Jubilant HollisterStier General Partnership(320-26-81)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

Warning Letter 320-26-81

May 28, 2026

Dear Mr. Preti:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Jubilant HollisterStier General Partnership, FEI 3001623073, at 16751 Trans-Canada Highway, Kirkland, from October 20 to November 3, 2025.

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

We reviewed your November 25, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. 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)).

A. Our inspection identified aseptic processing design deficiencies which pose significant hazards to drug product sterility, as well as multiple inadequacies in your smoke studies. For example:

• During a smoke study simulating an aseptic intervention of the (b)(4) line, an operator extended their upper body over the conveyor. This design flaw disrupted (b)(4) air and compromised protection of the critical ISO 5 zone. Smoke studies demonstrated air movement across the operator’s body and flowing toward exposed vials.

• You also performed a smoke study on the (b)(4) filling line to evaluate removal of vials from the (b)(4) at the (b)(4). During this study an operator (b)(4) the large (b)(4) and placed their upper torso inside the ISO 5 classified area. The operator also used gloved hands instead of sterile tools to remove vials.

• In order to (b)(4) the (b)(4), operators opened a small (b)(4) by reaching their entire forearm inside the ISO 5 classified area and manually turning a (b)(4).

These and other hazardous interventions occurred at critical locations in your aseptic processing area. Any compromise of (b)(4) protection exposes sterile drug product to potential microbiological contamination.

Our inspection also noted other deficient smoke studies. For example, the video evaluating connection of the (b)(4) to the (b)(4) demonstrated inadequate smoke at the site of the critical activity. However, despite the inadequate airflow visualization, you concluded the airflow was “Excellent.” We previously discussed inadequate smoke generation in our November 15, 2024, regulatory meeting with your firm.

Your response states that the quality assurance unit at another Jubilant site will conduct a comprehensive assessment of your smoke studies with support from your third party consultants. You state you will identify interventions that represent the highest contamination risk and re-execute studies as needed.

Your response is inadequate. You do not provide sufficient detail on the re-execution of smoke studies, nor do you ensure sufficient third party oversight responsibilities. You also do not address the risk insufficient smoke studies pose, including inadequate identification of hazards posed by the (b)(4), various manual activities, and intervention ergonomics.

We acknowledge your firm’s long term commitment to improving your manufacturing operation, including, but not limited to, better quality oversight and replacing aging equipment with contemporary equipment, including restricted access barrier systems and (b)(4) systems.

B. Your aseptic process simulations (media fills) failed to demonstrate the maximum duration of (b)(4) interventions observed during commercial aseptic filling operations. They also did not sufficiently represent the risk to your aseptic process posed by lengthy interventions.

For example, the duration of (b)(4) was nearly (b)(4) for (b)(4) injection commercial batch (b)(4). In contrast, the (b)(4) simulation for (b)(4) during the (b)(4) media fill was between (b)(4). We also cited deficient aseptic process simulations during our February 2023 and June 2024 inspections. You have failed to adequately correct this deficiency.

In your response, you mention that a reference published by an external technical organization did not specify that maximum duration of interventions must be simulated during media fills.

Your response is inadequate. Lengthy (b)(4) interventions expose the aseptic processing line to high contamination risk. Including such interventions is integral to ensuring an accurate simulation of your operation. You do not adequately address the significant discrepancy between your simulated and actual intervention durations.

Additionally, you state your media fills will “incorporate the longest intervention durations observed in commercial batches,” with a corrective action and preventive action (CAPA) plan due date of June 30, 2026. However, you provide no revised procedures in your response. Furthermore, your response fails to address the intervention and (b)(4) discrepancies cited in deviation PR 256484. It continues to be unclear whether the (b)(4) was actually simulated.

C. During our inspection, we also observed (b)(4) discoloration on multiple (b)(4) surfaces below the HEPA filters and inside the (b)(4) filling line where (b)(4) sterile drug products are exposed.

In your response, you acknowledge the observed discoloration and state that you opened a deviation. You state the root cause of the observed discoloration was due to a lack of specific provisions in room and equipment inspection criteria for evaluating the condition of light fixtures. You indicate that there is no drug product impact based on acceptable environmental monitoring results, successful media fills, and the absence of out-of-specification findings related to microbiological contamination or sterility.

Additionally, you state that production, maintenance, and quality assurance representatives conducted a walkthrough of the Sterile Production Department to identify similar risks across other production zones but provide no further details of those assessments in the response.

