RadionuclideImpurityChecker

Radionuclide Impurity

decay correction endotoxins impurities PET radionuclide purity radiopharma SPECT sterility

Radionuclide Impurity Checker — Universal utility for radionuclide impurity calculation from gamma spectrometry data

ℹ️  Utility automatically calculates radionuclide impurity percentage with half-life correction. Activity is decay-corrected to reference time (calibration/production time).
ℹ️  Supports any radionuclide combinations — just specify half-lives.
ℹ️  Does not use machine learning — only physics calculations using formula: A_ref = A_meas × exp(λ × t)

Usage:
  RadionuclideImpurityChecker.exe                            → demo mode (console output)
  RadionuclideImpurityChecker.exe input.csv output.json      → calculate with your data

Input format:
BatchNumber,MainRadionuclide,MainActivityMeasMBq,ImpurityRadionuclide,ImpurityActivityMeasMBq,TimeDiffHours,MainHalfLifeHours,ImpurityHalfLifeHours

Field explanation:
• BatchNumber — product batch number
• MainRadionuclide — main radionuclide (e.g., "Lu-177")
• MainActivityMeasMBq — main radionuclide activity at measurement time (MBq)
• ImpurityRadionuclide — impurity radionuclide (e.g., "Lu-177m")
• ImpurityActivityMeasMBq — impurity activity at measurement time (MBq)
• TimeDiffHours — time from reference time (calibration) to measurement in hours (≥0)
• MainHalfLifeHours — main radionuclide half-life (hours)
• ImpurityHalfLifeHours — impurity half-life (hours)

⚠️ CRITICAL:
• Input activities MUST be measured at the SAME time!
• Measurement time MUST be after reference time (TimeDiffHours ≥ 0)
• Activities must be obtained from gamma spectrometry with proper detector calibration
• Half-lives must match reference data

— HOW IT WORKS?
1. Utility calculates decay factor for main radionuclide:
   λ_main = ln(2) / T½_main
   Factor_main = exp(λ_main × TimeDiffHours)
   
2. Calculates decay factor for impurity similarly
   
3. Decay-corrects activities to reference time:
   A_main_ref = A_main_meas × Factor_main
   A_imp_ref = A_imp_meas × Factor_imp
   
4. Calculates impurity percentage:
   Impurity % = (A_imp_ref / A_main_ref) × 100%
   
5. Compares with pharmacopoeial limit for radionuclide pair
   (if unknown pair — uses 1.0% limit with "Default" note)

📌 Built-in pharmacopoeial limits:
• Lu-177 + Lu-177m: ≤0.1% (Ph. Eur. / EMA for Lutathera®)
• I-131 + I-132: ≤0.1% (USP <823>)
• Ra-223 + Ra-226: ≤0.001% (Xofigo® specification)
• Tc-99m + Mo-99: ≤0.015% (Ph. Eur. for generators)
• Sr-89 + Sr-85: ≤0.02% (Ph. Eur.)
• Ga-68 + Ge-68: ≤0.001% (Ph. Eur. for generators)

💡 Usage tips:
1. Obtain main and impurity activities from gamma spectrometer (already corrected for detector efficiency and emission probability)
2. Determine time between calibration (reference time) and measurement in hours
3. Use accurate half-lives from reference table (see below)
4. For unknown pairs, utility uses 1.0% limit — ALWAYS verify with your product specification!

📚 Half-life reference (hours):
Lu-177: 160.08    | Lu-177m: 3840      | I-131: 192        | I-132: 2.3
Ra-223: 277.2     | Ra-226: 1295040    | Mo-99: 66         | Tc-99m: 6.01
Sr-89: 1295       | Sr-85: 15984       | Ga-68: 1.13       | Ge-68: 21360
F-18: 1.83        | Cu-64: 12.7        | Y-90: 64.1        | In-111: 67.3

⚠️ IMPORTANT:
• Radionuclide impurities increase patient radiation dose WITHOUT therapeutic benefit!
• Some impurities have long half-lives (e.g., Lu-177m: 160 days) — even 0.1% creates significant chronic burden
• For diagnostic agents, impurities reduce image quality and increase dose
• Utility does NOT replace validated analytical method but allows rapid assessment of gamma spectrometry results

input.csv

BatchNumber,MainRadionuclide,MainActivityMeasMBq,ImpurityRadionuclide,ImpurityActivityMeasMBq,TimeDiffHours,MainHalfLifeHours,ImpurityHalfLifeHours
RNI-Lu177-2026-001,Lu-177,5000.0,Lu-177m,0.8,24.0,160.08,3840.0
RNI-I131-2026-001,I-131,3700.0,I-132,1.5,12.0,192.0,2.3
RNI-Ra223-2026-001,Ra-223,1100.0,Ra-226,0.005,48.0,277.2,1295040.0

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: RadionuclideImpurityCheckerAPI / object: Radionuclide ImpurityCategory: Radiopharmaceuticals

1. Scope

The Radionuclide Impurity Checker utility is used for Radionuclide Impurity. 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, impurities, PET, radionuclide purity, radiopharma, SPECT, sterility

2. Execution modes

RadionuclideImpurityChecker.exe                            → demo mode (console output)
RadionuclideImpurityChecker.exe input.csv output.json      → calculate with your data

3. Key controlled areas

purity and impurities
microbiology and pathogens
pH and physicochemical parameters
activity, decay and radiochemical purity

