Challenge

A medical device manufacturer developing a short-term contact Class II device received guidance from an external toxicologist indicating the need for simulated-use extractables and leachables (E&L) testing. This recommendation was made after several compounds identified in the existing extractables study exceeded the Threshold of Toxicological Concern (TTC), and no compound-specific toxicity data were readily available.

The sponsor, concerned about the cost, timeline, and regulatory complexity of simulated use testing, engaged Chemva to explore whether an alternative toxicological justification could be made using existing data.

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Chemva’s Solution

Chemva conducted a comprehensive Toxicological Risk Assessment (TRA) using a read-across strategy, allowing us to bridge data gaps with scientifically valid surrogate information. Our process was aligned with ISO 10993-17, FDA expectations, and other state-of-the-art practices.

1. Read-Across Approach Development:
   • For each data-lacking constituent, we identified one or more structural analogs with robust toxicological datasets.
   • Assessed functional group reactivity, metabolic similarity, and toxicokinetics to ensure analogs were appropriate for conservative safety estimates.
   • Where data were sparse, applied worst-case uncertainty factors to preserve safety margins.
2. Risk Characterization and Exposure Assessment:
   • Calculated tolerable intake (TI) values for each compound using analog-based NOAELs and standard uncertainty factors.
   • Compared estimated patient exposure from E&L data to analog-derived TIs, confirming all reported concentrations fell well below acceptable safety thresholds.
3. Regulatory Justification Documentation:
   • Compiled a complete TRA report with detailed read-across rationale, toxicity summaries, and side-by-side comparisons to TTC levels.
   • Clearly documented that no simulated-use testing was necessary, and that existing extractables data were sufficient for regulatory submission.

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Impact Delivered

The strategy was accepted by both the notified body and US FDA without further inquiry, and the device moved forward toward market clearance on schedule.
Chemva’s read-across-based toxicological justification:

• Eliminated the need for simulated-use E&L testing, saving the sponsor an estimated $200K in testing costs and 6-9 months in development time.
• Provided a scientifically defensible, regulator-ready TRA that aligned with both FDA and EU MDR requirements.
• Enabled the client to proceed with submission without further delays or data gaps, and helped them establish an internal precedent for future E&L data TRASs.