OECD GLP Series - The Intertwined Strands: ISO & OECD GLP for Quality in Laboratory Testing
Intertwined Strands
While both ISO guidelines and the OECD Principles of Good Laboratory Practice (GLP) promote quality and rigor in processes, they cater to distinct aspects of scientific research and testing. This article explores the relationship between these two frameworks, highlighting their areas of overlap and divergence.
ISO: A Framework for Management Systems
The International Organization for Standardization (ISO) establishes a comprehensive library of international standards (ISO standards) applicable across various industries and disciplines. These standards provide a framework for organizations to develop and implement management systems encompassing quality, environment, information security, and more.
Focus of ISO Standards in a Testing Context
While there isn’t a single ISO standard specifically for good laboratory practices, ISO 17025, titled “General requirements for the competence of testing and calibration laboratories,” holds significant relevance for laboratories conducting safety and efficacy testing. This standard emphasizes:
- Technical Competence:Ensuring personnel possess the necessary qualifications, training, and experience to perform tests accurately and reliably.
- Quality Management System:Establishing a documented system with defined processes, procedures, and controls to ensure consistent test quality.
- Testing Procedures:Following validated testing methodologies and maintaining records of calibration certificates and test equipment.
- Data Integrity:Ensuring the accuracy, traceability, and completeness of all data generated during testing.
- Reporting:Issuing clear and concise test reports that accurately reflect the test results and methodology.
OECD GLP: A Set of Principles for Non-Clinical Laboratory Studies
The Organization for Economic Co-operation and Development (OECD) established the GLP principles to promote the quality and integrity of non-clinical safety studies used in regulatory submissions for pharmaceuticals, chemicals, pesticides, and other products. These principles cover a broader scope than ISO 17025, focusing on:
- Organizational Structure:Clearly defining roles and responsibilities for study personnel, including the Study Director who oversees the entire study.
- Facilities:Maintaining adequate facilities to ensure the proper conduct of studies, including segregated areas for test substances and animals.
- Test Substances:Characterizing and managing test substances appropriately, with clear labelling and documentation.
- Protocol and Conduct:Following a detailed study protocol outlining the study objectives, methodology, and data collection procedures.
- Quality Assurance Unit:Establishing an independent Quality Assurance Unit (QAU) to monitor compliance with GLP principles throughout the study.
- Recordkeeping and Archiving:Maintaining comprehensive and accurate records of all study-related activities and data, ensuring their secure storage for a specified period.
Areas of Overlap and Synergy
Both ISO 17025 and OECD GLP emphasize the importance of:
- Quality Management System:Having a documented system to manage testing activities and ensure consistent quality.
- Technical Competence:Employing qualified personnel with the necessary expertise to conduct tests effectively.
- Data Integrity:Recording and reporting data accurately and reliably, ensuring traceability.
- Documentation:Maintaining complete and thorough records of all testing activities.
By adhering to both sets of guidelines, laboratories can achieve a robust quality management system, enhancing the reliability and credibility of their testing results.
Key Divergences: Specificity and Focus
However, there are crucial differences between ISO 17025 and OECD GLP:
- Scope:ISO 17025 applies to a broader range of testing activities, including those not necessarily submitted for regulatory approval. OECD GLP is specific to non-clinical safety studies used in regulatory submissions.
- Detail and Comprehensiveness:OECD GLP principles are more prescriptive and detailed, outlining specific requirements for facilities, recordkeeping, and quality assurance procedures.
- Role of Quality Assurance:While ISO 17025 encourages quality management activities, OECD GLP mandates an independent QAU to actively monitor study conduct and ensure compliance with GLP principles.
Choosing the Right Framework
The choice between adhering to ISO 17025 or OECD GLP depends on the specific context of the testing:
- For General Testing:Laboratories conducting routine safety or performance testing not intended for regulatory submissions might benefit from implementing ISO 17025.
