Genotoxic_Impurity_Screener_M7

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface, user requirements and functional behaviour of Genotoxic_Impurity_Screener_M7. The utility is intended for automated verification of laboratory, pharmacopoeial, analytical or manufacturing QC parameters using input.csv and producing a structured output.json result.

Domain limits and critical parameters

• • Nitrosamines: ≤ Specific Limit (e.g., 96 ppb for NDMA)
• • Alkyl Sulfonates: ≤ Calculated Limit (TTC/MDD)
• • Alkyl Halides: ≤ Calculated Limit (TTC/MDD)
• • Hydrazines: ≤ Calculated Limit (TTC/MDD)
• ⚠️ CRITICAL: Exceeding limits → carcinogenicity risk!
• • Compound classes: nitrosamines, alkyl sulfonates, alkyl halides, hydrazines, aromatic amines, etc.
• • Threshold of Toxicological Concern (TTC) is 1.5 mcg/day for most impurities.
• • For some substances (e.g., nitrosamines), stricter specific Acceptable Intakes (AI) are established.
• • Analysis is typically performed by mass spectrometry due to low detection limits (ppm/ppb level).
• • Control is necessary to ensure patient safety during long-term drug administration.
• • Nitrosamines (NDMA, NDEA, NMBA, etc.) are under close regulatory scrutiny.
• • Alkyl sulfonates (methyl methanesulfonate, ethyl methanesulfonate) can form when alcohols are used in the presence of sulfonic acids.
• • Limit calculation depends on the Maximum Daily Dose (MDD) of the drug.
• • Absence of impurities must be confirmed by validated methods with appropriate Limit of Quantitation (LOQ).
• • Assessment of compliance with ICH M7 limits.
• • Consideration of Maximum Daily Dose for threshold calculation.

URS — User Requirements Specification

input.csv contract

BatchNumber,Nitrosamines_ppb,AlkylSulf_ppm,AlkylHal_ppm,Hydrazines_ppm,MDD_grams
API-M7-2026-001,50.0,0.5,0.2,0.1,1.0
API-M7-2026-002,90.0,1.2,0.8,0.4,1.0
API-FAIL-M7-003,150.0,2.5,1.5,0.8,1.0

FS — Functional Specification

Example output.json

{
  "utilityId": "genotoxic-impurity-screener-m7",
  "utilityName": "Genotoxic_Impurity_Screener_M7",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "API-M7-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Nitrosamines_ppb",
      "value": "50.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "AlkylSulf_ppm",
      "value": "0.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "AlkylHal_ppm",
      "value": "0.2",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Hydrazines_ppm",
      "value": "0.1",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "MDD_grams",
      "value": "1.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    }
  ],
  "criticalFindings": [],
  "warnings": [],
  "generatedFor": "QA/QC review and LIMS integration"
}

Traceability matrix

OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating the validator, documentation and test set.
• Retain input.csv, output.json, executable version, documentation and checksum.
• Before production use, perform IQ/OQ/PQ or equivalent CSV/CSA verification.
• Critical limits must be verified against the approved specification, local SOPs and registration dossier.