Apollo Care, LLC

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 September 14, 2017, and most recently on December 24, 2025. From March 10, 2025, to March 27, 2025, an FDA investigator inspected your facility, Apollo Care, LLC, located at 3801 Mojave Court, Suite 101, Columbia, MO 65202. During the inspection, the investigator 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 March 27, 2025. FDA acknowledges that on April 15, 2025, your firm initiated a voluntary recall of Lot AC-016878 of Fentanyl 500mcg (2mcg/mL) and Ropivacaine HCl 250mg (0.1%) added to 250 mL, 0.9% Sodium Chloride Injection (For Epidural Use Only), within expiry, due to lack of sterility assurance. FDA also acknowledges receipt of your facility’s responses, dated April 17, 2025, June 10, 2025, and September 8, 2025. Based on this inspection, it appears you produced drugs that violate 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.

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.

The FDA investigator 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 investigator observed:

1. You used sanitizing and sporicidal agents without providing adequate segregation in preventing contamination of in-process bulk drug solution. Specifically, your operator repeatedly sprayed a microfiber mop head with cleaning agents near the beaker containing non-sterile bulk drug solution that was loosely covered with aluminum foil in the ISO (b)(4) classified Hallway/Anteroom (b)(4) during area cleaning.

2. You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO (b)(4) aseptic processing area. Instead, your firm approved and distributed drug products that were produced with 1 CFU recoveries found on ISO (b)(4) operator gowning gloves or sleeves.

3. Your firm had foreign matter in the production area. Specifically, white fiber-like particles and debris were observed on the floor of the ISO (b)(4) Lab, where ISO (b)(4) laminar air flow hoods (LAFHs) are located, and the ISO (b)(4) Hallway/Anteroom (b)(4) following area cleaning that included equipment, ceilings, walls, and floors.

4. Your firm had production areas or equipment that are difficult to clean or contain porous, particle-generating, or visibly dirty (e.g., rusty) equipment or surfaces (e.g., shelving, floors, walls, doors, ceilings). Specifically, wall panels overlaid on top of your ISO (b)(4) Hallway/Anteroom (b)(4) walls are not smooth. The textured surface is difficult to clean and may harbor contamination and generate particles when other materials come into contact with it.

The FDA investigator 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. You 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)).

2. You failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).

3. Your firm’s aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).

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.

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.

We have reviewed your facility’s responses to the Form FDA 483. We acknowledge your voluntary recall of Lot AC-016878 of Fentanyl 500mcg (2mcg/mL) and Ropivacaine HCl 250mg (0.1%) added to 250mL, 0.9% Sodium Chloride Injection (For Epidural Use Only), within expiry, due to lack of sterility assurance on April 15, 2025. We also acknowledge that you have contracted with third party consultants.

Some of your corrective actions appear adequate. However, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:

1. Regarding your smoke studies, we acknowledge you have initiated a revision of SOP CQI025 Air Flow Pattern Visualization and intended to conduct “formal static and dynamic smoke studies,” as stated in your June 10, 2025, response. Your September 8, 2025, response provided the protocol and report in Attachment 2 for the May 30, 2025, static smoke studies of the (b)(4) hoods, as part of CAPA C-25-013. However, the protocol and report did not specify what production equipment was included during testing. Without accompanying videos, we lack evidence to evaluate or verify whether you have resolved the issue of turbulence around production equipment such as the repeater pump. This turbulence will persist given that the repeater pump represents a substantial piece of equipment within a (b)(4) laminar flow hood. The report only provided a general statement indicating that “[t]hese static conditions were tested using an LFH [laminar flow hood] with all production materials inside but without any operational tasks being conducted.” Given that these hoods are located in (b)(4) separate rooms and serve distinct functions, each would require different equipment/materials that should have been specifically documented and evaluated.

2. Regarding the bulk drug solution exposed to (b)(4) during (b)(4) cycles, we acknowledge you will no longer store the bulk solution in (b)(4) Lab (b)(4) during any (b)(4) cycle until you “can demonstrate there is no opportunity for (b)(4) ingress for the exposure concentration and hold duration.” You also engaged (b)(4), a (b)(4) equipment manufacturer, to assist in developing a (b)(4) penetration study protocol specific to the (b)(4) bag material and provided the results of the (b)(4) penetration study in your September 8, 2025, response. You stated this study utilized the (b)(4) exposure time, the (b)(4) exposure, and the (b)(4) bag to demonstrate compatibility. However, this study appeared to test empty bags and bags filled with (b)(4). It is not clear why you did not test bags filled with any bulk drug product, such as bulk Vancomycin solution, or whether you have conducted other container closure compatibility studies as part of the process validation of the drug products. Therefore, we lack data to fully evaluate whether the storage bags filled with your bulk drug solution are suitable for their intended use, including exposure to the (b)(4) used in your facility.

