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extractables-and-leachables
Extractables and Leachables 21 CFR 174.5 General Requirements for Indirect Food Additives – E&L21 CFR 175.300 Resinous and Polymeric Coatings – Leachables Control21 CFR 176.170 Substances in Contact with Aqueous Foods – Extractables21 CFR 177.1520 Leachable Migration Limits for Polyolefins21 CFR 177.1630 Polyethylene Terephthalate Polymers – Leachables LimitASTM D6288 Volatile Organic Compounds Determination by GC/MSASTM D6499 N-nitrosamines Extraction from Rubber ComponentsASTM D7823 Screening of Phthalates in Plastic ComponentsASTM D7896 Analysis of Leachables in Water by LC-MS/MSASTM D8147 Non-Volatile Extractables in Polymeric MaterialsASTM E2406 Leachables from Sterile Barrier SystemsASTM F1980 Accelerated Aging for Stability of ExtractablesASTM F2459 Extractable Residue from Metallic Medical ComponentsASTM F3136 Evaluation of Leachables in Drug Delivery DevicesEMA Guideline on Plastic Immediate Packaging Materials – E&LEP 2.9.47 Container Closure System Integrity Testing for ExtractablesEP 3.1.3 Polyolefins in Contact with Injectable PreparationsEP 3.1.4 Polypropylene for Containers in ParenteralsEP 3.1.5 Polyethylene Used in Pharmaceutical ContainersEP 3.1.6 Polyethylene Terephthalate Containers – Leachable SafetyEP 3.2.2 Plastic Containers and Closures for Pharmaceutical UseEP 3.2.8 Closures for Containers for Aqueous Parenteral PreparationsEP 3.2.9 Rubber Closures – Extractables AnalysisEP 5.1.1 Biological Safety – Leachables Toxicity AssessmentFDA 21 CFR 211.94 Container Closure System Suitability – Extractables RiskFDA Guidance: Container Closure Systems for Drug Products – E&L FocusFDA Guidance: Orally Inhaled and Nasal Drug Products – Leachables ReviewHealth Canada GUI-0069 Plastic Components in Contact with Drug ProductsICH Q3D Risk-Based Assessment of Elemental Impurities in LeachablesISO 10993-12 Sample Preparation for Extractables TestingISO 10993-13 Degradation Products Analysis for Polymeric Medical DevicesISO 10993-14 Identification of Degradation Products from CeramicsISO 10993-15 Identification of Degradation Products from MetalsISO 10993-17 Toxicological Risk Assessment for LeachablesISO 10993-18 Chemical Characterization of Medical Device MaterialsISO 11607-1 Package Integrity for Sterile Medical DevicesISO 11607-2 Manufacturing Validation for Sterile Barrier SystemsISO 11979-5 Extractables in Intraocular Lens MaterialsISO 14937 Sterilization and Extractables Safety AssuranceISO 15759 Analysis of Packaging for Contact with Parenteral DrugsISO 17664 Processing of Leachable-Safe Reusable Medical DevicesISO 18562-1 Leachables Testing for Breathing Gas Pathways in HealthcareISO 18562-2 Volatile Organic Compounds Testing from Medical DevicesISO 18562-3 Condensate Leachables Testing from Gas Pathway EquipmentISO 18562-4 Leachable Particulates in Medical Gas Pathway DevicesISO/TR 10993-33 Guidance on E&L Assessment Strategy for DevicesJP 2.20 Extractables from Rubber Stoppers by GC-MSJP 6.02 Aluminum Cap Material Leachables TestingJP 6.07 Plastic Containers for Aqueous Injections – Leachable StandardsJP 6.10 Gas Permeability and Volatile Leachable ReleaseJP 7.02 Residual Solvent and Leachable IdentificationJP 7.04 Container/Closure Leachable Migration EvaluationPDA TR No. 66 Defining Leachables Risk in Biologics ProductionPDA TR No. 85 Extractables and Leachables in Manufacturing SystemsPh. Int. General Method 3.10 Leachable Profiling of Packaging MaterialsUSP <1031.1> Analytical Instrument Qualification for Extractables StudiesUSP <1031> Analytical Method Validation for Extractables StudiesUSP <1058> Analytical Instrument Qualification for Leachables TestingUSP <1079> Good Storage and Distribution Practices – Leachable RiskUSP <1086> Impurities – Extractables Risk ProfilingUSP <1088> Inhalation and Nasal Drug Products – Leachables TestingUSP <1207> Container Closure Integrity and Leachable EntryUSP <1231> Water for Pharmaceutical Purposes – Leachables RiskUSP <1661> Evaluation of Plastic Packaging Systems for Drug ProductsUSP <1663> Extractables Testing for Plastic Components in Drug PackagingUSP <1664> Leachables Analysis for Container Closure SystemsUSP <381> Elastomeric Closures for Injections: Extractable ProfileUSP <601> Aerosols – Extractables in Metered Dose InhalersUSP <661.1> Physicochemical Testing of Plastic Packaging SystemsUSP <661.2> Biological Reactivity Tests for Plastic MaterialsUSP <661> Packaging System Suitability for ExtractablesUSP <671> Stability and Buffering Capacity in Plastic ContainersUSP <800> Hazardous Drug Handling – Leachables from PackagingUSP <87> Biological Reactivity Test: In Vitro CytotoxicityUSP <88> Biological Reactivity Test: In Vivo Irritation & ToxicityUSP <905> Uniformity of Dosage Units – Leachable InfluenceWHO TRS 961 Annex 9 Guidelines on Packaging Materials – Leachables

Comprehensive Guide to Extractables and Leachables Laboratory Testing Services

Extractables and Leachables (EL) testing is a critical laboratory test used to assess the potential risks associated with contaminants leaching from medical devices, equipment, and materials into pharmaceuticals, biologics, and other products. The testing is governed by various international and national standards, which provide a framework for ensuring the safety and quality of these products.

