EUROLAB
usp-661-packaging-system-suitability-for-extractables
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 <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 USP <661> Packaging System Suitability for Extractables Testing Services by Eurolab

USP <661> Packaging System Suitability for Extractables testing is a laboratory test that evaluates the potential extractables from packaging materials used in pharmaceutical and biopharmaceutical products. This test is governed by various international and national standards, including:

  • USP <661> Packaging System Suitability for Extractables

  • ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity

  • ASTM E2593-08(2020) Standard Guide for Evaluating the Stability of Extractables in Pharmaceutical Packaging Materials

  • EN ISO 11133:2014 Plastics - Medical devices - Packaging materials and their labels

    • These standards ensure that pharmaceutical and biopharmaceutical products are safe for human use by evaluating the potential extractables from packaging materials.

    Legal and Regulatory Framework

    The legal and regulatory framework surrounding USP <661> Packaging System Suitability for Extractables testing is governed by various national and international regulations, including:

  • Good Manufacturing Practice (GMP) guidelines

  • International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)

  • European Medicines Agency (EMA)

  • US Food and Drug Administration (FDA)

    • These regulations ensure that pharmaceutical and biopharmaceutical products are manufactured in compliance with GMP principles, which include the testing of packaging materials for extractables.

    International and National Standards

    The international standards governing USP <661> Packaging System Suitability for Extractables testing include:

  • ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity

  • ASTM E2593-08(2020) Standard Guide for Evaluating the Stability of Extractables in Pharmaceutical Packaging Materials

    • National standards include:

  • USP <661> Packaging System Suitability for Extractables (US)

  • EN ISO 11133:2014 Plastics - Medical devices - Packaging materials and their labels (EU)

    • Standard Development Organizations

    The standard development organizations responsible for governing USP <661> Packaging System Suitability for Extractables testing include:

  • International Organization for Standardization (ISO)

  • American Society for Testing and Materials (ASTM)

  • European Committee for Standardization (CEN)

    • These organizations ensure that standards are developed, published, and updated in a transparent and collaborative manner.

    Standard Evolution and Update

    Standards evolve and get updated to reflect advances in technology, changes in regulations, and new scientific knowledge. The standard development process involves:

    1. Identification of needs

    2. Literature review

    3. Expert input

    4. Drafting of standards

    5. Balloting and voting

    6. Publication and implementation

    Specific Standard Numbers and Scope

    The following are specific standard numbers and their scope related to USP <661> Packaging System Suitability for Extractables testing:

  • ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity

    • Scope: Evaluates the potential extractables from packaging materials used in pharmaceutical and biopharmaceutical products.

  • ASTM E2593-08(2020) Standard Guide for Evaluating the Stability of Extractables in Pharmaceutical Packaging Materials

    • Scope: Provides guidance on evaluating the stability of extractables in pharmaceutical packaging materials.

    Standard Compliance Requirements

    Compliance with standards is essential to ensure that pharmaceutical and biopharmaceutical products are safe for human use. The standard compliance requirements include:

  • ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity

    • Requirements: Evaluate the potential extractables from packaging materials used in pharmaceutical and biopharmaceutical products.

  • ASTM E2593-08(2020) Standard Guide for Evaluating the Stability of Extractables in Pharmaceutical Packaging Materials

    • Requirements: Provide guidance on evaluating the stability of extractables in pharmaceutical packaging materials.

    Standard Compliance in Different Industries

    The standard compliance requirements vary depending on the industry. For example:

  • Pharmaceuticals and biopharmaceuticals: Comply with USP <661> Packaging System Suitability for Extractables testing.

  • Medical devices: Comply with ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity.

    • Industry-Specific Examples and Case Studies

    Examples and case studies demonstrate the practical application of standards in different industries. For example:

  • A pharmaceutical company uses USP <661> Packaging System Suitability for Extractables testing to evaluate the potential extractables from packaging materials used in their products.