- For Regulatory Testing:Laboratories conducting non-clinical safety studies for regulatory purposes must comply with OECD GLP principles. In some cases, national regulations might require additional regional or country-specific GLP requirements.
Understanding the complementary nature of ISO guidelines and OECD GLP principles is crucial for laboratories involved in safety testing. While ISO 17025 provides a robust framework for general laboratory competence, OECD GLP offers a specific set of requirements for regulatory testing. By implementing the appropriate guidelines or aiming for combined compliance, laboratories can ensure the quality, integrity, and reliability of their testing data.
ISO Standards and Their Integration in OECD GLP Compliance
For laboratories conducting non-clinical safety studies on products like pharmaceuticals, medical devices, industrial chemicals and more, adherence to OECD GLP principles is critical for generating reliable and accepted data. While OECD GLP provides overarching requirements for processes and quality systems, it does not prescribe technical protocols for specific test methods. This is where internationally recognized standards published by the International Organization for Standardization (ISO) play a vital role.
ISO develops voluntary standards covering a wide range of technical areas through a consensus-based process involving experts from industry, academia and regulatory bodies globally. Many of these standards are directly applicable and complementary to OECD GLP studies.
Integration of ISO Standards in GLP Studies
OECD GLP principles state that non-clinical safety tests should be conducted using “procedures selected and described in the test or study plan.” ISO standards represent validated, globally harmonized test methods that can be incorporated as the procedural components of GLP study plans and protocols. Some key examples include:
1. Analytical Methods (e.g. ISO 19825, ISO 10695)
ISO provides standards for a wide variety of chemical analysis techniques used for characterizing test and reference substances in toxicology studies.
ISO has developed several standards related to analytical chemical methods that can be leveraged in OECD GLP studies requiring characterization and analysis of test and reference substances. Some key examples are:
a) ISO 19825: Guidance Relating to Analytical Terminology
This standard provides guidance on acceptable terminology, definitions, and abbreviations used in analytical method documentation. It aims to harmonize communication and facilitate consistent interpretation when describing analytical procedures and results across different laboratories. Adherence to these terminology conventions supports proper documentation for GLP studies.
b) ISO 10695: Guidance for Evaluating Residual Drug Substances in Pharmaceutical Products
Specific to the pharmaceutical industry, ISO 10695 outlines validated analytical procedures, test methodologies, and criteria for evaluating and controlling levels of residual drug substances and their degradation products in drug products. These standards can be referenced for studies characterizing pharmaceutical test items under GLP.
c) ISO/IEC 17025: General Requirements for Competence of Testing and Calibration Labs
While not an analytical method per se, ISO/IEC 17025 specifies overarching requirements for ensuring quality and technical competence of laboratories performing tests and calibrations, including analytical chemistry work. Many of its requirements around method validation, equipment calibration, traceability, etc. are highly relevant to GLP analytical activities.
ISO standards for specific analytical techniques:
- ISO 12675 – Ion Chromatography
- ISO 19835 – Bioanalytical Methods
- ISO 16703 – Soil Quality – Determination of Elemental Composition
- ISO 10390 – Particle Size Analysis
By referencing these ISO standards, GLP labs can directly incorporate internationally harmonized and validated analytical protocols into their study plans, eliminating the need to develop proprietary methods from scratch.
Moreover, the documentation requirements and quality control criteria specified in ISO analytical standards provide built-in support for GLP principles around data traceability, equipment calibration, method validation, reporting, and personnel competency.
So in summary, OECD GLP test facilities can leverage ISO’s analytical method standards as technical procedures, while benefiting from the embedded quality control and documentation aspects that bolster GLP compliance. This integration facilitates consistent, high-quality chemical analysis for characterization of test substances across global R&D programs.
2. Physical/Chemical Property Testing (e.g. ISO 10360 series, ISO 10787)
Determination of parameters like vapor pressure, water solubility, partition coefficients etc. as per ISO standardized methods.
