CutoffTraceabilityChecker

Cutoff Traceability

Liquid Biopsy жидкостная биопсия cfDNA ctDNA CTC exosomes NGS qPCR

Utility description: Cutoff Traceability

Cutoff Traceability Checker — Diagnostic Cutoff Traceability Verification

ℹ️ Utility performs audit of diagnostic cutoff validity and traceability according to FDA SaMD guidance, EU IVDR Annex I and CLSI EP28:
• Cutoff Match: Reconciliation of current threshold with validated value.
• Method Version Link: Binding of cutoff to specific analytical method or algorithm version.
• Validation Documentation: Presence of identifiable validation document.
• Revalidation Currency: Control of scheduled revalidation deadlines.
• Regulatory Status: Currency of regulatory approval (FDA PMA, CE-IVDR).
• Clinical Evidence: Presence of clinical justification (not only analytical).

⚠️ IMPORTANT:
• Cutoff without traceability = clinically illegitimate result.
• Method version change without cutoff revalidation is unacceptable.
• Analytically justified cutoff without clinical correlation may be clinically useless.

Usage:
CutoffTraceabilityChecker.exe → demo mode (console output)
CutoffTraceabilityChecker.exe input.csv output.json → evaluate your data

Input format:
AssayName,Biomarker,CurrentCutoff,CutoffUnit,ValidatedCutoff,MethodVersion,ValidatedMethodVersion,ValidationDocumentID,ValidationDate,NextRevalidationDate,RegulatoryApprovalRef,ApprovalActive,JustificationSource,HasClinicalEvidence

Example:
OncoPanel,TMB,10.0,mut/Mb,10.0,v4.2,v4.2,VAL-2025-042,2025-09-15,2026-09-15,PMA_P210012,true,ROC+KEYNOTE,true

📍 Scope of Application (Usage Where):
• Clinical Laboratories: Audit of all cutoffs before routine use.
• IVD/SaMD Developers: Lifecycle management of threshold values.
• Regulatory Inspections: Demonstration of cutoff management system.
• CAP/ISO Accreditation: Confirmation of cut-off verification requirements compliance.

— WHY IS THIS NEEDED?
Diagnostic cutoff determines patient fate: treatment or observation.
Non-traceable threshold means no one can confirm its clinical validity.
Automated verification eliminates use of "forgotten" or outdated thresholds.
This is fundamental patient safety and regulatory compliance requirement.

⚠️ CRITICAL:
• Cutoff Mismatch: Current ≠ validated = IMMEDIATE BLOCKING.
• Undocumented: No validation document = cutoff does not exist regulatorily.
• Revalidation Overdue: Expired revalidation = validity has lapsed.
• Method Version: Cutoff is valid ONLY for specified method version.
• Clinical Evidence: Analytical LoD ≠ clinical cutoff.

Key features:
• Six-parameter traceability check
• Separation into critical violations and warnings
• Support for multiple justification types (ROC, trials, literature)
• Regulatory-ready audit report generation
• Compliance with FDA SaMD, EU IVDR, CLSI EP28

Critical parameters:
• Current Cutoff = Validated Cutoff
• Method Version = Validated Method Version
• Validation Document: Present
• Revalidation: Not overdue
• Regulatory Approval: Active
• Clinical Evidence: Present

💡 Usage tips:
1. Cutoff Registry: Maintain centralized registry of all thresholds with full traceability.
2. Change Control Link: Any method change must trigger cutoff review.
3. Revalidation Calendar: Set automatic reminders 90 days before deadline.
4. Clinical Justification: For each cutoff, retain link to clinical study or ROC analysis.
5. Archiving: Upon cutoff replacement, retain old record with date and reason for change.

⚠️ Note: This utility is a traceability audit tool. It does not replace cutoff establishment and validation process but guarantees that every used threshold has complete documentary chain of justification.

input.csv

AssayName,Biomarker,CurrentCutoff,CutoffUnit,ValidatedCutoff,MethodVersion,ValidatedMethodVersion,ValidationDocumentID,ValidationDate,NextRevalidationDate,RegulatoryApprovalRef,ApprovalActive,JustificationSource,HasClinicalEvidence
OncoPanel_CGP,TMB,10.0,mut/Mb,10.0,v4.2,v4.2,VAL-2025-TMB-042,2025-09-15,2026-09-15,PMA P210012/S015,true,ROC analysis + KEYNOTE-158 correlation,true
LiquidBiopsy_cfDNA,VAF_LOD,0.25,%,0.50,v3.1,v3.0,VAL-2024-VAF-018,2024-03-01,2025-03-01,CE-IVDR 2024/0567,true,Analytical LoD study,false
CRC_Screen_Blood,Algorithm_Score,0.65,score,0.65,v2.0,v2.0,,2025-06-01,2026-06-01,,false,,false
MSI_Panel,MSI_Score,0.4,ratio,0.4,v1.3,v1.3,VAL-2025-MSI-007,2025-11-20,2026-11-20,PMA P190034,true,Clinical concordance study,true

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of CutoffTraceabilityChecker for Cutoff Traceability Checker.

