Introduction
When organizations ask how to conduct an Extractables and Leachables (E&L) study, the answer lies in following a carefully designed process that ensures patient safety and regulatory compliance. Extractables and Leachables testing plays a critical role in pharmaceuticals, biologics, and medical devices because it identifies chemical compounds that may migrate from packaging or device materials into the drug product or the human body.
At ResolveMass Laboratories Inc., we guide manufacturers through every step—from sample preparation to toxicological risk assessment—ensuring results that meet international guidelines. This scientific approach safeguards patient health, supports regulatory approvals, and strengthens product confidence. By combining advanced technology with regulatory insight, we help manufacturers minimize risks while streamlining their development journey.
Quick Summary: How to Conduct Extractables and Leachables Study
- Proper sample preparation forms the base of every E&L study.
- Extractables testing predicts potential chemical release under harsh conditions.
- Leachables testing confirms what compounds migrate during real use.
- Sophisticated tools such as GC-MS, LC-MS, and ICP-MS are essential.
- Data interpretation ensures alignment with regulatory expectations.
- Risk assessment evaluates whether detected compounds pose health hazards.
- Partnering with ResolveMass Laboratories Inc. guarantees compliance and safety confidence.
Each phase builds a complete safety profile for the product. Without this structured process, harmful risks may remain hidden. Our integrated workflow allows manufacturers to generate reproducible results that regulators can review and trust.
What is an Extractables and Leachables (E&L) Study?
An Extractables and Leachables study is both a chemical and toxicological assessment designed to detect potential risks from materials that come into contact with a product. Extractables are compounds released under extreme laboratory conditions, while leachables are those that actually migrate during storage or patient use.
Both types of compounds must be detected, measured, and evaluated to confirm that exposure levels remain safe. Well-structured E&L studies are essential not only for regulatory filings but also for product approvals and long-term patient safety. They also help manufacturers confirm that materials are compatible with their intended use.
👉 Learn more at our Extractable and Leachable E&L Services.
Step 1: Sample Preparation in an E&L Study
Sample preparation is the first and most critical step in how to conduct an Extractables and Leachables study. Reliable outcomes depend on preparing test materials with precision. At this stage:
- Materials are cleaned, cut, or conditioned with great care.
- Simulated solvents (aqueous, organic, acidic, and basic) are chosen to replicate drug contact.
- Stress factors such as heat, pH changes, or solvent exposure are applied for extractables testing.
Meticulous preparation ensures that testing reflects realistic exposure conditions. If mistakes occur here, the entire study’s accuracy may be compromised. Laboratories customize preparation methods based on the type of product or device, making sure that the approach fits the study design.
👉 For device-specific guidance, see our E&L Testing for Medical Devices.
Step 2: Extractables Testing
Extractables testing is designed to detect potential chemical risks before the product is used in real-world conditions. During this stage:
- Samples undergo harsh conditions like solvent reflux, heating, or exposure to strong acids/bases.
- Instruments such as GC-MS, LC-MS, and ICP-MS are used to capture detailed chemical profiles.
- A broad list of possible migrating substances is generated for analysis.
This “worst-case scenario” helps manufacturers anticipate long-term chemical stability issues. By identifying risks early, companies can redesign packaging or materials to reduce patient hazards. Extractables testing is fundamental in ensuring products align with international regulations.
📌 For detailed method options, visit our Analytical Techniques for E&L Testing.
| Test Parameter | Purpose | Example Techniques |
|---|---|---|
| Organic Extractables | Detects solvents, monomers | GC-MS, LC-MS |
| Inorganic Extractables | Detects metals | ICP-MS |
| Volatile Organic Compounds | Detects gases | Headspace GC |
Step 3: Leachables Testing
Leachables testing verifies which compounds actually migrate into the product under normal storage and usage. At this stage:
- Test articles are stored with real formulations or simulated drug products.
- Periodic stability checks confirm migration patterns across time.
- Detected compounds are prioritized for toxicological risk evaluations.
This step provides real-world confirmation of earlier extractables results. Even trace levels of leachables may cause safety concerns if ignored. By integrating stability study results, manufacturers obtain vital data to ensure product safety and patient protection.
