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,IgG1_mg_ml,IgG2_mg_ml,IgG3_mg_ml,IgG4_mg_ml,Total_IgG_mg_ml
PLASMA-SUB-2026-001,IVIG 10% Liquid,68.0,24.0,5.5,3.5,101.0
PLASMA-SUB-2026-002,SCIG 16%,105.0,38.0,9.0,5.0,157.0
PLASMA-SUB-2026-003,Hyperimmune Anti-Tetanus,70.0,20.0,6.0,4.0,100.0

input.csv fields

Utility description

IgG Subclass Distribution Analyzer — Plasma Product IgG Subclass Distribution Analyzer

IgG Subclass Distribution Analyzer — Plasma Product IgG Subclass Distribution Analyzer

ℹ️ Utility analyzes immunoglobulin G subclass profile:
• % IgG1 (main component, ~65%)
• % IgG2 (response to polysaccharides, ~25%)
• % IgG3 (potent complement activator, ~6%)
• % IgG4 (allergic reactions, ~4%)

⚠️ CRITICAL: Subclass imbalance reduces therapy efficacy!
For example, IgG2 deficiency worsens protection against encapsulated bacteria.

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

Input format:
BatchNumber,ProductName,IgG1_mg_ml,IgG2_mg_ml,IgG3_mg_ml,IgG4_mg_ml,Total_IgG_mg_ml

Example:
PLASMA-SUB-2026-001,IVIG 10% Liquid,68.0,24.0,5.5,3.5,101.0

— WHY IS THIS NEEDED?
IgG subclass control is critical for IVIG and specific immunoglobulins (CSL, Grifols, Octapharma):
• Different subclasses have different biological functions and half-lives
• IgG1 and IgG3 effectively activate complement and ADCC
• IgG2 is critical for protection against bacterial polysaccharide capsules (pneumococcus, H. influenzae)
• Fractionation process (ethanol, PEG, chromatography) may selectively lose certain subclasses
• Matching physiological donor plasma profile ensures broad protection spectrum

⚠️ CRITICAL:
• IgG1: ~60-70% (Main pool of antibodies against protein antigens)
• IgG2: ~20-30% (Key for protection against bacterial infections)
• IgG3: ~4-8% (Shortest T1/2, but most potent effector)
• IgG4: ~2-6% (Least interaction with complement)
• Sum of subclasses must correlate with total IgG content

Key features:
• Calculation of percentage distribution for each subclass
• Comparison with reference normal human plasma profile
• Detection of selective losses during production
• Raw material (plasma pool) quality control

Critical parameters:
• IgG1: 65% ± 10%
• IgG2: 25% ± 10%
• IgG3: 6% ± 5%
• IgG4: 4% ± 5%
• Sum recovery: 90-110%

💡 Usage tips:
1. Use specific monoclonal antibodies for detection of each subclass (ELISA/Nephelometry)
2. Calibrate method using WHO international standards
3. Account that some purification methods may enrich or deplete certain subclasses
4. For specific immunoglobulins (e.g., anti-D), profile may differ from standard IVIG
5. Monitor subclass stability during long-term storage (IgG3 is most labile)

⚠️ Note: Unlike total IgG titer, subclass profile reflects quality and breadth of immune protection. A product with high total titer but low IgG2 will be ineffective against certain types of bacterial infections. The utility helps ensure completeness of replacement therapy.

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,IgG1_mg_ml,IgG2_mg_ml,IgG3_mg_ml,IgG4_mg_ml,Total_IgG_mg_ml
PLASMA-SUB-2026-001,IVIG 10% Liquid,68.0,24.0,5.5,3.5,101.0
PLASMA-SUB-2026-002,SCIG 16%,105.0,38.0,9.0,5.0,157.0
PLASMA-SUB-2026-003,Hyperimmune Anti-Tetanus,70.0,20.0,6.0,4.0,100.0

Output JSON

{
  "Header": {
    "UtilityName": "IgG_Subclass_Distribution_Analyzer",
    "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
        }
      ]
    }
  ]
}