FDA 就 Round Lake 工厂无菌注射剂 CGMP 缺陷向 Baxter 发出警告信（320-26-132）

Delivery Method:

VIA UNITED PARCEL SERVICE AND VIA E-MAIL

Reference #:

320-26-132

Product:

Drugs

Recipient:

Recipient Name

Mr. Andrew Hider

Recipient Title

President and CEO

Baxter International Inc.

One Baxter Parkway
Deerfield, IL 60015
United States

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

September 29, 2026

WARNING LETTER
Reference number: 320-26-132

To Andrew Hider:

This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.

FDA Inspection

Violations were observed and documented during an inspection of your drug manufacturing facility, Baxter Healthcare Corporation, FDA Establishment Identifier (FEI) 1416980, at 25212 W Illinois Route 120, Round Lake, from March 23 to April 2, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.

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 April 23, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

Violations of the Federal Food, Drug, and Cosmetic Act

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

1. 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 (21 CFR 211.42(c)).

You manufacture various injectable drugs products including cephalosporins (a beta-lactam drug product) and (b)(4) drug products at your facility. You failed to ensure complete and comprehensive separation of cephalosporin and (b)(4) drug products in this shared facility.

Lack of Complete and Comprehensive Separation

Your facilities and controls were inadequate to prevent the conditions that would allow for cephalosporin contamination of (b)(4) drugs.

Your building is divided into (b)(4) beta lactams, (b)(4) production. These building segments are separated by a physical wall that you consider to be fully sealed, along with dedicated HVAC units.

However, since January 2025, your environmental monitoring (EM) program used to monitor containment of beta-lactam drug products has detected cephalosporin in several instances and in multiple areas of the (b)(4) side of the building.

Inadequate Cephalosporin Monitoring

While your monitoring program detected recurring cross-contamination, it was inadequate to promptly detect loss of containment and cephalosporin contamination in your facility. For example:

• EM sampling was insufficient in both number and location.
• Swab sampling qualification was inadequate to assure low-level recovery.
• Samples were evaluated beyond established solution stability time allowances.

These inadequacies create risk for underrepresentation of true contamination hazards throughout your facility, create potential for false negative results, and inhibit meaningful data collection upon which your quality unit (QU) can make sound risk-based decisions.

A rigorous monitoring program is essential for facility qualification, early detection of contamination hazards, and timely corrective action and preventive action (CAPA).

In addition, your testing of (b)(4) drug products for potential contamination consisted of a single unit regardless of batch size. However, contamination is generally nonuniformly distributed. Results obtained from testing a small sample size are unlikely to detect contamination that may exist in a batch exposed to the contamination hazards identified at your firm. Consequently, substantial residual uncertainty remains regarding the actual variability of contamination that may exist in batches you produce.

We also note that you mistakenly discarded multiple failing cephalosporin environmental samples before further analysis could be conducted.

In your response, you commit to strengthen investigations into positive cephalosporin findings, create a tracking form to help prevent missed samples, and improve low-level recovery. Your response also indicates that significant uncertainty remains regarding the causes of the recurring findings of facility contamination. You indicate that personnel movement was a weakness in your containment strategy while adding that personnel movement is likely not the sole contributing factor.

Your response is inadequate because it fails to adequately address how you will ensure complete and comprehensive separation. You also failed to thoroughly reevaluate your original risk management decisions, including supportive risk assessments and associated risk controls, to ensure prevention of beta-lactam cross-contamination. Although your cephalosporin and (b)(4) areas exist within the same external building structure that you claim is completely and comprehensively separated by a (b)(4), it is essential that your design completely precludes any potential for incidental air, personnel, materials, equipment, or other interaction that could be a vector of contamination. A rigorous quality risk management program should comprehensively assess the design and determine if it provides as much protection against cross-contamination as is achieved by manufacturing in a separate building.

We note that data shared during our recall discussions revealed additional cephalosporin contamination events in the (b)(4) area, including as recently as (b)(4).

