Establishing Toxicological/Biological Equivalence After Undisclosed Additive Change in Medical-Grade Resin
Solutions
Toxicology Risk Assessment
Industries
Medical Devices; Combination Products; Drug Products, Personal Care Products

Challenge

A medical device manufacturer was informed by their polymer supplier that the additive package in a key resin had been modified due to global sourcing constraints. While the base polymer remained unchanged, the supplier declined to disclose full chemical identities of the new additives, citing proprietary formulation protection.
The sponsor had already completed an E&L study on the original resin for their device and now needed to determine if the new resin posed any new toxicological risk, without access to a full additive disclosure and without repeating all biocompatibility testing.

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Chemva’s Solution

Chemva recommended a dual Toxicological Risk Assessment (TRA) strategy, using results from E&L testing performed on both the original and modified resins, to establish toxicological equivalency based on exposure safety, aligned with ISO 10993-17 and FDA/EU expectations.
Step-by-Step Approach:

  1. Review of Available Data:
    • Evaluated supplier-provided CoAs and technical documentation.
    • Confirmed that both resins as part of the finished device underwent E&L testing under ISO 10993-18 conditions, using identical extraction protocols and analytical platforms.
  2. Extractables Comparison:
    • Cross-referenced the compounds detected between the two materials.
    • We identified a small number of new constituents in the updated device, but the general chemistry was similar to the original device.
    • Performed TRAs on both E&L datasets and determined the margin of safety (MoS) for all constituents was above 1.
  3. Equivalency Justification:
    • Documented a side-by-side comparison of E&L profiles, highlighting that no significantly hazardous new compounds were introduced.
    • Developed a Toxicological Equivalence Justification Report referencing ISO 10993-17 and aligning with FDA guidance on material changes.

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Impact Delivered

  • Chemva’s TRA-based approach eliminated the need for additional biological testing in addition to E&L studies, saving the sponsor an estimated $100K and 6 months in testing.
  • Enabled the sponsor to secure continued supply and move forward with device production despite limited transparency from the supplier.
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