Updated: 27th June 2026
Reviewed by: David Small BSc (Hons), MSc, MTOPRA (Founder and CEO)
What Are Extractables and Leachables Studies?
Extractables and leachables (E&L) studies play a critical role in the Biological Evaluation of medical devices by identifying chemical substances that may migrate from a device during its intended clinical use. Rather than assessing a biological response directly, these studies generate chemical characterisation data that helps manufacturers understand what patients may be exposed to and whether those substances present an unacceptable toxicological risk. As a result, extractables and leachables testing forms an important part of the evidence used to demonstrate the biological safety of medical devices.
The internationally recognised framework for chemical characterisation is provided by ISO 10993-18, while ISO 10993-17 describes how identified chemical constituents should be evaluated through toxicological risk assessment to determine whether patient exposure remains within acceptable limits. Together, these standards support the wider risk-based Biological Evaluation required by ISO 10993-1:2025, helping manufacturers determine whether existing chemical evidence is sufficient or whether additional biological testing may be scientifically justified.
However, ISO 10993-1:2025 reinforces that extractables and leachables studies should not be performed routinely for every medical device. Instead, manufacturers are expected to consider factors such as the device’s intended purpose, nature and duration of body contact, material composition, manufacturing processes, sterilisation methods, chemical characterisation data, existing toxicological evidence and foreseeable patient exposure before deciding whether additional chemical investigations are required.
This guide explains the difference between extractables and leachables, how E&L studies are designed and performed, the analytical techniques commonly used to identify chemical constituents, how toxicological risk assessments are undertaken and how extractables and leachables data supports the wider Biological Evaluation and regulatory compliance of medical devices.
Key ISO Standards for Extractables and Leachables Studies
Extractables and leachables studies form part of a wider risk-based Biological Evaluation. The following international standards work together to support the assessment of chemical and biological safety:
- ISO 10993-1 – Establishes the overall framework for Biological Evaluation and determines whether chemical characterisation and biological testing are scientifically justified.
- ISO 10993-12 – Provides guidance on sample preparation, extraction media, extraction conditions and reference materials used during chemical and biological investigations.
- ISO 10993-17 – Describes how identified chemical constituents should be evaluated through toxicological risk assessment to determine whether patient exposure remains acceptable.
- ISO 10993-18 – Defines the internationally recognised approach to chemical characterisation, including extractables, leachables and the identification of chemical constituents released from medical device materials.
- ISO 14971 – Provides the medical device risk management framework used to identify, evaluate, control and monitor chemical and biological risks throughout the product lifecycle.
New to Biological Evaluation?
Extractables and leachables studies are only one part of a risk-based Biological Evaluation. If you're looking for a complete introduction to ISO 10993, Biological Evaluation Plans (BEPs), Biological Evaluation Reports (BERs), biocompatibility testing, chemical characterisation, toxicological risk assessment and biological endpoints, explore our Complete Guide to Biological Evaluation of Medical Devices.
Extractables vs Leachables: What's the Difference?
Although the terms extractables and leachables are often used together, they describe two distinct categories of chemical substances identified during the chemical characterisation of medical devices. Understanding the difference is essential because each provides different information about the potential chemical exposure experienced by patients and supports different stages of the Biological Evaluation.
Extractables
Extractables are chemical substances that can be released from a medical device when exposed to exaggerated or exhaustive laboratory extraction conditions. These conditions are intentionally more aggressive than normal clinical use and may involve elevated temperatures, extended extraction times or the use of polar and non-polar solvents to recover as many potentially releasable compounds as reasonably possible.
The purpose of an extractables study is to establish the potential chemical universe associated with a device. Rather than representing actual patient exposure, extractables identify the chemicals that could migrate from the device under worst-case conditions and therefore require further consideration during toxicological risk assessment.
Extractables may originate from:
- Base polymers and elastomers.
- Plasticisers and stabilisers.
- Colourants and pigments.
- Adhesives and coatings.
- Processing aids and mould release agents.
- Sterilisation residues.
- Manufacturing contaminants.
- Degradation products.
Leachables
Leachables are substances that actually migrate from the medical device under its intended or reasonably foreseeable conditions of clinical use. Unlike extractables studies, which deliberately maximise chemical recovery, leachables studies evaluate patient exposure under conditions that closely simulate normal use.
For example, a syringe may be assessed using the medicinal product it will contain, while an intravenous administration set may be evaluated using representative infusion solutions flowing through the device over the expected duration of treatment.