Contamination of (b)(4) with beta-lactam drugs presents a serious risk to patient safety, including potential life-threatening (b)(4). (b)(4) responses can occur in susceptible patients exposed to (b)(4) beta-lactams. Therefore, no safe level of beta-lactam contamination has been determined to be a tolerable risk.

In response to this letter, provide:

• A comprehensive, independent evaluation of the sufficiency of facility modifications implemented in an attempt to achieve complete and comprehensive separation (e.g., physical wall, dedicated air handling) between cephalosporin and (b)(4) areas.
• An updated comprehensive, independent risk assessment of all beta-lactam contamination hazards with respect to your procedures, equipment, and facilities, including but not limited to, the following:
  o Identification of all contamination hazards (e.g., personnel, material, air systems, infrastructure vulnerabilities).
  o Hazard identification using formal hazard identification tools.
  o Expanded risk-based EM including appropriate, scientifically justified, sampling methods, locations, and frequencies (e.g., inside production rooms, equipment surfaces, walls, contractor and operator garments, boots, shared forklifts trucks, shared lab cabinet, other potential cross-contamination locations), with consideration of all associated containment elements.
  o More responsive systems to vigilantly respond to any contamination, including enhanced trending systems.
  o Personnel flow and material flow (comprehensive mapping of all such potential interactions between all facilities that may introduce a potential hazard).
  o Scientifically justified sampling of (b)(4) finished drug product batches.
  o Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment.
• A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to design (e.g., facility changes) and explain how this CAPA plan will robustly remediate your deficiencies. Include a description of any residual risk that may remain following these remediations, and describe whether it enables risk acceptance. Also include a commitment to implement thorough change effectiveness activities and to revisit the risk assessment when necessary.
• A comprehensive assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous (ALCOA) records throughout your operation.
• Full investigations and data pertaining to any failing cephalosporin samples that were discarded since August 2024, including but not limited to sampling location, date, recovery amount, and any extra testing that was to be performed.

2. 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)). Your firm also 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)).

You operate (b)(4) processing lines used to aseptically manufacture sterile injectable drug products for the U.S. market. Your (b)(4) were inadequately validated to ensure that they were capable of consistently (b)(4) interior surfaces of your (b)(4) lines in preparation for aseptic production. In addition, your aseptic process simulations did not sufficiently represent worst-case conditions, and you lacked adequate sampling of your ISO 5 (Grade A) area.

Biological Indicator Recoveries and Inadequate (b)(4) Validation

Inadequacies in your (b)(4) process were demonstrated through a trend of routine recoveries of biological indicator (BI) growth at the completion of (b)(4) cycle re-qualification (validation) runs since (b)(4).

Notably, your acceptance criteria were inappropriate in that they allowed routine recovery of multiple BI survivors per re-qualification run. An adverse trend of numerous positive BIs were identified in multiple re-qualification cycles across multiple (b)(4) lines. For example, for line (b)(4), positive BIs occurred at numerous locations ((b)(4) of (b)(4) locations) and the positive findings included multiple replicates per location ((b)(4) recoveries of (b)(4) replicates). In addition, other lines had similar substantial findings of positive BIs. However, you considered all re-qualification studies to be acceptable and did not further evaluate the excessive variability of your (b)(4), including the potential impact to product. These significant recurring BI failures indicate poor (b)(4) method efficacy and require further investigation.

We also noted additional deficiencies in your (b)(4) reliability. For example:

• You lacked adequate scientific justification for BI locations.
• You allowed repetition of re-qualification cycles without proper investigation into observed BI growth.
• You did not align with technical references you cited in your procedures.

We note that you recovered (b)(4), from an (b)(4) inside your (b)(4) during production.

In your response, you commit to engaging a (b)(4) to help improve (b)(4), revising acceptance criteria to align with industry standards, and initiating non-conformance reports to investigate the observed BI growth. You also commit to evaluating alternative (b)(4) technology.

