Fagron BV(WL # 724551)

Issuing Office:

Center for Drug Evaluation and Research (CDER)

United States

WARNING LETTER

WL # 724551

May 12, 2026

Dear Mr. Padilla:

You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]1 on April 21, 2017, and most recently on November 22, 2025. From October 9, 2025, to November 5, 2025, FDA investigators inspected your facility, Fresenius Kabi Compounding, LLC dba Fagron Sterile Services, located at 20 Dan Rd, Canton, MA 02021. During the inspection, investigators noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.

FDA issued a Form FDA 483 to your facility on November 5, 2025. FDA reviewed your facility’s responses, dated November 26, 2025, December 1, 2025, and December 5, 2025, and acknowledge receipt of your subsequent correspondence. FDA further acknowledges that your firm initiated a voluntary recall on February 5, 2026, of various lots of drug products, within expiry, produced using (b)(4) IV Bags intended or expected to be sterile due to lack of sterility assurance. Based on this inspection, it appears you produced drugs that violate the FDCA.

A. Compounded Drug Products under the FDCA

Under section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.2

An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.

B. Violations of the FDCA

Adulterated Drug Products

The FDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigators observed that:

1. You exposed sterile drugs and materials to lower than ISO-5 quality air.

Specifically, operators' arms blocked the first air to sterile vancomycin vials during reconstitution. Additionally, operators vigorously shook the vials during this process. This rapid movement likely disrupts the unidirectional airflow within the ISO 5 aseptic processing area, creating a contamination risk.

2. You failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.

Specifically, airflow visualization studies (i.e., smoke studies) do not accurately reflect the actual quantity and positioning of equipment, materials, and other components used during production. Consequently, it cannot be determined whether adequate, uninterrupted, unidirectional airflow is maintained throughout the aseptic drug production process.

The FDA investigators also noted CGMP violations at your facility that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:

1. Your quality control unit failed to exercise its responsibility to ensure that drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality and purity (21 CFR 211.22).

2. You failed to thoroughly investigate any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed (21 CFR 211.192).

3. You failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile (21 CFR 211.113(b)).

4. You failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).

5. You failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).

6. You failed to maintain buildings used in the manufacture, processing, packing or holding of drug products in a good state of repair (21 CFR 211.58).

Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance, Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.

Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.

C. Corrective Actions

We have reviewed your facility’s responses to the Form FDA 483, dated November 26, 2025, December 1, 2025, and December 5, 2025. We also acknowledge your firm initiated a voluntary recall on February 5, 2026, of various lots of drug products, within expiry, produced using (b)(4) IV Bags intended or expected to be sterile due to lack of sterility assurance.

We are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:

1. Regarding your firm’s failure 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 processes:

a. We acknowledge your interim and long-term corrective action plans to address deficiencies in your current (b)(4) process for intravenous fluid bags. We note your intention to (b)(4) and, if necessary, (b)(4)—are implemented and qualified. Once these planned enhancements are complete, and the revised process implemented, FDA will evaluate the adequacy and safety of your (b)(4) processes. This evaluation will include an assessment to ensure there is no adverse impact on the quality of drug components and finished drug products.

b. Regarding your firm's failure to ensure that personnel monitoring practices (i.e., gloved fingertip and gowned (b)(4) sampling) provide meaningful results, we acknowledge your plan to modify SOP # FSSBOS-SOP-0014, Aseptic Technique for the (b)(4) at the Canton Compounding Facility. However, the adequacy of this corrective action cannot be fully evaluated until the modifications are fully implemented and supporting documentation, such as executed batch production records, are provided for assessment.

c. We acknowledge your plan to conduct a new “Dynamic Airflow Qualification” study to address your firm's failure to perform adequate smoke studies under dynamic conditions representative of actual production. However, since you estimate the study will not be complete until March 31, 2026, we cannot evaluate the adequacy of your corrective action at this time. We remain concerned about your inability to verify adequate airflow patterns within the ISO 5 aseptic processing area.

