CareFusion 213, LLC MARCS-CMS 722729 — April 30, 2026

WARNING LETTER

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• Delivery Method: Via Electronic Mail - Return Receipt Requested
• Reference #: 320-26-72
• Product: Drugs

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• Recipient: Mr. Thomas E. Polen, Jr.; Chairman, CEO and President ; CareFusion 213, LLC; 1 Becton Drive; Franklin Lakes, NJ 07417-1880; United States

• Issuing Office: Center for Drug Evaluation and Research (CDER); United States

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Warning Letter 320-26-72

April 30, 2026

Dear Mr. Polen:

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, CareFusion 213, LLC (a wholly-owned subsidiary of Becton, Dickinson and Company (BD)), FEI 3004932373, at 1550 Northwestern Drive, El Paso, Texas, from October 15 to 24, 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 17, 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 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 manufactures sterile drug products for (b)(4), including (b)(4), which are used (b)(4). (b)(4) is also specifically labeled for use in (b)(4). Your manufacturing process includes sterilizing the drug solution in sealed (b)(4) ampoules. Some (b)(4) undergo (b)(4).

Inadequate Complaint Investigations

Since September 2023, your firm has received more than 2,500 customer complaints about your drug products including reports of foreign matter (e.g., (b)(4) particles and suspected mold), missing components, empty (b)(4), and compromised package seals. Your investigations into these complaints were inadequate, as you repeatedly failed to conduct thorough investigations, adequately identify root causes, provide scientific rationale for your conclusions, and extend investigations to other potentially affected batches. As a result, your corrective actions and preventive actions (CAPAs) were ineffective.

For example, your investigation into a complaint of black specks and possible mold on sterile (b)(4) was deficient. You concluded the most likely root cause was the unintentional introduction of particulate matter from the manufacturing environment, yet you failed to extend the investigation to other lots that were manufactured under the same conditions or on the same equipment. Additionally, your investigation did not sufficiently examine potential contributing factors such as facility and equipment cleaning and maintenance, and personnel practices. Your investigation concluded that “a project has been opened to further investigate the reported issue,” but you lacked evidence that the follow-up project was actually initiated.

Furthermore, your investigation into a complaint identifying (b)(4) pieces, missing (b)(4), and illegible printing on your (b)(4) was also inadequate. You indicated that the probable root cause of (b)(4) pieces and missing (b)(4) was equipment vibrations during manufacturing, but you did not extend the investigation to other batches processed on the same equipment. Your investigation also did not address the illegible printing on the (b)(4) identified in the complaint.

FDA investigators observed numerous other examples in which your firm failed to conduct thorough investigations related to complaints, including failing to follow investigation procedures, failing to extend investigations to other potentially impacted batches, and failing to conduct appropriate market action assessments.

Inadequate Out-of-Specification (OOS) Investigations and CAPA

Your OOS investigations and CAPA were deficient. For example, (b)(4) Lot (b)(4) failed a sterility test during stability testing. You initiated a recall and concluded that (b)(4) in the (b)(4) used to seal the (b)(4) caused the sterility failure. The (b)(4) created (b)(4) that compromised the sterile barrier. Your (b)(4) supplier informed you that (b)(4) are inherent and cannot be entirely eliminated, and you determined that you had no in-process inspection criteria for (b)(4) defects.

Although your investigation examined other batches manufactured with the same lot of (b)(4) and identified (b)(4) in multiple batches, you failed to properly extend your investigation to batches manufactured with other lots of (b)(4) from the same supplier. Notably, the investigation failed to address the scope and severity of a container-closure integrity issue that led to non-sterility and a product recall. Your quality system did not ensure that systemic problems with both the (b)(4) material and your inspection process were addressed by a comprehensive CAPA.

In your response, you state that you have engaged a consultant to perform a comprehensive review of your quality system, revised your standard operating procedures for complaint handling, implemented an enhanced training program for complaint investigators and quality personnel, and are conducting a retrospective review of past complaints. Regarding the (b)(4) sterility failure, you state that you extended your investigation to all (b)(4) lots, inspected retain samples, found additional (b)(4) but no sterility failures, and concluded the failure was isolated to the recalled lot.