Your response is inadequate in that it does not provide sufficient detail or supporting documentation to describe how adequate (b)(4) will be achieved during the interim period prior to completion of long-term remediation.

Incomplete exposure of interior surfaces to (b)(4) compromises (b)(4) effectiveness and places your (b)(4) environment at risk. The (b)(4) (Grade A) area is critical because sterile products are exposed during aseptic production and therefore vulnerable to contamination if operations are not well designed and diligently controlled. Aseptic processing operations should be designed and executed to minimize exposure of sterile articles to potential contamination hazards in the manufacturing operation. Flaws in the design or control of cleanrooms and aseptic processing operations can enable entry of contaminants into the critical (b)(4) processing area and lead to product contamination.

Inadequate Aseptic Process Simulation

The intervention of (b)(4) was simulated approximately (b)(4) times during a media fill, but production records indicate a significantly higher occurrence of this intervention.

In your response you commit to updating the minimum number of (b)(4) simulations to (b)(4) based on your 2026 retrospective review, which only covered approximately (b)(4). Your response is inadequate as it does not ensure worst-case production activities and conditions are challenged across all (b)(4) lines. If a media fill program fails to incorporate contamination risk factors and closely simulate actual drug production, the state of process control and assurance of sterility cannot be accurately assessed.

Inadequate Environmental Monitoring

Your (b)(4) processing lines include critical operational steps conducted in (b)(4). However, there was only a (b)(4) in one of these (b)(4). In addition, surfaces were not monitored for microbiological contamination.

Vigilant and responsive environmental monitoring programs provide meaningful information on the state of control of the aseptic processing operation and enable an early warning system that identifies emerging contamination hazards before sterility is compromised.

Inadequate Airflow

Although your (b)(4) configurations can vary (e.g., (b)(4) bag capacity, (b)(4) configuration), you lacked airflow visualization studies in (b)(4) of your (b)(4) lines. In addition, your airflow visualization studies were insufficient (e.g., worst-case (b)(4) conditions).

We note that you have had a history of sporadic sterility test positives since 2013 (testing is routinely performed in a (b)(4)) and persistent particulate contamination issues.

Your airflow visualization studies also revealed substantial turbulence in your (b)(4), in which critical process steps are performed. Your firm acknowledged turbulent non-unidirectional airflow within your (b)(4), which houses processing equipment.

Our overall findings indicate significant deficiencies in the design of your aseptic processing operation. Your current equipment, process, and airflow design pose excessive contamination risk.

Turbulent airflow may be appropriate for a (b)(4) that does not house aseptic processing equipment. In contrast, your firm uses (b)(4) that include processing line equipment.

A strong quality system is essential to oversee design and construction of aseptic processing lines, cleanrooms, and supporting utilities, and to ensure ongoing proper operational control to safeguard against contamination hazards throughout the facility lifecycle.

Well-designed aseptic processing (b)(4) represent a significant technological advance over traditional operational designs. Because all technologies have failure modes, it is essential to implement a robust design and control program that enables an ongoing state of control.

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.

In your response, you commit to improving your EM program and performing airflow visualization studies on all of your lines. You also state that you will use data from these studies to identify locations for BIs and EM.

Your response is inadequate as you lack a commitment to upgrade your manufacturing infrastructure, including equipment replacement, as part of your long-term remediation plan. In addition, the timeline for implementation of additional viable air monitoring in the (b)(4) is unclear.

