1Aseptic processing and sterility assurance
Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination. 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…
2Deviation, CAPA, and investigation
Regarding particulate matter testing of your finished drug products: a. We have reviewed your document titled, “Retrospective Review Investigation of Reported OOS incidents (1B).” Within that document, you state, “Tailstorm has researched the product Avastin, which contains Bevacizumab, a protein that may interfere with liquid-borne particle count testing. The nature of the product can lead to inconsistent results when tested microscopically using Method (b)(4) .” You also…
3Aseptic processing and sterility assurance
You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO 5 aseptic processing area.
4Aseptic processing and sterility assurance
Regarding your personnel monitoring program, we have reviewed your provided evaluation and acknowledge your statement that, “the practice of breaking first air with the head and chest during open (b)(4) doors interventions has been remediated.” We also acknowledge that you have updated your SOP to “add personnel monitoring sample sites of the right shoulder and left shoulder for the machine assembly process.” However, in our review of your updated smoke study titled “Act 15”…
5Equipment and facility
Your facility’s drug products, such as Semaglutide Injection 1mg/0.2ml and Tirzepatide Injection 2.5mg/0.5ml, did not include the following on the label: “Office Use Only.” 2. Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations). Specifically, your facility’s procedures for…
6Aseptic processing and sterility assurance
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…
7Aseptic processing and sterility assurance
Regarding your updated smoke studies provided in your response: a. The dynamic smoke study in your video titled “Removal of (b)(4) layer from the tub” under file name “Act 21” does not show smoke in the area in which the open tub of what appears to be product syringes is moved during time 00:51 to 00:58. This same area shows air turbulence during your static smoke study video “ (b)(4) Removal” under file name “Act (b)(4) ” during time (b)(4) . b. The smoke study in your video titled “Replacement of Needle (Open door)” under file name “Act 44” does not appear to encompass all areas within the ISO 5 (b)(4) including but not limited to the interventions performed by the operator during needle replacement.
8Deviation, CAPA, and investigation
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).
