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,ProductName,Isotope,Intact_Complex_Percent,Free_Metal_Percent,Colloidal_Form_Percent,Challenge_Type,Incubation_Time_Hours,Temperature_C,Min_Intact_Percent
RPH-STAB-2026-001,Cu-64-DOTA-TATE,Cu-64,98.5,1.0,0.5,Human Serum,24.0,37.0,95.0
RPH-STAB-2026-002,Al[18F]F-PSMA,F-18,99.2,0.5,0.0,Saline,4.0,25.0,95.0
RPH-STAB-2026-003,Cu-64-SarAr-PEG,Cu-64,92.0,6.0,2.0,EDTA Challenge,2.0,37.0,95.0

input.csv fields

Utility description

Cu-64/F-18 Chelator Stability Monitor — Cu-64/F-18 Chelator Stability Monitor

Cu-64/F-18 Chelator Stability Monitor — Cu-64/F-18 Chelator Stability Monitor

ℹ️ Utility evaluates radiopharmaceutical resistance to decay/dissociation:
• Intact complex % (≥95%)
• Free isotope % (≤2%)
• Colloidal form % (≤1%)
• Serum/EDTA challenge tests

⚠️ CRITICAL: Cu-64 is prone to transchelation to blood proteins!
Unstable chelate leads to accumulation in liver and kidneys.

Usage:
Cu64F18ChelatorStabilityMonitor.exe → demo mode (console output)
Cu64F18ChelatorStabilityMonitor.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,ProductName,Isotope,Intact_Complex_Percent,Free_Metal_Percent,Colloidal_Form_Percent,Challenge_Type,Incubation_Time_Hours,Temperature_C,Min_Intact_Percent

Example:
RPH-STAB-2026-001,Cu-64-DOTA-TATE,Cu-64,98.5,1.0,0.5,Human Serum,24.0,37.0,95.0

— WHY IS THIS NEEDED?
Chelator stability control is critical for theranostics (Novartis, Bayer):
• Cu-64 has 12.7h half-life, requiring high in vivo stability
• Copper ion is easily displaced by serum proteins (transchelation) if chelate is weak
• For F-18, new binding methods (Al[18F]F, covalent bonds) also require hydrolysis checks
• Instability leads to false PET signal and toxicity to healthy organs

⚠️ CRITICAL:
• Complex integrity ≥95% after incubation in serum or with competitor (EDTA)
• Free isotope ≤2% — indicator of dissociation
• Colloidal form ≤1% — especially important for Cu-64 at neutral pH
• Tests must mimic physiological conditions (37°C, pH 7.4)

Key features:
• Transchelation resistance assessment (serum challenge)
• Competition resistance assessment (EDTA challenge)
• Colloid formation control
• Support for various isotopes (Cu-64, F-18) and chelators (DOTA, NOTA, SarAr)

Critical parameters:
• Intact Complex: ≥95%
• Free Isotope: ≤2%
• Colloidal Form: ≤1%

💡 Usage tips:
1. Use human serum for most relevant results
2. Perform tests at different time points (1h, 4h, 24h)
3. For Cu-64, must check colloid formation upon dilution
4. Compare different chelators (e.g., DOTA vs SarAr) to select optimal one
5. Account that in vitro stability does not always guarantee in vivo stability, but is a prerequisite

⚠️ Note: Unlike Lu-177 (which binds very strongly to DOTA), copper and aluminum require more careful ligand selection. The utility helps identify weaknesses in chemical structure before clinical trials.

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,ProductName,Isotope,Intact_Complex_Percent,Free_Metal_Percent,Colloidal_Form_Percent,Challenge_Type,Incubation_Time_Hours,Temperature_C,Min_Intact_Percent
RPH-STAB-2026-001,Cu-64-DOTA-TATE,Cu-64,98.5,1.0,0.5,Human Serum,24.0,37.0,95.0
RPH-STAB-2026-002,Al[18F]F-PSMA,F-18,99.2,0.5,0.0,Saline,4.0,25.0,95.0
RPH-STAB-2026-003,Cu-64-SarAr-PEG,Cu-64,92.0,6.0,2.0,EDTA Challenge,2.0,37.0,95.0

Output JSON

{
  "Header": {
    "UtilityName": "Cu64_F18_Chelator_Stability_Monitor",
    "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
        }
      ]
    }
  ]
}