4. Domain limits and critical parameters

TimeDiffHours — time from reference time (calibration) to measurement in hours (≥0)
⚠️ CRITICAL:
Input activities MUST be measured at the SAME time!
Measurement time MUST be after reference time (TimeDiffHours ≥ 0)
Activities must be obtained from gamma spectrometry with proper detector calibration
Half-lives must match reference data
1. Utility calculates decay factor for main radionuclide:
λ_main = ln(2) / T½_main
2. Calculates decay factor for impurity similarly
3. Decay-corrects activities to reference time:
4. Calculates impurity percentage:
Impurity % = (A_imp_ref / A_main_ref) × 100%
5. Compares with pharmacopoeial limit for radionuclide pair
(if unknown pair — uses 1.0% limit with "Default" note)
Lu-177 + Lu-177m: ≤0.1% (Ph. Eur. / EMA for Lutathera®)
I-131 + I-132: ≤0.1% (USP <823>)
Ra-223 + Ra-226: ≤0.001% (Xofigo® specification)
Tc-99m + Mo-99: ≤0.015% (Ph. Eur. for generators)
Sr-89 + Sr-85: ≤0.02% (Ph. Eur.)
Ga-68 + Ge-68: ≤0.001% (Ph. Eur. for generators)
1. Obtain main and impurity activities from gamma spectrometer (already corrected for detector efficiency and emission probability)
2. Determine time between calibration (reference time) and measurement in hours
3. Use accurate half-lives from reference table (see below)
4. For unknown pairs, utility uses 1.0% limit — ALWAYS verify with your product specification!

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 Radionuclide Impurity 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, 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	`RNI-Lu177-2026-001`	mandatory field; used for batch/lot traceability
2	`MainRadionuclide`	text	as specified	Main Radionuclide	`Lu-177`	mandatory value; format and acceptability are checked by the utility
3	`MainActivityMeasMBq`	decimal	MBq	Main Activity Meas MBq	`5000.0`	mandatory numeric value; rule comparison is performed by the utility
4	`ImpurityRadionuclide`	decimal	as specified	Impurity Radionuclide	`Lu-177m`	numeric value; compared with individual or total impurity limit
5	`ImpurityActivityMeasMBq`	decimal	MBq	Impurity Activity Meas MBq	`0.8`	numeric value; compared with individual or total impurity limit
6	`TimeDiffHours`	decimal	h	Time Diff Hours	`24.0`	mandatory numeric value; rule comparison is performed by the utility
7	`MainHalfLifeHours`	decimal	h	Main Half Life Hours	`160.08`	mandatory numeric value; rule comparison is performed by the utility
8	`ImpurityHalfLifeHours`	decimal	h	Impurity Half Life Hours	`3840.0`	numeric value; compared with individual or total impurity limit

CSV example

BatchNumber,MainRadionuclide,MainActivityMeasMBq,ImpurityRadionuclide,ImpurityActivityMeasMBq,TimeDiffHours,MainHalfLifeHours,ImpurityHalfLifeHours
RNI-Lu177-2026-001,Lu-177,5000.0,Lu-177m,0.8,24.0,160.08,3840.0

7. FS — functional specification

ID	Function	Implementation description
FS-001	CLI entry point	The executable `RadionuclideImpurityChecker.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 Radionuclide Impurity, 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": "RadionuclideImpurityChecker",
  "api": "Radionuclide Impurity",
  "batchNumber": "RNI-Lu177-2026-001",
  "overallStatus": "PASS|WARNING|FAIL",
  "checkedAtUtc": "2026-05-18T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "RNI-Lu177-2026-001",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "MainRadionuclide",
      "value": "Lu-177",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "MainActivityMeasMBq",
      "value": "5000.0",
      "unit": "MBq",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ImpurityRadionuclide",
      "value": "Lu-177m",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ImpurityActivityMeasMBq",
      "value": "0.8",
      "unit": "MBq",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "TimeDiffHours",
      "value": "24.0",
      "unit": "h",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "MainHalfLifeHours",
      "value": "160.08",
      "unit": "h",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ImpurityHalfLifeHours",
      "value": "3840.0",
      "unit": "h",
      "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-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

PetRad QC Suite

A specialised utility package for radiopharmaceutical quality control: PET, SPECT, therapeutic radionuclides, generators and decay calculations.

Open

Radiology QC Suite

QC package for radiology and diagnostic imaging: radiopharmaceuticals, PET/SPECT, contrast media, iodinated and gadolinium products, plus particle, sterility and endotoxin checks.

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RPH use case: generators, isotope purity and starting radionuclides

Control of generator eluate, breakthrough, radionuclidic purity, isotope mix, carrier/free radionuclides and starting radionuclides before labeling.

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RPH workflow: generators and isotope purity

Generator eluate, breakthrough, radionuclidic purity, isotope mix and starting radionuclides.

Open

RPH workflow: instruments, devices and radiation safety

PET/gamma-camera state, calibration, detector QC, energy window, TOF, shielding and radiation safety.

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RPH workflow: product release QC

Assay, purity, sterility, endotoxins, pH, impurities, appearance and batch-release checks.

Open

RPH workflow: stability, storage, decay and waste

Kinetic stability, shelf life, decay correction, expiry, storage, trend and radioactive waste.

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RPH: combined radiopharmaceutical QC package

RPH combines PetRad, PetRad2 and PetRad3 into one umbrella package for PET/SPECT, therapeutic radionuclides, generators, labelled compounds, decay calculations, sterility, endotoxins and radiochemical/radionuclidic purity.

Open