mRNAVaccineIntegrityAndLNP_QualityChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of mRNAVaccineIntegrityAndLNP_QualityChecker for mRNA Vaccine Integrity & LNP Quality Checker.

Domain limits and critical parameters

• ℹ️ Utility assesses Critical Quality Attributes (CQA) of mRNA vaccines according to modern FDA, EMA, and ICH Q5A/Q6B guidelines:
• • dsRNA Impurity: Double-stranded RNA is a byproduct of synthesis and a potent activator of innate immunity (undesirable reactogenicity).
• ⚠️ CRITICAL:
• • High dsRNA levels (>200-500 ppm) can cause cytokine storm and severe side effects.
• • Low mRNA integrity (<90%) means a significant portion of the dose will not work.
• • Large LNP size (>100 nm) or high PDI (>0.25) indicates issues with the mixing process.
• • Stability: mRNA is prone to hydrolysis. Parameters must be controlled throughout shelf life.
• • Control of critical impurity (dsRNA)
• • Compliance with GMP requirements for Novel Platforms
• Critical parameters:
• • Full-Length mRNA: ≥ 90%
• • PDI: ≤ 0.25
• • Encapsulation: ≥ 85%
• • dsRNA: ≤ 200 ppm
• 4. Purification: Effective chromatographic purification (TFF, HPLC) is critical for removing dsRNA and free mRNA.

URS — User Requirements Specification

input.csv contract

BatchNumber,ProductName,FullLength_mRNA_Percent,LNP_Size_ZAvg_nm,PDI,EncapsulationEfficiency_Percent,dsRNA_Content_ppm,LipidConcentration_mg_per_ml,pH
MRNA-COVID-2026-001,SARS-CoV-2 mRNA Vaccine,96.5,85.0,0.12,92.0,150.0,1.2,7.4
MRNA-FLU-2026-002,Influenza mRNA Vaccine,94.0,78.0,0.15,89.0,120.0,1.0,7.2
MRNA-FAIL-2026-003,Experimental mRNA,85.0,110.0,0.35,75.0,600.0,1.1,7.0

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "mrnavaccineintegrityandlnp-qualitychecker",
  "utilityFolder": "mRNAVaccineIntegrityAndLNP_QualityChecker",
  "package": "huvac",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "MRNA-COVID-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "ProductName",
      "value": "SARS-CoV-2 mRNA Vaccine",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "FullLength_mRNA_Percent",
      "value": "96.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "LNP_Size_ZAvg_nm",
      "value": "85.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "PDI",
      "value": "0.12",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "EncapsulationEfficiency_Percent",
      "value": "92.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "dsRNA_Content_ppm",
      "value": "150.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "LipidConcentration_mg_per_ml",
      "value": "1.2",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "pH",
      "value": "7.4",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    }
  ],
  "criticalFindings": [],
  "warnings": [],
  "audit": {
    "inputHash": "sha256:<calculated at runtime>",
    "rulesVersion": "<utility executable version>",
    "documentation": "mRNAVaccineIntegrityAndLNP_QualityChecker.documentation.html"
  }
}

Traceability matrix

IQ/OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating validator, documentation 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 limits shall be verified against the approved specification, registration dossier and local SOPs.
• The utility provides structured QC decision support; final release decision remains with QA/QP and approved procedures.