Leachables therefore provide the most clinically relevant estimate of patient exposure and form an important input into the toxicological risk assessment described by ISO 10993-17.
It is important to recognise that not every medical device requires a dedicated leachables study. Whether such testing is necessary depends on the device’s intended use, contact duration, material composition, route of exposure, existing chemical data and the conclusions reached during the risk-based Biological Evaluation required by ISO 10993-1:2025.
Although extractables and leachables are closely related, they answer different scientific questions. Extractables identify what could potentially be released from a medical device under exaggerated laboratory conditions, whereas leachables estimate what patients may actually be exposed to during normal clinical use. Together, these studies provide complementary evidence supporting chemical characterisation and toxicological risk assessment within the wider Biological Evaluation.
Designing an Extractables and Leachables Study
The quality of an extractables and leachables study depends heavily on its design. Before any laboratory analysis begins, manufacturers should define a scientifically justified testing strategy that reflects the intended clinical use of the medical device and the potential routes of patient exposure.
Selecting the Test Article
The first step is deciding which samples should be tested. Wherever possible, studies should use the finished, sterilised medical device because this most accurately represents the product that will reach patients.
Manufacturers should consider:
- Patient-contacting materials.
- Fluid-path components.
- Adhesives and coatings.
- Printing inks and markings.
- Lubricants and processing aids.
- Packaging materials where interaction is possible.
- Manufacturing and sterilisation residues.
Testing representative components rather than the finished device should always be scientifically justified.
Selecting Extraction Media
Extraction media should be selected to recover the widest practical range of chemical constituents while remaining scientifically appropriate for the intended device.
Common extraction media include:
- Polar aqueous solutions.
- Semi-polar solvents.
- Non-polar organic solvents.
Using multiple solvents helps identify both hydrophilic and hydrophobic compounds that may migrate from the device.
Extraction Conditions
Extraction conditions significantly influence the substances recovered during testing. Manufacturers should justify:
- Extraction temperature.
- Extraction duration.
- Surface area or mass-to-volume ratio.
- Agitation method.
- Exhaustive or exaggerated extraction strategy.
Conditions should maximise chemical recovery without creating degradation products that would not occur during normal clinical use.
Controls and Quality Assurance
Appropriate controls are essential to demonstrate that detected substances originate from the medical device rather than the laboratory environment.
Studies commonly include:
- Solvent blanks.
- Container blanks.
- Laboratory background controls.
- System suitability checks.
- Instrument calibration standards.
Analytical Techniques Used for Extractables and Leachables Studies
Following extraction, sophisticated analytical techniques are used to identify and quantify chemical constituents released from the medical device.
| Analytical Technique | Typical Target Compounds | Main Advantages | Limitations |
|---|---|---|---|
| Headspace GC-MS | Highly volatile organic compounds | Excellent sensitivity for volatile substances | Limited to volatile chemicals |
| GC-MS | Volatile and semi-volatile organic compounds | Broad compound identification and structural information | Less suitable for highly polar or thermally unstable compounds |
| LC-MS | Non-volatile and polar organic compounds | Excellent for complex organic mixtures and higher molecular weight compounds | Unknown compound identification can be challenging |
| ICP-MS | Metallic elements and elemental impurities | Extremely sensitive for trace metals | Provides elemental rather than molecular information |
| Gravimetric / Non-Volatile Residue Analysis | Total non-volatile extractables | Useful screening tool for total extractable content | Does not identify individual substances |
In practice, extractables and leachables studies rarely rely on a single analytical technique. Instead, complementary methods are combined to maximise chemical coverage across volatile, semi-volatile, non-volatile, polar, non-polar and inorganic substances. This orthogonal analytical approach increases confidence that clinically relevant chemical constituents have been identified and appropriately assessed during the Biological Evaluation.
Understanding the Analytical Evaluation Threshold (AET)
One of the most important concepts in extractables and leachables studies is the Analytical Evaluation Threshold (AET). The AET is a scientifically derived reporting threshold that helps determine which detected chemical constituents require identification and toxicological assessment.
Compounds detected above the AET are generally expected to be identified and evaluated because they may contribute meaningfully to patient exposure. Compounds detected below the threshold are less likely to represent a toxicological concern, although they may still require consideration depending on their chemical identity, route of exposure and clinical context.
Importantly, the AET is not a safety limit. Instead, it is an analytical decision threshold used to focus resources on substances that are most likely to influence patient safety. The final determination of biological safety is made through the toxicological risk assessment, taking into account the estimated patient exposure, available toxicological data and intended clinical use of the medical device.
