EthinylestradiolNorgestimateQualityChecker

Ethinylestradiol Norgestimate

assay contraceptives dissolution fixed-dose combinations heavy metals hormones impurities microbiology

Ethinylestradiol + Norgestimate Quality Checker — Combined Tablets (Cilest, Sprintec) (Ph. Eur., ICH Q6A)

ℹ️ The utility checks content of both active substances, impurities (17-epimer EE, 17-deacetyl and Δ⁴-isomer norgestimate), weight variation, disintegration, dissolution, microbiology (including pathogens), friability.
ℹ️ Does not use machine learning — rule-based logic only.
⚠️ Critical for COC production (Cilest, Sprintec). Strict norgestimate impurity control is mandatory due to impact on progestogenic activity and safety profile!

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

Input format:
BatchNumber,EthinylestradiolContent,NorgestimateContent,ImpurityEthinylestradiol,Impurity17DeacetylNorgestimate,ImpurityDelta4Isomer,TotalImpuritiesNorgestimate,WeightVariationRSD,DisintegrationTime,DissolutionEthinylestradiol,DissolutionNorgestimate,HeavyMetals,TAMC,TYMC,EColiDetected,SalmonellaDetected,EthanolPPM,AcetonePPM,Friability

Example (EColiDetected/SalmonellaDetected: 0=not detected, 1=detected):
EENG-2026-001,98.5,99.2,0.3,0.2,0.1,0.4,3.5,15.0,85.0,87.0,10,500,50,0,0,800,500,0.6

— WHY IS THIS NEEDED?
Combined tablets (ethinylestradiol + norgestimate) — modern third-generation COCs for:
• Contraception (Cilest, Sprintec, Celest)
• Acne and seborrhea treatment in women
• Menstrual cycle regulation with improved thrombogenic risk profile
⚠️ CRITICAL:
• Dissolution of both components ≥80% — ensures bioavailability and contraceptive efficacy
• EE impurity (17-epimer) ≤0.5% — affects estrogenic activity
• 17-Deacetyl-norgestimate ≤0.5% — active metabolite, but as API impurity reduces stability
• Δ⁴-Isomer ≤0.5% — degradation product, affects progestogenic activity
• Total norgestimate impurities ≤1.0% — critical due to unique norgestimate profile (low androgenic index)
• Absence of pathogens (E. coli, Salmonella) — mandatory for oral preparations
⚠️ Special attention: Norgestimate — third-generation progestogen with minimal androgenic activity. Impurities can disrupt this profile! 17-Deacetyl impurity is especially critical — affects metabolism and stability. Norgestimate rapidly metabolizes to levonorgestrel in the body, but must be pure in API.
Critical parameters:
• EE content: 90.0–110.0% of declared
• Norgestimate content: 90.0–110.0% of declared
• EE impurity (17-epimer): ≤0.5%
• 17-Deacetyl-norgestimate: ≤0.5%
• Δ⁴-Isomer: ≤0.5%
• Total norgestimate impurities: ≤1.0%
• Weight variation (RSD): ≤5.0%
• Disintegration: ≤30 minutes
• EE dissolution: ≥80% (at 30 min)
• Norgestimate dissolution: ≥80% (at 30 min)
• Heavy metals: ≤20 ppm
• Microbiology: TAMC ≤1000 CFU/g, TYMC ≤100 CFU/g
• Absence of E. coli and Salmonella
• Friability: ≤1.0% (for uncoated tablets)
• Residual solvents: ethanol ≤5000 ppm, acetone ≤5000 ppm
⚠️ Note: Norgestimate is sensitive to hydrolysis and oxidation! Requires storage in moisture- and light-protected packaging at temperature not exceeding 25°C. Analysis must be performed under moisture- and light-protected conditions! Dissolution is tested separately for each component (different HPLC methods).

