Purpose

Define user requirements for a standalone FUZKK utility that accepts laboratory CSV data, evaluates the records using limits embedded in code, and produces LabWare-compatible JSON.

Scope

The utility is intended for preliminary QC/QA review, integration testing, LIMS/LabWare flow and evidence-trail preparation. Final release decisions remain under the laboratory's validated procedure and responsible personnel.

Users

QC analyst, QA reviewer, CSV/validation engineer, LIMS/LabWare integration engineer, responsible laboratory specialist.

User requirements

1. The utility shall run without arguments and print its self-description, a built-in input.csv example from GetDemoData(), and demo evaluation for the embedded records.
2. The utility shall run with two arguments: input.csv output.json.
3. The utility shall not read input.csv and shall not write output.json when started without arguments.
4. CSV numeric values shall be parsed using CultureInfo.InvariantCulture.
5. Output shall be generated as LabWare-compatible JSON with Header, Samples, Results, Status, StatusCode, ErrorMessage, Description and DescriptionEN.
6. For PASS records, ErrorMessage shall be an empty string.
7. Embedded limits shall follow this priority: Ph. Eur. → British Pharmacopoeia / UK implementation → EAEU / regional requirements → EMA/ICH/EU guidance → USP fallback.
8. If an exact monograph is not known, strict standard API limits are used where applicable: assay 98–102%, total impurities ≤1.0%, individual impurity ≤0.5%.
9. For biologics and mAb-like products, aggregation, sterility and endotoxin checks shall be included where relevant to the utility purpose.
10. If a parameter may arrive in different units, the unit shall be represented as a separate input field or explicitly reflected in the input.csv field name.

Input CSV

BatchNumber,ProductName,Mass_Stage1,Mass_Stage2,Mass_Stage3,Mass_Stage4,Mass_Stage5,Mass_Stage6,Mass_Stage7,Mass_MOC,TotalRecoveredMass,ThroatDeposit,FlowRate_L_min,TestDuration_sec,TargetDose_mcgr
INH-NGI-2026-001,Budesonide DPI,15.0,12.0,10.0,8.0,15.0,20.0,10.0,10.0,100.0,20.0,60.0,2.0,200.0
INH-NGI-2026-002,Salbutamol MDI,5.0,8.0,12.0,15.0,20.0,25.0,10.0,5.0,100.0,10.0,30.0,1.5,100.0
INH-NGI-2026-003,Fluticasone DPI,20.0,15.0,10.0,5.0,10.0,15.0,15.0,10.0,100.0,30.0,60.0,2.0,250.0

input.csv fields

Utility description

Inhaler APSD NGI Profiler — Aerodynamic Particle Size Distribution Profiler (NGI)

Inhaler APSD NGI Profiler — Aerodynamic Particle Size Distribution Profiler (NGI)

ℹ️ Utility calculates key APSD parameters from NGI impactor data:
• MMAD (Mass Median Aerodynamic Diameter)
• GSD (Geometric Standard Deviation)
• FPF (Fine Particle Fraction <5 μm)
• Emitted Dose (ED)
• Mass Balance (Recovery)

⚠️ CRITICAL: Airflow must be stable!
Stage distribution determines lung delivery efficiency.

Usage:
InhalerAPSDNGIProfiler.exe → demo mode (console output)
InhalerAPSDNGIProfiler.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,ProductName,Mass_Stage1,Mass_Stage2,Mass_Stage3,Mass_Stage4,Mass_Stage5,Mass_Stage6,Mass_Stage7,Mass_MOC,TotalRecoveredMass,ThroatDeposit,FlowRate_L_min,TestDuration_sec,TargetDose_mcgr

Example:
INH-NGI-2026-001,Budesonide DPI,15.0,12.0,10.0,8.0,15.0,20.0,10.0,10.0,100.0,20.0,60.0,2.0,200.0

— WHY IS THIS NEEDED?
APSD analysis is critical for inhalers (AZ, GSK, BI):
• Determines fraction reaching alveoli (fine particles <5 μm)
• MMAD and GSD characterize aerosol homogeneity
• FPF correlates with clinical efficacy
• NGI data is gold standard for regulators

⚠️ CRITICAL:
• MMAD 1-5 μm — optimal range for lower airway delivery
• GSD < 2.5 — narrow distribution ensures predictable dose
• FPF ≥30% (example) — sufficient fine particles
• Mass balance 75-125% — confirms experiment validity
• Airflow must strictly match device specification (30, 60, or 90 L/min)