The AET is typically derived using factors such as the Threshold of Toxicological Concern (TTC), the maximum clinical exposure to the device and analytical uncertainty. Consequently, the AET is device-specific and should always be scientifically justified rather than adopted as a universal reporting threshold.
Toxicological Risk Assessment
Once chemical constituents have been identified, manufacturers must determine whether the estimated patient exposure presents an acceptable biological risk. This evaluation is performed in accordance with ISO 10993-17 and forms a key part of the wider Biological Evaluation.
The toxicological risk assessment considers:
- Chemical identity.
- Estimated patient exposure.
- Route of exposure.
- Frequency and duration of exposure.
- Available toxicological data.
- Tolerable intake values where available.
- Margin of safety.
- Patient population.
- Scientific uncertainties.
Rather than simply asking whether a chemical is present, the assessment determines whether the expected exposure is likely to result in an unacceptable toxicological risk during the intended clinical use of the device.
Could Extracted Chemicals Cause Skin Irritation?
Chemical characterisation helps identify substances that may migrate from a medical device, but manufacturers must also determine whether those substances could cause skin irritation during clinical use. Learn how ISO 10993-23 uses reconstructed human epidermis (RHE) models to evaluate irritation potential as part of a risk-based Biological Evaluation in our Complete Guide to In Vitro Skin Irritation Testing.
Interpreting Toxicological Risk
In practice, toxicological risk assessment often involves a degree of scientific judgement because complete toxicological data may not be available for every identified constituent. Where appropriate, toxicologists may apply scientifically justified approaches such as read-across, using toxicity data from structurally similar compounds to estimate the potential hazards of substances for which limited information exists. This approach can provide a robust assessment while avoiding unnecessary additional testing, provided that the scientific rationale is clearly documented.
The assessment may also consider the Threshold of Toxicological Concern (TTC), an internationally recognised risk assessment concept that establishes conservative exposure thresholds below which there is a very low probability of appreciable risk to human health. The TTC can help prioritise identified compounds for further evaluation, particularly where substance-specific toxicological data are limited. However, the TTC should always be applied within an appropriate scientific and regulatory context and should not replace a comprehensive toxicological assessment where adequate compound-specific data are available.
Where uncertainty exists, toxicologists generally adopt conservative assumptions to ensure patient safety. These assumptions may include estimating worst-case patient exposure, assuming maximum chemical release, considering prolonged or repeated clinical use and evaluating sensitive patient populations where appropriate. Applying conservative assumptions helps minimise the likelihood that biological risks are underestimated during the Biological Evaluation.
Ultimately, toxicological risk assessment is not a purely mathematical exercise but a structured scientific evaluation requiring expert judgement. Experienced toxicologists integrate analytical chemistry data, estimated patient exposure, published toxicological literature, clinical context, device-specific information and recognised risk assessment principles to determine whether the identified chemical constituents present an acceptable biological risk. The scientific rationale supporting these conclusions should be fully documented within the Biological Evaluation Report (BER) and linked to the wider ISO 14971 risk management process.
When Are Extractables and Leachables Studies Required?
Extractables and leachables studies should not be viewed as routine testing for every medical device. Instead, manufacturers should determine whether additional chemical characterisation is scientifically justified as part of the risk-based Biological Evaluation described in ISO 10993-1:2025.
Additional studies may be appropriate where:
- Novel materials or formulations are introduced.
- Material composition is incompletely characterised.
- Manufacturing processes change.
- New suppliers are introduced.
- Sterilisation methods change.
- Adhesives, coatings or additives may migrate.
- Long-term or permanent patient contact is expected.
- Drug-contacting or fluid-path devices are developed.
- Existing chemical evidence is insufficient.
- Previous biological data no longer reflects the finished device.
Conversely, where robust chemical characterisation and existing evidence adequately demonstrate biological safety, further E&L testing may not be necessary.
What Happens When a Chemical Is Detected?
The detection of a chemical constituent during an extractables or leachables study does not automatically indicate that the medical device presents an unacceptable biological risk.
Instead, manufacturers should investigate:
- What substance has been detected?
- At what concentration?
- What is the estimated patient exposure?
- Is the exposure route clinically relevant?
- What toxicological information is available?
- Does the exposure remain within acceptable limits?
- Is additional testing or risk control required?
The outcome of this assessment should be documented within the Biological Evaluation Report (BER) alongside the supporting toxicological evidence, chemical characterisation data and overall biological risk assessment.
