Bismuth213QualityChecker

1. Scope

This document defines requirements and functional behaviour for Bismuth213QualityChecker used to control: Bismuth-213. The utility is intended for QC use and applies deterministic rules, not machine learning.

2. Execution modes

• Bismuth213QualityChecker.exe — demo mode or help output.
• Bismuth213QualityChecker.exe input.csv output.json — process user data and write result.

3. Key source-derived controls

• Bismuth-213 Quality Checker — Bismuth-213 for targeted alpha therapy
• ℹ️ Utility checks critical parameters of bismuth-213:
• • Radionuclidic purity (≥99.9%)
• • Actinium-225 breakthrough (≤0.01%) — CRITICAL! (Generator leakage)
• • Radiochemical purity (≥95%)
• • Free bismuth (≤5%) — kidney accumulation risk
• • pH (4.0–6.0), endotoxins, sterility
• ⚠️ CRITICAL: Actinium-225 breakthrough >0.01% → uncontrolled alpha emission in healthy tissues!
• BatchNumber,ActivityMBq,RadionuclidicPurityPercent,Ac225BreakthroughPercent,RadiochemicalPurityPercent,FreeBismuthPercent,pH,EndotoxinsEU,SterilityTest,ProductType
• Example (sterility: 0=sterile, 1=contaminated):
• • ANTIBODY — targeted alpha therapy with monoclonal antibodies
• Bismuth-213 is a potent alpha-emitter obtained from an Ac-225/Bi-213 generator:
• • Alpha radiation (8.4 MeV) — high LET, effectively destroys resistant cells
• ⚠️ CRITICAL:
• • Radionuclidic purity ≥99.9% — absence of other radioactive impurities
• • Actinium-225 breakthrough ≤0.01% — CRITICAL! Ac-225 (T½=10 days) has a long decay chain. If it enters the drug, it will circulate in the blood and irradiate bone marrow and kidneys with long-lived daughters.
• • Radiochemical purity ≥95% — free Bi-213 rapidly accumulates in kidneys, causing nephrotoxicity.
• • Free bismuth ≤5% — controls chelation efficiency (DOTA, CHX-A''-DTPA).
• • pH 4.0–6.0 — optimal for stability of Bi-213 complexes and preventing hydrolysis.
• • Endotoxins ≤175 EU/vial — critical for IV administration!

4. URS — user requirements

5. input.csv contract

BatchNumber,ActivityMBq,RadionuclidicPurityPercent,Ac225BreakthroughPercent,RadiochemicalPurityPercent,FreeBismuthPercent,pH,EndotoxinsEU,SterilityTest,ProductType
BI213-DEMO-001,300.0,99.95,0.005,98.0,1.5,5.0,40.0,0,PSMA
BI213-FAIL-002,280.0,99.0,0.05,90.0,8.0,3.5,100.0,0,DOTATATE

6. FS — functional specification

7. output.json example

{
  "utilityId": "bismuth213-quality-checker",
  "api": "Bismuth-213",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "BI213-DEMO-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ActivityMBq",
      "value": "300.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadionuclidicPurityPercent",
      "value": "99.95",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Ac225BreakthroughPercent",
      "value": "0.005",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadiochemicalPurityPercent",
      "value": "98.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "FreeBismuthPercent",
      "value": "1.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "pH",
      "value": "5.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "EndotoxinsEU",
      "value": "40.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    }
  ],
  "criticalFindings": []
}

8. OQ/PQ test scenarios

9. QA/QC and change control

• Do not rename columns without validator update.
• Store input.csv, output.json, executable version and checksum.
• Before production use perform IQ/OQ/PQ or equivalent CSV/CSA verification.
• Critical radiopharmaceutical limits must be checked against the approved specification and local SOPs.