Purpose

Define user requirements for a standalone FUZKK utility that accepts laboratory CSV data, evaluates the records using limits embedded in code, and produces LabWare-compatible JSON.

Scope

The utility is intended for preliminary QC/QA review, integration testing, LIMS/LabWare flow and evidence-trail preparation. Final release decisions remain under the laboratory's validated procedure and responsible personnel.

Users

QC analyst, QA reviewer, CSV/validation engineer, LIMS/LabWare integration engineer, responsible laboratory specialist.

User requirements

1. The utility shall run without arguments and print its self-description, a built-in input.csv example from GetDemoData(), and demo evaluation for the embedded records.
2. The utility shall run with two arguments: input.csv output.json.
3. The utility shall not read input.csv and shall not write output.json when started without arguments.
4. CSV numeric values shall be parsed using CultureInfo.InvariantCulture.
5. Output shall be generated as LabWare-compatible JSON with Header, Samples, Results, Status, StatusCode, ErrorMessage, Description and DescriptionEN.
6. For PASS records, ErrorMessage shall be an empty string.
7. Embedded limits shall follow this priority: Ph. Eur. → British Pharmacopoeia / UK implementation → EAEU / regional requirements → EMA/ICH/EU guidance → USP fallback.
8. If an exact monograph is not known, strict standard API limits are used where applicable: assay 98–102%, total impurities ≤1.0%, individual impurity ≤0.5%.
9. For biologics and mAb-like products, aggregation, sterility and endotoxin checks shall be included where relevant to the utility purpose.
10. If a parameter may arrive in different units, the unit shall be represented as a separate input field or explicitly reflected in the input.csv field name.

Input CSV

BatchNumber,PatientID,RadioligandPair,Diag_Activity_MBq,Diag_HalfLife_h,Tumor_Uptake_SUV,Kidney_Uptake_SUV,Ther_HalfLife_h,Max_Tolerated_Dose_Gy,Target_Tumor_Dose_Gy,S_Factor_Tumor,S_Factor_Kidney
RPH-DOSE-2026-001,PAT-001,Ga-68/Lu-177-PSMA,200.0,1.1,15.0,25.0,161.0,23.0,40.0,0.0005,0.0008
RPH-DOSE-2026-002,PAT-002,F-18/Ac-225-PSMA,150.0,1.8,20.0,30.0,240.0,15.0,50.0,0.0006,0.001
RPH-DOSE-2026-003,PAT-003,Ga-68/Lu-177-DOTATATE,180.0,1.1,10.0,15.0,161.0,23.0,30.0,0.0004,0.0005

input.csv fields

Utility description

Theranostic Paired Dose Calculator — Theranostic Paired Dose Calculator

Theranostic Paired Dose Calculator — Theranostic Paired Dose Calculator

ℹ️ Utility calculates personalized therapeutic dose:
• Based on diagnostic PET/CT data
• Considering critical organ dose limits (kidneys)
• Considering target tumor dose

⚠️ CRITICAL: Incorrect dose calculation leads to organ failure!
Theranostics requires precise conversion between isotopes.

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

Input format:
BatchNumber,PatientID,RadioligandPair,Diag_Activity_MBq,Diag_HalfLife_h,Tumor_Uptake_SUV,Kidney_Uptake_SUV,Ther_HalfLife_h,Max_Tolerated_Dose_Gy,Target_Tumor_Dose_Gy,S_Factor_Tumor,S_Factor_Kidney

Example:
RPH-DOSE-2026-001,PAT-001,Ga-68/Lu-177-PSMA,200.0,1.1,15.0,25.0,161.0,23.0,40.0,0.0005,0.0008

— WHY IS THIS NEEDED?
Dose personalization is critical for theranostics (Novartis, Bayer):
• Standard fixed doses do not account for individual patient pharmacokinetics
• High accumulation in kidneys can lead to radiation nephropathy
• Low accumulation in tumor makes therapy ineffective
• Conversion of activity from diagnostic (short-lived) to therapeutic (long-lived) isotope requires complex dosimetry models

⚠️ CRITICAL:
• Kidney dose must not exceed 23 Gy (for Lu-177) or specific limits for alpha emitters
• Tumor dose must be sufficient for tissue ablation
• Account for differences in half-lives and radiation types
• Use of S-factors (MIRD) for accurate absorbed dose calculation

