Challenge

A medical device manufacturer developing a Class III cardiovascular implant required a robust Extractables and Leachables (E&L) testing protocol to support their global regulatory submissions.

While an initial protocol was in place, the sponsor sought Chemva’s expertise to ensure the approach would satisfy the complex requirements of ISO 10993-18, FDA biocompatibility guidance, and the EU MDR. Without refinement, the original protocol risked regulatory rejection due to methodological gaps and incomplete toxicological context.

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Chemva’s Solution

Chemva conducted a comprehensive review of the E&L protocol, evaluating analytical strategies, extraction conditions, and toxicological relevance. Key activities included:

1. Gap Analysis of Analytical Methodology:
   • Identified weaknesses in analytical method selection
   • Flagged sample preparation issues, such as concentration of extracts without spike-recovery reports
   • AET (Analytical evaluation threshold) calculation inconsistencies
2. Toxicological Risk Assessment (TRA)
   • Once the E&L reports were ready, we performed a compound-by-compound risk evaluation per ISO 10993-17: 2023.
   • Addressed compounds without available toxicity data using in-silico predictive toxicology tools and read-across techniques.
   • Compiled the TRA into a regulator-ready risk justification, clearly linking analytical results with human exposure risk thresholds.
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Impact Delivered

Chemva’s scientifically rigorous refinements gave the manufacturer confidence in their E&L strategy and positioned them for smooth regulatory interactions.
Key outcomes included:

•  Avoidance of data insufficiency rejections from FDA and EU notified bodies.
• A compliant, risk-based safety narrative that met global regulatory expectations.
• Improved traceability and defensibility in both the E&L report and the Biological Evaluation Report (BER).
• Significant timeline savings by avoiding costly rework or agency requests for additional testing.

The enhanced protocol review became a reusable framework for future product submissions, helping the partner establish a higher internal standard for biocompatibility testing and regulatory preparedness.