  • A medical device manufacturer complies with ISO 10993-18:2017 Biological evaluation of medical devices Part 18: Tests for genotoxicity, carcinogenicity, and reproductive toxicity by evaluating the potential extractables from packaging materials used in their products.

    • Standard-Related Information Conclusion

    In conclusion, USP <661> Packaging System Suitability for Extractables testing is governed by various international and national standards. These standards ensure that pharmaceutical and biopharmaceutical products are safe for human use by evaluating the potential extractables from packaging materials. The standard development process involves identifying needs, literature review, expert input, drafting of standards, balloting and voting, publication, and implementation.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as laboratory procedures, equipment, and personnel requirements, as well as quality control and assurance measures.

    The laboratory procedures for USP <661> Packaging System Suitability for Extractables testing include:

    1. Sample preparation

    2. Extraction of extractables from packaging materials

    3. Chromatographic analysis of extractables

    4. Data interpretation and reporting

    Sample Preparation

    Sample preparation involves collecting, storing, and preparing the packaging materials for extraction.

  • Collect packaging materials from various sources (e.g., suppliers, manufacturers)

  • Store packaging materials in a controlled environment to prevent contamination

  • Prepare packaging materials for extraction by cutting, crushing, or grinding as required

    • Extraction of Extractables from Packaging Materials

    Extraction involves using solvents or other reagents to extract the potential extractables from packaging materials.

  • Use a suitable solvent (e.g., water, methanol, acetonitrile) to extract the potential extractables

  • Heat or stir the extraction mixture as required

  • Filter the extracted solution to remove particulate matter

    • Chromatographic Analysis of Extractables

    Chromatographic analysis involves separating and identifying the potential extractables using various techniques.

  • Use a suitable chromatography technique (e.g., HPLC, GC) to separate and identify the potential extractables

  • Select a suitable column or detector for the chromatography technique used

  • Calibrate the chromatography system according to manufacturers instructions

    • Data Interpretation and Reporting

    Data interpretation involves analyzing the results from the chromatographic analysis to determine the presence and quantity of potential extractables.

  • Compare the chromatogram with standard curves or reference materials to identify and quantify potential extractables

  • Evaluate the data for any discrepancies or anomalies

  • Report the results according to established protocols (e.g., USP <661> Packaging System Suitability for Extractables testing)

    • Quality Control and Assurance Measures

    Quality control and assurance measures ensure that laboratory procedures are followed accurately and consistently.

  • Use quality control samples (e.g., blanks, standards) to monitor the extraction process

  • Evaluate the chromatography system for performance using quality control samples

  • Document all laboratory procedures and results according to established protocols

    • Laboratory Procedures Conclusion

    In conclusion, the laboratory procedures for USP <661> Packaging System Suitability for Extractables testing involve sample preparation, extraction of extractables from packaging materials, chromatographic analysis, data interpretation, and reporting. The quality control and assurance measures ensure that laboratory procedures are followed accurately and consistently.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as personnel requirements, equipment, and quality control measures.

    The personnel requirements for USP <661> Packaging System Suitability for Extractables testing include:

    1. Laboratory personnel

    2. Technical personnel

    3. Quality control personnel

    Laboratory Personnel

    Laboratory personnel are responsible for conducting the laboratory procedures.

  • Conduct sample preparation, extraction of extractables from packaging materials, chromatographic analysis, and data interpretation

  • Follow established protocols and guidelines (e.g., USP <661> Packaging System Suitability for Extractables testing)

  • Maintain accurate records of all laboratory procedures and results

    • Technical Personnel

    Technical personnel are responsible for maintaining equipment and providing technical support.

  • Ensure that equipment is properly calibrated and maintained according to manufacturers instructions

  • Provide technical support for laboratory personnel during the extraction process

  • Evaluate the chromatography system for performance using quality control samples

    • Quality Control Personnel

    Quality control personnel are responsible for ensuring compliance with established protocols and guidelines.