Key features:
• Integration of imaging data (SUV) into dose calculation
• Automatic calculation of maximum safe activity
• Prediction of dose to target and critical organs
• Safety margin assessment

Critical parameters:
• Kidney Dose: ≤23 Gy (example)
• Tumor Dose: ≥ Target
• Safety Margin: >0%

💡 Usage tips:
1. Use high-quality PET/CT data with attenuation correction
2. Update S-factors according to latest MIRD model versions
3. Account for patient organ mass when calculating S-factors
4. For alpha therapy, use micro-dosimetric models
5. Always manually verify calculation before administering drug to patient

⚠️ Note: Unlike external beam radiotherapy where dose is planned on CT, in systemic radionuclide therapy dose depends on biological distribution of the drug. The utility helps link diagnosis and therapy into a single safe treatment protocol.

Traceability and limitations

• The URS is used as the source document for functional specification, CSV review and later validation work.
• This document does not replace an approved pharmacopoeial monograph, validated analytical method or internal product specification.
• For product-specific limits, the approved customer specification takes priority.

The functional specification describes the behaviour of the standalone FUZKK console utility, input-data format, evaluation algorithm and output JSON structure.

Functional flow

1. Main() checks the number of arguments.
2. If no arguments are provided: PrintHello() prints the description and built-in input.csv example, then RunDemoEvaluation() executes Evaluate() over GetDemoData() and prints demo JSON.
3. If two arguments are provided: RunWithFiles(input.csv, output.json) reads CSV, evaluates each record and writes LabWare-compatible JSON.
4. LoadData() uses CultureInfo.InvariantCulture and shall not be called in no-arguments mode.
5. Evaluate() returns a named tuple with BatchNumber, ProductName, Parameters, CriticalFailCount, WarningCount, Recommendation and RecommendationEN.
6. GetIssues() builds messages for ErrorMessage in WARNING/FAIL cases.

Evaluation rules

• PASS: CriticalFailCount = 0 and WarningCount = 0.
• WARNING: CriticalFailCount = 0 and WarningCount > 0.
• FAIL: CriticalFailCount > 0.
• ERROR: exception during reading or processing.
• ErrorMessage remains empty for PASS.
• Limits are embedded in Program.cs; no external limit configuration is required.

Input and fields

BatchNumber,PatientID,RadioligandPair,Diag_Activity_MBq,Diag_HalfLife_h,Tumor_Uptake_SUV,Kidney_Uptake_SUV,Ther_HalfLife_h,Max_Tolerated_Dose_Gy,Target_Tumor_Dose_Gy,S_Factor_Tumor,S_Factor_Kidney
RPH-DOSE-2026-001,PAT-001,Ga-68/Lu-177-PSMA,200.0,1.1,15.0,25.0,161.0,23.0,40.0,0.0005,0.0008
RPH-DOSE-2026-002,PAT-002,F-18/Ac-225-PSMA,150.0,1.8,20.0,30.0,240.0,15.0,50.0,0.0006,0.001
RPH-DOSE-2026-003,PAT-003,Ga-68/Lu-177-DOTATATE,180.0,1.1,10.0,15.0,161.0,23.0,30.0,0.0004,0.0005

Output JSON

{
  "Header": {
    "UtilityName": "Theranostic_Paired_Dose_Calculator",
    "Version": "1.0.0",
    "Timestamp": "UTC",
    "InstrumentID": "FUZKK-QC-WORKSTATION",
    "OperatorID": "Admin"
  },
  "Samples": [
    {
      "SampleID": "from BatchNumber",
      "BatchNumber": "from CSV",
      "ProductName": "from CSV",
      "TestName": "utility-specific test",
      "AnalysisCode": "utility-specific code",
      "Status": "PASS | WARNING | FAIL | ERROR",
      "StatusCode": "1 | 2 | 0 | -1",
      "ErrorMessage": "",
      "Description": "Russian recommendation",
      "DescriptionEN": "English recommendation",
      "Results": [
        {
          "ParameterName": "parameter",
          "ResultValue": 0.0,
          "UnitOfMeasure": "unit",
          "SpecificationLimit": "limit",
          "IsWithinSpec": true
        }
      ]
    }
  ]
}