👉 Learn about regulatory perspectives in our USP Extractables & Leachables Testing Guide.
Step 4: Data Interpretation and Compliance
Data interpretation is where laboratory results are connected to international regulations. At this step:
- Identified compounds are compared against accepted safety thresholds like PDE and TTC.
- Quantitative findings are checked against ISO 10993-18 requirements for medical devices.
- Unknown peaks are structurally analyzed to confirm safety compliance.
This process ensures that no compound posing a safety risk goes unnoticed. Accurate interpretation supports stronger regulatory submissions, minimizing approval delays. Manufacturers also receive transparent reports that regulators can audit with confidence.
👉 Read our ISO 10993-18 E&L Testing Overview.
Step 5: Toxicological Risk Assessment
Risk assessment is the final stage in how to conduct an Extractables and Leachables study. At this point:
- Each compound is assessed for carcinogenic, mutagenic, reproductive, or systemic effects.
- Established safety thresholds are applied to determine patient exposure limits.
- A complete risk-based report is created to support regulatory submissions.
By carefully assessing toxicological risks, manufacturers can prove product safety and compliance. This step gives regulators confidence that any leachables present will not cause harm over long-term use.
👉 See this in practice in our E&L Compliance Case Study.
Why Partner with ResolveMass Laboratories Inc.?
At ResolveMass Laboratories, our specialists combine extensive expertise with modern technology to deliver accurate and compliant results. Whether you need a custom study design, compliance support, or cost evaluation, our team ensures transparency and precision at every stage.
By partnering with us, manufacturers benefit from advanced instrumentation, proven workflows, and deep regulatory knowledge. Our integrated approach ensures that every potential risk is addressed, giving you confidence in both product safety and regulatory success.
Conclusion
Knowing how to conduct an Extractables and Leachables study is vital for ensuring patient safety, gaining regulatory approval, and confirming product reliability. Each phase—from preparation to toxicological risk assessment—requires expertise and precision. At ResolveMass Laboratories Inc., we provide complete E&L testing solutions backed by advanced tools and deep regulatory understanding.
📌 Get started today: Contact ResolveMass
FAQs: How to Conduct Extractables and Leachables Study
Sample preparation ensures that the test reflects real-world scenarios. If materials are not cleaned, cut, or conditioned properly, the results may not be reliable. Careful preparation helps laboratories generate accurate chemical profiles that represent true patient exposure.
Different techniques are used depending on the type of compounds. GC-MS is often applied to detect volatile and semi-volatile organics, LC-MS helps analyze non-volatile substances, and ICP-MS is used for metals. Headspace GC is also valuable for identifying gases released from materials.
E&L studies are guided by well-recognized standards such as USP <1663> and <1664>, ISO 10993-18, and FDA guidelines. Following these ensures that products meet global safety expectations and improves the chances of smooth regulatory approval.
Not every device requires E&L testing, but those that directly contact patients or interact with drug products usually do. Testing ensures that any chemical release from the device does not compromise patient safety or product performance.
Yes, advanced laboratories use powerful spectral libraries and structural analysis tools to identify both known and unknown compounds. This allows for a more complete chemical profile, ensuring that no potential risk is overlooked.
Risk assessment involves evaluating the toxicological impact of all detected compounds. Toxicologists review data against established safety thresholds to confirm that exposure levels are acceptable for patients over both short and long-term use.
References
- European Medicines Agency. (2025). ICH Q3E extractables and leachables scientific guideline. EMA. https://www.ema.europa.eu/en/ich-q3e-extractables-leachables-scientific-guideline
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2025). ICH Q3E: Extractables and leachables (Step 2 draft guideline). ICH. https://database.ich.org/sites/default/files/ICH_Q3E_EWG_Step2_DraftGuideline_2025_0704.pdf
- European Pharmaceutical Review. (2022, June 28). Advancing extractables and leachables testing. European Pharmaceutical Review. https://www.europeanpharmaceuticalreview.com/article/170814/advancing-extractables-and-leachables-testing/
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