US FDA Environmental monitoring findings

Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)). Inaccurate Microbiology Laboratory Records You failed to accurately document microbiology testing results. Specifically, multiple environmental monitoring and (b)(4) samples were documented in logbooks as collected and incubated; however, the corresponding plates could not be located in incubators during the inspection. Colony forming unit (cfus) counts had been recorded as if incubation was actively in progress. In interviews conducted by your management, your analysts confirmed these samples were not collected. In addition, your Laboratory Information Management System (LIMS) did not include a dilution factor to calculate the number of cfus per gram or milliliter of product for microbial limit test results, as required by your own procedures and applicable compendial methods. By releasing drug products based solely on raw plate count averages entered into your LIMS without applying the required dilution factor, you lack scientific evidence that each batch conforms to predetermined specifications prior to distribution. Appropriate testing is an essential part of ensuring that the drug products you manufacture conform to CGMP. Collectively, these deficiencies indicate a significant risk of systematic underreporting of microbial findings, which directly undermines your firm's ability to ensure the safety and quality of drug products distributed to patients. Reliability of data is fundamentally compromised when there is a failure to record data or to maintain complete and accurate records of test results. Furthermore, the lack of reliable data compromises the ability of your quality unit (QU) to exercise its function of ensuring compliance to applicable standards and deprives you of the ability to adequately investigate deviations. Inadequate Electronic Records Controls Your firm did not have adequate controls to prevent the deletion or overwriting of (b)(4) integrity testing electronic data. Specifically, reports were not saved with unique file names, resulting in data being overwritten after every (b)(4) tests. In addition, (b)(4) integrity testing was not performed for Plant (b)(4) . Therefore, your firm has no means of tracking or retrieving records of failed leak tests. The lack of adequate electronic records controls undermines the reliability and integrity of your laboratory data. (b)(4) integrity is critical to preventing product contamination. Routine (b)(4) integrity tests should be performed. The monitoring and maintenance program should identify and eliminate any (b)(4) lacking integrity and minimize the possibility of placing a sterile product at risk. All data must be complete, accurate and retained to enable appropriate assessment and decisions by the QU. The lack of control over the integrity of your data raises questions about the authenticity and reliability of your analytical data and the quality of your drug products. Your response states “the unaccounted samples may have been misplaced”. This explanation is contradictory as it does not address the fact that your own analysts confirmed during management interviews that the microbiological samples were never collected, nor does it address the broader pattern of inaccurate recordkeeping identified during the inspection. Your response indicates your commitment to hiring third parties to conduct a data integrity remediation plan, risk assessment, and product impact assessment. Your response is inadequate. You do not provide sufficient detail including specific timelines and deliverables on your data integrity remediation plan, risk assessment and product assessment. Furthermore, your response does not define the scope of third-party oversight responsibilities or establish accountability measures for the remediation effort. Additionally, you acknowledge deficiencies in your “ (b)(4) integrity testing controls” and conducted a retrospective review. Your response is inadequate because although you conclude there is, “no evidence of product contamination attributable to (b)(4) failure”, the thoroughness of this review cannot fully support a definitive risk-based conclusion since you acknowledge that “historical traceability was incomplete”. We acknowledge your firm’s long-term commitment to improving your manufacturing operation, including, but not limited to, hiring additional microbiological laboratory staff and building a larger microbiological laboratory. Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP: Questions and Answers for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download. We acknowledge that you are using independent third-party consultants to audit your operation and assist in meeting FDA requirements. In response to this letter, provide: A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include: o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude. o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party. o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies.…

Your environmental monitoring program is deficient.

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 firm lacked adequate systems to ensure sufficient and timely investigations. A. Your firm failed to investigate multiple action-level environmental monitoring excursions that occurred between January and June 2025 in the ISO 5 and 7 areas. Your…

Inadequate routine environmental monitoring in the ISO 5 area.

You did not disinfect materials during transfer from the ISO 7 cleanroom into the ISO 5 laminar airflow workstation (LAFW). Specifically, an operator removed the outer packaging of stoppers in the ISO 7 area and the inner bag was then transferred from the ISO 7 area into the ISO 5 LAFW without surface disinfection. The inner bag of stoppers could be held for up to (b)(4) within the ISO 7 area before being transferred into the ISO 5 LAFW.

Regarding white fiber-like particles and debris observed on the floor of the ISO (b)(4) Lab and the ISO (b)(4) Hallway/Anteroom (b)(4) following area cleaning, we acknowledge you rejected and destroyed the three affected lots. However, you have not provided any preventive actions regarding particles observed in the anteroom and in the cleanroom space where ISO (b)(4) LAFH used for production are located. In your June 10, 2025 response, the specification sheet from (b)(4) . (refer to pages 95-96 of the Response Attachment 3) appeared to be a specification sheet for (b)(4) Mop, which is a different product line, with part numbers such as (b)(4) , none of which appeared to match the mops being used at your firm.