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,Activity_Ac225,Activity_Fr221,Activity_Bi213,Time_Hours,Max_Allowed_Free_Bi213_Percent
RPH-AC-2026-001,Ac-225-PSMA-617,10.0,9.8,0.5,2.0,2.0
RPH-AC-2026-002,Ac-225-DOTATATE,5.0,4.9,0.1,1.0,2.0
RPH-AC-2026-003,Ac-225-PSMA-617 (Unstable),10.0,8.0,2.5,2.0,2.0

input.csv fields

Utility description

Ac-225 Daughter Recoil Analyzer — Ac-225 Daughter Recoil Analyzer

Ac-225 Daughter Recoil Analyzer — Ac-225 Daughter Recoil Analyzer

ℹ️ Utility evaluates alpha-emitting product stability:
• Free Bi-213 percentage (≤2%)
• Fr-221/Ac-225 equilibrium
• Recoil energy (theoretical estimate)

⚠️ CRITICAL: Alpha decay breaks chemical bonds!
Daughter isotopes may accumulate in kidneys and bones.

Usage:
Ac225DaughterRecoilAnalyzer.exe → demo mode (console output)
Ac225DaughterRecoilAnalyzer.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,ProductName,Activity_Ac225,Activity_Fr221,Activity_Bi213,Time_Hours,Max_Allowed_Free_Bi213_Percent

Example:
RPH-AC-2026-001,Ac-225-PSMA-617,10.0,9.8,0.5,2.0,2.0

— WHY IS THIS NEEDED?
Recoil control is critical for alpha therapy (Novartis, Bayer, AAA):
• During Ac-225 alpha decay, nucleus experiences strong recoil (~100 keV)
• This energy significantly exceeds chelate bond energy (~2-5 eV)
• Daughter isotopes (Fr-221, Bi-213) may escape complex and become free
• Free alpha emitters are highly toxic to healthy tissues (especially kidneys)
• Regulators require proof that most daughters remain bound or are safely excreted

⚠️ CRITICAL:
• Free Bi-213 ≤2% of parent activity — strict safety limit
• Fr-221 equilibrium must be reached quickly (half-life 4.9 min)
• Deviation from equilibrium indicates isotope loss from product
• Post-labeling purification is needed to remove free daughters

Key features:
• Decay chain activity ratio calculation
• "Escaped" daughter isotope percentage assessment
• Secular equilibrium achievement control
• Support for various chelating agents (DOTA, Macropa)

Critical parameters:
• Free Bi-213: ≤2%
• Fr-221 Ratio: 0.9–1.1 (equilibrium)
• Time post-purification: accounting for activity growth period

💡 Usage tips:
1. Perform analysis immediately after purification and at specific intervals
2. Use separation methods (TLC, columns) to distinguish bound Bi-213 from free
3. Account for detector geometry when measuring alpha and gamma activity
4. For new chelators (e.g., Macropa), perform extended stability tests
5. Compare data with pharmacokinetic distribution models in body

⚠️ Note: Unlike beta emitters (Lu-177) where nuclear recoil is negligible, in alpha therapy recoil is a fundamental physical limitation of product stability. The utility helps quantify this risk and confirm therapy safety.

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,Activity_Ac225,Activity_Fr221,Activity_Bi213,Time_Hours,Max_Allowed_Free_Bi213_Percent
RPH-AC-2026-001,Ac-225-PSMA-617,10.0,9.8,0.5,2.0,2.0
RPH-AC-2026-002,Ac-225-DOTATATE,5.0,4.9,0.1,1.0,2.0
RPH-AC-2026-003,Ac-225-PSMA-617 (Unstable),10.0,8.0,2.5,2.0,2.0

Output JSON

{
  "Header": {
    "UtilityName": "Ac225_Daughter_Recoil_Analyzer",
    "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
        }
      ]
    }
  ]
}