Turbare Manufacturing — FDA Warning Letter Findings

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic processes (21 CFR 211.113(b)).

Your firm failed to establish acceptance criteria for the sampling and testing conducted by the quality control unit that are adequate to assure that batches of drug products meet appropriate statistical quality control criteria as a condition for their approval and release (21 CFR 211.165(d)).

Regarding your firm’s failure to establish an adequate system for monitoring environmental conditions in aseptic processing areas: a. We acknowledge your firm’s actions, taken in response to your failure to implement written procedures which adequately describe the process for investigating environmental monitoring excursions. We recognize enhancements made to SOP-048 ( Environmental Monitoring Program ), including section 6.10.1 which describes the processes for conducting…

Your firm failed to conduct process simulation (media fill) studies that closely simulate aseptic production operations under the worst-case, most challenging, and stressful conditions. The FDA investigator also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example…

Regarding your firm’s failure to establish acceptance criteria for the sampling and testing conducted by the quality control unit that are adequate to assure that batches of drug products meet appropriate statistical quality control criteria as a condition for their approval and release: a. We acknowledge actions taken by your firm in response to your failure to establish statistically valid sampling plans as part of your visual inspection program. Specifically, we…

Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Regarding your firm’s failure to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic processes: a. We acknowledge your firm’s actions, taken in response to your failure to conduct media fills that closely simulate aseptic production operations under the worst-case, most challenging, and stressful conditions, pursuant to an approved…

Regarding your firm’s failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed: a. We acknowledge the actions taken by your firm in response to your failure to investigate the recovery of 1 cfu mold (i.e., Curvularia intermedia ) from an operator’s (b)(4) sample during personnel monitoring, performed in association with (aseptic…

Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a…