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,ACA_Value_CH50,C3a_Concentration_ng_ml,C4a_Concentration_ng_ml,Aggregates_Percent,Osmolality_mOsm_kg,Positive_Control_Result,Negative_Control_Result,CV_Percent
PLASMA-ACA-2026-001,IVIG 10% Liquid,25.0,45.0,30.0,0.8,300.0,90.0,5.0,6.5
PLASMA-ACA-2026-002,Albumin 20%,10.0,15.0,10.0,0.2,280.0,92.0,4.0,5.0
PLASMA-ACA-2026-003,Factor IX Concentrate,65.0,120.0,110.0,2.5,310.0,88.0,6.0,12.0

input.csv fields

Utility description

Anti-Complement Activity Assay Reviewer — Plasma Product Anti-Complement Activity Reviewer

Anti-Complement Activity Assay Reviewer — Plasma Product Anti-Complement Activity Reviewer

ℹ️ Utility assesses complement system activation risk:
• Anti-complementary activity (CH50)
• Anaphylatoxin C3a and C4a levels
• Correlation with aggregates

⚠️ CRITICAL: High ACA causes anaphylaxis and back pain!
IgG aggregates are the main trigger for complement activation.

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

Input format:
BatchNumber,ProductName,ACA_Value_CH50,C3a_Concentration_ng_ml,C4a_Concentration_ng_ml,Aggregates_Percent,Osmolality_mOsm_kg,Positive_Control_Result,Negative_Control_Result,CV_Percent

Example:
PLASMA-ACA-2026-001,IVIG 10% Liquid,25.0,45.0,30.0,0.8,300.0,90.0,5.0,6.5

— WHY IS THIS NEEDED?
Anti-complementary activity (ACA) control is critical for IVIG and Albumin (CSL, Grifols, Octapharma):
• Plasma products may contain protein aggregates that activate patient's complement system
• Complement activation leads to release of anaphylatoxins (C3a, C4a, C5a)
• Clinical manifestations: back/chest pain, hypotension, dyspnea, anaphylactoid reactions
• Pharmacopoeias (Ph.Eur., USP) set strict limits on ACA for intravenous immunoglobulins

⚠️ CRITICAL:
• ACA (CH50) ≤50 U/mL (or specific % inhibition) — safety standard
• C3a and C4a ≤100 ng/mL — markers of no active complement degradation in product
• High correlation with aggregate level (>1-2%)
• Low osmolality may enhance complement activation
• Test must be validated with positive and negative controls

Key features:
• Infusion side effect risk assessment
• Anaphylatoxin level monitoring
• Correlation analysis with aggregation data (SEC-HPLC)
• Bioassay quality control

Critical parameters:
• ACA (CH50): ≤50 U/mL
• C3a: ≤100 ng/mL
• C4a: ≤100 ng/mL
• Assay CV: ≤15%

💡 Usage tips:
1. Use fresh rabbit or human serum for hemolysis test (CH50)
2. Avoid freeze-thaw cycles for C3a/C4a samples
3. High C4a indicates classical pathway activation (often due to immune complexes)
4. If high ACA observed, check pasteurization and pH incubation process
5. Compare results with reference products for calibration

⚠️ Note: Unlike sterility, ACA is a functional safety parameter. Even a sterile product can be dangerous if it contains aggregates activating complement. The utility helps prevent release of batches causing severe infusion reactions.

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,ACA_Value_CH50,C3a_Concentration_ng_ml,C4a_Concentration_ng_ml,Aggregates_Percent,Osmolality_mOsm_kg,Positive_Control_Result,Negative_Control_Result,CV_Percent
PLASMA-ACA-2026-001,IVIG 10% Liquid,25.0,45.0,30.0,0.8,300.0,90.0,5.0,6.5
PLASMA-ACA-2026-002,Albumin 20%,10.0,15.0,10.0,0.2,280.0,92.0,4.0,5.0
PLASMA-ACA-2026-003,Factor IX Concentrate,65.0,120.0,110.0,2.5,310.0,88.0,6.0,12.0

Output JSON

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