ICH Q3E Extractables and Leachables (E&L) Testing Services are essential for showing that packaging materials, device parts, and manufacturing components do not release harmful chemicals into drug products. Working with a specialized CRO gives organizations dependable data, stronger analytical execution, and documentation that meets global review standards. A focused partner adds deeper scientific understanding, proven workflows, and technical expertise that general labs cannot match. This article explains why an experienced E&L CRO is important, how ICH Q3E updates expectations, and how companies like ResolveMass Laboratories Inc. strengthen compliance and quality.
Summary of This Article (Key Takeaways)
ICH Q3E requires detailed and well-documented E&L risk assessment, which specialized CROs handle with validated methods, trained analysts, and strong regulatory alignment. These partners help avoid rework, study delays, and data gaps during global submissions. Their processes support accuracy, traceability, and clear scientific justification.
Early-phase ICH Q3E Extractables and Leachables (E&L) Testing Services reduce the chance of regulatory issues with FDA, EMA, and PMDA by detecting risks early. This allows teams to address material concerns, extraction errors, or missed analytes before they impact timelines.
Specialized CROs also offer robust method development and cross-platform expertise in GC-MS, LC-MS, ICP-MS, and advanced screening techniques. These skills help identify polymer additives, oligomers, and difficult unknowns that might cause compliance issues.
This guide explains ICH Q3E expectations, E&L study design, timelines, evaluator thresholds, and how to choose the right CRO, with links and references for stronger planning and regulatory success.
Introduction
ICH Q3E Extractables and Leachables (E&L) Testing Services help pharmaceutical and medical device manufacturers identify and control chemical species that may migrate from packaging or process-contact materials into drug products. These assessments reduce uncertainty around material compatibility and long-term stability. Partnering with a specialized CRO ensures full alignment with ICH Q3E, ISO 10993-18, and FDA expectations, protecting programs from avoidable regulatory challenges.
A qualified E&L partner supports risk management, cost control, and method consistency across all stages of testing. Experienced organizations like ResolveMass Laboratories Inc. deliver reliable science, validated methodology, and clear justification tailored to global regulatory needs.
What Is ICH Q3E and Why Does It Change the E&L Landscape?
ICH Q3E provides a unified global framework for evaluating extractables and leachables in drug products. It outlines best practices for study design, analytical techniques, risk evaluation, and acceptance criteria. This harmonized approach removes regional differences and helps teams create predictable submission pathways.
The guideline also encourages industry-wide consistency, scientific reasoning, and clear toxicological relevance, giving manufacturers a structured approach to E&L compliance.
Upfront Answer
ICH Q3E is important because it defines global expectations for Extractables and Leachables studies across FDA, EMA, and PMDA regions. It reduces uncertainty for sponsors, aligns scientific standards, and allows companies to prepare stronger, more defensible submissions. Organizations following ICH Q3E benefit from clearer study design and improved regulatory confidence.
Key Aspects of ICH Q3E
- Clear definition of extractables vs. leachables
- Emphasis on risk-based decision making
- Focus on toxicological relevance rather than raw detection
- Requires orthogonal analytical techniques
- Requires justified AET (Analytical Evaluation Threshold)
- Applies to packaging, devices, and manufacturing components
Useful references from ResolveMass:
https://resolvemass.ca/extractables-leachables-testing/
https://resolvemass.ca/extractable-and-leachable-el-services/
https://resolvemass.ca/extractables-and-leachables-fda-guidance/
Why Work With a Specialized CRO for ICH Q3E E&L Testing?
Upfront Answer
Specialized CROs deliver validated test methods, skilled E&L scientists, and documentation built specifically for ICH Q3E compliance. Unlike general labs, they offer advanced tools, deeper analytical knowledge, and the ability to detect low-level unknowns. Their focused support improves study reliability, reduces risk, and supports smooth communication with global health authorities.