Could a Detected Chemical Cause Cell Damage?
Identifying a chemical constituent is only the first step. Where chemical characterisation and toxicological assessment indicate that additional biological evidence may be required, manufacturers may need to evaluate cytotoxicity in accordance with ISO 10993-5. Learn how cytotoxicity testing assesses the potential for medical device materials and extracts to damage living cells in our Complete Guide to Cytotoxicity Testing.
Worked Example: Extractables and Leachables Assessment for an IV Administration Set
A manufacturer introduces a new polymer supplier for a single-use intravenous administration set. Although the material specification appears equivalent, the supplier change introduces uncertainty regarding the device’s chemical profile. During the Biological Evaluation, the manufacturer determines that updated chemical characterisation is required and documents this decision within the Biological Evaluation Plan (BEP).
Representative finished, sterilised devices are selected for testing and extracted using both polar and non-polar solvents under scientifically justified extraction conditions. The resulting extracts are analysed using GC-MS, LC-MS and ICP-MS to identify and quantify organic compounds, volatile substances and elemental impurities.
Several chemical constituents are detected above the Analytical Evaluation Threshold (AET) and are subsequently identified. A toxicological risk assessment is then performed in accordance with ISO 10993-17, considering the estimated patient exposure, route of administration, duration of use and available toxicological data for each identified substance.
The assessment concludes that all identified compounds remain within acceptable exposure limits and do not present an unacceptable biological risk for the intended clinical use of the device. The findings are incorporated into the Biological Evaluation Report (BER) together with the chemical characterisation data and updated ISO 14971 Risk Management File. Based on the complete body of evidence, the manufacturer concludes that no additional biological testing is required.
This example demonstrates how extractables and leachables studies support a risk-based Biological Evaluation, providing chemical evidence that enables manufacturers to evaluate patient exposure and demonstrate the biological safety of their medical devices.
Developing Drug-Contacting Medical Devices?
Extractables and leachables studies are particularly important for syringes, infusion sets, administration bags and other drug-contacting medical devices, where material interactions may affect both patient safety and medicinal product quality. Learn how manufacturers assess drug compatibility, material interactions, extractables, leachables and stability throughout the product lifecycle in our Complete Guide to Drug Stability in Medical Devices.
Key Takeaways
- Extractables identify chemicals that could migrate from a medical device under exaggerated laboratory extraction conditions.
- Leachables represent substances that patients may actually be exposed to during the intended clinical use of the device.
- ISO 10993-18 provides the internationally recognised framework for chemical characterisation and supports extractables and leachables studies.
- ISO 10993-17 guides the toxicological risk assessment of identified chemical constituents to determine whether patient exposure remains acceptable.
- ISO 10993-1:2025 requires manufacturers to determine whether extractables and leachables studies are scientifically justified as part of a documented, risk-based Biological Evaluation.
Conclusion
Extractables and leachables studies are a fundamental component of the Biological Evaluation of many medical devices, providing detailed chemical characterisation data that helps manufacturers understand what substances may migrate from a device and whether those substances present an unacceptable toxicological risk to patients. By identifying and evaluating potential chemical exposure, these studies support informed decision-making throughout the product development lifecycle and contribute to the demonstration of biological safety.
However, as reinforced by ISO 10993-1:2025, extractables and leachables studies should not be regarded as routine testing for every medical device. Instead, they should be performed as part of a comprehensive, risk-based Biological Evaluation, taking into account the device’s intended purpose, nature and duration of body contact, material composition, manufacturing processes, sterilisation methods, existing chemical data and all other available biological evidence before determining whether additional chemical investigations are scientifically justified.
When extractables and leachables studies are required, ISO 10993-18 provides the internationally recognised framework for chemical characterisation, while ISO 10993-17 supports the toxicological assessment of identified chemical constituents and estimated patient exposure. Together with ISO 14971 risk management, these standards enable manufacturers to systematically identify, evaluate and control chemical risks throughout the medical device lifecycle.
By integrating extractables and leachables data into a well-documented Biological Evaluation Plan (BEP), Biological Evaluation Report (BER) and wider Technical Documentation, manufacturers can generate robust scientific evidence demonstrating that chemical risks have been appropriately assessed and remain acceptable for the device’s intended clinical use. This evidence not only supports compliance with the EU Medical Device Regulation (EU MDR 2017/745) and other international regulatory frameworks but also helps ensure that medical devices continue to meet the highest standards of biological safety and patient protection.