In response to this letter, provide:

• A detailed program for designing, validating, maintaining, controlling and monitoring each of your (b)(4) that includes vigilant monitoring to ensure an ongoing state of control.
• 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 (b)(4) area (e.g., risk reduction or elimination of manual interventions wherever possible)
  o Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficiency of space for operations
  o Air quality in the (b)(4) area including, but not limited to, air unidirectionality
  o Facility layout
  o Personnel flow and material flow (movement throughout all rooms used to conduct and support sterile operations, and all material transfers)
  o (b)(4) practices and procedures (e.g., (b)(4) efficacy, appropriate (b)(4) and configuration)
  o Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessment
• A detailed remediation plan 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 at your facility and explain how this CAPA plan will systematically remediate your deficient sterile manufacturing operations. Include detailed changes to the design of both your aseptic processing lines and cleanrooms. Your action plan should include both an interim plan as well as long-term steps to fully remediate your facility, equipment, and process design.
• An independent review, detailed report, CAPA, and timelines for remediation of your (b)(4) methods (e.g., (b)(4) parameters, optimized airflow, improved surface exposure). This comprehensive, independent analysis should incorporate any differences between the design and operation of each (b)(4) and its processing equipment (e.g., dimensions, orientation, (b)(4) design, air volume, (b)(4), (b)(4) bowls, bag capacity, etc.).
• An independent, comprehensive evaluation of airflow unidirectionality in your aseptic processing operations. Ensure smoke studies are conducted under dynamic conditions with thorough and complete assessments of aseptic processing line airflow unidirectionality, including the impact of aseptic interventions, worst-case (b)(4) pattern, and dynamic interactions with the surrounding cleanroom. Conduct these smoke studies after you remediate your aseptic operation and using proper practices (e.g., (b)(4) media) to appropriately visualize airflow.
• A comprehensive, independent review of your process simulation (e.g., media fill) program to ensure accurate simulations of commercial aseptic manufacturing operations, including, but not limited to, appropriate incorporation of worst-case conditions.
• A summary table of all EM (includes surfaces, air, and (b)(4)) results within your (b)(4) lines that revealed microbial growth since January 1, 2023. Include line sample location, date, colony forming unit (CFU) count, microorganism identification, and any associated investigations.

3. 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 manual visual inspection program was inadequate to reliably detect defects and ensure your sterile injectable drug products were essentially free of visible particulates.

For example, operators performing (b)(4) visual inspection were not properly qualified, as evidenced by the following:

• Operators were not appropriately challenged to ensure they were capable of reliably detecting particulates within the lower end of the visible spectrum.
• Particulates in challenge kits were excessively large (e.g., greater than (b)(4) microns), approximately (b)(4) times larger than what operators should be capable of reliably detecting.
• Operators’ rate of inspection was excessively fast (e.g., (b)(4) per unit) and did not align with the standards referenced in your procedures.
• Notably, you also demonstrated poor detection rates when you used significantly longer inspection times during Acceptable Quality Limit (AQL) sampling.

Your approach to identifying product defects compromises reliable detection and the quality of data inputs to support batch release and CAPA decisions made by your quality unit.

In addition, the significant particulate matter complaints received between 2023 to 2025 indicate an inadequate visual inspection program. For example, on May 9, 2025, after testing a returned cefazolin complainant sample you confirmed foreign particulate contamination was consistent with cardboard (approximately (b)(4) mm). Your investigation concluded that inadequacies of visual inspection were a contributing cause, but you did not implement sufficient CAPA to ensure remediation of your visual inspection program.

Your investigation specifically cited potential for compromised product quality and potential patient safety risks, but stated that field action was not warranted. We acknowledge that on July 17, 2026, you agreed to voluntarily recall cefazolin, Lot LD175708, only after the Agency contacted you.

In your response you commit to enhancing your visual inspection program including performing probability of detection (PoD) studies using the (b)(4) per unit inspection duration.

Your response is inadequate. You indicate that data from post-market complaint evaluations and retain sample reviews confirm that your controls remain effective. However, you have identified particulate matter in retain and complaint samples after product was released. In addition, your response does not adequately address the spike in particulate matter defects from 2024 ((b)(4) defects) to 2025 ((b)(4) defects). There remains a lack of assurance that your injectable drug products are essentially free from visible particulates while you work on long-term remediation.

