Copper67QualityChecker

Copper67

decay correction endotoxins heavy metals impurities microbiology PET radionuclide purity radiopharma

Copper-67 Quality Checker — Copper-67 for targeted radionuclide therapy

ℹ️ Utility checks critical parameters of copper-67:
• Specific activity (≥100 MBq/μmol for conjugates)
• Radiochemical purity (≥95%)
• Copper-64 impurity (≤0.1%) — CRITICAL!
• Free copper (≤5% for conjugates)
• pH, endotoxins, sterility, heavy metals

⚠️ CRITICAL: Copper-64 impurity >0.1% → increased radiation burden!
Free copper >5% → liver/kidney toxicity!

Usage:
Copper67QualityChecker.exe → demo mode (console output)
Copper67QualityChecker.exe input.csv output.json → evaluate your data

Input format:
BatchNumber,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,Copper64ImpurityPercent,FreeCopperPercent,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM,ProductType

Example (sterility: 0=sterile, 1=contaminated):
CU67-PSMA-2026-001,150.0,97.0,0.05,3.0,6.0,100.0,0,5,PSMA

Supported product types:
• PSMA — targeted therapy for prostate cancer
• DOTATATE — targeted therapy for neuroendocrine tumors
• FREECU67 — unconjugated copper-67 (for custom conjugation)

— WHY IS THIS NEEDED?
Copper-67 — promising beta-emitter for targeted radionuclide therapy:
• 61.8-hour half-life (2.58 days) — sufficient for synthesis and delivery
• Beta radiation (0.577 MeV) — effective tumor cell destruction
• Gamma radiation (185 keV) — allows imaging (theranostics)
• Used in conjugates with PSMA, DOTATATE for metastatic cancer treatment

⚠️ CRITICAL:
• Specific activity ≥100 MBq/μmol — ensures sufficient dose for tumor cell destruction
• Copper-64 impurity ≤0.1% — CRITICAL! Copper-64 (T½=12.7 hours) — positron emitter, creates ADDITIONAL RADIATION BURDEN to patient without therapeutic benefit. Even 0.11% is unacceptable!
• Free copper ≤5% — UNBOUND copper accumulates in liver and kidneys, causing toxicity!
• Radiochemical purity ≥95% — ensures radiation delivery specifically to tumor cells
• pH 4.0–7.5 — critical for blood compatibility during IV administration
• Endotoxins ≤175 EU/vial — critical for IV administration!
• Sterility — MANDATORY for all parenteral forms!

Key features:
• Check of critical copper-64 impurity (≤0.1%) — main quality parameter
• Free copper control for conjugates (≤5%)
• Support for different product types (conjugates and unconjugated copper)
• Specific limits for unconjugated Cu-67 (≥200 MBq/μmol)
• Critical warnings about free copper toxicity and Cu-64 impurity

Critical parameters:
• Specific activity: ≥100 MBq/μmol (conjugates), ≥200 MBq/μmol (unconjugated)
• Radiochemical purity: ≥95.0%
• Copper-64 impurity: ≤0.1% (CRITICAL!)
• Free copper: ≤5.0% (conjugates), N/A (unconjugated)
• pH: 4.0–7.5
• Endotoxins: ≤175 EU/vial
• Sterility: no microbial growth
• Heavy metals: ≤10 ppm

💡 Usage tips:
1. Copper-64 impurity controlled by gamma spectrometry (511 keV peak)
2. Free copper controlled by TLC or HPLC
3. For unconjugated Cu-67 focus on specific activity and Cu-64 impurity
4. All measurements should be performed within 24 hours after synthesis
5. If Cu-64 impurity >0.1% detected — batch rejected (critical parameter)!

⚠️ Note: Copper-67 is a THERANOSTIC isotope (therapy + imaging). Copper-64 impurity distorts dosimetry calculations and increases radiation burden to patient. Control of this impurity is MANDATORY for clinical use.

input.csv

BatchNumber,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,Copper64ImpurityPercent,FreeCopperPercent,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM,ProductType
CU67-PSMA-2026-001,150.0,97.0,0.05,3.0,6.0,100.0,0,5,PSMA

URS & FS — user requirements and functional specification

This document defines user requirements and functional specification for the quality-control utility. It supports deployment discussion, IQ/OQ preparation and QC workflow integration.

Utility: Copper67QualityCheckerAPI / object: Copper67Category: Radiopharmaceuticals

1. Scope

The Copper67 Quality Checker utility is used for Copper67. The actual input.csv is the source of truth for the input structure; control criteria are defined by the executable and the domain description.

The utility does not use machine learning; decisions are produced by deterministic rules.