2. Regarding your failure to establish an adequate system for cleaning and disinfecting the room to produce aseptic conditions:

We acknowledge your response regarding the brown, rust-like residue found on the wheelbases of the laminar flow hoods and tables in your ISO 7 areas. We note your plan to update procedures to enhance inspection and cleaning of these surfaces as necessary. However, your response did not include evidence—such as photographs or other documentation—demonstrating that remedial actions (e.g., cleaning) have been completed. Without this documentation, we are unable to evaluate the adequacy of your corrective action at this time.

3. Regarding your failure to maintain buildings used in the manufacture, processing, packing, or holding of drug products in a good state of repair, including paint chipping on air returns and a door, and a divot in the floor, all in ISO 7 areas:

We acknowledge your plans to repair and refinish the affected air returns and doors, as well as to repair the floor. However, you failed to provide evidence, such as photos or executed work orders, demonstrating that the repairs have been completed. Consequently, we cannot evaluate the adequacy of your corrective action at this time.

Some of your corrective actions appear deficient:

1. Regarding your Quality Unit’s failure to exercise its responsibility to ensure drug products produced are in compliance with CGMP, and meet established specifications for identity, strength, quality and purity:

We acknowledge the actions your firm has planned in response to its failure to adequately manage an adverse trend involving defects associated with your intravenous fluid bags. We note the following action items:

• Assess Fresenius Kabi vendor status based on review of defects noted.
  Target completion due date: 31Jan2025 [sic; date assumed to be 31Jan2026]

• Assess supplier qualification process regarding managing vendor complaints and escalations.
  Target completion due date: 31Jan2025 [sic; date assumed to be 31Jan2026]

• Update supplier qualification SOP based on closure of assessment.
  Target completion due date: 31Jan2025[sic; date assumed to be 31Jan2026]

However, your response fails to address fundamental deficiencies in how your Quality Unit managed a significant adverse trend related to the container-closure system of your sterile drug products. For example, although the IV bag manufacturer/supplier acknowledged defects in the IV bags’ injection and infusion ports, they never communicated a definitive root cause. Without this root cause determination, you could not verify whether the manufacturer/supplier's corrective actions (e.g., equipment “maintenance”) adequately resolved the issue. Your firm continued to rely solely on visual inspection processes as the primary control mechanism to prevent defective units from reaching patients.

Furthermore, requiring personnel to focus primarily on detecting port defects during visual inspection of finished sterile drug products raises concerns, as this may compromise their ability to identify particulates and other defects unrelated to ports.

2. Regarding your failure to thoroughly review any unexplained discrepancy and the failure of a batch or any of its components to meet any of its specifications whether or not the batch has been already distributed:

We acknowledge the actions your firm has planned in response to its failure to adequately investigate and respond to an adverse trend involving defects associated with your intravenous fluid bags. We note the following action items:

• Assess bag storage and shipping configuration to determine if current storage & configuration has potential compressive stress on the seam of the (b)(4) IV Bag units.
  Target completion due date: 06Jan2026

• Assess the need for updates to the incoming inspection requirements of (b)(4) IV Bags.
  Target completion due date: 06Jan2026

• Update the customer complaint investigation process in FSSBOS-SOP-0041 to require that for “leaking unit” complaints, photos of the defective unit(s) are requested, and the units be returned to the facility for inspection.
  Target completion due date: 06Jan2026

However, although you identified a trend involving defects with the (b)(4) infusion port seal across multiple supplier lots of various (b)(4) IV Bag configurations, you failed to take meaningful action such as pausing production or distribution. Instead, you opened an “Issue” to document and trend the events. You did not conduct a comprehensive risk analysis and never identified a definitive root cause. Despite failing to determine a definitive root cause through communication with the IV bag supplier ((b)(4)) for the observed defects—including (b)(4) port seals with (b)(4) “stress” marks, loose (b)(4) port seals, and partially seated (b)(4) port seals—you continued using these IV bags in production. You relied solely on visual inspection to identify and segregate defective units. This practice is inconsistent with good manufacturing practices, which require a drug process to remain in a state of control throughout its lifecycle. Knowingly using potentially defective container-closures in the production of a sterile drug product places the product at risk of contamination and puts patients at risk.