Key Advantages
- Expertise in ICH Q3E, ISO 10993-18, USP <661>, <1663>, <1664>
- Ability to detect trace-level and unknown compounds
- Skilled structural elucidation chemists
- Proven success in regulatory submissions
- Multi-technique analytical capability
- Complete toxicological risk assessment
Core Benefits of Specialized ICH Q3E Extractables and Leachables (E&L) Testing Services
1. More Accurate Material Risk Assessment
ICH Q3E demands detailed knowledge of material composition, and specialized CROs deliver accurate Bill of Materials (BOM) evaluation and container closure system mapping. These steps strengthen justification for extraction conditions and support toxicological relevance. They also model worst-case scenarios to prevent regulatory gaps.
See related guidance:
How to conduct Extractables and Leachables study
Controlled Extractables Study
2. Study Designs Tailored to ICH Q3E Expectations
A specialized CRO creates customized study plans based on product type, material risk, and exposure conditions. Instead of generic templates, forced extraction studies are scientifically justified. Orthogonal solvent sets cover organic, inorganic, and semi-volatile species, improving monitoring quality and data interpretation.
Learn more:
https://resolvemass.ca/custom-el-study-design-services/
3. Advanced Analytical Techniques for Accurate Identification
High-level structural elucidation is essential in ICH Q3E compliance. Specialized CROs use advanced platforms and trained experts who understand polymer additives, impurities, and chemical behavior. Orthogonal data streams help confirm structures and reduce uncertainty.
Typical Platforms
| Technique | Purpose |
|---|---|
| GC-MS | Volatile & semi-volatile organics |
| LC-MS/MS | Non-volatiles & polymer additives |
| ICP-MS | Elemental impurities |
| FTIR / NMR | Structural confirmation |
See:
Analytical Techniques for E&L Testing Medical Devices
4. Proper AET (Analytical Evaluation Threshold) Justification
ICH Q3E requires well-supported AET calculations based on toxicology, dose, and method capability. Specialized CROs create defensible AET values aligned with FDA and ICH expectations, preventing misinterpretation of low-level signals.
Reference:
Analytical Evaluation Threshold in E&L Testing
5. Faster Timelines and Stronger Regulatory Confidence
Specialized CROs reduce delays through optimized scheduling and structured reporting. Their experience with FDA, EMA, and PMDA helps produce submission-ready documentation. This support is especially valuable for programs with tight timelines.
Why ResolveMass Laboratories Inc. Stands Out
ResolveMass follows strong EEAT principles and offers deep specialization in E&L science across biologics, injectables, inhalation products, ophthalmics, and medical devices. Their team includes dedicated groups for extractables, leachables, toxicology, and regulatory strategy, ensuring complete and coordinated oversight.
Their transparent communication, validated methods, and clear documentation support regulatory confidence. With strict internal review processes and quality assurance, ResolveMass delivers reliable, defensible data designed for global submissions.
ICH Q3E E&L Study Workflow with a CRO
Upfront Answer
The ICH Q3E workflow includes material assessment, extractables testing, method validation, leachables monitoring, data evaluation, and final toxicology review. Each step builds a complete scientific picture and helps identify issues early. Specialized CROs follow this workflow to ensure full compliance with ICH Q3E expectations.
Study Steps
- Material assessment and CCS mapping
- Controlled extractables study
- Targeted and non-targeted screening
- AET determination
- Method validation for leachables
- Real-time and accelerated leachables monitoring
- Toxicological risk assessment
- Regulatory documentation
Useful pages:
ISO 10993-18 and E&L Testing
E&L Testing Support for Regulatory Submissions
Extractables and Leachables for Medical Devices Under ICH Q3E
Medical devices interacting with drug products or patient fluids require careful E&L evaluation. ICH Q3E supports a risk-based approach considering material type, patient exposure, and migration pathways. Specialized CROs ensure device-specific behavior is properly evaluated for both pharmaceutical and device regulatory expectations.
