This is a ready-to-use verification protocol for a compendial (pharmacopeial) analytical procedure under USP General Chapter <1226>. Replace every <<FILL: ...>> placeholder with your own specifics, set your document numbers and dates, and get it reviewed and approved before execution. A worked filled specimen follows the template. This is general guidance to adapt, not regulatory advice; confirm the current USP-NF edition and the cited regulation before you rely on them.
Document control header
| Field | Entry |
|---|---|
| Title | Verification of Compendial Procedure: <<FILL: attribute / method>> |
| Document number | <<FILL: protocol ID>> |
| Version | <<FILL>> |
| Status | Pre-approved before execution (required) |
| Author | <<FILL>> |
| Effective date | <<FILL>> |
State clearly in the title: “Verification of Compendial Procedure,” not “validation.” The wrong title invites the wrong scrutiny.
1. Purpose and scope
| Field | Entry |
|---|---|
| Article (product / substance) | <<FILL>> |
| Attribute tested | <<FILL: e.g. assay, related substances>> |
| Compendial reference | <<FILL: monograph or general chapter, with the current USP-NF edition and supplement>> |
| Specification the result supports | <<FILL: e.g. 90.0 to 110.0 percent>> |
| Instruments / column lot / CDS | <<FILL>> |
| Analysts in scope | <<FILL>> |
2. Regulatory and compendial basis
USP General Chapter <1226>, Verification of Compendial Procedures (cite the current USP-NF edition). 21 CFR 211.194(a)(2): test methods used must be verified under actual conditions of use. 21 CFR 211.165(e): accuracy, sensitivity, specificity, and reproducibility of test methods must be established and documented. Where chromatographic adjustments are made, USP General Chapter <621> (and Ph. Eur. 2.2.46 equivalent) for allowable adjustments.
Confirm the current chapter content and edition before issue; USP is revised continuously.
3. Description of the compendial procedure
Summarise the published procedure as written, and quote the system suitability requirements verbatim so there is no ambiguity about what “passes” means.
| Field | Entry |
|---|---|
| Procedure summary | <<FILL: column, mobile phase, detection, sample prep, run conditions as published>> |
| System suitability (verbatim) | <<FILL: resolution, tailing, plate count, replicate %RSD as the monograph states>> |
4. Risk assessment summary and characteristics to verify
Reference the characteristic-selection assessment (see assessment-compendial-verification-characteristic-selection). Record which characteristics are verified and the rationale for those excluded.
| Characteristic | Verify? | Rationale |
|---|---|---|
| Specificity / selectivity | <<FILL: usually Yes>> | <<FILL: your matrix is the variable>> |
| Accuracy (recovery) | <<FILL>> | <<FILL>> |
| Repeatability | <<FILL>> | <<FILL>> |
| Intermediate precision | <<FILL>> | <<FILL: yes if more than one analyst/day/instrument>> |
| Detection / quantitation limit | <<FILL>> | <<FILL: low-level impurity work only>> |
| Linearity / range | <<FILL>> | <<FILL: often excluded if published range brackets your spec>> |
5. Materials, standards, and instruments
| Item | Detail / traceability |
|---|---|
| Reference standard(s) and lot | <<FILL>> |
| Reagents and columns (lot) | <<FILL>> |
| Instruments (ID, qualification status) | <<FILL: confirm AIQ current, see analytical-instrument-qualification>> |
| Software / CDS (version) | <<FILL>> |
6. Test design (per selected characteristic)
| Characteristic | Design |
|---|---|
| Specificity | <<FILL: inject diluent blank, placebo, placebo spiked with analyte, forced-degradation sample; confirm no interference at the analyte retention time; peak purity if PDA>> |
| Accuracy | <<FILL: spiked placebo at e.g. 80/100/120 percent, triplicate per level, calculate recovery>> |
| Repeatability | <<FILL: six independent preparations at 100 percent, one analyst/day/instrument, report %RSD>> |
| Intermediate precision | <<FILL: second analyst, different day and instrument, repeat preparations; compare>> |
7. Acceptance criteria (pre-defined; do not change after seeing data)
| Characteristic | Acceptance criterion (justify per method) |
|---|---|
| Specificity | <<FILL: no interfering peak above a stated threshold at the analyte RT; peak purity passes>> |
| Accuracy | <<FILL: mean recovery within a stated band, e.g. 98.0 to 102.0 percent for an assay>> |
| Repeatability | <<FILL: %RSD at or below a method-appropriate limit, e.g. <= 2.0 percent>> |
| Intermediate precision | <<FILL: %RSD within a stated limit; analyst mean difference within a stated absolute>> |
| LOQ/LOD (if tested) | <<FILL: signal-to-noise typically >= 10 (LOQ) and >= 3 (LOD), or the method's stated approach>> |
| System suitability | Meets the compendial SST exactly as written |
8. Deviation and OOS handling
Any failure is raised as a deviation and investigated; results are not rerun until they pass. Reference <<FILL: deviation SOP-ID>> and <<FILL: OOS SOP-ID>>. A failed verification is a signal about method suitability for your article, not a reason to quietly adjust the method.
9. Roles and approvals
| Role | Name | Signature | Date |
|---|---|---|---|
| Author (QC SME) | <<FILL>> | ||
| Reviewer (method validation group) | <<FILL>> | ||
| Approver (QA, independent of execution) | <<FILL>> |
QA approval must be independent of execution; the same person cannot author, execute, and provide the sole quality approval.
Filled specimen
A pre-approved verification protocol for an example finished-product assay by HPLC, where the formulation has two excipients not in the monograph’s typical matrix and two analysts will run it (illustrative).
| Field | Entry |
|---|---|
| Compendial reference | USP monograph assay, current USP-NF edition |
| Specification | 90.0 to 110.0 percent of label |
| Characteristics verified | Specificity, accuracy, repeatability, intermediate precision |
| Excluded (with rationale) | Linearity/range (published range brackets the 90 to 110 percent spec; detector linearity well documented); LOQ (major-component assay) |
| Specificity design | Diluent blank, placebo, placebo spiked at nominal, forced-degradation sample |
| Accuracy design | Spiked placebo at 80/100/120 percent, triplicate each |
| Acceptance: accuracy | Mean recovery 98.0 to 102.0 percent per level |
| Acceptance: repeatability | %RSD <= 2.0 percent (n=6) |
| Acceptance: intermediate precision | Combined %RSD (n=12) <= 3.0 percent; analyst mean difference <= 2.0 percent absolute |
The protocol targets the two characteristics the risk assessment flagged (specificity and accuracy, because the matrix is the variable) plus the precision the multi-analyst use demands. It does not redo the full ICH Q2 battery, which is the shape of a <1226> study.
Common findings this protocol prevents
- A compendial method used for release with no verification (a direct 21 CFR 211.194(a)(2) citation).
- Acceptance criteria set or moved after the data (testing into compliance).
- A modified method called “verified” when the change went beyond <621> allowable adjustments.
- No documented rationale for the characteristics that were excluded.
- Verification on an unqualified instrument or against a stale compendial edition.
How to adapt this protocol
- Title it precisely and number it under document control.
- Quote the actual monograph system suitability verbatim in section 3.
- Let the characteristic-selection risk assessment drive section 4.
- Justify each acceptance criterion against your spec and matrix, not a copied table.
- Get QA pre-approval before any data is generated, and confirm the USP edition is current.