Challenge

A medical device manufacturer had completed in vivo and in vitro biocompatibility testing for all endpoints required under ISO 10993-1 for their resorbable implantable Class III device, except for carcinogenicity. Confident that the other endpoints covered the necessary biological risks, they submitted their EU MDR technical documentation, only to receive a regulatory deficiency letter from their Notified Body requesting justification for the omission of the carcinogenicity endpoint.

The client faced two high-cost options: perform a long-term carcinogenicity study or initiate a full extractables and leachables (E&L) study; both of which risked delaying the CE mark by at least nine months and significantly increasing program costs.

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Chemva’s Solution

Chemva proposed and executed a paper-based Material Risk Assessment (MRA) specifically designed to address both genotoxic and non-genotoxic carcinogenicity pathways. Our strategy was aligned with ISO 10993-17, ISO 10993-18, and MDR.

1. Comprehensive Material Review:
   • Collected detailed bill of materials (BOM) and formulation data from all suppliers and manufacturing steps.
   • Confirmed that all materials in contact with tissue were well-characterized polymers or metals with a history of safe use for their intended use.
   • Verified the absence of known carcinogenic monomers, additives, or degradation products through literature, supplier declarations, and toxicology databases.
2. Genotoxicity Linkage:
   • Demonstrated that genotoxicity had already been evaluated and passed through compliant in vitro and in vivo assays (e.g., Ames, micronucleus).
   • Cited regulatory guidance stating that genotoxicity is a key trigger for considering carcinogenicity, and no triggers were present.
3. Non-Genotoxic Carcinogenicity Assessment:
   • Reviewed chemical classes and physicochemical properties of the materials for potential non-genotoxic mechanisms (e.g., hormonal disruption, chronic irritation).
   • Showed no evidence of such mechanisms based on mode-of-action reviews, implantation study histopathology, and absence of chronic inflammatory signals.
4. Regulatory Justification:
   • Compiled a well-structured Carcinogenicity Justification Report, mapping each element of the assessment to the relevant ISO 10993-1 decision tree.
   • Provided a clear rationale for why no additional testing or E&L studies were necessary for this specific device and use scenario.

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Impact Delivered

Chemva’s paper-based approach:

• Resolved the regulatory deficiency without requiring carcinogenicity testing or an extractables study.
• Avoided 9-12 months of delays and an estimated $200k in testing costs.
• Enabled the client to achieve CE mark approval under EU MDR and advance to commercialization on schedule.

The methodology also served as a repeatable framework for addressing higher-tier endpoints in future EU and FDA submissions where traditional testing is not feasible or scientifically justified.