input.csv

BatchNumber,EthinylestradiolContent,NorgestimateContent,ImpurityEthinylestradiol,Impurity17DeacetylNorgestimate,ImpurityDelta4Isomer,TotalImpuritiesNorgestimate,WeightVariationRSD,DisintegrationTime,DissolutionEthinylestradiol,DissolutionNorgestimate,HeavyMetals,TAMC,TYMC,EColiDetected,SalmonellaDetected,EthanolPPM,AcetonePPM,Friability
EENG-2026-001,98.5,99.2,0.3,0.2,0.1,0.4,3.5,15.0,85.0,87.0,10,500,50,0,0,800,500,0.6

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: EthinylestradiolNorgestimateQualityCheckerAPI / object: Ethinylestradiol NorgestimateCategory: Contraceptives

1. Scope

The Ethinylestradiol Norgestimate Quality Checker utility is used for Ethinylestradiol Norgestimate. 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: Contraceptives

Tags: assay, contraceptives, dissolution, fixed-dose combinations, heavy metals, hormones, impurities, microbiology, radiopharma, residual solvents, solid dosage

2. Execution modes

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

3. Key controlled areas

assay / content
purity and impurities
dissolution / disintegration
residual solvents
microbiology and pathogens
heavy metals / elemental impurities
pH and physicochemical parameters

4. Domain limits and critical parameters

⚠️ Critical for COC production (Cilest, Sprintec). Strict norgestimate impurity control is mandatory due to impact on progestogenic activity and safety profile!
⚠️ CRITICAL:
Dissolution of both components ≥80% — ensures bioavailability and contraceptive efficacy
EE impurity (17-epimer) ≤0.5% — affects estrogenic activity
17-Deacetyl-norgestimate ≤0.5% — active metabolite, but as API impurity reduces stability
Δ⁴-Isomer ≤0.5% — degradation product, affects progestogenic activity
Total norgestimate impurities ≤1.0% — critical due to unique norgestimate profile (low androgenic index)
Absence of pathogens (E. coli, Salmonella) — mandatory for oral preparations
⚠️ Special attention: Norgestimate — third-generation progestogen with minimal androgenic activity. Impurities can disrupt this profile! 17-Deacetyl impurity is especially critical — affects metabolism and stability. Norgestimate rapidly metabolizes to levonorgestrel in the body, but must be pure in API.
Critical parameters:
EE content: 90.0–110.0% of declared
Norgestimate content: 90.0–110.0% of declared
EE impurity (17-epimer): ≤0.5%
17-Deacetyl-norgestimate: ≤0.5%
Δ⁴-Isomer: ≤0.5%
Total norgestimate impurities: ≤1.0%
Weight variation (RSD): ≤5.0%
Disintegration: ≤30 minutes
EE dissolution: ≥80% (at 30 min)
Norgestimate dissolution: ≥80% (at 30 min)
Heavy metals: ≤20 ppm
Microbiology: TAMC ≤1000 CFU/g, TYMC ≤100 CFU/g
Absence of E. coli and Salmonella
Friability: ≤1.0% (for uncoated tablets)