Categories: Radiopharmaceuticals

Tags: decay correction, endotoxins, heavy metals, impurities, microbiology, PET, radionuclide purity, radiopharma, SPECT, sterility

2. Execution modes

Copper67QualityChecker.exe                            → demo mode (console output)
Copper67QualityChecker.exe input.csv output.json      → evaluate your data

3. Key controlled areas

purity and impurities
microbiology and pathogens
heavy metals / elemental impurities
pH and physicochemical parameters
activity, decay and radiochemical purity

4. Domain limits and critical parameters

ℹ️ Utility checks critical parameters of copper-67:
Specific activity (≥100 MBq/μmol for conjugates)
Radiochemical purity (≥95%)
Copper-64 impurity (≤0.1%) — CRITICAL!
Free copper (≤5% for conjugates)
pH, endotoxins, sterility, heavy metals
⚠️ CRITICAL: Copper-64 impurity >0.1% → increased radiation burden!
Free copper >5% → liver/kidney toxicity!
⚠️ CRITICAL:
Specific activity ≥100 MBq/μmol — ensures sufficient dose for tumor cell destruction
Copper-64 impurity ≤0.1% — CRITICAL! Copper-64 (T½=12.7 hours) — positron emitter, creates ADDITIONAL RADIATION BURDEN to patient without therapeutic benefit. Even 0.11% is unacceptable!
Free copper ≤5% — UNBOUND copper accumulates in liver and kidneys, causing toxicity!
Radiochemical purity ≥95% — ensures radiation delivery specifically to tumor cells
pH 4.0–7.5 — critical for blood compatibility during IV administration
Endotoxins ≤175 EU/vial — critical for IV administration!
Sterility — MANDATORY for all parenteral forms!
Check of critical copper-64 impurity (≤0.1%) — main quality parameter
Free copper control for conjugates (≤5%)
Support for different product types (conjugates and unconjugated copper)
Specific limits for unconjugated Cu-67 (≥200 MBq/μmol)
Critical warnings about free copper toxicity and Cu-64 impurity
Critical parameters:
Specific activity: ≥100 MBq/μmol (conjugates), ≥200 MBq/μmol (unconjugated)
Radiochemical purity: ≥95.0%

Limits stated in the description must be verified against the current approved specification, pharmacopoeial monograph and registration dossier before production use.

5. URS — user requirements

ID	Requirement	Criticality	Acceptance criterion
URS-001	The system shall accept an `input.csv` file for Copper67 with the exact columns listed in the “Input data contract” section.	High	A file with the correct header is processed without manual editing; missing mandatory columns produce FAIL/import error.
URS-002	The system shall support execution without arguments in demo mode and execution with `input.csv output.json` for user data.	Medium	Both execution scenarios produce a predictable result or clear diagnostic error.
URS-003	The system shall perform rule-based controls for: purity and impurities, microbiology and pathogens, heavy metals / elemental impurities, pH and physicochemical parameters, activity, decay and radiochemical purity.	High	Each controlled parameter receives a status and message; the result does not depend on hidden Excel formulas or ML.
URS-004	The system shall preserve traceability between batch/lot, source values, applied rules and final verdict.	High	Output includes batch identifier, source values, parameter statuses and critical findings.
URS-005	The system shall generate machine-readable `output.json` for LIMS/ELN/MES, batch record and QA/QC review.	High	JSON contains overall status, check array, warnings, failures and source-file reference.
URS-006	The system shall support use in the client validation package: URS/FS, IQ/OQ preparation, installation and operational scenario checks.	High	The document, test scenarios and reproducible CSV/JSON flow are suitable for audit and internal approval.
URS-007	The system shall clearly separate technical data errors from specification nonconformities.	Medium	Schema/type errors are not mixed with pharmacopoeial deviations and are reported separately.

6. input.csv data contract

The source of truth for the input schema is the actual input.csv header. Column names are technical identifiers and are not translated.

#	Column	Type	Unit	Description	Sample	Control rule
1	`BatchNumber`	identifier	as specified	Batch Number	`CU67-PSMA-2026-001`	mandatory field; used for batch/lot traceability
2	`SpecificActivityMBqPerUmol`	decimal	MBq	Specific Activity MBq per Umol	`150.0`	mandatory numeric value; rule comparison is performed by the utility
3	`RadiochemicalPurityPercent`	decimal	%	Radiochemical Purity %	`97.0`	numeric value; compared with assay/purity limit from specification or method
4	`Copper64ImpurityPercent`	decimal	%	Copper64 Impurity %	`0.05`	numeric value; compared with individual or total impurity limit
5	`FreeCopperPercent`	decimal	%	Free Copper %	`3.0`	mandatory numeric value; rule comparison is performed by the utility
6	`pH`	decimal	pH	p H	`6.0`	mandatory numeric value; rule comparison is performed by the utility
7	`EndotoxinsEU`	decimal	as specified	Endotoxins EU	`100.0`	numeric value; critical safety attribute compared with endotoxin limit
8	`SterilityTest`	boolean / flag	0/1	Sterility Test	`0`	valid flag required; prohibited organisms and growth are normally expected as 0 / absent
9	`HeavyMetalsPPM`	decimal	ppm	Heavy Metals PPM	`5`	numeric value; checked as elemental/metal impurity
10	`ProductType`	text	as specified	Product Type	`PSMA`	mandatory value; format and acceptability are checked by the utility