Learn more:
Choosing the Right CRO for E&L Testing in Medical Devices
E&L Testing for Medical Devices
ICH Q3E E&L Testing for Biopharmaceuticals
Biologics are highly sensitive to leachables, which may cause protein degradation or loss of potency. Specialized CROs identify risks coming from elastomers, tubing, filters, and storage components used during production. Early detection prevents stability issues and supports long-term product performance.
More info:
Extractables and Leachables (E&L) Testing in Biopharma
Cost-Effective ICH Q3E E&L Testing
Optimized study design helps keep ICH Q3E testing cost-effective. Specialized CROs streamline solvent selection and analytical sequencing while focusing on high-risk components. This approach reduces unnecessary testing and keeps total cost under control without affecting data quality.
See:
Cost-Effective E&L Testing Solutions
Multi-Matrix Testing Services
Some programs require E&L evaluation across drug products, diluents, reagents, cleaning solutions, and device materials. Multi-matrix testing ensures migration risks are evaluated across real-use scenarios. Specialized CROs apply targeted and non-targeted methods to support complete toxicological and regulatory assessment.
Reference:
Multi-Matrix E&L Testing
ICH Q3E and Carcinogenicity Considerations
Some extractables may have genotoxic or carcinogenic potential. ICH Q3E encourages proper identification and toxicology review to address these risks. Specialized CROs provide clear interpretation of analytical data to help determine safety relevance and ensure consistent regulatory justification.
Learn more:
Extractables and Leachables (E&L) in Carcinogenicity Risk
Conclusion
ICH Q3E Extractables and Leachables (E&L) Testing Services provide essential assurance that packaging, devices, and processes remain safe throughout a product’s lifecycle. Specialized CROs deliver accurate data, advanced techniques, and regulatory-ready documentation that support global approval. ResolveMass Laboratories Inc. combines scientific rigor, strong method development, and transparent communication to help clients achieve reliable and compliant E&L results.
Contact ResolveMass Laboratories Inc.
Most Asked FAQs About ICH Q3E Extractables and Leachables Testing
ICH Q3E is a global guideline that standardizes how extractables and leachables are evaluated to ensure patient safety. It helps reduce regional differences between regulators and ensures companies follow consistent scientific principles. By using risk-based approaches, it improves the quality and defensibility of E&L data packages.
Products like injectables, biologics, inhalation therapies, ophthalmics, medical devices, and any drug stored in polymer packaging may require E&L testing. These products face higher chances of material interaction. Early testing helps identify risks and avoid stability or compatibility issues later.
AET is calculated using safety thresholds, product dosage, toxicology principles, and analytical method capability. This ensures the study focuses on compounds that may affect patient safety. Proper AET justification strengthens the reliability of the final risk assessment.
E&L testing requires advanced instrumentation, method validation, and structural elucidation expertise. Specialized CROs have trained scientists who understand polymer chemistry and impurity pathways. Their documentation also aligns with global submission requirements, supporting regulatory success.
Instruments include GC-MS, LC-MS/MS, ICP-MS, FTIR, NMR, headspace analysis, and high-resolution MS. Each tool is selected based on the type of compound being evaluated. Using multiple platforms increases confidence in compound identification and supports regulatory expectations.
Unknowns are identified using spectral libraries, fragmentation behavior, isotopic patterns, and orthogonal confirmation. Experienced analysts combine these details to narrow down possible structures. High-resolution MS is often used for more complex or low-level unknowns.
FDA expects method descriptions, validation data, extractables tables, leachables results, toxicology assessments, and complete risk summaries. All information must show clear traceability from raw data to final conclusions. Specialized CROs prepare submission-ready documentation that meets these expectations.
Yes. Devices that contact drug products or patients often require E&L testing under ISO 10993-18 and ICH Q3E. This ensures materials do not release harmful extractables. Combination products may need additional justification, which specialized CROs can support.
References
- United States Pharmacopeial Convention. (n.d.). Extractables and leachables. Retrieved October 10, 2025, from https://www.usp.org/impurities/extractables-and-leachables
- Balfour, H. (2022, April 29). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
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