1Cleaning validation
Inadequately cleaned and maintained equipment can lead to cross contamination and poor quality drug products. Your response states that the (b)(4) was not disassembled during the cleaning process because engineering staff was not available. The residue and powder were from the previously manufactured drug product (which was the same drug). You also confirm the shiny fragments on the (b)(4) gaskets are (b)(4) and stated that the shedding of metal fragments most likely…
2Equipment and facility
Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63). You failed to identify and use equipment suitable for the filling of your viscous parenteral drug product. Inappropriately designed vial filling equipment led to substantial extraneous matter contamination in…
3Environmental monitoring
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). Your investigations into water leaks in your cleanroom were inadequate because they lacked appropriate CAPA and failed to extend to other potentially affected batches. For example, water leaked from the service floor through the heating, ventilation, and…
4Cleaning validation
Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)). You failed to adequately clean and maintain your equipment used for drug product manufacturing. For example: A. Our investigators observed visible residue on (b)(4) 1 after it was identified as clean. Also, colored particles and pellets were observed inside a crevice where the (b)(4) was attached to (b)(4)…
5Aseptic 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 and sterilization processes (21 CFR 211.113(b)). Inadequate Media Fills Your media fills failed to accurately simulate commercial operations. Our inspection found the aseptic operations simulated during your media fills were not sufficiently representative of…
6Equipment and facility
During the inspection your analytical testing identified that the pellets contained (b)(4) API. The equipment cleaning record indicated a Type-B cleaning was performed on (b)(4) 1, which is defined as complete removal of previous drug product and involves dismantling of (b)(4) . B. Our investigators observed numerous scratches and dents on product contact surfaces of the (b)(4) 1 bowl-II. Additionally, shiny metal fragments were observed on the top of the (b)(4) gaskets that connected the (b)(4) in (b)(4)…
7Aseptic processing and sterility assurance
Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.42(c)(10)). Cleanroom Design Your ISO 5 cleanroom areas used for aseptic compounding and filling were poorly designed and lacked adequate protection. For example, your ISO 5 area in Room (b)(4) lacked physical barriers to prevent…
