EndotoxinAndSterilityChecker

Endotoxin And Sterility

biologics dermal fillers endotoxins hyaluronic acid injectables microbiology particles rheology

Endotoxin & Sterility Checker — Microbiological Safety (Ph. Eur. 2.6.1, 2.6.14 / USP <71>, <85>)

ℹ️  The utility checks test validity (controls), sterility result (growth/no growth), and endotoxin levels (LAL).
ℹ️  Does not use machine learning — pharmacopoeial rules only.
⚠️  CRITICAL! Positive control must be 50-200%. Sterility must be absolute. Endotoxins below limit!

Usage:
  EndotoxinAndSterilityChecker.exe                            → demo mode
  EndotoxinAndSterilityChecker.exe input.csv output.json      → evaluate data

Input format:
BatchNumber,Sterility_Test_Result,Endotoxin_EU_ml,Endotoxin_Limit_EU_ml,Dilution_Factor,Positive_Control_Recovery_Percent,Negative_Control_OD,Sample_pH,Sample_Temperature_C,Validity_Check,Method_Type

Example (Sterility: 0=Pass, 1=Fail; Validity: 1=Valid, 0=Invalid):
STER-ENDO-2026-001,0,0.15,0.5,1.0,85.0,0.02,7.2,37.1,1,Chromogenic

— WHY IS THIS NEEDED?
Sterility and endotoxin control — mandatory requirement for all injectable products and implantable devices:
• Sterility (Ph. Eur. 2.6.1 / USP <71>): No viable microorganisms after 14 days incubation
• Bacterial Endotoxins (Ph. Eur. 2.6.14 / USP <85>): Limit of pyrogens (gram-negative bacterial cell wall components) causing fever and shock
• LAL Method (Limulus Amebocyte Lysate): Gold standard for endotoxin detection (gel-clot, turbidimetric, chromogenic)
⚠️ CRITICAL:
• Test Validity — FIRST of all! If positive/negative controls fail, test result is invalid
• Positive Control (Recovery): 50–200% — confirms reagent works and no inhibitors in sample
• Negative Control: Must be clean (low OD/no gel) — confirms no reagent contamination
• Sterility: Any growth (even in one tube) = FAIL. Investigation required
• Endotoxins: Must be STRICTLY below established limit (e.g., 0.5 EU/mL for injections, 0.2 EU/mL for intrathecal)
• Conditions: pH 6.0–8.0, temperature 37±1°C — critical for LAL enzyme activity
⚠️ Note: Utility first checks Validity. If test is invalid (controls failed), verdict is "INVALID" regardless of sample result. This prevents false release or false rejection. For endotoxins, Safety Margin is calculated. Sterility assessed binary (0/1) as it is qualitative test.

input.csv

BatchNumber,Sterility_Test_Result,Endotoxin_EU_ml,Endotoxin_Limit_EU_ml,Dilution_Factor,Positive_Control_Recovery_Percent,Negative_Control_OD,Sample_pH,Sample_Temperature_C,Validity_Check,Method_Type
STER-ENDO-2026-001,0,0.15,0.5,1.0,85.0,0.02,7.2,37.1,1,Chromogenic

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: EndotoxinAndSterilityCheckerAPI / object: Endotoxin And SterilityCategory: Dermal fillers

1. Scope

The Endotoxin And Sterility Checker utility is used for Endotoxin And Sterility. 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: Dermal fillers

Tags: biologics, dermal fillers, endotoxins, hyaluronic acid, injectables, microbiology, particles, rheology, sterility

2. Execution modes

EndotoxinAndSterilityChecker.exe                            → demo mode
EndotoxinAndSterilityChecker.exe input.csv output.json      → evaluate data