Domain limits URS input.csv FS IQ/OQ/PQ

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.

• CAP/ISO Accreditation: Confirmation of cut-off verification requirements compliance.
⚠️ CRITICAL:
• Separation into critical violations and warnings
Critical parameters:
2. Change Control Link: Any method change must trigger cutoff review.

URS — User Requirements Specification

ID	Requirement	Criticality	Acceptance criterion
URS-001	The utility shall accept an input.csv file for Cutoff Traceability 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	`AssayName`	string / controlled vocabulary	`OncoPanel_CGP`	Controlled input parameter for deterministic QC rules.
2	`Biomarker`	string / controlled vocabulary	`TMB`	Controlled input parameter for deterministic QC rules.
3	`CurrentCutoff`	decimal	`10.0`	Controlled input parameter for deterministic QC rules.
4	`CutoffUnit`	string / controlled vocabulary	`mut/Mb`	Controlled input parameter for deterministic QC rules.
5	`ValidatedCutoff`	string / controlled vocabulary	`10.0`	Controlled input parameter for deterministic QC rules.
6	`MethodVersion`	string / controlled vocabulary	`v4.2`	Method or process approach; controlled reference value.
7	`ValidatedMethodVersion`	string / controlled vocabulary	`v4.2`	Method or process approach; controlled reference value.
8	`ValidationDocumentID`	string / controlled vocabulary	`VAL-2025-TMB-042`	Controlled input parameter for deterministic QC rules.
9	`ValidationDate`	string / controlled vocabulary	`2025-09-15`	Controlled input parameter for deterministic QC rules.
10	`NextRevalidationDate`	string / controlled vocabulary	`2026-09-15`	Controlled input parameter for deterministic QC rules.
11	`RegulatoryApprovalRef`	string / controlled vocabulary	`PMA P210012/S015`	Controlled input parameter for deterministic QC rules.
12	`ApprovalActive`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
13	`JustificationSource`	string / controlled vocabulary	`ROC analysis + KEYNOTE-158 correlation`	Controlled input parameter for deterministic QC rules.
14	`HasClinicalEvidence`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.

AssayName,Biomarker,CurrentCutoff,CutoffUnit,ValidatedCutoff,MethodVersion,ValidatedMethodVersion,ValidationDocumentID,ValidationDate,NextRevalidationDate,RegulatoryApprovalRef,ApprovalActive,JustificationSource,HasClinicalEvidence
OncoPanel_CGP,TMB,10.0,mut/Mb,10.0,v4.2,v4.2,VAL-2025-TMB-042,2025-09-15,2026-09-15,PMA P210012/S015,true,ROC analysis + KEYNOTE-158 correlation,true
LiquidBiopsy_cfDNA,VAF_LOD,0.25,%,0.50,v3.1,v3.0,VAL-2024-VAF-018,2024-03-01,2025-03-01,CE-IVDR 2024/0567,true,Analytical LoD study,false
CRC_Screen_Blood,Algorithm_Score,0.65,score,0.65,v2.0,v2.0,,2025-06-01,2026-06-01,,false,,false

Input validation rules

ID	Field	Rule	Criticality
VR-001	`AssayName`	The field shall match an approved dictionary or accepted string representation.	High
VR-002	`Biomarker`	The field shall match an approved dictionary or accepted string representation.	High
VR-003	`CurrentCutoff`	The field shall match an approved dictionary or accepted string representation.	High
VR-004	`CutoffUnit`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-005	`ValidatedCutoff`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-006	`MethodVersion`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-007	`ValidatedMethodVersion`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-008	`ValidationDocumentID`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-009	`ValidationDate`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-010	`NextRevalidationDate`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-011	`RegulatoryApprovalRef`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-012	`ApprovalActive`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-013	`JustificationSource`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-014	`HasClinicalEvidence`	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 Cutoff Traceability 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": "cutofftraceabilitychecker",
  "utilityFolder": "CutoffTraceabilityChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "AssayName",
      "value": "OncoPanel_CGP",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "Biomarker",
      "value": "TMB",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "CurrentCutoff",
      "value": "10.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "CutoffUnit",
      "value": "mut/Mb",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "ValidatedCutoff",
      "value": "10.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "MethodVersion",
      "value": "v4.2",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "ValidatedMethodVersion",
      "value": "v4.2",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "ValidationDocumentID",
      "value": "VAL-2025-TMB-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "ValidationDate",
      "value": "2025-09-15",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "NextRevalidationDate",
      "value": "2026-09-15",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "RegulatoryApprovalRef",
      "value": "PMA P210012/S015",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "ApprovalActive",
      "value": "true",
      "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": "CutoffTraceabilityChecker.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.

Included in packages

Liquid Biopsy QC Suite

QC and pre-analytical control package for liquid biopsy workflows: cfDNA/ctDNA, CTC, EV/exosomes, methylation, NGS/qPCR/ddPCR, sample quality, contamination, sensitivity and reporting checks.

Open