Introduction
The new guideline ICH Q3E Extractables & Leachables (E&L) for Medical Devices represents a major step toward global alignment in chemical safety for healthcare products. It provides a clear scientific pathway to identify, measure, and control chemical substances that may migrate from device materials or drug-device components. By creating a unified standard, ICH Q3E reduces regional differences and gives manufacturers a predictable route during development. It also raises the level of patient protection by ensuring that all chemical risks are evaluated with strong scientific methods and consistent criteria.
At ResolveMass Laboratories Inc., we support full compliance with ICH Q3E, ISO 10993-18, and USP expectations through our advanced E&L testing services. Our experienced team helps manufacturers prepare complete data packages, streamline regulatory submissions, and move confidently through global approval pathways.
🔍 Summary of Key Insights
- ICH Q3E Extractables & Leachables (E&L) for Medical Devices brings global consistency to E&L studies performed for medical devices and drug-device combination systems.
- ResolveMass Laboratories provides E&L programs designed to fully meet ICH Q3E, ISO 10993-18, and related regulatory expectations.
- The guideline encourages a structured, risk-based approach for identifying and controlling chemical hazards across the product lifecycle.
- Strong analytical science, toxicology, and material expertise are essential for generating regulatory-ready E&L datasets.
- Trends include AI-supported chromatographic interpretation, automated workflows, and rapid screening tools that shorten timelines.
- Manufacturers experience better efficiency and reduced rework through integrated CRO support that prepares them for global regulatory submissions.
What Is ICH Q3E and Why It Matters for Medical Devices
The guideline ICH Q3E Extractables & Leachables (E&L) for Medical Devices sets a unified global approach for evaluating chemical safety in both standalone medical devices and drug-device combination products. It allows companies to work under one harmonized standard rather than adapting different studies for each region. This reduces confusion, enhances consistency, and ensures that chemical risks are assessed using strong scientific principles. By guiding manufacturers through structured decision-making, the guideline supports safe, high-quality products across the full device lifecycle.
Key objectives of ICH Q3E include:
- Reducing regulatory variability across ICH regions (US, EU, Japan).
- Promoting a science-based, risk-focused approach to chemical safety.
- Supporting lifecycle management with standardized analytical processes.
For more details, visit ICH Q3E E&L Testing Services.
Evolution of Extractables and Leachables (E&L) Standards in Medical Devices
From ISO 10993-18 to ICH Q3E Extractables & Leachables (E&L) for Medical Devices
ISO 10993-18 has long served as the baseline for evaluating chemical constituents in medical device materials. However, it did not fully address the unique challenges of combination products, where drug formulations interact directly with device components. Although effective, its regional nature created differences in expectations across global markets. The introduction of ICH Q3E closes these gaps by creating a harmonized framework that aligns with ICH Q3D and USP <1663>/<1664>. This gives manufacturers a unified structure for presenting chemical safety data worldwide and reduces unnecessary repeat testing. It also encourages better collaboration between analytical teams and toxicologists to support more consistent regulatory outcomes.
Explore our ISO 10993-18 E&L Testing and USP Extractables and Leachables Services for complete program support.
Scope and Application of ICH Q3E Extractables & Leachables (E&L) for Medical Devices in Combination Products
The ICH Q3E guideline applies to any system where a drug formulation interacts directly with a device component, such as autoinjectors, prefilled syringes, drug-coated stents, and inhalation devices. This framework ensures that any substance migrating from device materials does not affect drug stability, product quality, or patient safety. It also highlights the importance of evaluating each interface where materials and drug substances meet, as these areas often present the highest risk for leachable compounds.
By using ICH Q3E Extractables & Leachables (E&L) for Medical Devices, manufacturers can better predict how materials behave over time under real clinical conditions. This unified approach simplifies global submissions and helps demonstrate that device components support safe and reliable drug delivery throughout their lifecycle.