CSV example

BatchNumber,SpecificActivityMBqPerUmol,RadiochemicalPurityPercent,Copper64ImpurityPercent,FreeCopperPercent,pH,EndotoxinsEU,SterilityTest,HeavyMetalsPPM,ProductType
CU67-PSMA-2026-001,150.0,97.0,0.05,3.0,6.0,100.0,0,5,PSMA

7. FS — functional specification

ID	Function	Implementation description
FS-001	CLI entry point	The executable `Copper67QualityChecker.exe` supports demo mode and `input.csv output.json` processing mode.
FS-002	CSV parser	The import module reads CSV, validates header, column presence/order, value count and encoding. Decimal values are expected with a dot separator.
FS-003	Field conversion	Each column is converted to the expected type: identifier, text, decimal number, date/time or boolean flag.
FS-004	Domain rule engine	For Copper67, explicit rules are applied: range, minimum, maximum, absence of prohibited flag, data completeness or calculation-based check.
FS-005	Criticality handling	Critical violations produce FAIL; non-critical deviations and incomplete data produce WARNING; full conformance produces PASS.
FS-006	JSON writer	`output.json` stores overall status, per-parameter results, source values, warnings, failures and diagnostic messages.
FS-007	Integration contract	The CSV → JSON format is stable for invocation from LIMS/ELN/MES, scheduled task or wrapper service.
FS-008	Error handling	Schema error, missing file, non-numeric value or JSON write failure returns diagnosable error without silent PASS.

8. output.json contract

The output file must be suitable for automated processing, audit review and correlation with the source input.csv row.

{
  "utility": "Copper67QualityChecker",
  "api": "Copper67",
  "batchNumber": "CU67-PSMA-2026-001",
  "overallStatus": "PASS|WARNING|FAIL",
  "checkedAtUtc": "2026-05-18T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "CU67-PSMA-2026-001",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "SpecificActivityMBqPerUmol",
      "value": "150.0",
      "unit": "MBq",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "RadiochemicalPurityPercent",
      "value": "97.0",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Copper64ImpurityPercent",
      "value": "0.05",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "FreeCopperPercent",
      "value": "3.0",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "pH",
      "value": "6.0",
      "unit": "pH",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "EndotoxinsEU",
      "value": "100.0",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "SterilityTest",
      "value": "0",
      "unit": "0/1",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    }
  ],
  "criticalFindings": [],
  "sourceFile": "input.csv"
}

9. OQ/PQ test scenarios

ID	Scenario	Expected result
TC-001	Valid CSV with expected header and sample row	All rows are processed; output contains PASS/WARNING/FAIL and parameter-level detail.
TC-002	A mandatory input.csv column is missing	Import is rejected or the row receives FAIL with schema reference.
TC-003	A numeric field contains text or a blank value	Type conversion error is recorded; the result is not hidden as PASS.
TC-004	A parameter is outside specification or critical limit	Critical parameters produce FAIL; non-critical deviations produce WARNING according to the rule.
TC-005	Positive pathogen/microbiological flag or microbiological limit excursion	Critical FAIL is produced with the offending parameter.
TC-008	Incorrect activity, reference time or radiochemical purity	FAIL/WARNING is produced with calculation traceability.

10. QA/QC, CSV and change control

Before production use, the client records executable version, checksum, specification/monograph version, test CSV, expected JSON and IQ/OQ results.
Column names must not be changed without updating the validator and test scenarios.
The source CSV, output.json and utility version should be stored together as an evidence package.
Any change in control rules must go through change control and repeated OQ scenario verification.

Included in packages

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Copper67QualityChecker

input.csv

1. Scope

2. Execution modes

3. Key controlled areas

4. Domain limits and critical parameters

5. URS — user requirements

6. input.csv data contract

CSV example

7. FS — functional specification

8. output.json contract

9. OQ/PQ test scenarios

10. QA/QC, CSV and change control

Included in packages

Andrology QC Suite

Endocrinology QC Suite

Neurology QC Suite

PetRad QC Suite

Radiology QC Suite

RPH isotope family: beta-emitting therapy

RPH organ/system: brain and CNS

RPH organ/system: endocrine, thyroid and NET

RPH organ/system: hepatobiliary and GI

RPH organ/system: oncology and theranostics

RPH organ/system: renal and urinary

RPH use case: generators, isotope purity and starting radionuclides

RPH workflow: dosimetry and therapy planning

RPH workflow: generators and isotope purity

RPH workflow: imaging QC and quantitative interpretation

RPH workflow: product release QC

RPH workflow: stability, storage, decay and waste

RPH workflow: synthesis, labelling and kit reconstitution

RPH: combined radiopharmaceutical QC package

Urology QC Suite