URS & FS — User Requirements and Functional Specification
This document describes the controlled interface and behaviour of PositiveNegativeControlTrendChecker for Positive/Negative Control Trend Checker.
Domain limits and critical parameters
Key fragments from the source description are shown below. Before production use, limits must be verified against the approved specification, registration dossier and local SOPs.
- Performs longitudinal control monitoring per CLSI EP23-A, CAP/CLIA, ISO 15189 §7.3 and FDA statistical QC guidance: Westgard rules (1-2S warning, 1-3S reject, 2-2S reject, R-4S reject, 4-1S reject, 10X reject), trend analysis via linear regression (minimum 5 points, significance threshold |slope| > 0.5×SD/N), predictive failure estimation (extrapolation to 3SD limit with alert at <20 runs), CV monitoring over rolling window, and direction-aware interpretation for control type. Three-tier classif
- ⚠️ Critical: Binary pass/fail does NOT detect gradual degradation; only trend analysis does. Westgard violation = IMMEDIATE result release block. 1-2S is WARNING not reject, but two consecutive warnings require investigation. For negative controls, direction matters: decreasing Ct = increasing signal = contamination. Historical data must be from STABLE period (post-validation, pre-lot-change). New baseline required at lot transition. Minimum 20 historical points for reliable statistics. Tool per
URS — User Requirements Specification
| ID | Requirement | Criticality | Acceptance criterion |
|---|
| URS-001 | The utility shall accept an input.csv file for Positive/Negative Control Trend Checker with headers defined in the data contract. | High | The file is processed without manual header editing. |
| URS-002 | The utility shall perform deterministic QC evaluation without machine learning and without probabilistic conformance decisions. | High | Identical input data, rule version and configuration produce reproducible results. |
| URS-003 | The utility shall validate mandatory fields, data types, ranges, units and domain plausibility. | High | Schema, conversion and range errors are explicitly reported. |
| URS-004 | The utility shall apply domain limits and rules from the description, approved specification, registration dossier and local SOPs. | High | Each check has PASS/WARNING/FAIL and a clear message. |
| URS-005 | The utility shall generate output.json with machine-readable results, source values, warnings, failures and critical findings. | High | JSON is suitable for LIMS/ELN/MES integration and QA/QC review. |
| URS-006 | The utility shall preserve traceability between batch/sample, input file, applied rules and final status. | High | Output contains identifiers, checked parameters and audit metadata. |
| URS-007 | The documentation shall support IQ/OQ/PQ, CSV/CSA and review by internal QA or inspectors. | Medium | URS, FS, input/output contract and test scenarios are supplied with the utility. |
| URS-008 | The utility shall be used as a QC decision-support tool and not as a substitute for approved specifications and QA/QP release decision. | Medium | Documentation states change control and limit-verification expectations. |
input.csv contract
| # | Field | Type | Sample | Purpose |
|---|
| 1 | ControlID | string / controlled vocabulary | POS-CTRL-001 | Control point/control sample for assay run validity. |
| 2 | ControlType | string / controlled vocabulary | Positive | Control point/control sample for assay run validity. |
| 3 | AssayName | string / controlled vocabulary | KRAS_ddPCR | Controlled input parameter for deterministic QC rules. |
| 4 | MetricName | string / controlled vocabulary | Copies_uL | Controlled input parameter for deterministic QC rules. |
| 5 | InstrumentID | string / controlled vocabulary | QX200-01 | Controlled input parameter for deterministic QC rules. |
| 6 | ReagentLot | string / controlled vocabulary | LOT-2026-0451 | Batch or lot identifier used for traceability. |
| 7 | HistoricalValues_Raw | string / controlled vocabulary | 2026-05-01:102.5;2026-05-05:99.8;2026-05-08:101.2;2026-05-12:100.5;2026-05-15:103.1;2026-05-19:98.7;2026-05-22:101.8;2026-05-26:100.2;2026-05-29:102.0;2026-06-02:99.5;2026-06-05:101.5;2026-06-08:100.8 | Controlled input parameter for deterministic QC rules. |
| 8 | CurrentValue | decimal | 100.8 | Controlled input parameter for deterministic QC rules. |
| 9 | CurrentDate | string / controlled vocabulary | 2026-06-08 | Controlled input parameter for deterministic QC rules. |
| 10 | EstablishedMean | integer / decimal | 100.0 | Controlled input parameter for deterministic QC rules. |
| 11 | EstablishedSD | decimal | 3.0 | Controlled input parameter for deterministic QC rules. |
| 12 | UpperLimit_3SD | decimal | 109.0 | Approved limit applied during result evaluation. |
