Jabil Inc. — FDA Warning Letter Findings

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. Your firm also failed to maintain buildings used in the manufacture, processing, packing, or holding of drug products in a good state of repair (21 CFR 211.113(b) and 21 CFR 211.58). Airflow Visualization (AFV) Smoke Study Deficiencies Our inspection noted deficient smoke studies. Our investigators determined you did not perform AFV smoke studies after modifying your (b)(4) Restricted Access Barrier Systems ( (b)(4) RABS) unit by removing the (b)(4) and remounting the nonviable particulate probe in suite (b)(4) of the (b)(4) filling line. Your validation department determined smoke studies were not necessary after the modification, despite your engineers proposing smoke studies be conducted. As another example, two interventions, including product spillage cleaning at the filling station and (b)(4) adjustment lacked adequate smoke to visualize unidirectional airflow. It is not clear whether airflow is adequate to protect the aseptic processing line. In your response, you state you will re-execute AFV studies, develop a standardized AFV protocol template, and revise the change control procedure. Your response is inadequate because you do not explain how you will ensure satisfactory conduct of smoke studies in the future. Thorough smoke studies are essential to evaluate the effects of such interventions on unidirectional airflow and suitability of design modifications. We also note that your Grade A suites (b)(4) are described as (b)(4) RABS. Although your firm characterizes these processing lines as (b)(4) RABS, their design and operation involve an excessive number of interventions and do not meet the minimum standards of a restricted access barrier system. The Grade A area is critical because sterile products are exposed during aseptic production and therefore are vulnerable to contamination if operations are not well designed and diligently controlled. Your aseptic processes should be designed, and operations executed, to prevent contamination hazards to your sterile product. Flaws in the design of cleanrooms and aseptic processing lines, or improper execution of operations, can promote influx of contamination into the critical processing area in which sterile drugs are exposed. Inadequate Environmental Monitoring We observed inadequate EM technique and insufficient EM locations. Our investigators observed the surface swabbing of the (b)(4) did not include the (b)(4) . Additionally, the analyst did not swab the maximum accessible area of the (b)(4) of each (b)(4) . In your response, you state the procedures will be updated and a retrospective EM review will be performed. You also performed a historical review of your EM data since 2024 which you indicate has no adverse trends. Your response is inadequate because the quality of the data was compromised by insufficient technique and locations. Environmental monitoring is only as meaningful as the quality of its sampling technique and locations. The purpose of environmental monitoring in an aseptic processing facility is to apply a risk-based approach to reliably detect routes of contamination. Facility Maintenance Deficiencies Your firm did not properly maintain classified areas used in the manufacture of drug products. Our inspection noted peeling paint on the walls and plastic debris on the floors within your Grade C hallway and product transfer room (b)(4) in Suite (b)(4) . In your response, you commit to implement post-cleaning visual inspection, require cleaning verification in the cleaning logs, and repair the facility. Your response is inadequate because your product impact evaluation states “…types of debris observed (e.g., paint, plastic) are non-viable particulates...” However, you do not explain the basis for the assertion that paint debris could not harbor microorganisms. In addition, your response does not adequately evaluate the cause of the paint bubbling and peeling from the walls and whether this has contributed to mold identified throughout all your classified areas. Deteriorating surfaces such as peeling paint are potential sources of particulate and microbial contamination. It is critical that the building is maintained to prevent exposure of sterile articles to potential contamination hazards in the manufacturing operation. In response to this letter, provide: Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to an independent assessment of the following with accompanying CAPA: o suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing operations o deficiencies in production management oversight, and identification of specific improvements to ensure effective and routine supervisory oversight for all batches o frequency and depth of quality unit oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operations o adequacy of written procedures o evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs A thorough, independent evaluation of airflow unidirectionality in your aseptic process. Ensure smoke studies are conducted under dynamic conditions, with thorough and complete evaluations of aseptic processing line airflow unidirectionality, including the impact of dynamic interactions and aseptic interventions. These thorough smoke studies should be performed after you remediate your aseptic operation and be conducted using proper practices (e.g., neutrally buoyant media) to appropriately visualize airflow. Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment.…

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 operates as a contract manufacturer of sterile injectables for (b)(4) . You failed to adequately investigate a sterility test failure as well as recurring mold recoveries in the ISO 5 (Grade A) filling area. Sterility Failure You did not adequately investigate a failed sterility test result for your aseptically filled (b)(4) mg/ (b)(4) ml. Your firm identified Ustilago spermophora , a fungi, in (b)(4) medium. Your investigation’s root cause finding of “undetermined” was inadequate. Although your firm rejected this batch, your investigation did not thoroughly examine all possible root causes including but not limited to potential routes of fungi migration through your classified areas (e.g., personnel/material flow hazards, HVAC hazards, inadequate disinfection). Additionally, your investigation lacked adequate corrective action and preventive action (CAPA) responses. In your response, we acknowledge your intentions to strengthen investigation requirements, perform a retrospective review of investigations, and review the facility’s contamination control strategy. However, your response does not specifically address the sterility failure investigation. Environmental Monitoring (EM) Action Level Excursions Your firm’s investigations into multiple instances of fungi contamination on and below the (b)(4) of aseptic processing lines have been inadequate. For example: On March 20, 2024, Chaetomium globosum was recovered below the (b)(4) of the (b)(4) vial machine in suite (b)(4) after filling a batch of (b)(4) mg/ (b)(4) ml. Your investigation was inadequate as it did not adequately evaluate potential root causes, including whether the mold was introduced during filling operations. You released the product without sufficient investigation. On May 16, 2025, fungi was recovered in two locations within the (b)(4) filling line in suite (b)(4) . The passive air sample recovered Didymella glomerata during the filling of (b)(4) injection. You attributed the mold recovery to a power failure that occurred during filling. Notably, surface monitoring below the (b)(4) also recovered Mycosphaerella africana after the power was restored. The investigation lacked sufficient CAPA. On June 4, 2025, Chaetomium cruentum/globosum was recovered from the (b)(4) of the (b)(4) vial machine in suite (b)(4) after filling a batch of (b)(4) mg/ (b)(4) ml. Your firm rejected the batch but failed to adequately investigate likely root causes. You stated within the investigation, “historically there has never been a mold hit isolated on the grade A space on the (b)(4) filling Line,” however the same mold, Chaetomium globosum , had been recovered, on March 20, 2024, on the same line. The investigation lacked CAPA. Overall, trends of fungal recoveries within your suites (b)(4) , and supporting cleanrooms, have significantly increased since 2023. Your firm has closed investigations without implementing robust CAPA. Your firm also has not adequately evaluated the ongoing trend of adverse findings of fungi within your aseptic production area, directly within product, and on product contact surfaces over time. In your response you commit to revise your procedures to perform routine trend analysis and strengthen your investigations. Your response is inadequate because you indicate that product impact conclusions in investigations were appropriate based on a lack of sterility failures, adverse environmental monitoring trends, and complaints, but fail to sufficiently address contamination sources. Your firm has not demonstrated that you have remediated your investigational capabilities to ensure scientifically rigorous investigations to effectively identify root causes so that appropriate CAPA can be implemented. To ensure proper root cause analysis and appropriate CAPA implementation, investigations must be thorough, well-documented, scientifically sound, and timely. Procedural updates and training alone do not address the systemic failures that allowed deficient investigations to persist undetected by quality unit (QU) oversight. In response to this letter, provide: A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted. An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigation trends, improves the CAPA program wherever needed, ensures final QU decision authority, and is fully supported by executive management. A comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to, the following: o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual interventions wherever possible) o Equipment suitability (e.g.…

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.