ISO has developed several standards providing harmonized test methods for determining key physicochemical properties of substances, which is an important aspect of non-clinical safety testing under OECD GLP principles. Some relevant ISO standards in this domain include:
a) ISO 10360 Series – Determination of Hazardous Substances
This multi-part standard covers test procedures for measuring critical parameters needed for hazard classification like flash point, auto-ignition temperature, corrosivity, oxidizing properties etc. Specific parts include:
- ISO 10360-1 – General Principles and Safety Data
- ISO 10360-2 – Flammability Testing
- ISO 10360-3 – Screening Tests for Low Concentration Flammable Liquids
- ISO 10360-4 – Sustained Combustibility Testing
b) ISO 10787 – Black/White Lists for VP/WS Screening
Provides lists of compounds categorized based on screening data for vapor pressure (VP) and water solubility (WS). Includes guidance on applying appropriate test methods for determination of VP and WS based on the categorization.
c) ISO 15009 – Zeta Potential Determination
Describes procedures for measuring the zeta potential of colloidal particles and porous solids to understand their surface properties and behavior.
d) ISO 10634 – Water Quality – Biodegradability Evaluation
Outlines various test methods (e.g. CO2 evolution, oxygen demand) for assessing the biodegradation potential of organic compounds in aqueous media.
e) ISO 14238 – Adsorption/Desorption Screening Tests
Defines batch and column screening tests to evaluate adsorption/desorption behavior of substances on soils and sediments under standardized conditions.
By prescribing validated, globally harmonized test protocols, these ISO physicochemical property standards fulfil a critical need within OECD GLP – ensuring non-clinical safety data is generated using recognized and mutually acceptable test methods across laboratories worldwide.
For OECD GLP test facilities, direct implementation of the ISO standards provides several key benefits:
- Avoids duplicative method development and validation efforts
- Increases confidence in regulatory acceptance of the data
- Supports consistency and comparability of results across studies
- Aligns with OECD GLP principles around documentation and calibration
Many regulatory bodies reference or recognize these ISO test methods for physico-chemical property determination within their technical guidance documents as well.
By strategically integrating relevant ISO standards into their standard operating procedures and study plans, OECD GLP test facilities can streamline their physicochemical testing activities while bolstering compliance with international quality and reliability expectations.
3. Biological Evaluation of Medical Devices (ISO 10993 series)
Internationally recognized test methods for assessing medical device biocompatibility, cytotoxicity, sensitization and more.
The ISO 10993 series of standards provides a comprehensive framework for the biological evaluation of medical devices to assess their biocompatibility. These standards play a crucial role in supporting OECD GLP studies related to medical device safety testing.
Here are some key aspects of the ISO 10993 standards and their utilization in an OECD GLP context:
a) Internationally Harmonized Test Methods
ISO 10993 consists of over 20 standards covering various biocompatibility tests like:
- Cytotoxicity (ISO 10993-5)
- Sensitization (ISO 10993-10)
- Systemic Toxicity (ISO 10993-11)
- Implantation Effects (ISO 10993-6)
- Genotoxicity, Carcinogenicity, Reproductive Toxicity (ISO 10993-3)
These standardized test methods are validated through international collaboration and provide a mutually acceptable technical basis for medical device biocompatibility assessments globally.
b) Risk-Based Test Selection
ISO 10993-1 provides an overarching framework to evaluate potential biological risks from the device materials and design, based on factors like nature, degree, and duration of device exposure. This guides selection of relevant biocompatibility tests for a given device.
c) Testing Requirements
Each part of ISO 10993 specifies the scope, rationale, test materials, methodologies, report elements, and pass/fail criteria for that particular biocompatibility endpoint in extensive detail.
d) Alignment with Regulatory Expectations
Major medical device regulatory bodies like U.S. FDA, Health Canada, EU regulatory authorities recognize and reference ISO 10993 standards as preferred methods for biocompatibility evaluations.
For OECD GLP test facilities conducting medical device studies, implementation of the ISO 10993 standards provides significant advantages:
- Eliminates need for proprietary test method development/validation
- Supports international acceptance of the biocompatibility data
- Aligns with OECD GLP expectations around standardized documented methods
- Incorporates quality measures like method criteria, reference materials etc.