Your response is inadequate. You have not adequately explained how your quality unit failed in its oversight of numerous investigations associated with repeated and systemic product quality deficiencies that led to customer complaints. Your conclusion that the sterility failure was isolated to one incoming (b)(4) lot is contradicted by the supplier’s statements that (b)(4) are inherent to their process and cannot be eliminated. You do not sufficiently address how you will detect when this inherent material attribute causes breaches in container-closure integrity to ensure that defective units are not distributed.

Regarding the recall, you performed your extended investigation only after FDA identified significant gaps in the original investigation. You do not discuss why you did not initially extend your investigation when you identified systemic issues with the packaging material.

We note that your firm has a history of sterility-related quality issues including multiple recalls and Field Alert Reports. It is essential that you assure sterility of your (b)(4) products.

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 oversight.

In response to this letter, provide:

• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, OOS 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, quality unit 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 investigations trends, improves the CAPA program when needed, implements final quality unit decisions, and is fully supported by executive management.
• A comprehensive, independent retrospective review of all complaint investigations for the last three years from the initial date of inspection. In particular, this review should prioritize critical complaints relating to foreign contamination, container-closure integrity, non-integral products (e.g., missing (b)(4)), functionality problems, and potential sterility issues. Include the following independent assessment for each investigation:
  o Determine whether the scientific justification and evidence relating to the identified root cause(s) were adequately documented. Where a complaint was attributed to factors outside of the firm’s control (e.g., user error), assess the strength of this determination and whether it was based on conclusive or inconclusive information.
  o Determine whether relevant complaint samples were available and the extent of efforts to obtain the complaint sample from the complainant. If insufficient attempts were made, identify the root cause(s) for not adequately pursuing their return.
  o For all complaint investigations found by the retrospective review to be deficient, to have an inconclusive root cause, or to have no root cause identified, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, OOS history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation and any identified CAPA (e.g., manufacturing operation improvements).
  o Identify any patterns or trends across complaints that may indicate systemic manufacturing, quality control, supplier qualification, or design issues requiring corrective action.
  o Based upon this independent review, provide a comprehensive assessment of your overall complaint handling program that identifies any deficiencies and corresponding CAPA.
• A comprehensive review and remediation plan for your OOS-result investigation systems. The CAPA should include but not be limited to addressing the following:
  o Quality unit oversight of laboratory investigations
  o Identification of adverse laboratory control trends
  o Resolution of causes of laboratory variation
  o Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified
  o Adequate scoping of each investigation and its CAPA
  o Revised OOS investigation procedures with these and other remediations
• Provide a comprehensive, independent review of your process capability and quality performance, including:
  o Comprehensive identification of all defects encountered at each manufacturing process stage.
  o Classification of each identified defect by type, frequency (i.e., average, range), severity, and root cause(s).
  o Analysis of multi-year, longitudinal batch-to-batch trending data for each defect.
  o Actual in-process and finished product yield data for each batch.
  o Process capability index calculations for all critical manufacturing steps.
  o A thorough independent assessment of both sporadic (i.e., unexpected spikes) and average variability observed based upon detailed review of above items. Provide analytical findings, associated operational weaknesses and root causes, and potential remediation options.
• Your commitment to implement CAPA based on the above process performance analysis and to begin conducting annual capability analysis with quality oversight across all product lines.

2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).

Your firm lacked appropriate spore population verification on in-house prepared biological indicators (BIs) used in your (b)(4) sterilization (b)(4) process. You used these BIs for verifying sterilization effectiveness and as a batch release specification for (b)(4) drug products.

You validated your method for preparing BIs for your (b)(4) process in 2015 and included a target specification for (b)(4) spores of (b)(4) colony forming units (CFU). However, you have failed to perform quantitative verification of the spore population for these BIs since the initial validation. Instead, your firm has relied on a combination of vendor certificates for the initial spore count, theoretical calculations, and qualitative (growth/no growth) testing after (b)(4) with the final prepared BIs to evaluate sterilization effectiveness. Your procedure for preparing BIs states that population verification is not required because the preparation method was validated. However, validation of a preparation method does not eliminate the need for ongoing verification.

In your response, you state that you have subsequently performed verification studies on recent BI preparations, and you commit to implementing ongoing verification. You also state that there is no impact to finished products because your (b)(4) parameters are set to ensure the reproducibility of the (b)(4) process.