I think this is the strongest conclusion of the four articles because it clearly differentiates the roles of the key standards:
- ISO 10993-1 – determines whether E&L studies are required.
- ISO 10993-18 – generates the chemical characterisation data.
- ISO 10993-17 – evaluates whether the detected substances present an acceptable toxicological risk.
- ISO 14971 – integrates those findings into the overall risk management process.
That neatly ties together everything the reader has learned and reinforces the central message of your entire Biological Evaluation content cluster.
Want to Learn What's New in ISO 10993-1:2025?
Extractables and leachables studies are now more closely integrated into the risk-based Biological Evaluation process under ISO 10993-1:2025. Discover the key changes to chemical characterisation, toxicological risk assessment, Biological Evaluation Plans (BEPs), Biological Evaluation Reports (BERs) and testing justification in our Guide to ISO 10993-1:2025.
When Is Biocompatibility Testing Actually Required?
Extractables and leachables studies are not automatically required for every medical device. Learn how manufacturers use Biological Evaluation Plans (BEPs), chemical characterisation, toxicological risk assessment and existing biological evidence to determine whether new testing is scientifically justified in our Guide to When Biocompatibility Testing Is Required.
Frequently Asked Questions relating to E&L Testing
Extractables and leachables (E&L) testing evaluates the presence of chemical substances that may migrate from a medical device’s materials into the patient’s body under normal use or accelerated conditions.
- Extractables: Compounds that can be extracted under exaggerated conditions (e.g., high heat or aggressive solvents).
- Leachables: Compounds that migrate from the device during actual use.
Extractables are chemical substances that can be released from a medical device under exaggerated laboratory extraction conditions using selected solvents, temperatures and extraction times. Leachables are substances that actually migrate from the device under its intended or reasonably foreseeable conditions of clinical use. Extractables studies identify the potential chemical profile of a device, while leachables studies estimate the substances that patients may realistically be exposed to during use.
No. ISO 10993-1:2025 promotes a risk-based approach to Biological Evaluation, meaning extractables and leachables studies should only be performed when they are scientifically justified. Manufacturers should consider factors such as the device’s intended purpose, material composition, duration of body contact, manufacturing processes, sterilisation methods and existing chemical evidence before determining whether additional testing is necessary.
Several international standards support extractables and leachables assessments. ISO 10993-18 provides the framework for chemical characterisation, ISO 10993-17 guides the toxicological risk assessment of identified chemical constituents, ISO 10993-12 specifies sample preparation and extraction methods, while ISO 10993-1 explains how these studies fit within the overall Biological Evaluation of a medical device.
The Analytical Evaluation Threshold (AET) is a scientifically derived reporting threshold used during extractables and leachables studies to determine which detected chemical constituents require identification and toxicological assessment. The AET is not a safety limit but an analytical decision tool that helps laboratories focus on substances that could contribute meaningfully to patient exposure and biological risk.
Laboratories typically use a combination of complementary analytical techniques to identify and quantify chemical constituents. These commonly include Gas Chromatography-Mass Spectrometry (GC-MS) for volatile and semi-volatile organic compounds, Liquid Chromatography-Mass Spectrometry (LC-MS) for non-volatile and polar substances, and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for elemental impurities and trace metals. Multiple techniques are often required to obtain a comprehensive chemical profile.
Detecting a chemical constituent does not automatically indicate that a medical device is unsafe. Each identified substance should be evaluated through a toxicological risk assessment considering factors such as its concentration, estimated patient exposure, route of exposure, duration of contact and available toxicological data. The conclusions are then documented within the Biological Evaluation Report (BER).
Toxicological risk assessment determines whether exposure to identified chemical constituents presents an acceptable biological risk for the intended clinical use of the medical device. The assessment considers estimated patient exposure, toxicological evidence, margins of safety, clinical context and scientific uncertainty to determine whether the device remains biologically safe.
Extractables and leachables studies provide scientific evidence supporting the Biological Evaluation required under Regulation (EU) 2017/745 (EU MDR) and other international regulatory frameworks. By demonstrating that chemical constituents have been identified, evaluated and shown to present an acceptable level of risk, manufacturers can strengthen their Technical Documentation and support conformity assessment activities.
In some cases, comprehensive chemical characterisation combined with a robust toxicological risk assessment may reduce the need for additional biological testing. However, this decision should always be scientifically justified as part of a documented, risk-based Biological Evaluation in accordance with ISO 10993-1:2025. The complete body of evidence should be considered before determining whether further testing is necessary.
