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,Thrombin_Activity_U_ml,PKA_Activity_U_ml,Factor_VIII_Inhibitor_BU_ml,Factor_IX_Inhibitor_BU_ml,APTT_sec,PT_sec,Max_Allowed_Thrombin,Max_Allowed_PKA
COAG-INH-2026-001,Human Albumin 20%,0.05,15.0,0.0,0.0,30.0,12.0,0.1,35.0
COAG-INH-2026-002,Factor VIII Concentrate,0.0,5.0,0.2,0.0,28.0,11.5,0.0,20.0
COAG-INH-2026-003,vWF/FVIII Complex,0.02,10.0,0.1,0.0,29.0,12.0,0.05,25.0

input.csv fields

Utility description

Coagulation Factor Inhibitor Screen — Plasma Product Coagulation Inhibitor Screen

Coagulation Factor Inhibitor Screen — Plasma Product Coagulation Inhibitor Screen

ℹ️ Utility checks for procoagulants and inhibitors:
• Thrombin activity (strictly <0.1 U/mL for albumin)
• PKA (Prekallikrein Activator)
• FVIII and FIX inhibitors (Bethesda Units)
• APTT (screening test)

⚠️ CRITICAL: Thrombin in albumin can cause DIC syndrome!
PKA causes hypotension and angioedema.

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

Input format:
BatchNumber,ProductName,Thrombin_Activity_U_ml,PKA_Activity_U_ml,Factor_VIII_Inhibitor_BU_ml,Factor_IX_Inhibitor_BU_ml,APTT_sec,PT_sec,Max_Allowed_Thrombin,Max_Allowed_PKA

Example:
COAG-INH-2026-001,Human Albumin 20%,0.05,15.0,0.0,0.0,30.0,12.0,0.1,35.0

— WHY IS THIS NEEDED?
Inhibitor and activator control is critical for plasma products (CSL, Grifols, Octapharma):
• Trace thrombin in albumin can trigger coagulation cascade in patient (DIC)
• PKA (prekallikrein activator) forms during contact system activation and causes blood pressure drop
• Factor concentrates must not contain inhibitors neutralizing patient's endogenous factors
• Pharmacopoeias require chromogenic tests to detect these activities

⚠️ CRITICAL:
• Thrombin: Not allowed or strictly limited (<0.1 U/mL)
• PKA: Limit depends on product, but usually <35 U/mL
• FVIII/FIX Inhibitors: <0.5 BU/mL (Bethesda Units)
• APTT: Must be within normal range or correctable with normal plasma
• Absence of procoagulant activity is a safety guarantee

Key features:
• Chromogenic analysis of thrombin and PKA activity
• Bethesda method screening for inhibitors
• Thromboembolic complication risk assessment
• Raw material and fractionation process quality control

Critical parameters:
• Thrombin: ≤0.1 U/mL (for albumin)
• PKA: ≤35.0 U/mL
• FVIII/FIX Inhibitors: ≤0.5 BU/mL
• APTT: Within normal range

💡 Usage tips:
1. Use specific substrates for thrombin and factor Xa
2. For PKA, use kallikrein formation test
3. If inhibitors suspected, perform mixing study
4. Control activity at each purification stage (especially after ion-exchange chromatography)
5. For albumin, thrombin test is mandatory for each batch release

⚠️ Note: Unlike viral safety, this risk is related to biochemical activity of the protein itself. Even slight activation of coagulation cascade during production can make product dangerous. The utility helps identify such "sleeping" threats.

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,Thrombin_Activity_U_ml,PKA_Activity_U_ml,Factor_VIII_Inhibitor_BU_ml,Factor_IX_Inhibitor_BU_ml,APTT_sec,PT_sec,Max_Allowed_Thrombin,Max_Allowed_PKA
COAG-INH-2026-001,Human Albumin 20%,0.05,15.0,0.0,0.0,30.0,12.0,0.1,35.0
COAG-INH-2026-002,Factor VIII Concentrate,0.0,5.0,0.2,0.0,28.0,11.5,0.0,20.0
COAG-INH-2026-003,vWF/FVIII Complex,0.02,10.0,0.1,0.0,29.0,12.0,0.05,25.0

Output JSON

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