1Deviation, 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 had already been distributed. [21 CFR 211.192]. For example, there were excursions of the action limit associated with microbial monitoring of personnel in the Grade (b)(4) environment where your products are manufactured. During the investigation of these excursions, CAPAs were proposed but never…
2Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions. [21 CFR 211.42(c)(10)(v)]. For example, you have not validated the cleaning process for the (b)(4) used in the production of your products purported to be sterile. Your Senior Vice President of Quality stated that your firm has not conducted a cleaning validation to ascertain that your cleaning process for manufacturing your products can…
3Environmental monitoring
Your firm failed to maintain the buildings used in the manufacture, processing, packing, or holding of a drug product in a clean and sanitary condition and to keep them free of infestation by rodents, birds, insects, and other vermin. Trash and organic waste matter shall be held and disposed of in a timely and sanitary manner. [21 CFR 211.56(a)]. Specifically, on July 14, 2023, your Quality Assurance team observed a box of food from June 16, 2023, covered in scuttle fly pupae in the mechanical room which houses the air handling units and failed to remove the box of food until July 31, 2023. After this event, scuttle fly larvae were found in ten environmental and personnel monitoring samples collected in the cleanrooms in July 2023. Additionally, on July 26, 2023, in Suite (b)(4) Clean Room (b)(4) (Grade (b)(4) ) a living scuttle fly was observed on the tube rack. Adequate control of insect infestation is needed to ensure product quality and safety.
4Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for preventing contamination and monitoring environmental conditions in aseptic processing areas. [21 CFR 211.42(c)(10)(iv)]. Your firm also failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile. [21 CFR 211.113(b)]. For example, a. Non-viable particulate monitoring is not being conducted during open manufacturing…
5Process validation
Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess. [21 CFR 211.100(a)]. For example, there was no procedure for 100% visual inspection of the final drug product to ensure that it is essentially free from visible particulates, which is necessary to ensure quality and purity prior to intravascular administration.