Device Type | Example | ICH Q3E E&L Consideration
| Device Type | Example | ICH Q3E E&L Consideration |
|---|---|---|
| Combination Devices | Prefilled syringes, autoinjectors | Leachables that may contact the drug product |
| Medical Devices | Catheters, tubing | Extractables from polymer-based materials |
| Drug-Device Interfaces | Reservoirs, seals | Migration studies and interaction assessment |
Learn more about E&L Testing for Medical Devices.
Key Testing Steps Under ICH Q3E Extractables & Leachables (E&L) for Medical Devices
At ResolveMass Laboratories, our E&L study workflow follows a structured and validated process designed to fully align with ICH Q3E Extractables & Leachables (E&L) for Medical Devices. Each stage is planned to capture both worst-case and real-use conditions so that manufacturers receive complete, defensible data for global submissions. Our approach blends strong scientific expertise, advanced analytical tools, and deep regulatory understanding to support reliable and repeatable evaluations.
We use high-performance analytical platforms, detailed extraction strategies, and comprehensive toxicological modeling to identify potential chemical risks. Every step is documented according to regulatory guidelines, ensuring that the final report supports compliance in the US, EU, Japan, and other global regions. This helps manufacturers move forward with confidence and avoid delays during regulatory reviews.
Material Characterization
Performed using GC-MS, LC-MS, ICP-MS, and other advanced instruments to identify possible chemical species present in device materials.
Explore: Analytical Techniques for E&L Testing
Controlled Extraction Studies
Carried out under exaggerated conditions to reveal the complete profile of extractables that may migrate under stress.
Read: Controlled Extractables Study
Leachables Testing
Evaluates chemicals that appear under real-use or simulated-use scenarios using validated and sensitivity-driven methods.
Toxicological Risk Assessment
Includes QSAR tools, threshold-based evaluations, and exposure modeling to determine whether detected compounds create safety concerns.
See: E&L Risk Assessment Services
Analytical and Toxicological Evaluation Under ICH Q3E Extractables & Leachables (E&L) for Medical Devices
The analytical phase under ICH Q3E Extractables & Leachables (E&L) for Medical Devices focuses on accurately detecting, identifying, and quantifying chemical compounds that may migrate from device materials. This stage relies on advanced chromatographic and spectroscopic tools to generate precise data. By using robust analytical setups, manufacturers gain clarity on the nature and concentration of extractables and leachables found in their products. Reliable data at this stage forms the backbone of a strong chemical safety assessment.
After analytical work is complete, toxicological evaluation determines whether the identified substances pose any safety concerns. ICH Q3E encourages the use of Analytical Evaluation Thresholds (AETs), which help define reporting limits based on toxicology principles, patient exposure, and device-specific use conditions. AETs simplify decision-making by offering a clear cutoff for which compounds require further identification or risk assessment. This approach ensures that safety evaluations remain meaningful, efficient, and aligned with modern regulatory expectations.
Learn more about Analytical Evaluation Thresholds.
How ResolveMass Laboratories Supports ICH Q3E Extractables & Leachables (E&L) for Medical Devices Compliance
ResolveMass Laboratories Inc. provides complete E&L testing programs designed to fully meet the expectations of ICH Q3E Extractables & Leachables (E&L) for Medical Devices, ISO 10993-18, USP guidelines, and FDA requirements. Our team uses advanced analytical technologies and validated methods to deliver high-quality, reproducible data from study design to final reporting. This structured approach helps manufacturers stay aligned with evolving global regulations and avoid common delays during submissions.
We work closely with clients to create tailored testing plans that match the specific materials, drug formulations, and device configurations involved. Our experts also provide early-stage recommendations to reduce chemical risks before products advance to later development phases. By combining strong analytical science with regulatory expertise, ResolveMass supports manufacturers in generating complete and defensible E&L packages that meet global expectations.
Our ICH Q3E E&L Testing Services Include:
- Study design following ICH Q3E, ISO 10993-18, USP, and FDA guidance.
