This is a ready-to-use matrix for building and defending a potency assurance strategy for a cell or gene therapy product, one built from several complementary measures rather than a single assay carrying the whole burden of proof. Its job is narrow and specific: state what biological claim the product actually has to demonstrate, then map each candidate measure, a transduction or expression readout, a functional bioassay, a molecular measure, against the piece of that claim it covers, so a reviewer can see the panel’s logic in one place instead of a list of assays with no stated rationale for why each one is there. Replace every <<FILL: ...>> placeholder with your own specifics. A worked filled specimen follows. Verify each cited reference against the current source before you rely on it.
Document control header
| Field | Entry |
|---|---|
| Document title | Potency Assurance Triangulation Matrix for <<FILL: product>> |
| Document number | <<FILL: e.g. POT-TM-2026-01>> |
| Version | <<FILL>> |
| Effective date | <<FILL>> |
| Linked potency assurance strategy document | <<FILL>> |
| Matrix owner | <<FILL: e.g. Potency Assay Lead / MSAT>> |
1. Purpose
This matrix states the product’s core biological claim, mechanism of action, in one sentence, then maps every measure in the potency panel against the specific piece of that claim it demonstrates, so the overall strategy’s coverage, and any gap, is visible in a single view rather than assumed from an assay list.
2. Scope
| Dimension | Decision |
|---|---|
| Product in scope | <<FILL>> |
| Stated mechanism of action / biological claim | <<FILL: one sentence, specific>> |
| Stage this matrix applies to | <<FILL: characterization, release, stability, or all three, stated separately if the panel differs by stage>> |
3. Potency panel mapping
| Measure | Type (transduction/expression readout, functional bioassay, molecular measure, other) | What piece of the biological claim it demonstrates | What it does NOT demonstrate on its own | Stage used (characterization / release / stability) | Status (qualified / validated / in development) |
|---|---|---|---|---|---|
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> | <<FILL>> |
Add one row per measure. A measure with no stated claim it demonstrates, or one whose “does not demonstrate” column is left blank, has not actually been evaluated for what it is contributing to the panel; do not carry an assay forward on the strength of “we have always run it.”
4. Coverage gap check
| Piece of the biological claim | Covered by which measure(s) above | Gap, if any | Plan to close |
|---|---|---|---|
<<FILL: e.g. transgene delivery to the target cell>> | <<FILL>> | <<FILL: none / stated gap>> | <<FILL>> |
<<FILL: e.g. functional biological activity of the expressed protein or edited outcome>> | <<FILL>> | <<FILL>> | <<FILL>> |
<<FILL: e.g. durability or persistence of the effect where relevant to the claim>> | <<FILL>> | <<FILL>> | <<FILL>> |
State this section as “no gap identified” rather than omitting it if every piece of the biological claim traces to at least one measure in section 3; a reviewer comparing this matrix against the mechanism-of-action claim is checking for exactly this kind of silent gap.
5. Disagreement handling
| Field | Entry |
|---|---|
| How the panel is interpreted when measures do not agree | <<FILL: e.g. no single measure is retired without a documented investigation into the disagreement; all results are reported, not just the cleanest one>> |
| Who reviews a disagreement before a release decision | <<FILL>> |
| Escalation path if a disagreement cannot be resolved before a release deadline | <<FILL>> |
A panel measure quietly dropped because it disagreed with the others, with no documented investigation, is the specific failure this section exists to prevent.
6. Conclusion
| Field | Entry |
|---|---|
| Panel provides full coverage of the stated biological claim? | <<FILL: Yes/No>> |
| Open gaps, with owner and target date | <<FILL>> |
| QA / Regulatory concurrence on the overall strategy | <<FILL>> |
7. References
FDA draft guidance, “Potency Assurance for Cellular and Gene Therapy Products” (December 2023). FDA draft guidance, “Potency Assessment of Active Immunotherapy Products” (August 2026), supplementing the December 2023 draft. FDA guidance, “Potency Tests for Cellular and Gene Therapy Products” (2011), for background on the original single-assay framing this strategy moves beyond.
Confirm the current version and finalization status of each reference before issue; both 2023 and 2026 documents above were in draft status at the time this template was written.
8. Revision history
| Version | Date | Author | Summary of change |
|---|---|---|---|
<<FILL: 1.0>> | <<FILL>> | <<FILL>> | Initial issue. |
9. Approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Author (Potency Assay Lead / MSAT) | <<FILL>> | ||
| Reviewer (Quality Assurance) | <<FILL>> | ||
| Reviewer (Regulatory / CMC) | <<FILL>> |
Filled specimen
Extract for an example AAV gene therapy product expressing a functional replacement protein. Company and product are illustrative.
| Measure | Type | What it demonstrates | What it does NOT demonstrate on its own | Stage used | Status |
|---|---|---|---|---|---|
| Vector genome titer by digital PCR | Molecular measure | Physical particle dose delivered per unit product | Whether delivered genomes are transcriptionally active or produce functional protein | Release | Validated |
| Transduction efficiency in a relevant cell model | Transduction/expression readout | Proportion of target cells successfully transduced and expressing transgene mRNA or protein | Whether the expressed protein is functionally active | Characterization, release | Validated |
| Cell-based functional bioassay (protein activity readout) | Functional bioassay | Biological activity of the expressed protein in a relevant functional assay | Absolute dose or delivery efficiency; higher variability than the molecular measure above | Release, stability | Validated, higher assay variability acknowledged and trended |
Section 4, coverage gap check: transgene delivery covered by vector genome titer and transduction efficiency; functional biological activity covered by the cell-based bioassay; no gap identified for this product’s stated mechanism of action.
Section 5: no single measure is retired without a documented investigation; when the functional bioassay result falls outside its historical range while the molecular and transduction measures are unremarkable, Quality Assurance and the Potency Assay Lead jointly review before any release decision, and all three results are reported in the batch record regardless of the outcome.
Conclusion: panel provides full coverage of the stated biological claim; no open gaps; concurrence documented from QA and Regulatory/CMC.
Common findings this matrix prevents
- A potency panel run and reported with no documented rationale for what each individual measure is contributing to the overall biological claim.
- A functional bioassay quietly dropped from routine use after a period of disagreement with other measures, with no investigation record.
- A release decision made from the cleanest-looking number among several, with the others’ results not carried into the batch record.
- A gap in biological claim coverage, most often the functional-activity piece, left unaddressed because the molecular and delivery measures looked sufficient on their own.
How to adapt this matrix
- State the mechanism-of-action claim in section 2 specifically enough that a reader unfamiliar with the product can tell what each measure in section 3 is supposed to prove.
- Fill the “does not demonstrate” column honestly for every measure; a measure with no acknowledged limitation is a measure whose role in the panel has not been thought through.
- Keep section 4 current as the product’s characterization matures; a gap accepted early in development needs a stated closure plan, not silent carryforward into commercial release.
- Revisit section 5’s disagreement-handling process before it is needed for the first time in a real release decision, not while a real batch is waiting on it.