Findings citing 21 CFR 211.42

Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit (21 CFR 211.22(d)). Your QU did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure: Documentation of all interventions during filling of sterile drug products. Our investigators observed multiple batch records in which operators failed to document most aseptic interventions. For example, the batch record for (b)(4) injection (b)(4) mg/ (b)(4) ml, on February 6, 2026, documented that 12 interventions had occurred during filling. However, records indicated approximately 200 interventions were conducted. Notably, critical interventions, including but not limited to removing vials from the filling zone and removing fallen vials from (b)(4) , were not documented. (21 CFR 211.188) Performance of adequate disinfectant efficacy studies. You failed to adequately evaluate your environmental isolates for inclusion in your disinfectant efficacy studies. Studies failed to adequately represent the full spectrum of microbes in your facility. (21 CFR 211.42(c)(10)(v)) Reproducible manufacturing processes in the production of sterile (b)(4) drug products. You did not perform a process validation study after implementing a new production step nor provide stability data within your response. (21 CFR 211.100(a)). In your response, you state you will ensure the QU has a role in verifying intervention documentation in batch records and establish a procedure to periodically evaluate disinfectant efficacy. Your response is inadequate because you fail to provide sufficient details on how interventions in your aseptic process simulations will be captured, simulated, and verified. You also do not describe the QU's oversight of the disinfection practices or identify the environmental isolates to be challenged in the disinfection efficacy studies. Complete and accurate batch production and control records are necessary to ensure that manufacturing processes are consistently followed and are reproducible. Additionally, incomplete manufacturing records fundamentally compromise your ability to reliably conduct batch record review, to adequately investigate deviations and batch failures, and to ensure a continued state of control. Your firm’s quality systems are inadequate. You may refer to FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download. In response to this letter, provide: A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to: o A determination of whether procedures used by your firm are robust and appropriate o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices o A complete and final review of each batch and its related information before the QU disposition decision o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products A CAPA plan, based on the retrospective assessment of your disinfection program, that includes appropriate remediations to your disinfection processes and practices, and timelines for completion. Include the following as part of the assessment and CAPA plan: o a detailed summary of vulnerabilities in your process for lifecycle management of equipment disinfection o a list of improvements, with an explanation how each will enhance disinfection effectiveness o improved ongoing verification of proper disinfection execution for all products and equipment o and, any other needed remediations. A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing vigilant monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. Also, describe your equipment and facility qualification program. A timeline for performing appropriate process performance qualification for each of your marketed drug products. Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced prior to performing any process validation studies. A comprehensive review of your complaints received for (b)(4) injection, including a retrospective review of all complaints for the last three years from the initial date of the inspection, with an assessment that includes but is not limited to evaluating and comparing the (b)(4) complaints received before and after the (b)(4) step. Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst-case in your drug manufacturing operation. This should include but not be limited to identification and evaluation of all worst-case: o drugs with higher toxicities o drugs with higher drug potencies o drugs of lower solubility in their cleaning solvents o drugs with characteristics that make their manufacturing equipment difficult to clean o swabbing locations for areas that are most difficult to clean o maximum hold times before cleaning A description of the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product. A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions, as required by 21 CFR 211.42(c)(10)(v). For example, you have not validated your processes for cleaning and disinfecting the ISO (b)(4) biological safety cabinet (BSC) where your products are exposed to the environment during aseptic processing.

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. 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 and that include validation of all aseptic and sterilization…

Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)). You had inadequate procedures for monitoring of your (b)(4) gloves. Your procedures required sampling from (b)(4) glove on ampoule filling line (b)(4) at the conclusion of batch filling. In addition, your procedure lacked instructions that ensure all gloves are tested and specifying when they must be tested. In addition, your firm…

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)). Your aseptic processing operation was inadequately designed to prevent contamination of your sterile (b)(4) drug products. Significantly, your room pressurization and facility monitoring systems were fundamentally flawed…

You 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)).