Mastering Extractables and Leachables Analysis for Medical Devices

Extractables and leachables analysis sits at the core of modern biocompatibility assessment for medical devices. If your device uses polymers, adhesives, colorants, tubing, coatings, or packaging, you are dealing with potential chemical migrants that regulators expect you to understand and control.

What Are Extractables and Leachables?

Extractables are chemical constituents that move out of a device or material under aggressive laboratory conditions, such as exaggerated temperature, solvent, or time. They define the chemical universe that could, in theory, become available to the patient.

Leachables are the subset of those chemicals that actually migrate under normal or simulated clinical use. These are the compounds that drive toxicological risk and patient safety decisions.

Why E&L Analysis Matters

For medical device manufacturers, CROs, and regulatory affairs teams, E&L data are not just analytical outputs. They support:

• Biocompatibility evaluation, by identifying potential toxicants before or in place of default biological testing.

• Patient safety protection, by linking exposure estimates to toxicological thresholds.

• Regulatory compliance, by aligning with ISO 10993 expectations and FDA’s current focus on chemical characterization and toxicological risk assessment.

• Lifecycle risk management, by providing a baseline for change control, supplier changes, and post market surveillance.

Robust E&L analysis is the bridge between chemistry, toxicology, and regulatory acceptance.

Key Considerations for Medical Device Manufacturers

Effective extractables and leachables strategy starts long before samples arrive at a lab. The most efficient programs begin at material selection and device design, with chemistry and toxicology at the table from the start.

Start With Materials and Design Intent

• Screen materials early using supplier information, prior E&L knowledge, and ISO 10993 guidance to avoid high risk chemistries.

• Consider contact type and duration when choosing polymers, additives, colorants, and coatings, since these factors drive test scope and regulatory expectations.

• Design for control by limiting unnecessary adhesives, complex laminates, and poorly defined supplier formulations.

Use Early E&L Assessment to Manage Toxicological Risk

• Plan screening level extractables studies to identify potential toxicants before design freeze.

• Align extraction conditions with intended use and clinical scenarios, not just generic worst case approaches.

• Engage a toxicologist to prioritize analytes, decide what drives risk, and avoid unfocused, over broad testing.

Integrate E&L Data Into Biocompatibility and Submissions

• Map E&L results into your ISO 10993 biological evaluation plan, including toxicological risk assessment and any remaining biological tests.

• Structure reports so regulators can follow the logic from device description to chemistry to risk conclusion.

• Ensure alignment with current FDA and US guidance, so chemical characterization and toxicology clearly support your safety narrative.

Supporting CROs with Toxicological Interpretation and Risk Assessment

CROs generate the analytical data that sits at the heart of extractables and leachables programs. Without clear toxicological interpretation, however, that data can create more regulatory questions than answers.

Why Expert Toxicological Input Matters

Analytical output is not a risk conclusion. CROs benefit from specialized toxicology support to:

• Differentiate relevant analytes from background or non critical signals.

• Translate extractables and leachables profiles into patient exposure estimates.

• Compare exposures against health based thresholds that align with ISO 10993 and FDA expectations.

• Document clear weight of evidence rationales for reporting and submission.

Enhancing CRO Service Offerings

With integrated toxicological risk assessment, CROs can move from data providers to strategic partners. This typically involves:

• Developing standardized risk assessment frameworks that link chemistry to clinical context.

• Preparing toxicological risk assessment reports ready for direct inclusion in client submissions.

• Advising on targeted follow up testing when initial data trigger concern.

Collaboration With Manufacturers for Regulatory Responses

Regulators expect a coherent story from device design to chemical data to patient risk. The strongest responses come from early collaboration among CROs, manufacturers, and toxicologists, with aligned assumptions, shared exposure calculations, and consistent safety conclusions across all reports.

Regulatory Affairs Considerations and Strategic Guidance

Regulatory expectations for extractables and leachables are now fully integrated into medical device biocompatibility in the United States. FDA reviewers expect E&L data to align with ISO 10993 principles, current FDA biocompatibility guidance, and a clear, risk based justification for all testing and toxicological conclusions.

Regulatory Framework for E&L in the US

• ISO 10993 chemical characterization as the foundation for E&L study design and reporting.

• FDA biocompatibility guidance as the reference for when chemical characterization can support or replace traditional biological testing.

• Risk management integration through a documented biological evaluation plan and report that incorporates E&L outcomes.

Building a Biocompatibility Strategy That Addresses E&L

• Plan E&L work within a structured biological evaluation plan, not as isolated chemistry reports.

• Define contact scenarios, patient populations, and clinical use before committing to test conditions.

• Align chemistry, toxicology, and biological testing so each element supports a single, consistent safety narrative.

Submissions, Deficiency Responses, and Global Alignment

• Organize submissions so regulators can trace device description, materials, E&L data, and toxicological risk assessment in a logical sequence.

• When you receive deficiency letters, respond with targeted clarifications, transparent assumptions, and clear justifications for analytical limits and toxicological thresholds.

• Where global filings are planned, harmonize your E&L strategy with ISO 10993 and other regional expectations, so one coherent data package supports multiple jurisdictions.

Conclusion and Best Practices for E&L Management

Effective extractables and leachables programs are built on deliberate planning, not last minute testing. From early material selection through post market surveillance, E&L considerations should sit inside your broader biocompatibility and risk management strategy.

Proactive E&L Across the Device Lifecycle

• Start early, screen materials and suppliers before design freeze.

• Align studies with clinical use, base extraction conditions and analyte priorities on realistic exposure scenarios.

• Integrate data, connect E&L outcomes to toxicological risk assessment and ISO 10993 biological evaluation, not stand alone reports.

• Maintain change control, revisit E&L impact when materials, suppliers, processes, or sterilization change.

• Support lifecycle vigilance, use post market findings to refine risk assessments and, when needed, update chemistry strategies.

Expert E&L Strategy and Toxicological Risk Assessment for Medical Devices

Extractables and leachables programs require more than analytical chemistry—they demand toxicological expertise to transform chemical data into regulatory-ready safety assessments. At JL Tox Consulting, we help medical device manufacturers and CROs develop strategic E&L programs that align with ISO 10993-18, support risk-based biological evaluation under ISO 10993-1:2025, and meet FDA expectations for chemical characterization and toxicological risk assessment.

Our specialized E&L consulting services include:

- Strategic E&L study design aligned with device contact scenarios and clinical use conditions

- Toxicological risk assessment of extractables and leachables data with health-based threshold comparisons

- ISO 10993-18 compliance guidance for extraction conditions, analytical methods, and reporting

- Integration with biological evaluation plans under the new ISO 10993-1:2025 risk-based framework

- Regulatory submission support including deficiency response preparation

- CRO collaboration and oversight to ensure analytical data supports clear toxicological conclusions

With over a decade of specialized experience in medical device biocompatibility and chemical characterization, Dr. James Lyons and the JL Tox team provide the toxicological expertise needed to transform E&L analytical data into compelling safety narratives that withstand regulatory scrutiny.

Contact JL Tox Consulting today to develop an E&L strategy that efficiently supports your biocompatibility evaluation and regulatory submissions.

Email: info@JLTox.com  

Phone: (877) 899-6568