Leveraging ISO 10993 facilitates consistent technical execution and documentation of biocompatibility testing across test facilities worldwide within the OECD GLP quality framework.
Overall, the availability of these internationally vetted and recognized standard methods enables efficient regulation of medical devices based on reliable, mutually accepted safety data generated following OECD GLP principles.
4. Environmental Fate Testing (e.g. ISO 10634, ISO 14238)
Standards for evaluating parameters like biodegradability, adsorption/desorption behavior to fulfil environmental testing requirements.
ISO has developed several internationally recognized standards for various environmental fate studies that are relevant for OECD GLP compliance. Some key examples include:
a) ISO 10634:1995 – Water Quality – Guidance for the Preparation and Treatment of Poorly Water-Soluble Organic Compounds for the Subsequent Evaluation of Their Biodegradability in an Aqueous Medium
This standard outlines procedures for proper preparation of poorly soluble test substances and their introduction into aqueous media for evaluating biodegradation potential through tests like CO2 evolution, DOC removal, OECD closed bottle test etc.
b) ISO 14238:2012 – Soil Quality – Biological Methods
Part of ISO’s extensive standards on soil quality testing, this document describes screening methods to evaluate the adsorption/desorption behavior of chemical substances on soils and sediments under standardized batch and column test conditions.
c) ISO 16703:2011 – Soil Quality – Determination of Content of Hydrocarbon in the Range C10 to C40 by Gas Chromatography
Specifies a GC-FID method for quantifying aliphatic and aromatic hydrocarbon contents in soils/sediments within the C10-C40 range. Relevant for environmental fate studies evaluating persistence of petroleum-derived substances.
d) ISO 11734:1995 – Water Quality – Evaluation of the “Ultimate” Anaerobic Biodegradability of Organic Compounds in Digested Sludge
Defines criteria and test methods, including biogas production measurement, to assess the anaerobic biodegradability of organic compounds by measuring the degree of conversion to methane from metabolism by digester sludge cultures.
By prescribing internationally standardized and validated test procedures, these ISO methods facilitate generation of reliable, consistent, and mutually acceptable environmental fate data across laboratories globally.
For OECD GLP test facilities, adoption of these ISO standards confers several benefits:
- Avoids duplicative method development efforts at each facility
- Supports international harmonization and regulatory acceptance of data
- Incorporates validated quality control and performance criteria
- Aligns with OECD GLP expectations around well-documented test methods
Many regulatory agencies for industrial chemicals and plant protection products recognize or reference these ISO standards for required environmental fate testing.
Overall, strategic integration of ISO’s environmental fate test methods streamlines OECD GLP studies by providing readily available technical protocols backed by international scientific consensus. This bolsters the quality, reliability and compliance of the environmental safety data submitted to regulators.
5. General Laboratory Practices (e.g. ISO 17025, ISO 19036)
ISO criteria for aspects like method validation, measurement traceability, proficiency testing – critical elements of GLP compliance.
ISO has developed several standards that provide overarching guidance on general laboratory practices and quality management systems, which are highly relevant and complementary to the OECD Principles of Good Laboratory Practice (GLP). Some key examples include:
a) ISO/IEC 17025 – General Requirements for the Competence of Testing and Calibration Laboratories
This standard specifies rigorous criteria for laboratories to demonstrate their technical competence and ensure the quality of their testing and calibration activities. Many of its requirements align closely with OECD GLP principles:
- Management system documentation and sufficient qualified personnel.
