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,TargetType,Urea_Linkage_Intact_Percent,Peptide_Oxidation_Percent,Kd_nM,Bmax_fmol_mg,IC50_nM,Free_Ligand_Percent,Hydrolysis_Product_Percent,Min_Binding_Percent
RPH-MAP-2026-001,Lu-177-PSMA-617,PSMA,99.5,0.1,2.5,150.0,3.0,0.5,0.2,90.0
RPH-MAP-2026-002,Lu-177-DOTATATE,SSTR,99.0,0.5,1.8,200.0,2.0,0.3,0.1,90.0
RPH-MAP-2026-003,Lu-177-PSMA-617 (Degraded),PSMA,92.0,0.2,15.0,140.0,12.0,1.5,1.2,90.0

input.csv fields

Utility description

PSMA/SSTR Radioligand Map Utility — PSMA/SSTR Radioligand Mapping Utility

PSMA/SSTR Radioligand Map Utility — PSMA/SSTR Radioligand Mapping Utility

ℹ️ Utility creates comprehensive quality map for targeted products:
• Structural integrity (urea bond/oxidation)
• Binding affinity (Kd, IC50)
• Free ligand and hydrolysis impurities
• Relative potency

⚠️ CRITICAL: Free ligand competes with drug for receptors!
Urea degradation in PSMA ligands drastically reduces efficacy.

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

Input format:
BatchNumber,ProductName,TargetType,Urea_Linkage_Intact_Percent,Peptide_Oxidation_Percent,Kd_nM,Bmax_fmol_mg,IC50_nM,Free_Ligand_Percent,Hydrolysis_Product_Percent,Min_Binding_Percent

Example:
RPH-MAP-2026-001,Lu-177-PSMA-617,PSMA,99.5,0.1,2.5,150.0,3.0,0.5,0.2,90.0

— WHY IS THIS NEEDED?
Radioligand mapping is critical for theranostics (Novartis, AAA):
• PSMA ligands contain urea group (Glu-CO-Lys) sensitive to hydrolysis
• SSTR ligands (octreotate) contain tryptophan residues prone to oxidation
• Free (non-radioactive) ligand competes with drug for receptors, reducing PET contrast and therapy efficacy
• High affinity (low Kd) is necessary for target capture at low drug concentrations

⚠️ CRITICAL:
• Urea bond integrity (PSMA) ≥98%
• Peptide oxidation (SSTR) ≤2%
• Kd ≤10 nM — high affinity standard
• Free ligand ≤2% — competition minimization
• Hydrolysis products ≤1% — degradation control

Key features:
• Specific checks for different target types (PSMA vs SSTR)
• Integration of structural (HPLC/MS) and functional (Bioassay) data
• Free ligand competition risk assessment
• Specific degradation pathway control

Critical parameters:
• Structural Integrity: ≥98%
• Kd: ≤10 nM
• Free Ligand: ≤2%
• Hydrolysis Products: ≤1%

💡 Usage tips:
1. Use LC-MS for precise identification of urea hydrolysis products
2. Perform binding tests with LNCaP (PSMA) or AR42J (SSTR) cell lines
3. Control free ligand level by UV detection in HPLC
4. For PSMA products, avoid long-term storage in aqueous solutions without stabilizers
5. Compare impurity profile with reference standard for each synthesis batch

⚠️ Note: Unlike standard radiopharmaceuticals where only radiochemical purity matters, biological specificity is critical for ligands. Even a small fraction of degraded product may have completely different distribution in body. The utility helps create a quality "passport" accounting for these nuances.

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,TargetType,Urea_Linkage_Intact_Percent,Peptide_Oxidation_Percent,Kd_nM,Bmax_fmol_mg,IC50_nM,Free_Ligand_Percent,Hydrolysis_Product_Percent,Min_Binding_Percent
RPH-MAP-2026-001,Lu-177-PSMA-617,PSMA,99.5,0.1,2.5,150.0,3.0,0.5,0.2,90.0
RPH-MAP-2026-002,Lu-177-DOTATATE,SSTR,99.0,0.5,1.8,200.0,2.0,0.3,0.1,90.0
RPH-MAP-2026-003,Lu-177-PSMA-617 (Degraded),PSMA,92.0,0.2,15.0,140.0,12.0,1.5,1.2,90.0

Output JSON

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