Visual detection of particulates is a probabilistic process that depends on, among other things, ensuring that visible particulates can be reproducibly detected by trained personnel with appropriate visual acuity. At a minimum, personnel should reliably be capable of detecting particulates of (b)(4) microns or greater at a (b)(4)% probability of detection. It is important that any visible particulate contamination is appropriately evaluated and investigated. Particulates in injectable products should be avoided through appropriate preventive measures built into your design and production controls. When categorizing any visible particles, extrinsic or foreign matter should receive special attention, as it may indicate possible microbial contamination. Extrinsic or foreign particulate contamination should occur very infrequently and trigger a thorough investigation and appropriate CAPA.

In response to this letter, provide:

• A comprehensive, independent assessment and remediation plan of your systems for the visual inspection of sterile injectable drugs for defects, including the presence of particulate matter. The assessment should include acceptance and rejection criteria, personnel training, supervision, equipment and personnel qualification, equipment maintenance, and process validation, and the procedures governing them. Also include product-specific knowledge, process experience (e.g., thorough assessment of the spike of (b)(4) particulate matter defects in 2025), deviation investigation analysis, and recall/complaint data. Provide your detailed remediation action plan that includes dates by which each remediation activity will be completed and a periodic independent reassessment of the plan’s effectiveness. Include a summary of the review and recommendations made by your independent consultant.
• A comprehensive, independent assessment of each lot of sterile injectable drugs distributed from your facility that remains within expiry to meet the requirement of being essentially free of visible particles. This comprehensive review should include a review of all relevant in-process and finished product data obtained by your firm including all batch records.
• An interim plan for risk mitigation while you perform broader studies to improve your visual inspection program. Provide a detailed list of your risk mitigations (e.g., sampling plans and methods for your proposed destructive testing).

4. 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).

There was a pattern of inadequate investigations into critical issues, including leaking drug products and sterility failures.

Leaking Units

Your investigations into the “systemic nature” of container-closure integrity failures lacked effective CAPA to address the significantly increased rate of leak defects in your injectable drug products. You did not implement sufficient CAPA to ensure remediation of your final inspection program. Further, since 2023, media fill units were found leaking during incubation and you have received numerous leak complaints for marketed products.

All sterile drugs must be packaged using container-closure systems with robust protection that prevents the ingress of microorganisms. A product’s ability to maintain integrity throughout anticipated stresses and external factors during manufacture, storage, distribution, and consumer use is critical to ensure product quality and safety. Loss of container-closure integrity is a direct cause of non-sterility.

In your response, you acknowledge that strengthening your investigation system is warranted and you will evaluate whether (b)(4) container closure integrity testing (CCIT) could be an effective layered control. You also commit to a retrospective review of critical non-conformance reports (NCR) and laboratory investigations for the last year.

Your response is inadequate. Limiting a retrospective review to (b)(4) lacks adequate scientific justification as your leak trending data illustrated the leak rate has consistently increased annually from 2023 to 2026. You also do not sufficiently address how a lack of highly capable leak detection systems impacts already produced products, or sufficiently detail improvements to your CAPA system. In addition, data from your firm indicates that although leak rate has increased, the number of NCRs opened has decreased.

Sterility Failure

Your investigation into a 2025 sterility failure for cefazolin, lot (b)(4), assigned the root cause as a non-integral test container. Test records had been signed and dated indicating that container integrity was initially verified. However, after observing turbidity, you subsequently stated in your investigation that container integrity was not verified, classifying it as a “no-test.” Without conducting a Phase II investigation, you concluded there was no risk to the manufacturing process or finished product. You invalidated the sterility result without adequate scientific justification and released this lot in July 2025.

Notably, the same container integrity problem had been observed in the sterility test of (b)(4), lot (b)(4), in (b)(4), which you rejected.

In addition, a “no-test” designation was used for an (b)(4) cycle requalification attempt that resulted in numerous positive BIs.