3. Regarding your failure to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile:

a. We acknowledge your response to the failure to ensure that operators’ behavior in the ISO 5 aseptic processing area does not block or otherwise compromise “first-air” to critical surfaces such as vials. We note your contention that vial reconstitution is not an aseptic practice, as well as your plans to reclassify this as such. However, sterile drug vial reconstitution is an aseptic process that must be performed in an ISO 5 area because it involves exposing a sterile product to the environment during manipulation. When reconstituting a sterile drug, the vial's closure system is breached to introduce a diluent, creating opportunities for microbial contamination. An ISO 5 environment provides the highest level of air cleanliness in the immediate work area, with stringent limits on airborne particulates that could carry microorganisms. This controlled environment, combined with proper aseptic technique, is essential to maintain product sterility and prevent contamination that could lead to serious patient harm. Additionally, while subsequent sterile (b)(4) of the bulk drug solution may provide a layer of protection, it does not eliminate the requirement to maintain aseptic conditions throughout the sterile drug production process.

We further acknowledge your claim that vigorous shaking of the [vancomycin] vials is necessary to ensure complete dissolution of the drug in the diluent, as well as your intent to improve this process by requiring the hood to “(b)(4)” following reconstitution and prior to resumption of aseptic activities. However, this strategy fails to address the primary risk. As previously stated, rapid movement (i.e., vigorous shaking of vials) creates significant air turbulence that disrupts laminar airflow and increases contamination risk. A (b)(4) alone without supporting scientific evidence is not an effective contamination control strategy.

b. We acknowledge your response regarding the failure to conduct all aseptic operations, including reconstitution of sterile vials and pooling of the resultant bulk drug solution, in a properly qualified ISO 5 environment. As previously stated, reconstituting sterile drug product vials and pooling them outside an ISO 5 environment creates a direct contamination risk. When performed outside an ISO 5 space, the process is no longer considered a sterile-to-sterile aseptic process. While we acknowledge the information you provided regarding sterilizing (b)(4) qualification (including compatibility and capacity) and additional controls such as full gowning, environmental monitoring within the ISO 7 mixing room, and sanitization of pooling bags, these measures do not replace the comprehensive validation process, including process simulation studies, necessary to validate such a process.

4. Regarding your failure to establish an adequate system for monitoring environmental conditions in aseptic processing areas:

We acknowledge your response regarding the failure to adequately perform active and passive air sampling within the ISO 5 area during aseptic operations, including your plan to initiate active air monitoring during filling operations. We recognize the importance of conducting effective environmental monitoring while minimizing the risk of contamination. However, your response fails to fully address the scope of the violation. Although conducting viable air sampling during filling represents an improvement, it does not address other critical steps in the aseptic operation where contamination risk is high and viable air monitoring may be necessary. Additionally, your response does not specify the duration of the production process or explain whether the frequency of viable air sampling adequately represents the processing environment throughout the entire production cycle. Furthermore, your response indicates that settle plate placement is described in FSSBOS-SOP-0013, “Cleaning Procedure for Classified Areas at the Canton Compounding Facility.” However, our review of this SOP indicates that it applies only to ISO-7, ISO-8, and ISO-9 areas. Consequently, the location of settle plates, used for passive air monitoring of the ISO 5 (b)(4) during aseptic operations, cannot be determined.

In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b)].

FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.

D. Conclusion

The violations cited in this letter are not intended to be an all-inclusive statement of violations 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. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.

You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.

Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.

All correspondence should refer to the Warning Letter Number above (# 724551) and include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.

Sincerely,
/S/

Matthew J. Lash
Acting Director
Office of Compounding Quality and Compliance
Office of Compliance
Center for Drug Evaluation and Research

cc:
Deborah E. McHugh, Vice President of Quality for North America
Fresenius Kabi Compounding, LLC
20 Dan Rd
Canton, MA, 02021-2809

___________________

1 See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).

2 We remind you that there are conditions, other than those discussed in this letter, that must be satisfied to qualify for the exemptions in section 503B of the FDCA.