Zirconium89TrastuzumabQualityChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of Zirconium89TrastuzumabQualityChecker for Zirconium-89 Trastuzumab.

Domain limits and critical parameters

• ℹ️ Utility checks critical parameters of Zr-89-Trastuzumab:
• • Immunoreactivity (≥80%) — MAIN PARAMETER!
• • Absence of aggregates (≤5%)
• • Radiochemical purity (≥95%)
• • Free zirconium (≤5%) — BONE UPTAKE!
• • Yttrium-88 impurity (≤0.001%)
• • Specific activity, pH, endotoxins, sterility
• ⚠️ CRITICAL: Labeling process must not damage the antibody.
• Example (sterility: 0=sterile, 1=contaminated):
• ⚠️ CRITICAL:
• • Immunoreactivity ≥80% — THE MOST IMPORTANT BIOLOGICAL PARAMETER. Shows what fraction of antibodies retained ability to bind HER2 antigen after chemical modification (DFO) and labeling. Measured by Lindmo assay. If IR < 80%, batch is rejected.
• • Aggregates ≤5% — Labeling can cause antibody aggregation. Aggregates are rapidly taken up by liver and spleen macrophages, creating false background and risk of immune reactions. Controlled by SEC-HPLC.
• • Free zirconium ≤5% — Zr4+ accumulates in bones. High skeletal background interferes with metastasis assessment.
• • Yttrium-88 impurity ≤0.001% — Long-lived impurity, critical for waste.

URS — User Requirements Specification

input.csv contract

BatchNumber,TotalActivityMBq,ProteinConcentrationMgPerMl,SpecificActivityGBqPerUmol,RadionuclidicPurityPercent,Yttrium88ImpurityPercent,RadiochemicalPurityPercent,FreeZirconiumPercent,ImmunoreactivityPercent,AggregatesPercent,pH,EndotoxinsEU,SterilityTest,ProductType
ZR89-TRAS-2026-001,185.0,1.0,120.0,99.9,0.0005,98.0,2.0,90.0,1.0,7.2,10.0,0,ImmunoPET
ZR89-TRAS-DAMAGED-002,180.0,1.0,115.0,99.8,0.0006,97.0,3.0,60.0,2.0,7.0,15.0,0,ImmunoPET
ZR89-TRAS-AGG-003,175.0,1.0,110.0,99.7,0.0008,96.0,4.0,85.0,8.0,7.1,12.0,0,ImmunoPET

FS — Functional Specification

Example output.json

{
  "utilityId": "zirconium89-trastuzumab-quality-checker",
  "api": "Zirconium-89 Trastuzumab",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "ZR89-TRAS-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "TotalActivityMBq",
      "value": "185.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ProteinConcentrationMgPerMl",
      "value": "1.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "SpecificActivityGBqPerUmol",
      "value": "120.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadionuclidicPurityPercent",
      "value": "99.9",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Yttrium88ImpurityPercent",
      "value": "0.0005",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadiochemicalPurityPercent",
      "value": "98.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "FreeZirconiumPercent",
      "value": "2.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    }
  ],
  "criticalFindings": []
}

OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating the validator and test set.
• Retain 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 verified against the approved specification and local SOPs.