Integra LifeSciences Corporation – FDA Warning Letter, May 17, 2023

The FDA conducted an inspection of TEI Biosciences, Inc., an Integra LifeSciences Company, in Boston, MA, from March 1 to May 17, 2023, concerning its collagen-based medical devices, including Durepair. The inspection revealed these devices are adulterated under 21 U.S.C. § 351(h) because manufacturing controls do not conform to the Quality System regulation (21 CFR Part 820). The firm had already initiated a recall of products manufactured from March 2018 to May 2023 and committed to a production hold.

Key violations include: 1) Failure to control non-conforming product (21 CFR 820.90(a)), with an inadequate response regarding an Out-of-Specification (OOS) result. 2) Failure to establish and maintain corrective and preventive action (CAPA) procedures (21 CFR 820.100(a)(1)), noted as a repeat deficiency from a 2019 Warning Letter, with an inadequate response on systemic issues. 3) Failure to validate processes (21 CFR 820.75(a)), citing issues with BET assay verification, protocol, and calculation errors, despite outsourcing testing. 4) Failure to store devices for proper stock rotation (21 CFR 820.150(a)).

The FDA deemed the firm's responses inadequate, requiring evidence of effective and sustainable CAPA systems, comprehensive review of all operations for validated processes, and confirmation of appropriate corrective actions. The firm must respond within fifteen business days with specific steps, prevention plans, and a timetable. Failure to comply may result in further regulatory actions, including seizure, injunction, civil money penalties, and impact on federal contracts, premarket approvals, and Certificates to Foreign Governments. An external expert consultant audit and CEO certification are also requested.