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 Ethinylestradiol Norgestimate 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: assay / content, purity and impurities, dissolution / disintegration, residual solvents, microbiology and pathogens, heavy metals / elemental impurities, pH and physicochemical parameters.	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	`EENG-2026-001`	mandatory field; used for batch/lot traceability
2	`EthinylestradiolContent`	decimal	as specified	Ethinylestradiol Content	`98.5`	numeric value; compared with assay/purity limit from specification or method
3	`NorgestimateContent`	decimal	as specified	Norgestimate Content	`99.2`	numeric value; compared with assay/purity limit from specification or method
4	`ImpurityEthinylestradiol`	decimal	as specified	Impurity Ethinylestradiol	`0.3`	numeric value; compared with individual or total impurity limit
5	`Impurity17DeacetylNorgestimate`	decimal	as specified	Impurity17 Deacetyl Norgestimate	`0.2`	numeric value; compared with individual or total impurity limit
6	`ImpurityDelta4Isomer`	decimal	as specified	Impurity Delta4 Isomer	`0.1`	numeric value; compared with individual or total impurity limit
7	`TotalImpuritiesNorgestimate`	decimal	as specified	Total Impurities Norgestimate	`0.4`	mandatory numeric value; rule comparison is performed by the utility
8	`WeightVariationRSD`	decimal	as specified	Weight Variation RSD	`3.5`	mandatory numeric value; rule comparison is performed by the utility
9	`DisintegrationTime`	decimal	min	Disintegration Time	`15.0`	numeric value; dissolution/disintegration profile checked according to method
10	`DissolutionEthinylestradiol`	decimal	as specified	Dissolution Ethinylestradiol	`85.0`	numeric value; dissolution/disintegration profile checked according to method
11	`DissolutionNorgestimate`	decimal	as specified	Dissolution Norgestimate	`87.0`	numeric value; dissolution/disintegration profile checked according to method
12	`HeavyMetals`	decimal	as specified	Heavy Metals	`10`	numeric value; checked as elemental/metal impurity
13	`TAMC`	decimal	as specified	TAMC	`500`	numeric value; compared with microbiological limits
14	`TYMC`	decimal	as specified	TYMC	`50`	numeric value; compared with microbiological limits
15	`EColiDetected`	boolean / flag	0/1	EColi Detected	`0`	valid flag required; prohibited organisms and growth are normally expected as 0 / absent
16	`SalmonellaDetected`	boolean / flag	0/1	Salmonella Detected	`0`	valid flag required; prohibited organisms and growth are normally expected as 0 / absent
17	`EthanolPPM`	decimal	ppm	Ethanol PPM	`800`	numeric value; checked as residual solvent against the applicable limit
18	`AcetonePPM`	decimal	ppm	Acetone PPM	`500`	numeric value; checked as residual solvent against the applicable limit
19	`Friability`	decimal	as specified	Friability	`0.6`	mandatory numeric value; rule comparison is performed by the utility

CSV example

BatchNumber,EthinylestradiolContent,NorgestimateContent,ImpurityEthinylestradiol,Impurity17DeacetylNorgestimate,ImpurityDelta4Isomer,TotalImpuritiesNorgestimate,WeightVariationRSD,DisintegrationTime,DissolutionEthinylestradiol,DissolutionNorgestimate,HeavyMetals,TAMC,TYMC,EColiDetected,SalmonellaDetected,EthanolPPM,AcetonePPM,Friability
EENG-2026-001,98.5,99.2,0.3,0.2,0.1,0.4,3.5,15.0,85.0,87.0,10,500,50,0,0,800,500,0.6

7. FS — functional specification

ID	Function	Implementation description
FS-001	CLI entry point	The executable `EthinylestradiolNorgestimateQualityChecker.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 Ethinylestradiol Norgestimate, 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": "EthinylestradiolNorgestimateQualityChecker",
  "api": "Ethinylestradiol Norgestimate",
  "batchNumber": "EENG-2026-001",
  "overallStatus": "PASS|WARNING|FAIL",
  "checkedAtUtc": "2026-05-18T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "EENG-2026-001",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "EthinylestradiolContent",
      "value": "98.5",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "NorgestimateContent",
      "value": "99.2",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ImpurityEthinylestradiol",
      "value": "0.3",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Impurity17DeacetylNorgestimate",
      "value": "0.2",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "ImpurityDelta4Isomer",
      "value": "0.1",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "TotalImpuritiesNorgestimate",
      "value": "0.4",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "WeightVariationRSD",
      "value": "3.5",
      "unit": "as specified",
      "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-006	Insufficient dissolution or excessive disintegration time	FAIL/WARNING is produced according to method criticality.
TC-007	Residual solvent above applicable limit	FAIL is produced with solvent name and measured value.

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

Contraceptives QC Suite

Quality-control package for contraceptives: hormonal APIs, fixed combinations, implants, rings and intrauterine systems.

Open

Endocrinology QC Suite

QC package for endocrinology: thyroid, pituitary/peptide hormones, corticosteroids, sex hormones and selected metabolic medicines.

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Gynecology QC Suite

QC package for gynecology: hormones, contraceptives, uterotonics, anti-infectives and women’s-health medicines.

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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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