Challenge

A medical device manufacturer preparing for a 510(k) submission faced tight timelines and was unable to schedule a Q-Sub meeting with FDA before completing their non-targeted extractables study. The device included polyether ether ketone (PEEK) with a known phosphite-based antioxidant additive, commonly used for thermal stabilization during processing. Based on Chemva’s experience, we anticipated that FDA may scrutinize potential degradation products from this additive class, particularly organophosphorus compounds that could raise toxicity concerns if not addressed directly.

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Chemva’s Solution

Chemva recommended modifying the traditional non-targeted E&L approach to include a semi-targeted overlay, designed to preempt likely FDA questions.
Our approach included:

1. Material-Specific Risk Analysis:
   • Identified tris (2,4-di-tert-butylphenyl) phosphite (Irgafos 168) as a likely additive in the PEEK formulation.
   • Assessed degradation pathways leading to potential phosphite oxidation products, including phosphonic acids and phenolic derivatives.
2. Surrogate Selection for Semi-Targeted Screening:
   • Integrated known breakdown products of phosphite antioxidants as analytical surrogates in the LC-MS and GC-MS methods.
   • Worked closely with the test lab to ensure that they were aligned with our strategy.
3. Documentation & Regulatory Justification:
   • Presented a full rationale within the E&L report, detailing the surrogate selection rational.

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Impact Delivered

Chemva’s semi-targeted E&L design eliminated potential FDA objections before they could be raised.
The sponsor was able to:

• Submit confidently without needing a Q-Sub, saving at least 3-4 months in regulatory lead time.
• Avoid repeat testing or addenda requests, which are common when potential additives or breakdown products are overlooked.
• Reinforce their material safety narrative with a data-driven, risk-based E&L profile tailored to the specific chemistry of their device.

This proactive approach ensured a smoother review process, mitigated regulatory risk, and helped the sponsor stay on track for a timely 510(k) clearance.