| 13 | LowerLimit_3SD | decimal | 91.0 | Approved limit applied during result evaluation. |
| 14 | UpperLimit_2SD | decimal | 106.0 | Approved limit applied during result evaluation. |
| 15 | LowerLimit_2SD | decimal | 94.0 | Approved limit applied during result evaluation. |
| 16 | Rule_1_2S_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 17 | Rule_1_3S_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 18 | Rule_2_2S_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 19 | Rule_R_4S_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 20 | Rule_4_1S_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 21 | Rule_10X_Enabled | string / controlled vocabulary | true | Controlled input parameter for deterministic QC rules. |
| 22 | MetricDirection | string / controlled vocabulary | Two_Sided | Controlled input parameter for deterministic QC rules. |
ControlID,ControlType,AssayName,MetricName,InstrumentID,ReagentLot,HistoricalValues_Raw,CurrentValue,CurrentDate,EstablishedMean,EstablishedSD,UpperLimit_3SD,LowerLimit_3SD,UpperLimit_2SD,LowerLimit_2SD,Rule_1_2S_Enabled,Rule_1_3S_Enabled,Rule_2_2S_Enabled,Rule_R_4S_Enabled,Rule_4_1S_Enabled,Rule_10X_Enabled,MetricDirection
POS-CTRL-001,Positive,KRAS_ddPCR,Copies_uL,QX200-01,LOT-2026-0451,2026-05-01:102.5;2026-05-05:99.8;2026-05-08:101.2;2026-05-12:100.5;2026-05-15:103.1;2026-05-19:98.7;2026-05-22:101.8;2026-05-26:100.2;2026-05-29:102.0;2026-06-02:99.5;2026-06-05:101.5;2026-06-08:100.8,100.8,2026-06-08,100.0,3.0,109.0,91.0,106.0,94.0,true,true,true,true,true,true,Two_Sided
NEG-CTRL-002,Negative,EGFR_T790M_BEAMing,Ct,LC480-02,LOT-2026-0467,2026-05-01:38.5;2026-05-05:38.2;2026-05-08:37.9;2026-05-12:37.5;2026-05-15:37.1;2026-05-19:36.8;2026-05-22:36.4;2026-05-26:36.0;2026-05-29:35.7;2026-06-02:35.3;2026-06-05:35.0;2026-06-08:34.6,34.6,2026-06-08,38.0,1.0,41.0,35.0,40.0,36.0,true,true,true,true,true,true,Higher_Is_Better
Input validation rules
| ID | Field | Rule | Criticality |
|---|
| VR-001 | ControlID | The field shall match an approved dictionary or accepted string representation. | High |
| VR-002 | ControlType | The field shall match an approved dictionary or accepted string representation. | High |
| VR-003 | AssayName | The field shall match an approved dictionary or accepted string representation. | High |
| VR-004 | MetricName | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-005 | InstrumentID | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-006 | ReagentLot | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-007 | HistoricalValues_Raw | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-008 | CurrentValue | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-009 | CurrentDate | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-010 | EstablishedMean | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-011 | EstablishedSD | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-012 | UpperLimit_3SD | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-013 | LowerLimit_3SD | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-014 | UpperLimit_2SD | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-015 | LowerLimit_2SD | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-016 | Rule_1_2S_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-017 | Rule_1_3S_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-018 | Rule_2_2S_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-019 | Rule_R_4S_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-020 | Rule_4_1S_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-021 | Rule_10X_Enabled | The field shall match an approved dictionary or accepted string representation. | Medium |
| VR-022 | MetricDirection | The field shall match an approved dictionary or accepted string representation. | Medium |
FS — Functional Specification
| ID | Function | Implementation |
|---|
| FS-001 | CLI execution | Support execution modes: demo mode without arguments and production mode input.csv output.json. |
| FS-002 | CSV import | Read input.csv in UTF-8/CSV-compatible format and validate header and expected columns. |
| FS-003 | Schema validation | Check mandatory fields, column count, unknown key fields and empty mandatory values. |
| FS-004 | Type conversion | Convert numeric, flag and text values; invalid format is recorded as a row-level error. |
| FS-005 | Domain rule engine | Apply rules for Positive/Negative Control Trend Checker, including critical limits from the description and approved specification. |
| FS-006 | Status aggregation | Produce final status: FAIL for critical failure, WARNING for non-critical deviation, PASS for conformance. |
| FS-007 | JSON export | Write output.json with detailed checks, source values, warnings, failures and critical findings. |
