bank
Reproducibility depends on a fixed starting point. First, confirm identity by short tandem repeat profiling or sequencing. Next, screen for mycoplasma and sterility. Finally, lock the material into a master cell bank before assay qualification begins. A deliberate cell banking strategy preserves that reference point for years.
Cell Culture Company supports this groundwork. Our team prepares master and working cell banks from 5 to 300 vials per lot under RUO/GLP or GMP-CNC conditions. Additionally, we run identity, stability, and expression testing using RT-qPCR, Western blot, and flow cytometry.
Practical Steps for Sponsors
Start early, because retrofitting potency data is expensive. First, define the mechanism of action you intend to measure. Next, bank the clone and document its passage window. Then qualify the assay against that banked material. Consequently, later manufacturing changes have a stable comparator. Finally, store the acceptance criteria alongside the bank record, so reviewers can follow the logic years afterward.
Frequently Asked Questions
When should potency assay development begin?
Begin during cell line selection. Early work links assay readouts to a documented clone, which simplifies comparability later.
Does the new draft guidance apply to antibodies?
Not directly. The draft targets active immunotherapy products. However, its emphasis on strategy and early planning is broadly useful. Draft guidance may also change before it is finalized.
