Integra Neurosciences PR, Inc. – FDA Warning Letter, Nov 14, 2012

The FDA issued a Warning Letter to Integra Life-Sciences Corporation, specifically Integra Neurosciences PR Inc., following an inspection from October 31 to November 14, 2012, at their Añasco, Puerto Rico facility. The inspection revealed that the firm's Absorbable Collagen Sponges (ACS) and Duragen Collagen products are adulterated under 21 U.S.C. § 351(h) because their manufacturing, packing, storage, or installation methods and controls do not conform to the Current Good Manufacturing Practice (CGMP) requirements of the Quality System Regulation (QSR), 21 C.F.R. Part 820. Key violations include: (1) Failure to ensure process validation with a high degree of assurance for processes whose results cannot be verified by subsequent inspection and test, as required by 21 CFR 820.75(a). This was a repeat deficiency from a 2008 inspection. (2) Failure to properly implement CAPA procedures, including inadequate investigation of nonconformities, lack of statistical methodology, and insufficient verification of corrective actions, as required by 21 C.F.R. § 820.100(a). This was also a repeat deficiency from a 2009 inspection. (3) Failure to establish and maintain procedures to control documents used during routine and non-routine operations, specifically regarding uncontrolled official forms, violating 21 CFR 820.40. The FDA deemed the firm's responses inadequate, highlighting concerns about the quality of all ACS and Duragen collagen products manufactured at the Añasco facility due to non-validated processes and lack of stability data. The letter concludes that management failed to ensure effective quality system requirements (21 C.F.R. § 820.20) and recommends engaging a third-party consultant. Integra must take prompt corrective actions, provide a written response within 15 working days detailing steps taken, and include a timetable for completion to avoid further regulatory actions like seizure, injunction, or civil money penalties, and impacts on product approvals or government contracts.