CompanionDiagnosticReportChecker

Companion Diagnostic Report

Liquid Biopsy жидкостная биопсия cfDNA ctDNA CTC exosomes NGS qPCR

Utility description: Companion Diagnostic Report

Companion Diagnostic Report Checker — CDx Report IFU Compliance Validation

ℹ️ Utility performs strict verification of CDx report compliance with Instructions for Use (IFU) requirements according to FDA 21 CFR Part 809, EU IVDR Annex I and CAP:
• Drug-Biomarker Pair: Verification that specified combination is approved indication for given CDx.
• Result Wording: Check of exact terminology match with IFU ("Positive" vs "Detected", etc.).
• Test Version: Reconciliation of used version with regulator-approved/validated version.
• Mandatory Statements: Presence of Intended Use, Limitations of Use sections and IFU reference.

⚠️ IMPORTANT:
• CDx report is a Class III medical device (EU) / Class III PMA (FDA).
• Any deviation from IFU renders result legally invalid and potentially dangerous.
• Different CDx tests for same biomarker may have DIFFERENT result wordings.

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

Input format:
ReportID,PatientID,CDx_TestName,CDx_TestVersion,Validated_TestVersion,AssociatedDrug,Biomarker,ReportedResult,ExpectedResultFormat,DrugBiomarkerPairValid,HasIFU_Reference,HasLimitationsStatement,HasIntendedUseStatement,ResultMatchesIFU_Wording

Example:
CDX-001,PAT-01,F1CDx,v4.0,v4.0,Osimertinib,EGFR_L858R,Positive,Positive,true,true,true,true,true

📍 Scope of Application (Usage Where):
• CDx Laboratories: Final check before oncologist delivery.
• Pharmaceutical Companies: Audit of partner lab reports in clinical trials.
• Regulatory Inspections: Demonstration of PMA/CE-IVDR approval condition compliance.
• CDx Development: Report template validation during new test creation.

— WHY IS THIS NEEDED?
Physician makes decision on prescribing expensive and potentially toxic therapy SOLELY based on CDx report.
Incorrect wording or wrong drug-biomarker pair may lead to off-label use without evidence base.
Automated verification eliminates human factor in critically important document.

⚠️ CRITICAL:
• Exact Wording: "Detected" ≠ "Positive" in context of some CDx. Use EXACT IFU wording.
• Approved Pair: Biomarker may be relevant but NOT approved as CDx for specific drug.
• Test Version: Using unvalidated version = using unapproved device.
• Mandatory Statements: Missing Limitations of Use violates FDA/EMA approval conditions.

Key features:
• Five-parameter IFU compliance check
• Separation into critical violations and warnings
• Support for multiple CDx platforms
• Regulatory-ready report generation
• Compliance with FDA 21 CFR 809 and EU IVDR

Critical parameters:
• Drug-Biomarker Pair: Approved indication only
• Result Wording: Exact IFU match
• Test Version: = Validated version
• IFU Reference: Present
• Mandatory Statements: All present

💡 Usage tips:
1. IFU Database: Maintain centralized registry of approved wordings for each CDx.
2. Updates: Upon IFU update, immediately update expected wording directory.
3. Training: Pathologists must understand difference between general molecular report and CDx report.
4. Templates: Use rigid templates with locked fields for mandatory statements.
5. Audit: Conduct retrospective review of issued CDx reports quarterly.

⚠️ Note: This utility verifies report compliance with regulatory IFU requirements. It does not replace clinical interpretation but guarantees that report is a valid medical device.

input.csv

ReportID,PatientID,CDx_TestName,CDx_TestVersion,Validated_TestVersion,AssociatedDrug,Biomarker,ReportedResult,ExpectedResultFormat,DrugBiomarkerPairValid,HasIFU_Reference,HasLimitationsStatement,HasIntendedUseStatement,ResultMatchesIFU_Wording
CDX-2026-001,PAT-3001,FoundationOne CDx,v4.0,v4.0,Osimertinib (Tagrisso),EGFR L858R,Positive,Positive,true,true,true,true,true
CDX-2026-002,PAT-3002,Oncomine Dx Target Test,v2.1,v2.3,Trastuzumab,HER2 Amplification,Detected,Positive,true,true,false,true,false
CDX-2026-003,PAT-3003,therascreen KRAS RGQ PCR Kit,v3.0,v3.0,Cetuximab,KRAS G12C,Negative,Negative,true,true,true,true,true

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of CompanionDiagnosticReportChecker for Companion Diagnostic Report 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.