In your response, you state your belief that the laboratory error of incubating non-integral sterility test containers was the definitive root cause. Your response is inadequate as it fails to address why your lab records described the test container as integral. It also fails to thoroughly address the lack of contemporaneous documentation of any subsequent deviation that could have theoretically occurred. You also commit to implementing a closed membrane sterility testing system in the future, but your proposal does not ensure timely remediation.

Product contamination may go undetected for substantial periods if your firm employs unreliable sterility testing practices. It should also be noted 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 a prompt review of the qualification status of the aseptic process.

Your firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidance documents: 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.

In response to this letter, provide:

• A comprehensive assessment and remediation plan to ensure your QU is given the authority, independence, and resources to effectively function. The assessment should also include, but not be limited to, the following:
  o A determination of whether procedures used by your firm are robust and appropriate
  o Provisions for independent QU oversight throughout your CGMP operations to ensure satisfactory procedures and adherence to appropriate practices
  o A complete and final review of each batch and its related information before the QU disposition decision, including all investigations
  o Oversight and approval of discharging of all QU duties to ensure identity, strength, quality, and purity of all products
  o Also, describe how executive management supports robust quality assurance at your firm, including, but not limited to, timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control
• A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit results, and failures. Provide a detailed action plan to remediate this system, encompassing the following:
  o Staff competencies (including use of appropriate subject matter experts)
  o Written procedures
  o Scientific rigor and foundation
  o Scope determination
  o Root cause evaluations
  o CAPA effectiveness
  o Quality unit lead functional roles, and oversight to ensure all phases of investigations are appropriately conducted
  o And, based on above, detailed systemic improvements to the investigation system
• An independent third-party 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 when needed, implements final quality unit decisions, and is fully supported by executive management.
• Provide a comprehensive, independent process capability assessment of your aseptic processing lines, with special emphasis on the capability of critical operational steps, including but not limited to, all container-closure integrity failure modes, and any related CAPA to be initiated in response to the capability assessment.
• Perform a holistic assessment across your facilities for similar issues noted at this site and implement appropriate CAPA across your corporate network.

CGMP Consultant

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit¹ of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

Your use of a consultant does not relieve your firm’s obligation to comply with CGMP.

Repeat Observations at Multiple Sites

In a previous regulatory meeting held on January 15, 2025, FDA discussed similar CGMP violations at this facility. You proposed specific remediations for these violations in your response.

FDA also cited similar CGMP violations at other facilities in your company’s network. These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate.

Your firm’s executive management remains responsible for fully resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance. You should immediately and comprehensively assess your company’s global manufacturing operations to ensure that systems, processes, and the products manufactured conform to FDA requirements.

Drug Recall

On July 17, 2026, FDA held a teleconference with your firm and recommended that you voluntarily recall one lot of cefazolin and various (b)(4) drugs currently in distribution from the U.S. market, to which you agreed.

The company announcement for the cardboard particulate recall was posted to the FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/baxter-issues-voluntary-nationwide-recall-cefazolin-dextrose-injection-usp-2g-100ml-20mg-ml-single

Request for a Meeting with FDA

After you submit your response to this warning letter, we recommend that you reach out to this office to arrange for a teleconference to discuss your corrective actions and preventive actions in detail. Direct your request to Kathryn Hall at [email protected].

Conclusion

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

Unresolved violations may 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.

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 [email protected], 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.

Send your written response to [email protected] within fifteen (15) business days of receipt of this letter². Identify your written response with FEI 1416980 and ATTN: Compliance Officer Matthew Schnupp in the letter or in the subject line of the email.

If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.

FDA posts warning letters to www.FDA.gov.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

cc:

Ivan Quadrio
Site Director and Associate Vice President of Engineering
Baxter Healthcare Corporation
25212 W Il Route 120
Round Lake, IL 60073
[email protected]

Scott Kaplan
Head of Quality, Regulatory Affairs, and Patient Safety
Baxter Healthcare Corporation
1 Baxter Parkway
Deerfield, IL 60015
[email protected]

___________________________

1 i.e., Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.

2 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.