- Full extractables and leachables profiling for all material-contact components.
- Accelerated, simulated-use, and long-term leachables studies.
- Toxicological assessments with expert-written risk reports.
- Custom Study Design Services for unique or complex devices.
Visit E&L Testing for Regulatory Submission to meet evolving global standards.
The Future of ICH Q3E Extractables & Leachables (E&L) for Medical Devices and AI Integration in E&L Testing
The future of ICH Q3E Extractables & Leachables (E&L) for Medical Devices is strongly shaped by advances in automation and artificial intelligence. Modern AI tools are transforming the way laboratories analyze complex chromatographic and spectral data, allowing faster and more accurate interpretation of chemical profiles. These systems can recognize patterns, predict migration pathways, and highlight potential risks long before traditional methods would detect them. As a result, manufacturers benefit from shorter study timelines and more reliable datasets.
AI-driven toxicology models also improve the accuracy of safety evaluations by using machine learning to predict chemical behavior and patient exposure risks. These technologies help reduce uncertainty and support stronger regulatory submissions. At ResolveMass Laboratories, we integrate AI-assisted chromatographic analysis into our workflows to deliver quicker turnaround times, high confidence in compound identification, and better overall decision-making for E&L studies. This modern approach ensures that clients stay ahead of evolving regulatory expectations.
Conclusion
The ICH Q3E Extractables & Leachables (E&L) for Medical Devices guideline establishes a consistent global standard for chemical safety evaluation. By promoting risk-based assessments, clear analytical strategies, and unified reporting expectations, ICH Q3E simplifies regulatory pathways that were once fragmented across regions. This harmonization helps manufacturers reduce study redundancies, gain stronger clarity during development, and ensure that patient safety remains the top priority throughout the product lifecycle.
ResolveMass Laboratories Inc. continues to support this mission with advanced analytical tools, multi-matrix testing workflows, and regulatory-ready E&L solutions. Our experts guide manufacturers from early development through final market approval, ensuring each device or combination product meets modern global requirements. With our comprehensive testing capabilities, clients can confidently address chemical risks and submit high-quality data packages that align with international standards.
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Most Asked FAQs on ICH Q3E Extractables & Leachables (E&L) for Medical Devices
ICH Q3E is a global guideline that standardizes how extractables and leachables are evaluated in medical devices and drug-device combination products. It creates one unified method for identifying chemical risks and ensures consistent safety reviews across major regulatory regions. This helps manufacturers prepare complete and science-based submissions.
E&L testing is essential because it identifies chemicals that may migrate from device materials during storage or use. These substances can impact drug quality or patient safety if not properly assessed. The testing ensures devices remain safe, stable, and compliant with global regulations.
Techniques include GC-MS, LC-MS, ICP-MS, and FTIR, each suited for detecting specific types of chemical compounds. These instruments provide detailed profiles that support accurate identification and quantification. They form the foundation of a reliable E&L evaluation.
AET is the reporting threshold used to determine which leachables must be identified and assessed for safety. It is based on toxicology principles, patient exposure, and device-specific use conditions. The AET ensures evaluations remain meaningful and focused on true safety concerns.
ISO 10993-18 focuses on the chemical characterization of device materials, while ICH Q3E offers a harmonized approach for chemical risk assessment across global regions. Together, they create a complementary framework supporting both biological and chemical safety. Manufacturers often rely on both for complete compliance.
New trends include automation, AI-assisted data interpretation, and predictive toxicology tools. These technologies help speed up analysis while improving accuracy and reducing human error. They also support faster regulatory submissions with stronger datasets.
References
- Balfour, H. (2022, April 29). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
- Rozio, M. G. (2025). Correcting detection and quantitation bias in extractables and leachables testing. Journal of Pharmaceutical Analysis, 15(2), 123–134. https://doi.org/10.1016/j.jpha.2025.04.004
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