- Traceability of measurements to national/international standards
- Use of validated and properly maintained methods/procedures
- Appropriate handling and transportation of test/calibration items
- Quality assurance of test/calibration data through quality control monitoring
- Regular internal audits and management reviews
By implementing a quality system conforming to ISO/IEC 17025, testing labs can establish robust processes that support OECD GLP compliance for activities like method validation, equipment calibration/maintenance, data traceability, and more.
b) ISO 19036 – Microbiology of the Food Chain – Estimation of Measurement Uncertainty for Quantitative Determinations
While focused on microbiological testing, this standard provides a standardized approach for estimating and expressing measurement uncertainty associated with quantitative test results. Proper accounting of measurement uncertainty is a key requirement under OECD GLP.
ISO 19036 covers identifying all potential uncertainty sources, quantifying individual components through experimental studies, and combining the components to derive an overall expanded uncertainty metric for a measurement process.
c) ISO/IEC 17043 – Conformity Assessment – General Requirements for Proficiency Testing
This standard establishes requirements for developing and operating proficiency testing programs, which allow laboratories to monitor their performance by analyzing identical proficiency test items.
Regular successful participation in relevant proficiency testing schemes is an effective way for OECD GLP test facilities to provide objective evidence of their technical competence.
By integrating these ISO standards focused on general laboratory practices and quality management, OECD GLP test facilities can establish harmonized processes that fulfill GLP expectations around:
- Validated test methods and data traceability
- Proper environmental / operating conditions
- Calibrated and maintained equipment/instruments
- Comprehensive quality assurance and control monitoring
- Demonstration of technical competence
This systematic implementation of ISO best practices within the OECD GLP framework enables laboratories to generate high-quality, reliable, and compliant study data while optimizing their operations and quality systems over time.
Benefits of ISO Integration
Some key benefits of integrating relevant ISO standards into OECD GLP test facilities and processes:
a) Access to Globally Recognized Best Practices: ISO standards are developed through a rigorous consensus-based process involving international experts across industry, academia, and regulatory bodies. Adopting ISO methods allows test facilities to leverage internationally vetted and accepted best practices.
b) Facilitation of Mutual Acceptance of Data: Data generated following harmonized ISO test methods is more likely to be accepted across different regulatory jurisdictions. This mutual acceptance reduces redundant testing requirements and supports more efficient product registrations globally.
c) Streamlining of Method Development and Validation: Rather than independently developing proprietary test methods, facilities can directly adopt ISO’s validated, standardized protocols. This streamlines operations and optimizes resource utilization.
d) Alignment with OECD GLP Principles: Many ISO standards incorporate quality control measures, acceptance criteria, documentation formats etc. that are well-aligned with OECD GLP expectations around standardized methods, data traceability, and quality assurance.
e) Support for Demonstrating Technical Competence: ISO standards often specify requirements around personnel expertise, equipment calibration/maintenance, proficiency testing, and quality management – all useful for demonstrating a facility’s technical competence per OECD GLP.
f) Continuous Improvement Driver: As ISO periodically updates standards based on evolving science and stakeholder inputs, adoption promotes an environment of continuous refinement and quality improvement within test facilities.
g) Operational Efficiency and Cost Optimization: By leveraging validated common protocols, test facilities can reduce duplicative method development costs, streamline training, and optimize resource utilization across their operations.
h) Enhanced Data Integrity and Compliance: With their basis in international consensus, adoption of ISO test methods alongside OECD GLP systems strengthens the reliability, traceability and overall integrity of the study data generated to meet regulatory requirements.
A strategic integration of applicable ISO standards enables OECD GLP test facilities to establish robust, efficient and harmonized processes that generate high-quality data accepted worldwide – optimizing their operations while facilitating regulatory compliance and building stakeholder confidence.