| FS-008 | Audit support | Keep result structure suitable for review, deviation investigation and calculation reproduction. |
| FS-009 | Integration contract | Support the scenario LIMS/ELN/MES → input.csv → utility → output.json → portal/admin review. |
| FS-010 | Error handling | Return explicit messages for missing file, empty CSV, invalid schema, output write failure and invalid format. |
Example output.json
{
"utilityId": "positivenegativecontroltrendchecker",
"utilityFolder": "PositiveNegativeControlTrendChecker",
"package": "LiquidBiopsy",
"overallStatus": "PASS|WARNING|FAIL",
"sourceFile": "input.csv",
"processedAtUtc": "2026-06-10T00:00:00Z",
"checks": [
{
"parameter": "ControlID",
"value": "POS-CTRL-001",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-001"
},
{
"parameter": "ControlType",
"value": "Positive",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-002"
},
{
"parameter": "AssayName",
"value": "KRAS_ddPCR",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-003"
},
{
"parameter": "MetricName",
"value": "Copies_uL",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-004"
},
{
"parameter": "InstrumentID",
"value": "QX200-01",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-005"
},
{
"parameter": "ReagentLot",
"value": "LOT-2026-0451",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-006"
},
{
"parameter": "HistoricalValues_Raw",
"value": "2026-05-01:102.5;2026-05-05:99.8;2026-05-08:101.2;2026-05-12:100.5;2026-05-15:103.1;2026-05-19:98.7;2026-05-22:101.8;2026-05-26:100.2;2026-05-29:102.0;2026-06-02:99.5;2026-06-05:101.5;2026-06-08:100.8",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-007"
},
{
"parameter": "CurrentValue",
"value": "100.8",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-008"
},
{
"parameter": "CurrentDate",
"value": "2026-06-08",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-009"
},
{
"parameter": "EstablishedMean",
"value": "100.0",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-010"
},
{
"parameter": "EstablishedSD",
"value": "3.0",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-011"
},
{
"parameter": "UpperLimit_3SD",
"value": "109.0",
"status": "PASS|WARNING|FAIL",
"message": "Deterministic rule-based check result",
"ruleReference": "FS-RULE-012"
}
],
"criticalFindings": [],
"warnings": [],
"audit": {
"inputHash": "sha256:<calculated at runtime>",
"rulesVersion": "<utility executable version>",
"documentation": "PositiveNegativeControlTrendChecker.documentation.html"
}
}
Traceability matrix
| URS | FS | Test | Evidence |
|---|
| URS-001 | FS-001, FS-002 | OQ-001 | Verify execution and import of valid input.csv. |
| URS-002 | FS-005, FS-006 | OQ-004 | Repeat the same dataset and compare output.json. |
| URS-003 | FS-003, FS-004, FS-010 | OQ-002, OQ-003 | Verify missing columns and invalid types. |
| URS-004 | FS-005, FS-006 | OQ-004, PQ-001 | Verify critical deviations on real/boundary data. |
| URS-005 | FS-007, FS-009 | OQ-005 | Verify JSON schema and downstream-system suitability. |
| URS-006 | FS-008 | OQ-006 | Verify identifiers and audit metadata. |
| URS-007 | FS-008, FS-010 | IQ-001, OQ-007 | Verify documentation completeness and control evidence. |
| URS-008 | FS-005, FS-008 | PQ-002 | Verify review workflow and no replacement of QA decision. |
IQ/OQ/PQ test scenarios
| ID | Scenario | Expected result |
|---|
| IQ-001 | Verify executable, input.csv, documentation and checksum availability. | Delivery set is complete; version is recorded. |
| OQ-001 | Valid sample row from input.csv. | PASS or acceptable WARNING according to rules. |
| OQ-002 | Remove a mandatory CSV column. | Schema error or FAIL with missing-column reference. |
| OQ-003 | Place a non-numeric value into a numeric field. | Type-conversion error with row/field reference. |
| OQ-004 | Set a critical parameter outside the limit. | FAIL and critical finding. |
| OQ-005 | Verify output.json structure. | All mandatory sections are present and JSON is valid. |
| OQ-006 | Verify batch/sample traceability. | Input and result identifiers match. |
| PQ-001 | Verify 3–5 real user batches/samples. | Result is confirmed by QC/QA review. |
| PQ-002 | Verify deviation workflow and manual QA decision. | Utility supports review but does not replace approved decision. |
QA/QC and change control
- Do not rename columns without updating validator, documentation and test set.
- Retain
input.csv, output.json, executable version and checksum. - Before production use, perform IQ/OQ/PQ or equivalent CSV/CSA verification.
- Critical limits shall be verified against the approved specification, registration dossier and local SOPs.
- The utility provides structured QC decision support; final release decision remains with QA/QP and approved procedures.