• Mandatory Statements: Presence of Intended Use, Limitations of Use sections and IFU reference.
ReportID,PatientID,CDx_TestName,CDx_TestVersion,Validated_TestVersion,AssociatedDrug,Biomarker,ReportedResult,ExpectedResultFormat,DrugBiomarkerPairValid,HasIFU_Reference,HasLimitationsStatement,HasIntendedUseStatement,ResultMatchesIFU_Wording
Automated verification eliminates human factor in critically important document.
⚠️ CRITICAL:
• Mandatory Statements: Missing Limitations of Use violates FDA/EMA approval conditions.
• Separation into critical violations and warnings
Critical parameters:
3. Training: Pathologists must understand difference between general molecular report and CDx report.

URS — User Requirements Specification

ID	Requirement	Criticality	Acceptance criterion
URS-001	The utility shall accept an input.csv file for Companion Diagnostic Report 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	`ReportID`	string / controlled vocabulary	`CDX-2026-001`	Controlled input parameter for deterministic QC rules.
2	`PatientID`	string / controlled vocabulary	`PAT-3001`	Controlled input parameter for deterministic QC rules.
3	`CDx_TestName`	string / controlled vocabulary	`FoundationOne CDx`	Controlled input parameter for deterministic QC rules.
4	`CDx_TestVersion`	string / controlled vocabulary	`v4.0`	Controlled input parameter for deterministic QC rules.
5	`Validated_TestVersion`	string / controlled vocabulary	`v4.0`	Controlled input parameter for deterministic QC rules.
6	`AssociatedDrug`	string / controlled vocabulary	`Osimertinib (Tagrisso)`	Controlled input parameter for deterministic QC rules.
7	`Biomarker`	string / controlled vocabulary	`EGFR L858R`	Controlled input parameter for deterministic QC rules.
8	`ReportedResult`	string / controlled vocabulary	`Positive`	Result/status used in final classification.
9	`ExpectedResultFormat`	string / controlled vocabulary	`Positive`	Result/status used in final classification.
10	`DrugBiomarkerPairValid`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
11	`HasIFU_Reference`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
12	`HasLimitationsStatement`	string / controlled vocabulary	`true`	Approved limit applied during result evaluation.
13	`HasIntendedUseStatement`	string / controlled vocabulary	`true`	Controlled input parameter for deterministic QC rules.
14	`ResultMatchesIFU_Wording`	string / controlled vocabulary	`true`	Result/status used in final classification.

ReportID,PatientID,CDx_TestName,CDx_TestVersion,Validated_TestVersion,AssociatedDrug,Biomarker,ReportedResult,ExpectedResultFormat,DrugBiomarkerPairValid,HasIFU_Reference,HasLimitationsStatement,HasIntendedUseStatement,ResultMatchesIFU_Wording
CDX-2026-001,PAT-3001,FoundationOne CDx,v4.0,v4.0,Osimertinib (Tagrisso),EGFR L858R,Positive,Positive,true,true,true,true,true
CDX-2026-002,PAT-3002,Oncomine Dx Target Test,v2.1,v2.3,Trastuzumab,HER2 Amplification,Detected,Positive,true,true,false,true,false
CDX-2026-003,PAT-3003,therascreen KRAS RGQ PCR Kit,v3.0,v3.0,Cetuximab,KRAS G12C,Negative,Negative,true,true,true,true,true

Input validation rules

ID	Field	Rule	Criticality
VR-001	`ReportID`	The field shall match an approved dictionary or accepted string representation.	High
VR-002	`PatientID`	The field shall match an approved dictionary or accepted string representation.	High
VR-003	`CDx_TestName`	The field shall match an approved dictionary or accepted string representation.	High
VR-004	`CDx_TestVersion`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-005	`Validated_TestVersion`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-006	`AssociatedDrug`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-007	`Biomarker`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-008	`ReportedResult`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-009	`ExpectedResultFormat`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-010	`DrugBiomarkerPairValid`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-011	`HasIFU_Reference`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-012	`HasLimitationsStatement`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-013	`HasIntendedUseStatement`	The field shall match an approved dictionary or accepted string representation.	Medium
VR-014	`ResultMatchesIFU_Wording`	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 Companion Diagnostic Report 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": "companiondiagnosticreportchecker",
  "utilityFolder": "CompanionDiagnosticReportChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "ReportID",
      "value": "CDX-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PatientID",
      "value": "PAT-3001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "CDx_TestName",
      "value": "FoundationOne CDx",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "CDx_TestVersion",
      "value": "v4.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "Validated_TestVersion",
      "value": "v4.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "AssociatedDrug",
      "value": "Osimertinib (Tagrisso)",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "Biomarker",
      "value": "EGFR L858R",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "ReportedResult",
      "value": "Positive",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "ExpectedResultFormat",
      "value": "Positive",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "DrugBiomarkerPairValid",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "HasIFU_Reference",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "HasLimitationsStatement",
      "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": "CompanionDiagnosticReportChecker.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