  • Monitor laboratory procedures to ensure accuracy and consistency

  • Evaluate the data for any discrepancies or anomalies

  • Report any deviations from established protocols to management

    • Personnel Requirements Conclusion

    In conclusion, the personnel requirements for USP <661> Packaging System Suitability for Extractables testing include laboratory personnel, technical personnel, and quality control personnel. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as equipment requirements, quality control measures, and regulatory compliance.

    The equipment requirements for USP <661> Packaging System Suitability for Extractables testing include:

    1. Chromatography system

    2. Extraction apparatus

    3. Sample preparation equipment

    Chromatography System

    The chromatography system is responsible for separating and identifying the potential extractables.

  • Use a suitable chromatography technique (e.g., HPLC, GC) to separate and identify the potential extractables

  • Select a suitable column or detector for the chromatography technique used

  • Calibrate the chromatography system according to manufacturers instructions

    • Extraction Apparatus

    The extraction apparatus is responsible for extracting the potential extractables from packaging materials.

  • Use a suitable solvent (e.g., water, methanol, acetonitrile) to extract the potential extractables

  • Heat or stir the extraction mixture as required

  • Filter the extracted solution to remove particulate matter

    • Sample Preparation Equipment

    The sample preparation equipment is responsible for preparing packaging materials for extraction.

  • Use a suitable device (e.g., cutting tool, grinder) to prepare packaging materials for extraction

  • Store packaging materials in a controlled environment to prevent contamination

    • Equipment Requirements Conclusion

    In conclusion, the equipment requirements for USP <661> Packaging System Suitability for Extractables testing include chromatography systems, extraction apparatus, and sample preparation equipment. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as quality control measures, regulatory compliance, and certification requirements.

    The quality control measures for USP <661> Packaging System Suitability for Extractables testing include:

    1. Internal quality control

    2. External quality control

    3. Proficiency testing

    Internal Quality Control

    Internal quality control involves monitoring laboratory procedures to ensure accuracy and consistency.

  • Use quality control samples (e.g., blanks, standards) to monitor the extraction process

  • Evaluate the chromatography system for performance using quality control samples

  • Document all laboratory procedures and results according to established protocols

    • External Quality Control

    External quality control involves comparing laboratory results with those from other laboratories.

  • Participate in external quality control programs (e.g., proficiency testing, round robin testing)

  • Compare laboratory results with those from other laboratories to evaluate accuracy and consistency

  • Evaluate the data for any discrepancies or anomalies

    • Proficiency Testing

    Proficiency testing involves evaluating laboratory performance against established standards.

  • Participate in proficiency testing programs (e.g., USP <661> Packaging System Suitability for Extractables testing)

  • Evaluate laboratory performance according to established standards (e.g., accuracy, precision, specificity)

  • Report any deviations from established protocols to management

    • Quality Control Measures Conclusion

    In conclusion, the quality control measures for USP <661> Packaging System Suitability for Extractables testing include internal quality control, external quality control, and proficiency testing. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as regulatory compliance, certification requirements, and ongoing education and training.

    The regulatory compliance for USP <661> Packaging System Suitability for Extractables testing includes:

    1. FDA regulations

    2. EPA regulations

    3. ISO standards

    FDA Regulations

    FDA regulations govern the safety of packaging materials used in pharmaceuticals.

  • Follow FDA guidelines for packaging materials (e.g., 21 CFR Part 211)

  • Ensure that packaging materials meet FDA regulations for extraction and leaching (e.g., 21 CFR Part 170)

  • Report any deviations from FDA regulations to management

    • EPA Regulations

    EPA regulations govern the environmental impact of packaging materials.

  • Follow EPA guidelines for packaging materials (e.g., 40 CFR Part 261)

  • Ensure that packaging materials meet EPA regulations for extraction and leaching (e.g., 40 CFR Part 261.31)

  • Report any deviations from EPA regulations to management

    • ISO Standards

    ISO standards govern the quality of packaging materials.

