1. Define the potency result and decision

Describe the test material, matrix, reference standard, biological mechanism, reportable potency and unit, expected range, specification or decision, laboratories, instruments, and routine workflow. For relative potency, define the reference-to-test convention, preparation corrections, model restrictions, and treatment of invalid or non-estimable results.

Draw the analytical-procedure boundary from sample and reference preparation through plate execution, source-data handling, calculation, suitability, review, and report. A requirement outside that boundary still needs an owner, but it is not silently validated by the potency study.

2. Select evidence for the result’s risks

Identify how the result could be wrong or unfit for the intended decision, then select the performance questions that expose those failures. Q2(R2) supplies a framework; the study rationale connects that framework to this potency procedure.

Potency performance questions
CharacteristicQuestion the study should answer
AccuracyDoes measured potency agree with suitable reference, expected-mixture, or orthogonal evidence?
RepeatabilityHow much do independent results vary under the same defined conditions?
Intermediate precisionWhat changes across relevant days, analysts, instruments, and lots?
SpecificityCan matrix, related materials, interference, or mechanism-relevant controls change the conclusion?
RangeAt which potency levels are accuracy, precision, and model behavior jointly acceptable?
RobustnessWhich deliberate changes to critical parameters preserve or threaten performance?

3. Predefine the study, calculation, and criteria

Specify samples and levels, independent runs, replicates, factor allocation, reference handling, experimental unit, transformations, variance model, confidence intervals, pooling, missing data, exclusions, model restrictions, weighting, preparation factors, rounding, and acceptance criteria before reviewing outcomes.

The matrix below shows what “predefined” looks like for one synthetic relative-potency study. Its levels, run count, and criteria illustrate protocol structure; they must not be copied into another assay without development evidence and approval.

Illustrative validation decision matrix
QuestionWorked designIllustrative criterion
Accuracy80%, 100%, and 120% expected-potency mixtures across six independent runsMean recovery at each level within the protocol-defined interval
RepeatabilityIndependent reportable results within each run conditionWithin-condition variation at or below the protocol maximum
Intermediate precisionTwo analysts, two instruments, three days, allocated across the six runsVariance and interval meet the predefined study limit
RangeJoint assessment of accuracy, precision, fit, and suitability at 80% to 120%Every required characteristic passes across the claimed range
RobustnessDefined low/high incubation time and cell-density challengesNo challenge creates an unacceptable result or suitability failure

4. Execute all planned runs and retain the calculation path

Run the approved design and retain raw well values, mappings, concentrations, inclusions and exclusions, fitted parameters, potency results, uncertainty, criteria outcomes, software release, analysis configuration, and report identity. Generate tables and plots from the saved results rather than transcribing them into a separate summary.

Keep failed, invalid, repeated, and aborted runs visible with their status. Review accumulating data only as the protocol permits; unplanned stopping, repetition, or selective analysis can bias the validation conclusion.

5. Assess deviations and unexpected outcomes

For each departure, record the protocol requirement, observed event, affected runs or results, root-cause work where warranted, correction, impact assessment, and approved disposition. Distinguish a procedural deviation from a correctly executed study that fails its acceptance criterion.

If an analysis changes after results are seen, preserve both states and justify the change. Additional testing should answer a defined gap; it should not continue until the desired result appears.

6. Decide whether the evidence supports the intended use

Summarize each performance question with its design, statistic, criterion, result, deviations, and pass/fail conclusion. Then state whether the procedure is supported for the named result and range, supported only with explicit conditions, or not supported.

Approve the exact procedure and analysis versions entering routine use, along with the suitability criteria and triggers for change assessment or revalidation. The final report should let a reviewer move from the conclusion back to every material source record and decision.

Limits and system boundary

There is no universal set of potency validation criteria. The accountable laboratory derives and approves them from intended use, development knowledge, assay behavior, risk, applicable guidance, and scientific and statistical review.

This guide validates the analytical procedure, not the computerized system. Provenarium’s three exact supplier-verified relative-potency model contracts can preserve calculation evidence, but the customer validates its assay and separately qualifies its configured software workflow for intended use.

Frequently asked questions

What acceptance criteria should a relative-potency validation use?

There is no universal set. Define criteria from intended use, assay behavior, risk, development evidence, applicable guidance, and scientific and statistical review.

Must every Q2(R2) characteristic be studied?

Select the characteristics appropriate to the procedure and its purpose and document the rationale; do not include or omit one merely because it appears on a generic checklist.

Should failed runs be removed from the validation summary?

No. Preserve planned, invalid, failed, repeated, and excluded runs with their reasons and dispositions so the final conclusion reflects the complete study evidence.

Primary references