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,VirusName,Input_Titer_Log10,Output_Titer_Log10,ProcessStep,LRV_Calculated,Required_LRV,Validated_Method
VAL-VIR-2026-001,IVIG 10%,PRV (Parvovirus),7.5,2.0,Nanofiltration (20nm),5.5,4.0,true
VAL-VIR-2026-002,Albumin 20%,HIV-1,8.0,1.5,Low pH Incubation,6.5,6.0,true
VAL-VIR-2026-003,Factor VIII,vBVDV (Model HCV),7.2,3.5,Pasteurization,3.7,4.0,false

input.csv fields

Utility description

Viral Clearance Validation Tracker — Plasma Product Viral Clearance Validation Tracker

Viral Clearance Validation Tracker — Plasma Product Viral Clearance Validation Tracker

ℹ️ Utility analyzes viral load reduction efficiency:
• LRV (Log Reduction Value) calculation
• Input titer control (≥6.0 Log10)
• Comparison with required limits (≥4.0 or ≥6.0)
• Safety margin assessment

⚠️ CRITICAL: Insufficient clearance leads to infection transmission risk!
Regulators require proof of enveloped and non-enveloped virus removal.

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

Input format:
BatchNumber,ProductName,VirusName,Input_Titer_Log10,Output_Titer_Log10,ProcessStep,LRV_Calculated,Required_LRV,Validated_Method

Example:
VAL-VIR-2026-001,IVIG 10%,PRV (Parvovirus),7.5,2.0,Nanofiltration (20nm),5.5,4.0,true

— WHY IS THIS NEEDED?
Viral clearance validation is critical for plasma products (CSL, Grifols, Octapharma):
• Products are made from thousands of donor plasma pools, high contamination risk
• Must prove removal/inactivation of both enveloped (HIV, HCV) and non-enveloped (HAV, Parvovirus B19) viruses
• Each step (precipitation, pasteurization, nanofiltration, low pH) contributes to overall safety
• Regulators (EMA/FDA) require total reduction >12-15 log10 for key viruses

⚠️ CRITICAL:
• LRV ≥4.0 per step is considered significant reduction
• LRV ≥6.0 required for steps claimed as "virus-specific"
• Input titer must be high (>6.0 Log10) for test validity
• Non-enveloped viruses (e.g., Parvovirus) are more resistant and harder to remove
• Total LRV of all steps must cover potential donor viral load

Key features:
• Automatic LRV calculation from titer data
• Regulatory compliance check (Ph.Eur. 5.1.7)
• Reliability assessment of each purification step
• Support for various model viruses

Critical parameters:
• LRV: ≥4.0 (min), ≥6.0 (target)
• Input titer: ≥6.0 Log10
• Safety margin: >0

💡 Usage tips:
1. Use different model viruses for different types (lipid/non-lipid, DNA/RNA)
2. Perform validation in scale-down model correlating with production
3. Account for potential virus "breakthrough" under filter overload
4. Document every step for regulatory audit
5. If low LRV observed, review process parameters (incubation time, filter pore size)

⚠️ Note: Unlike synthetic drugs, plasma safety depends entirely on purification processes. The utility helps mathematically justify batch safety based on process validation data.

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,VirusName,Input_Titer_Log10,Output_Titer_Log10,ProcessStep,LRV_Calculated,Required_LRV,Validated_Method
VAL-VIR-2026-001,IVIG 10%,PRV (Parvovirus),7.5,2.0,Nanofiltration (20nm),5.5,4.0,true
VAL-VIR-2026-002,Albumin 20%,HIV-1,8.0,1.5,Low pH Incubation,6.5,6.0,true
VAL-VIR-2026-003,Factor VIII,vBVDV (Model HCV),7.2,3.5,Pasteurization,3.7,4.0,false

Output JSON

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