Key features:
• Automatic MMAD and GSD calculation via cumulative distribution interpolation
• FPF and emitted dose calculation
• Mass balance (recovery) check
• Test condition control (flow, time)

Critical parameters:
• MMAD: 1.0–5.0 μm
• GSD: ≤2.5
• FPF: ≥30% (product dependent)
• Emitted dose: ≥85%
• Mass balance: 75–125%

💡 Usage tips:
1. Thoroughly rinse impactor stages for complete drug extraction
2. Use correct cut-off diameters for selected airflow
3. Correct data for background (blank runs)
4. Use pre-separator for MDIs to remove large droplets
5. Compare profiles with Reference Listed Drug

⚠️ Note: Particle distribution in inhalers heavily depends on device design and patient inhalation technique. NGI allows modeling this process in vitro. The utility helps standardize aerosol quality assessment for different device types (DPI, MDI, SMI).

Traceability and limitations

• The URS is used as the source document for functional specification, CSV review and later validation work.
• This document does not replace an approved pharmacopoeial monograph, validated analytical method or internal product specification.
• For product-specific limits, the approved customer specification takes priority.

The functional specification describes the behaviour of the standalone FUZKK console utility, input-data format, evaluation algorithm and output JSON structure.

Functional flow

1. Main() checks the number of arguments.
2. If no arguments are provided: PrintHello() prints the description and built-in input.csv example, then RunDemoEvaluation() executes Evaluate() over GetDemoData() and prints demo JSON.
3. If two arguments are provided: RunWithFiles(input.csv, output.json) reads CSV, evaluates each record and writes LabWare-compatible JSON.
4. LoadData() uses CultureInfo.InvariantCulture and shall not be called in no-arguments mode.
5. Evaluate() returns a named tuple with BatchNumber, ProductName, Parameters, CriticalFailCount, WarningCount, Recommendation and RecommendationEN.
6. GetIssues() builds messages for ErrorMessage in WARNING/FAIL cases.

Evaluation rules

• PASS: CriticalFailCount = 0 and WarningCount = 0.
• WARNING: CriticalFailCount = 0 and WarningCount > 0.
• FAIL: CriticalFailCount > 0.
• ERROR: exception during reading or processing.
• ErrorMessage remains empty for PASS.
• Limits are embedded in Program.cs; no external limit configuration is required.

Input and fields

BatchNumber,ProductName,Mass_Stage1,Mass_Stage2,Mass_Stage3,Mass_Stage4,Mass_Stage5,Mass_Stage6,Mass_Stage7,Mass_MOC,TotalRecoveredMass,ThroatDeposit,FlowRate_L_min,TestDuration_sec,TargetDose_mcgr
INH-NGI-2026-001,Budesonide DPI,15.0,12.0,10.0,8.0,15.0,20.0,10.0,10.0,100.0,20.0,60.0,2.0,200.0
INH-NGI-2026-002,Salbutamol MDI,5.0,8.0,12.0,15.0,20.0,25.0,10.0,5.0,100.0,10.0,30.0,1.5,100.0
INH-NGI-2026-003,Fluticasone DPI,20.0,15.0,10.0,5.0,10.0,15.0,15.0,10.0,100.0,30.0,60.0,2.0,250.0

Output JSON

{
  "Header": {
    "UtilityName": "Inhaler_APSD_NGI_Profiler",
    "Version": "1.0.0",
    "Timestamp": "UTC",
    "InstrumentID": "FUZKK-QC-WORKSTATION",
    "OperatorID": "Admin"
  },
  "Samples": [
    {
      "SampleID": "from BatchNumber",
      "BatchNumber": "from CSV",
      "ProductName": "from CSV",
      "TestName": "utility-specific test",
      "AnalysisCode": "utility-specific code",
      "Status": "PASS | WARNING | FAIL | ERROR",
      "StatusCode": "1 | 2 | 0 | -1",
      "ErrorMessage": "",
      "Description": "Russian recommendation",
      "DescriptionEN": "English recommendation",
      "Results": [
        {
          "ParameterName": "parameter",
          "ResultValue": 0.0,
          "UnitOfMeasure": "unit",
          "SpecificationLimit": "limit",
          "IsWithinSpec": true
        }
      ]
    }
  ]
}