1Aseptic processing and sterility assurance
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 adequately investigate the sterility failure of bevacizumab, lot # 20250428-488A81, and to extend the investigation to other potentially affected batches of drug product…
2Laboratory and QC controls
Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).
3Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing area (21 CFR 42(c)(10)(iv)).
4Material and supplier control
Regarding your firm’s failure to establish the reliability of your component supplier’s test analyses (i.e., Certificates of Analysis) at appropriate intervals, as well as your failure to conduct at least one test to verify the identity of each shipment of every lot of components: We acknowledge the actions your firm has taken in response to the failure to conduct at least one identity test on each shipment of every lot of components, including APIs. Specifically, we note…
5Documentation and records
Regarding your firm’s failure to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced: We acknowledge the actions your firm has taken in response to the failure to consistently record the lot numbers of sterile, (b)(4) beakers ( (b)(4) Sterile Beakers) and sterile (b)(4) in the batch production records for Lidocaine 2% Injection. We note your commitment to verify the accuracy and…
6Aseptic processing and sterility assurance
Regarding your firm’s failure to establish an adequate system for monitoring environmental conditions in aseptic processing area: a. We acknowledge the actions your firm has taken in response to the failure to perform adequate viable air monitoring within the ISO 5 laminar flow hood during sterile drug production activities. We note your plan to (b)(4) “to provide a better representative air sample in ISO 5 conditions.” However, you have not fully implemented and documented…
7Deviation, CAPA, and investigation
Your firm failed 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 (21 CFR 211.192).
8Aseptic processing and sterility assurance
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)).
9Material and supplier control
Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1), 211.84(d)(2)).
10Aseptic processing and sterility assurance
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: We acknowledge the actions your firm has taken in response to the failure to ensure that components of your container-closure system, used for sterile ophthalmic drug products, are handled in a manner that maintains their sterility. We note your statement that “All Betadine (povidone-iodine) production has been suspended as of 28-AUG-2025 to allow the quality unit to assess and evaluate a potential new container-closure system and the repackaging process.” While we acknowledge that temporarily suspending production of this drug product mitigates immediate risk, you have not submitted documentation describing your Quality Unit's evaluation of any process modification designed to prevent microbiological contamination. Your response did not include a timeframe for completion of this evaluation or a plan outlining the specific steps your firm will take to resolve this deficiency.
11Laboratory and QC controls
Regarding your firm’s failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity: We acknowledge the actions your firm has taken in response to the failure to employ appropriately validated analytical methods for assay testing of active pharmaceutical ingredients (API)…
12Documentation and records
Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FD&C Act. 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…
