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_Tb161,Activity_Tb160,Activity_Gd153,Activity_Eu152,Max_Tb160_Percent,Max_Other_Impurities_Percent
RPH-TB-2026-001,Tb-161-DOTATATE,1000.0,0.5,0.1,0.05,0.1,0.5
RPH-TB-2026-002,Tb-161-PSMA,500.0,0.1,0.05,0.02,0.1,0.5
RPH-TB-2026-003,Tb-161-Batch (High Impurity),800.0,2.0,0.5,0.3,0.1,0.5

input.csv fields

Utility description

Tb-161 Radionuclidic Purity Checker — Tb-161 Radionuclidic Purity Analyzer

Tb-161 Radionuclidic Purity Checker — Tb-161 Radionuclidic Purity Analyzer

ℹ️ Utility analyzes gamma spectra for impurities:
• Tb-161 purity (≥99.9%)
• Tb-160 impurity (≤0.1%)
• Target (Gd-153) and activation (Eu-152) impurities

⚠️ CRITICAL: Tb-160 has a half-life of 72 days!
Its accumulation increases patient radiation dose without benefit.

Usage:
Tb161RadionuclidicPurityChecker.exe → demo mode (console output)
Tb161RadionuclidicPurityChecker.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,ProductName,Activity_Tb161,Activity_Tb160,Activity_Gd153,Activity_Eu152,Max_Tb160_Percent,Max_Other_Impurities_Percent

Example:
RPH-TB-2026-001,Tb-161-DOTATATE,1000.0,0.5,0.1,0.05,0.1,0.5

— WHY IS THIS NEEDED?
Radionuclidic purity control is critical for Tb-161 therapy (Novartis, PSI):
• Tb-161 is produced by neutron irradiation of Gd-160
• Side reaction (n, gamma) on Gd-160 can lead to Gd-161, which decays to Tb-161, but Tb-160 can also form via other paths or target impurities
• Tb-160 (T1/2 = 72.3 d) is a long-lived impurity compared to Tb-161 (T1/2 = 6.9 d)
• Presence of Tb-160 significantly increases integral patient dose after therapeutic isotope clearance
• Target impurities (Gd-153) and container activation products (Eu-152) are also controlled

⚠️ CRITICAL:
• Tb-161 radionuclidic purity ≥99.9%
• Tb-160 impurity ≤0.1% (strictly due to long half-life)
• Sum of other impurities ≤0.5%
• High-resolution gamma spectrometry (HPGe) is mandatory for separating close peaks

Key features:
• Calculation of percentage content for each radionuclide
• Specific control of Tb-160 as critical impurity
• Accounting for target and activation product activity
• Support for various limits depending on regulatory requirements

Critical parameters:
• Tb-161 Purity: ≥99.9%
• Tb-160 Impurity: ≤0.1%
• Other Impurities: ≤0.5%

💡 Usage tips:
1. Use calibrated HPGe detector with high efficiency
2. Perform measurements after sufficient cooling time to reduce short-lived isotope background
3. Account for sample geometry when calculating absolute activity
4. Compare spectra with reference libraries for accurate peak identification
5. For Tb-161, low-energy peaks (25-49 keV) are especially important, ensure correct detection

⚠️ Note: Unlike Lu-177 where main impurities are Lu-177m or Lu-176, for Tb-161 the main problem is Tb-160 due to large difference in half-lives. The utility helps guarantee that patient receives only therapeutic dose without long-term radiation tail.

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_Tb161,Activity_Tb160,Activity_Gd153,Activity_Eu152,Max_Tb160_Percent,Max_Other_Impurities_Percent
RPH-TB-2026-001,Tb-161-DOTATATE,1000.0,0.5,0.1,0.05,0.1,0.5
RPH-TB-2026-002,Tb-161-PSMA,500.0,0.1,0.05,0.02,0.1,0.5
RPH-TB-2026-003,Tb-161-Batch (High Impurity),800.0,2.0,0.5,0.3,0.1,0.5

Output JSON

{
  "Header": {
    "UtilityName": "Tb161_Radionuclidic_Purity_Checker",
    "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
        }
      ]
    }
  ]
}