Your response is inadequate. You do not explain the cause of the (b)(4) discoloration, and you attribute the failure to a procedural gap. Additionally, your retrospective drug product impact assessment of distributed batches does not include a review of visible particulate inspection data to determine whether any rejected units contained (b)(4) particles or other unusual particles.

In response to this letter, provide:

• Comprehensive, independent risk assessment by a qualified consultant of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to:
  o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual interventions wherever possible)
  o Equipment placement and suitability, including ergonomics for each human interaction and sufficient cleanroom space
  o Air quality in the ISO 5 area and surrounding room including, but not limited to air volume and flow (e.g., review of smoke studies for each line)
  o Reduction or elimination of aseptic manipulations
  o Facility layout
  o Personnel Flow and Material Flow throughout all rooms used to conduct and support sterile operations

• A detailed remediation plan from the independent consultant with timelines to address the findings of the contamination hazards risk assessment. Describe comprehensive improvements to be made to aseptic processing operation design and control for each aseptic processing line at your facility and explain how this CAPA plan will robustly remediate your deficient sterile manufacturing operations. Include comprehensive changes to the design of each of your aseptic processing lines and cleanrooms, the specific barrier system to be used (e.g., Restricted Access Barrier, (b)(4)), and associated timelines. Also, describe your plans for qualification and validation of your extensively remediated operations.

• Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including not but 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 the risk assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.

• Deviation and CAPA reports related to the (b)(4) discoloration on the light fixtures in the aseptic core, and any steps taken to ensure suitability of the environment after replacement of the fixtures. Provide the assessment results of the walkthrough of the Sterile Production Department that was conducted to identify whether similar deficiencies existed.

• Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review. Your plan should also ensure that appropriate actions are taken throughout the company network.

2. 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 environmental monitoring revealed an adverse trend of mold recoveries on personnel for the months of February, March, May, and June. However, you did not open a trend investigation until August 27, 2025.

For example, you recovered 83 colony forming units, including mold, from sampling an operator’s neck in the ISO 7 area in (b)(4). Your action level is (b)(4) or more colony forming units, but you did not initiate a deviation investigation.

Notably, there were multiple additional instances of excessively high microbial counts recovered from cleanroom personnel during this period.

You continued to not conduct investigations of environmental monitoring action level excursions in “non-product related” areas (ISO 7 and ISO 8), such as gowning rooms and corridors. We previously discussed this insufficient oversight of environmental control in our November 15, 2024, regulatory meeting. Your failure to promptly investigate these excursions may allow microbiological contamination hazards to persist and worsen in your classified areas.

In your response, you state investigations were not opened because two former microbiology supervisors incorrectly advised personnel that non-product-related excursions did not require investigation initiation. You also note that you have rejected (b)(4) batches in response to significant environmental monitoring deviations, and you have extended your shutdown to continue until you verify remediations to aseptic processing facility control including improved gowning, cleanroom behavior, and environmental monitoring.

We acknowledge these efforts. However, your response does not adequately address the responsibility of your quality unit to ensure procedures are followed and environmental monitoring excursions are appropriately investigated.

B. Your investigation into visible particulate (e.g. (b)(4)) contamination of (b)(4) batches of (b)(4) was not conducted in a timely manner. You opened the investigation on June 4, 2025, and the status of the investigation on November 3, 2025, five months later, was still in progress. You continued to manufacture additional batches on the same processing line without definitive root causes identified.

In your response, you note that at the time of our inspection you were continuing to investigate the visible particulate and assess its impact on the batches. You state you notified the application holder about the particulate contamination and took several corrective actions. These include establishing a new quality operations position to oversee investigations and deviation management, and increasing personnel to reduce the deviation backlog. You also provided awareness training to staff and are requiring all deviations to be initiated using TrackWise software. Additionally, you state you placed an inventory block on the implicated stopper lot that may have contributed to the visible particulate contamination.

Your response is inadequate. Your response does not confirm whether the particulate investigation is complete, nor does it provide an updated investigation report including your final root cause analysis and all associated actions taken by your firm.

In response to this letter, provide:

• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit (e.g., action limits), 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, quality assurance 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, analyses investigation trends, improves the CAPA program when needed, implements final quality assurance decisions, and is fully supported by executive management.

• A summary of updated deviations and related CAPA reports. Provide effectiveness checks for the adverse trend in mold recoveries.

• A drug product impact assessment of the particulate contamination and your associated investigation.

Ineffective Quality System

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.

Failure to address any violations may also result in the FDA refusing admission of articles manufactured at Jubilant HollisterStier General Partnership at 16751 Trans-Canada Highway, Kirkland, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3001623073 and ATTN: Erika V. Butler.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
____________________

1 Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.