Your response is inadequate because you did not assess the impact of the lack of quantitative verification of your BIs. Your assertion of (b)(4) process reproducibility assumes the BIs consistently contained adequate spore populations, which you have not demonstrated.

Without quantitative verification, you cannot determine whether “no growth” results after (b)(4) are due to an effective sterilization cycle or are because the BIs are lacking sufficient viable spore population.

In response to this letter, provide:

• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
  o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
• For any (b)(4) products that are not terminally sterilized by your company (or its contract facilities), explain whether you distribute these unsterilized products with the expectation that your customers will ultimately perform terminal sterilization of these batches.
• A comprehensive plan and timeline to transition all (b)(4) drug products to terminal sterilization. If your firm does not intend to transition all (b)(4) drug products to terminal sterilization, provide a detailed rationale justifying your scientific and public health basis. Also include a risk assessment that addresses your history of sterility-related quality issues.
• A comprehensive process description for all (b)(4) products your firm distributes. When describing each of the process options that your firm can use, detail whether the (b)(4) finished product is sterilized. For any process option that does not involve (b)(4) (including (b)(4)) prior to sterilization, comprehensively describe the (b)(4) steps that occur following the interim sterilization step. Also explain whether (b)(4) are sterilized, and if not, what your microbial bioburden specifications are for these parts and under what cleanroom conditions (b)(4) occurs.

3. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment; and failed to perform operations within specifically defined areas of adequate size; and failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.67(b) and 21 CFR 211.42(c)).

During our inspection, we observed inadequate cleaning and inadequate contamination control throughout your manufacturing facility where sterile drug products are assembled and packaged.

For example, our investigators found (b)(4) and (b)(4) inside your (b)(4) chambers which sterilize your drug product ampoules. During the inspection, your firm confirmed that the chamber cleaning procedure involved (b)(4) the (b)(4) chambers (b)(4) to remove (b)(4). However, we noted multiple instances of your operators’ failure to appropriately document (b)(4) during a period when multiple U.S. batches were being sterilized. Additionally, you did not test the (b)(4) used in your (b)(4) process for chemical or microbiological specifications. Unsuitable (b)(4) quality could introduce (b)(4), (b)(4), and bioburden – further compromising chamber cleanliness and sterilization efficacy.

FDA investigators observed (b)(4) residue on air vents, walls, and equipment surfaces in your main production area, packaging lines, ampoule rinsing room, and equipment washroom, despite cleaning logs documenting these areas had been cleaned. FDA investigators also observed broken (b)(4) on (b)(4) with sterilized ampoules next to assembly lines where these ampoules are (b)(4).

Your contamination control practices were also inadequate. FDA investigators observed personnel wearing face masks improperly in violation of your gowning procedures. Your quality notification QN 201162939 documented a bioburden excursion in non-sterile (b)(4) product showing (b)(4) CFU with Streptococcus pneumoniae identified, a significant opportunistic pathogen commonly found in the nose and throat.

Multiple environmental monitoring (EM) excursions also occurred in your filling areas. These contamination control failures are particularly worrisome if your (b)(4) do not ultimately undergo terminal sterilization on the (b)(4), including the (b)(4). When terminal sterilization is not applied to the finished product, robust aseptic processing control becomes critical to ensuring product sterility.

Notably, robust manufacturing design and control to prevent contamination also applies if (b)(4) are not intended to be sterile, when appropriate based on their indication. Such products must be free of microbes that may be objectionable in view of their intended use.

See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.

Your response states that you engaged an independent third-party expert to review and redesign your cleaning validation program and committed to implementing cleaning validation for equipment and product-contact surfaces. You identified the (b)(4) residue as (b)(4) used in certain (b)(4) and stated you evaluated chromatography data to confirm the absence of cross-contamination to other products. You conducted a risk assessment of your cleaning program and concluded that existing process controls at various manufacturing stages would detect and reject products containing residues, contaminants, or microorganisms beyond acceptable limits.

Your response is inadequate. Your commitment to implement cleaning validation does not address products currently in distribution manufactured under the conditions documented during the inspection. Your conclusion that existing controls would robustly detect contamination is contradicted by the nature of the customer complaints received by your firm, particularly given the extent of contamination, debris, gowning violations, and EM excursions documented during the inspection. Additionally, your identification of the (b)(4) residue and review of chromatography data do not address why your cleaning procedures failed to prevent its accumulation.