3. Key controlled areas

microbiology and pathogens
pH and physicochemical parameters

4. Domain limits and critical parameters

⚠️ CRITICAL! Positive control must be 50-200%. Sterility must be absolute. Endotoxins below limit!
Sterility (Ph. Eur. 2.6.1 / USP <71>): No viable microorganisms after 14 days incubation
Bacterial Endotoxins (Ph. Eur. 2.6.14 / USP <85>): Limit of pyrogens (gram-negative bacterial cell wall components) causing fever and shock
⚠️ CRITICAL:
Test Validity — FIRST of all! If positive/negative controls fail, test result is invalid
Positive Control (Recovery): 50–200% — confirms reagent works and no inhibitors in sample
Negative Control: Must be clean (low OD/no gel) — confirms no reagent contamination
Sterility: Any growth (even in one tube) = FAIL. Investigation required
Endotoxins: Must be STRICTLY below established limit (e.g., 0.5 EU/mL for injections, 0.2 EU/mL for intrathecal)
Conditions: pH 6.0–8.0, temperature 37±1°C — critical for LAL enzyme activity
⚠️ Note: Utility first checks Validity. If test is invalid (controls failed), verdict is "INVALID" regardless of sample result. This prevents false release or false rejection. For endotoxins, Safety Margin is calculated. Sterility assessed binary (0/1) as it is qualitative test.

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 Endotoxin And Sterility 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: microbiology and pathogens, 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	`STER-ENDO-2026-001`	mandatory field; used for batch/lot traceability
2	`Sterility_Test_Result`	boolean / flag	0/1	Sterility Test Result	`0`	valid flag required; prohibited organisms and growth are normally expected as 0 / absent
3	`Endotoxin_EU_ml`	decimal	as specified	Endotoxin EU ml	`0.15`	numeric value; critical safety attribute compared with endotoxin limit
4	`Endotoxin_Limit_EU_ml`	decimal	as specified	Endotoxin Limit EU ml	`0.5`	numeric value; critical safety attribute compared with endotoxin limit
5	`Dilution_Factor`	decimal	as specified	Dilution Factor	`1.0`	mandatory numeric value; rule comparison is performed by the utility
6	`Positive_Control_Recovery_Percent`	boolean / flag	%	Positive Control Recovery %	`85.0`	mandatory numeric value; rule comparison is performed by the utility
7	`Negative_Control_OD`	boolean / flag	as specified	Negative Control OD	`0.02`	mandatory numeric value; rule comparison is performed by the utility
8	`Sample_pH`	decimal	pH	Sample p H	`7.2`	mandatory numeric value; rule comparison is performed by the utility
9	`Sample_Temperature_C`	decimal	°C	Sample Temperature C	`37.1`	mandatory numeric value; rule comparison is performed by the utility
10	`Validity_Check`	decimal	as specified	Validity Check	`1`	mandatory numeric value; rule comparison is performed by the utility
11	`Method_Type`	text	as specified	Method Type	`Chromogenic`	mandatory value; format and acceptability are checked by the utility

CSV example

BatchNumber,Sterility_Test_Result,Endotoxin_EU_ml,Endotoxin_Limit_EU_ml,Dilution_Factor,Positive_Control_Recovery_Percent,Negative_Control_OD,Sample_pH,Sample_Temperature_C,Validity_Check,Method_Type
STER-ENDO-2026-001,0,0.15,0.5,1.0,85.0,0.02,7.2,37.1,1,Chromogenic

7. FS — functional specification

ID	Function	Implementation description
FS-001	CLI entry point	The executable `EndotoxinAndSterilityChecker.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 Endotoxin And Sterility, 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": "EndotoxinAndSterilityChecker",
  "api": "Endotoxin And Sterility",
  "batchNumber": "STER-ENDO-2026-001",
  "overallStatus": "PASS|WARNING|FAIL",
  "checkedAtUtc": "2026-05-18T00:00:00Z",
  "checks": [
    {
      "parameter": "BatchNumber",
      "value": "STER-ENDO-2026-001",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Sterility_Test_Result",
      "value": "0",
      "unit": "0/1",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Endotoxin_EU_ml",
      "value": "0.15",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Endotoxin_Limit_EU_ml",
      "value": "0.5",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Dilution_Factor",
      "value": "1.0",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Positive_Control_Recovery_Percent",
      "value": "85.0",
      "unit": "%",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Negative_Control_OD",
      "value": "0.02",
      "unit": "as specified",
      "status": "PASS|WARNING|FAIL",
      "message": "Rule-based check result"
    },
    {
      "parameter": "Sample_pH",
      "value": "7.2",
      "unit": "pH",
      "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.

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

Dermal Fillers QC Suite

Package for injectable implants and dermal fillers: hyaluronic acid, CaHA, PLLA, PMMA, collagen and related tests.

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