Practical Implementation by GLP Test Facilities
For OECD GLP test facilities to effectively leverage ISO standards and realize their associated benefits, a systematic approach to practical implementation is crucial. Here are some key steps and considerations:
a) Comprehensive Gap Analysis
Facilities should conduct a thorough analysis to identify the specific ISO standards relevant to their scope of OECD GLP testing activities across different scientific domains like analytical chemistry, environmental fate studies, physicochemical property testing, etc.
b) Maintaining Updated Standard Versions
As ISO standards undergo periodic revisions, facilities must have processes to ensure their internal documentation references the latest versions of adopted ISO methods. Subscriptions to update services can streamline this process.
c) Developing Customized SOPs
While ISO provides technical guidelines, test facilities need to develop comprehensive, customized standard operating procedures (SOPs) detailing how each ISO method will be executed within their specific systems, workflows and quality frameworks.
d) Personnel Training and Competency
Robust training programs must be implemented to ensure analytical staff, study directors and quality assurance personnel have a comprehensive understanding of adopted ISO methods and requirements for proper execution.
e) Verification of Competency
Mechanisms like personnel certification, performance evaluation samples, and proficiency testing schemes can objectively verify staff competency in conducting ISO test methods per OECD GLP expectations.
f) Quality Assurance Oversight
Quality assurance units must thoroughly understand the quality control measures and acceptance criteria specified in each adopted ISO standard to enable effective study audits and data reviews.
g) Equipment Qualification
Analytical instruments, environmental chambers, and other equipment need to be qualified against iso requirements for calibration, performance verification, maintenance, etc. before deployment.
h) Reporting System Integration
LIMS, ELNs and other data management systems should be configured to capture metadata and present final results in formats compliant with adopted ISO reporting templates.
i) Change Management
Facilities must institute formal change control procedures to properly evaluate, approve and document any deviations or modifications from adopted ISO methods.
j) External Assessments
Periodic audits and inspections by accreditation bodies and regulators can provide an objective external review of the facility’s implementation of ISO standards within their OECD GLP compliance program.
By systematically integrating ISO standards through these implementation activities, OECD GLP test facilities can optimize their operations, generate reliable data accepted globally, and continually elevate their quality systems over time.
To properly leverage ISO standards, GLP test facilities should:
- Maintain updated versions of relevant ISO standards
- Incorporate ISO methods directly in study protocols and standard operating procedures
- Conduct personnel training on properly executing ISO test methods
- Implement quality measures and system suitability checks per ISO criteria
- Generate study records and reports following ISO reporting templates
With this strategic integration of ISO standards, GLP test facilities can streamline their non-clinical safety testing activities while generating data with high standards of reliability, traceability and international acceptability.
Conclusion:
The combined approach of adhering to both ISO guidelines and OECD GLP principles fosters trust in several key areas:
- Regulatory Bodies: By complying with OECD GLP, laboratories demonstrate their commitment to meeting the rigorous standards required for regulatory submissions. This builds trust with regulatory agencies that rely on these studies for product safety assessments.
- Clients and Stakeholders: When laboratories implement both sets of guidelines, they showcase their dedication to quality and data integrity. This fosters trust with clients who rely on the accuracy and reliability of the testing results.
- Scientific Community: Following both ISO and GLP principles ensures the scientific rigor and reproducibility of testing data. This enhances the scientific credibility of the research and promotes trust from other scientists and researchers.
- General Public: Ultimately, the combined approach contributes to a safer environment for consumers. By ensuring the quality and integrity of non-clinical safety studies, laboratories help ensure the safety and efficacy of products before they reach the public market.
By strategically integrating applicable ISO analytical standards, testing laboratories can leverage these core objectives to optimize their operations, generate reliable data with high integrity, facilitate regulatory compliance, and build a strong reputation for technical competence – all of which are fundamental expectations under OECD GLP principles as well.
OECD GLP provides the comprehensive quality framework for study management processes, while ISO standards complement this framework with validated, harmonized technical procedures for executing critical test methods across various scientific domains. This synergistic approach enhances quality, efficiency and regulatory compliance for safety testing studies worldwide.
In conclusion, ISO guidelines and OECD GLP principles work in concert to achieve a common goal: ensuring the quality, reliability, and ethical generation of scientific data used for regulatory decision-making on the safety of products. By implementing these complementary frameworks, laboratories can foster trust in their research and contribute to advancements in various fields, ultimately promoting public health and well-being.
Linkedin Link
Medical Device Testing
Laboratory Testing