  • Follow ISO guidelines for packaging materials (e.g., ISO 9001)

  • Ensure that packaging materials meet ISO standards for extraction and leaching (e.g., ISO 17025)

  • Report any deviations from ISO standards to management

    • Regulatory Compliance Conclusion

    In conclusion, the regulatory compliance for USP <661> Packaging System Suitability for Extractables testing includes FDA regulations, EPA regulations, and ISO standards. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as certification requirements, ongoing education and training, and best practices.

    The certification requirements for USP <661> Packaging System Suitability for Extractables testing include:

    1. Certification by a recognized accrediting body

    2. Training in USP <661> Packaging System Suitability for Extractables testing

    3. Continuing education and training

    Certification by a Recognized Accreditating Body

    Certification by a recognized accrediting body ensures that the laboratory meets established standards.

  • Obtain certification from a recognized accrediting body (e.g., AOAC International, NELAC)

  • Ensure that the laboratory meets established standards for extraction and leaching (e.g., USP <661>)

  • Report any deviations from established standards to management

    • Training in USP <661> Packaging System Suitability for Extractables Testing

    Training in USP <661> Packaging System Suitability for Extractables testing ensures that personnel are competent in the test method.

  • Complete training in USP <661> Packaging System Suitability for Extractables testing

  • Ensure that personnel understand the test method and its application (e.g., 21 CFR Part 211)

  • Report any deviations from established protocols to management

    • Continuing Education and Training

    Continuing education and training ensures that personnel stay up-to-date with changes in regulations and technology.

  • Complete continuing education and training in USP <661> Packaging System Suitability for Extractables testing

  • Ensure that personnel understand changes in regulations and technology (e.g., 21 CFR Part 211)

  • Report any deviations from established protocols to management

    • Certification Requirements Conclusion

    In conclusion, the certification requirements for USP <661> Packaging System Suitability for Extractables testing include certification by a recognized accrediting body, training in USP <661> Packaging System Suitability for Extractables testing, and continuing education and training. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as best practices, quality control measures, and regulatory compliance.

    The best practices for USP <661> Packaging System Suitability for Extractables testing include:

    1. Use of validated methods

    2. Calibration and maintenance of equipment

    3. Documentation and record-keeping

    Use of Validated Methods

    Validated methods ensure that the test results are accurate and reliable.

  • Use validated methods (e.g., USP <661>) for extraction and leaching testing

  • Ensure that the method is suitable for the packaging material being tested (e.g., 21 CFR Part 211)

  • Report any deviations from established protocols to management

    • Calibration and Maintenance of Equipment

    Calibration and maintenance of equipment ensure that the test results are accurate and reliable.

  • Calibrate all equipment used in extraction and leaching testing (e.g., chromatography system, extraction apparatus)

  • Maintain equipment according to manufacturers instructions (e.g., cleaning, storage)

  • Report any deviations from established protocols to management

    • Documentation and Record-Keeping

    Documentation and record-keeping ensure that the test results are accurately recorded and maintained.

  • Maintain accurate records of all testing procedures (e.g., calibration, maintenance, extraction and leaching results)

  • Document all deviations from established protocols (e.g., 21 CFR Part 211)

  • Report any deviations from established protocols to management

    • Best Practices Conclusion

    In conclusion, the best practices for USP <661> Packaging System Suitability for Extractables testing include use of validated methods, calibration and maintenance of equipment, and documentation and record-keeping. The personnel must follow established protocols and guidelines, maintain accurate records, and ensure compliance with regulations.

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    Please note that this is a part of the comprehensive guide to USP <661> Packaging System Suitability for Extractables testing services by Eurolab. The rest of the guide will cover other topics such as ongoing education and training, certification requirements, and regulatory compliance.

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