Patient Guard supports medical device manufacturers throughout the planning, coordination and interpretation of extractables and leachables studies. Our consultants assist with study strategy, Biological Evaluation Plans (BEPs), laboratory coordination, chemical characterisation reviews, toxicological risk assessments, Biological Evaluation Reports (BERs) and Technical Documentation to help manufacturers demonstrate compliance with EU MDR, UK MDR and internationally recognised ISO 10993 standards.
References
This guide is based on the following legislation, international standards and official regulatory guidance relating to extractables and leachables studies, chemical characterisation, toxicological risk assessment and the Biological Evaluation of medical devices.
| Organisation | Reference | Why it's relevant |
|---|---|---|
| European Union | Regulation (EU) 2017/745 on Medical Devices (MDR) | Provides the legal framework for placing medical devices on the European Union market and requires manufacturers to identify, evaluate and control biological and chemical risks through compliance with the General Safety and Performance Requirements. |
| International Organization for Standardization (ISO) | ISO 10993-1:2025 – Biological Evaluation of Medical Devices – Part 1: Requirements and General Principles for the Evaluation of Biological Safety Within a Risk Management Process | Provides the overarching risk-based framework for Biological Evaluation and explains how manufacturers determine whether chemical characterisation, extractables and leachables studies, toxicological assessment or additional biological testing are required. |
| International Organization for Standardization (ISO) | ISO 10993-18:2020 – Biological Evaluation of Medical Devices – Part 18: Chemical Characterisation of Medical Device Materials Within a Risk Management Process | Defines the internationally recognised framework for chemical characterisation, including the identification and quantification of chemical constituents that may be present in or released from medical device materials. It provides the principal basis for extractables, leachables and simulated-use assessment strategies. |
| International Organization for Standardization (ISO) | ISO 10993-18:2020/Amd 1:2022 – Amendment 1: Determination of the Uncertainty Factor | Amends ISO 10993-18 by providing requirements relating to the determination of the analytical uncertainty factor used when establishing and applying reporting thresholds such as the Analytical Evaluation Threshold. |
| International Organization for Standardization (ISO) | ISO 10993-17:2023 – Biological Evaluation of Medical Devices – Part 17: Toxicological Risk Assessment of Medical Device Constituents | Specifies the process for evaluating whether exposure to identified medical device constituents is without appreciable harm, including exposure estimation, toxicological data review, tolerable exposure values, margins of safety and the assessment of scientific uncertainty. |
| International Organization for Standardization (ISO) | ISO 10993-17:2023/Amd 1:2025 – Amendment 1 | Provides the published amendment applicable to ISO 10993-17:2023 and should be considered when conducting and documenting toxicological risk assessments of medical device constituents. |
| International Organization for Standardization (ISO) | ISO 10993-12:2021 – Biological Evaluation of Medical Devices – Part 12: Sample Preparation and Reference Materials | Provides requirements and guidance for selecting test samples, preparing medical device extracts, choosing extraction media and defining extraction ratios, temperatures, durations and other conditions used during biological and chemical investigations. |
| International Organization for Standardization (ISO) | ISO 10993-12:2021/Amd 1:2025 – Amendment 1 | Provides the current published amendment to ISO 10993-12:2021 and should be considered when defining and justifying sample-preparation and extraction strategies. |
| International Organization for Standardization (ISO) | ISO 14971:2019 – Medical Devices – Application of Risk Management to Medical Devices | Provides the internationally recognised risk management framework used to identify, evaluate, control and monitor chemical and biological risks throughout the medical device lifecycle. |
| U.S. Food and Drug Administration (FDA) | Chemical Analysis for Biocompatibility Assessment of Medical Devices | Provides FDA recommendations on the design, performance and reporting of chemical analysis used to support medical device biocompatibility assessments, including extractables studies, analytical method selection, compound identification and toxicological evaluation. |
| U.S. Food and Drug Administration (FDA) | Chemicals List for Analytical Performance (CLAP) | Provides a regulatory science dataset intended to help analytical laboratories demonstrate that their methods can detect a broad range of chemicals that may be encountered during non-targeted extractables and leachables analysis. |
Extractables and leachables studies should be planned and performed as part of a documented, risk-based Biological Evaluation rather than treated as routine testing for every medical device. Manufacturers should consult the latest published legislation, recognised international standards, applicable amendments and official regulatory guidance when selecting test articles, defining extraction conditions, establishing analytical thresholds, assessing patient exposure and documenting toxicological conclusions within the Biological Evaluation Report and Risk Management File.
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