Holmium166QualityChecker

1. Scope

This document defines requirements and functional behaviour for Holmium166QualityChecker used to control: Holmium-166. The utility is intended for QC use and applies deterministic rules, not machine learning.

2. Execution modes

• Holmium166QualityChecker.exe — demo mode or help output.
• Holmium166QualityChecker.exe input.csv output.json — process user data and write result.

3. Key source-derived controls

• Holmium-166 Quality Checker — Radiopharmaceutical (SIRT/Therapy) (Ph. Eur., USP)
• ℹ️ The utility checks particle size, RCP, free ions, sterility, endotoxins.
• ⚠️ CRITICAL! Particle size 20-50 um. Free ions ≤5%. Endotoxins ≤20 EU/mL!
• BatchNumber,Formulation_Type,Radionuclidic_Purity_Percent,Radiochemical_Purity_Percent,Specific_Activity_MBq_mg,Particle_Size_Mean_um,Particle_Size_Min_um,Particle_Size_Max_um,Particles_Out_of_Range_Percent,Free_Holmium_Ion_Percent,Target_Material_Residue_ppm,pH_Value,SterilityTest,Bacterial_Endotoxins_EU_per_mL,Appearance_Score,Microbial_Count_TAMC,Microbial_Count_TYMC,EColi_Detected,Salmonella_Detected
• HO166-MS-2026-001,Microspheres,99.9,98.5,1500.0,35.0,20.0,50.0,2.0,1.0,5.0,6.5,0,10.0,0,0,0,0,0
• • Particle Size: For microspheres, the 20–50 um range is critical. Particles <20 um may shunt to lungs causing radiation pneumonitis. Particles >50 um may occlude large vessels.
• • Radiochemical Purity: Free $^{166}\text{Ho}^{3+}$ is osteotropic (accumulates in bones), leading to bone marrow toxicity. RCP must be ≥95%.
• • Sterility and Endotoxins: Drug is administered intra-arterially. Requirements are strict.
• ⚠️ CRITICAL:
• • Radionuclidic Purity: ≥ 99.0%
• • Radiochemical Purity: ≥ 95.0%
• • Free Holmium Ions: ≤ 5.0%
• • Particles Out of Range: ≤ 5.0%
• • pH: 4.0–8.0
• • Endotoxins: ≤ 20.0 EU/mL (or per instruction)
• • Sterility: No growth
• ⚠️ Note: Utility focuses on specific microsphere parameters for SIRT: particle size and absence of free ions. Deviation in particle size is a critical defect leading to severe complications (pneumonitis, embolism).

4. URS — user requirements

5. input.csv contract

BatchNumber,Formulation_Type,Radionuclidic_Purity_Percent,Radiochemical_Purity_Percent,Specific_Activity_MBq_mg,Particle_Size_Mean_um,Particle_Size_Min_um,Particle_Size_Max_um,Particles_Out_of_Range_Percent,Free_Holmium_Ion_Percent,Target_Material_Residue_ppm,pH_Value,SterilityTest,Bacterial_Endotoxins_EU_per_mL,Appearance_Score,Microbial_Count_TAMC,Microbial_Count_TYMC,EColi_Detected,Salmonella_Detected
HO166-MS-2026-001,Microspheres,99.9,98.5,1500.0,35.0,20.0,50.0,2.0,1.0,5.0,6.5,0,10.0,0,0,0,0,0

6. FS — functional specification

7. output.json example

{
  "utilityId": "holmium166-quality-checker",
  "api": "Holmium-166",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "HO166-MS-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Formulation_Type",
      "value": "Microspheres",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Radionuclidic_Purity_Percent",
      "value": "99.9",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Radiochemical_Purity_Percent",
      "value": "98.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Specific_Activity_MBq_mg",
      "value": "1500.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Particle_Size_Mean_um",
      "value": "35.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Particle_Size_Min_um",
      "value": "20.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Particle_Size_Max_um",
      "value": "50.0",
      "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.