Inadequate removal of debris and residues from manufacturing equipment during cleaning can lead to contamination of drug products subsequently manufactured on the equipment. In addition, inadequate operational controls to prevent contamination can jeopardize patient safety by potentially compromising the sterility of products designed to (b)(4).

In response to this letter, provide:

• A comprehensive, independent assessment of your bioburden control program for non-sterile components and finished drug products. This assessment should include:
  o Bioburden testing and trending data for each lot of incoming (b)(4) received over the last three years, including total aerobic microbial count (TAMC), total yeast and mold count (TYMC), as well as all identification testing performed and organisms detected.
  o Bioburden and sterility testing data for all finished product batches manufactured over the last three years, including all data obtained when testing in-process and finished product batch units, as well as complete microbial identification of all organisms detected.
  o A comprehensive review by the independent third party of all microbiological test results (TAMC, TYMC, sterility tests, and organism identifications) for the last three years, including any OOS results that were subsequently invalidated. For any invalidated OOS results, assess the adequacy of the scientific justification and evidence supporting the invalidation decision.
  o An independent third-party review of your laboratory’s microbiological methods. The review should determine whether the methods are scientifically sound and capable of reliably detecting, quantifying, and identifying any bioburden present in incoming (b)(4) and finished drug products.
  o A summary report of all bioburden and sterility data collected from the above assessments, including trend analysis, identification of any patterns or excursions, and corresponding CAPA to address any deficiencies identified.
• A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one product.
• A CAPA plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program including enhancements to cleaning effectiveness, improved ongoing verification of proper cleaning execution for all products and equipment, and all other needed remediations.
• 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 them difficult to clean
  o swabbing locations for areas that are most difficult to clean
  o maximum hold times before cleaning
• Describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.
• 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.
• An independent, comprehensive review of your EM program to ensure vigilant, timely detection and response to potential product contamination hazards in your manufacturing environment. This assessment should include, but not be limited to:
  o establishing appropriate limits
  o sampling methods
  o sampling locations and frequencies
  o trend analysis
  o appropriate investigation of deviations and adverse trends
  o and a comprehensive CAPA plan based on the findings of the assessment
• A procedure for your (b)(4) system monitoring that specifies routine microbial and chemical testing of (b)(4) to ensure its acceptability for use in each batch of drug products produced by your firm, as well as its use in sterilization processes.
• The current action/alert limits for total counts and objectionable organisms used for your (b)(4) system.
• A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your (b)(4) system consistently produces (b)(4) meeting appropriate chemical and microbial limits for use in (b)(4) process.

Assurance of Sterility – Terminal Sterilization

It should be noted that although the sterility test is a critical final quality control for (b)(4) finished products that purport to be sterile, it cannot be solely relied upon as justification to release each drug product batch. The sterility test is only the last in a series of design and control provisions intended to protect the consumer from distribution of an unsafe batch. Sample sizes for sterility testing are typically small compared to the total number of units in a batch and may not detect sporadic non-sterility. For example, a failure to consistently execute a terminal sterilization cycle of the finished product within its validated state, or a sporadic container-closure issue, may go undetected for substantial periods if your firm places too much reliance on the final quality control test for sterility to identify a sterility assurance problem. It is also essential to note that any positive sterility test result represents a serious CGMP issue that requires a comprehensive investigation into the cause and extent of the problem, and prompt review of the validated status of your terminal sterilization process.

Repeat Observations at Facility

In previous inspections occurring in 2023 and 2016, FDA has repeatedly cited similar CGMP observations. In 2016, FDA cited your firm for failure to perform adequate investigations of product failures. In 2023, FDA cited your firm for failure to ensure adequate laboratory controls and failure to maintain facilities in a good state of repair. The current inspection reveals these deficiencies have persisted or recurred, demonstrating that executive management oversight and control over the manufacture of drugs is inadequate.

Quality Unit Authority

Significant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.

For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA’s guidances: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at
https://www.fda.gov/media/167721/download, and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download.

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.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. 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 address any violations.

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 days. 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 3004932373 and ATTN: Bryce Hammer.

Sincerely,
/S/

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