Overview of Relevant Standards

The following standards are relevant to EL testing:

  • ISO 10993-18:2017: Biological evaluation of medical devices - Part 18: Chemical characterization of materials

  • ASTM F2849-13(2020): Standard Guide for Leachables and Extractables Testing for Medical Devices in Simulated Physiological Environments

  • EN ISO 14155:2010: Clinical investigation of medical devices for human subjects - Good clinical practice

    • Standard Development Organizations

    The International Organization for Standardization (ISO) is responsible for developing standards related to EL testing. Other standard development organizations, such as the American Society for Testing and Materials (ASTM), also contribute to the development of relevant standards.

    Evolution of Standards

    Standards evolve over time due to advancements in technology, changes in regulatory requirements, or new scientific discoveries. Regular updates ensure that standards remain relevant and effective in ensuring product safety.

    Standard Compliance Requirements

    Compliance with relevant standards is mandatory for manufacturers seeking to market their products globally. The following industries require EL testing:

  • Medical devices

  • Pharmaceuticals

  • Biologics

  • Cosmetics

    • Consequences of Non-Compliance

    Non-compliance with EL testing regulations can result in significant consequences, including product recalls, financial losses, and damage to brand reputation.

    EL testing is essential for ensuring the safety and quality of products. The following reasons highlight the importance of this test:

  • Business and Technical Reasons: EL testing provides a means of mitigating potential risks associated with leachable contaminants, thus protecting product manufacturers from liability.

  • Consequences of Non-Testing: Failure to conduct EL testing can result in costly recalls, damaged brand reputation, and financial losses.

    • Industries Requiring EL Testing

    The following industries require EL testing:

  • Medical devices

  • Pharmaceuticals

  • Biologics

  • Cosmetics

    • Risk Factors and Safety Implications

    EL testing identifies potential risks associated with leachable contaminants. Failure to conduct this test can result in adverse health effects, product recalls, and financial losses.

    Quality Assurance and Quality Control Aspects

    EL testing contributes to quality assurance by ensuring the safety and reliability of products. Regular testing also helps maintain compliance with regulatory requirements.

    Competitive Advantages of EL Testing

    Companies that conduct regular EL testing demonstrate their commitment to product safety, potentially resulting in increased customer trust and loyalty.

    Cost-Benefit Analysis

    The cost-benefit analysis of conducting EL testing highlights the importance of this test. The costs associated with non-compliance far outweigh those of conducting regular testing.

    EL testing involves a series of steps to assess the leachable contaminants from medical devices, equipment, and materials into pharmaceuticals, biologics, and other products.

    Step-by-Step Explanation

    The following is a step-by-step explanation of how EL testing is conducted:

    1. Sample Preparation: The test sample is prepared according to relevant standards.

    2. Testing Equipment and Instruments: Specific equipment and instruments are used for the test.

    3. Testing Environment Requirements: The testing environment must meet specific requirements, including temperature, humidity, and pressure.

    4. Measurement and Analysis Methods: The measurement and analysis methods involve assessing the leachable contaminants.

    5. Calibration and Validation Procedures: Calibration and validation procedures ensure accurate results.

    6. Data Collection and Recording: Data is collected and recorded according to relevant standards.

    Test results are documented and reported in a structured format, following specific guidelines.

    Report Format and Structure

    The report format and structure include:

  • Introduction

  • Methods

  • Results

  • Discussion

  • Conclusion

    • Interpretation of Test Results

    The interpretation of test results involves assessing the safety and reliability of products based on leachable contaminants.

    Certification and Accreditation Aspects

    Certification and accreditation aspects involve ensuring that the testing laboratory meets specific requirements, including ISO/IEC 17025:2017.

    Traceability and Documentation Requirements

    Test results are traceable to the original samples and documented according to relevant standards.

    Electronic Reporting Systems Used

    Electronic reporting systems used include:

  • Laboratory Information Management System (LIMS)

  • Electronic Data Capture (EDC)

    • Confidentiality and Data Protection Measures

    Confidentiality and data protection measures involve ensuring that test results remain confidential and protected from unauthorized access.

    Conclusion

    EL testing is a critical laboratory test used to assess the potential risks associated with contaminants leaching from medical devices, equipment, and materials into pharmaceuticals, biologics, and other products. The testing is governed by various international and national standards, which provide a framework for ensuring the safety and quality of these products.

    By understanding the importance of EL testing, manufacturers can ensure compliance with regulatory requirements, mitigate potential risks, and maintain product quality and safety.

    References

  • ISO 10993-18:2017. Biological evaluation of medical devices Part 18: Chemical characterization of materials.

  • ASTM F2849-13(2020). Standard Guide for Leachables and Extractables Testing for Medical Devices in Simulated Physiological Environments.

  • EN ISO 14155:2010. Clinical investigation of medical devices for human subjects Good clinical practice.

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