Some of your corrective actions appear deficient:

1. Regarding your firm’s cleaning of the ISO (b)(4) Hallway/Anteroom (b)(4) while non-sterile in-process bulk drug solution was stored there, your firm lacked assurance that the non-sterile in-process bulk drug solutions exposed to cleaning agents during this cleaning process do not alter the quality and purity of sterile compounded finished drug product produced from the exposed bulk drug solution.

We acknowledge you will no longer store the bulk drug solution in the area while the cleaning or (b)(4) cycles are ongoing, and that SOP PRC004 (b)(4) Process requires disinfection and cleaning of any supplies that must be transferred from an unclassified space to an ISO environment. However, the effectiveness of using a (b)(4) lid to replace foil covering on the bulk drug solution beaker has not been demonstrated or validated through appropriate methods such as media fills. Additionally, your SOP and related batch record forms do not require or specify how to clean and/or disinfect the large beaker, including the new (b)(4) lid, containing non-sterile bulk drug solution formulated in ISO (b)(4) Storage/Anteroom (b)(4) when transferring from one area to another, particularly from Anteroom (b)(4) (ISO (b)(4)) to (b)(4) Lab (ISO (b)(4)).

2. Regarding your firm’s use of the Hallway/Anteroom (b)(4) as both ISO (b)(4) and ISO (b)(4) space depending on whether you are conducting non-sterile or sterile activities, your response is inadequate because you provided contradictory and incomplete information on how the ISO (b)(4) Lab will be accessed. You continue using the Hallway/Anteroom (b)(4) as an entry to reach both non-sterile and sterile activities. In your June 10, 2025, follow-up response, you reiterated that “this hallway is used as an entry to both an ISO (b)(4) and an ISO (b)(4) space” and acknowledged the risk of using Hallway/Anteroom (b)(4) for an entry to both ISO (b)(4) and ISO (b)(4) rooms.

The following responses appear to be contradictory:

In your April 17, 2025, response to Observation 2A, you stated, “Per Change Control 25-CM-016, the non-sterile bulk drug solution is now moved from the ISO (b)(4) Anteroom into the ISO (b)(4) room after the technician completes full sterile gowning with sterile gloves and completes a thorough wipe down of the beaker with (b)(4). The ISO (b)(4) Anteroom is then subjected to a full cleaning.”

In your June 10, 2025, response to Observation 2B, you stated, “Apollo Care requires that Anteroom (b)(4), or what was referred to as the hallway, to undergo a full clean prior to gowning and entry into the ISO (b)(4) environment. This requirement is in place when ISO (b)(4) activities have occurred immediately prior to the need for ISO (b)(4) entry.”

In your response to Observation 2A, non-sterile bulk solution is moved into the ISO (b)(4) room before a full clean of Hallway/Anteroom (b)(4), while in your response to Observation 2B, you state that ISO (b)(4) access first requires sterile garbing and full cleaning of Hallway/Anteroom (b)(4).

3. Regarding the EM (environmental monitoring) Alert and Action limits for personnel who access the ISO (b)(4) environment, we acknowledge you have defined (b)(4) and (b)(4) support compounding personnel in SOP EMP001 (b)(4) Support Compounding Personnel Job Description and SOP EMP002 (b)(4) Support Compounding Personnel Job Description. You also updated SOP CQI003 Clean Room Monitoring to define respective Alert and Action Limits for (b)(4) and (b)(4) support compounding personnel and require labeling “(b)(4)” for (b)(4) support compounding, and “(b)(4)” for (b)(4) support compounding on the Personnel Monitoring plates.

However, you have not designated fields to document (b)(4) Support Compounding Personnel in related forms used in batch records, such as EM/PM form F002. For example, in the newest version of form F002, you still list “(b)(4)” and “(b)(4)” under each category of Direct Compounding Personnel and (b)(4) Support Compounding Personnel Contact Plates. Furthermore, the scope of the (b)(4)’s role during compounding operations has not been specified in batch record instructions, or in any updated written procedure.

4. Regarding white fiber-like particles and debris observed on the floor of the ISO (b)(4) Lab and the ISO (b)(4) Hallway/Anteroom (b)(4) following area cleaning, we acknowledge you rejected and destroyed the three affected lots. However, you have not provided any preventive actions regarding particles observed in the anteroom and in the cleanroom space where ISO (b)(4) LAFH used for production are located. In your June 10, 2025 response, the specification sheet from (b)(4). (refer to pages 95-96 of the Response Attachment 3) appeared to be a specification sheet for (b)(4) Mop, which is a different product line, with part numbers such as (b)(4), none of which appeared to match the mops being used at your firm.

5. Regarding documentation of incomplete (b)(4) cycles, your SOP PRC002 Facility Cleaning Procedure only mandates documentation of “all executed facility cleanings.” However, the SOP fails to address the documentation requirements for incomplete (b)(4) cycles within individual rooms or incomplete “full clean” of the cleanroom suite (all (b)(4) rooms). CGMP regulations require comprehensive documentation of all CGMP activities, including those that are incomplete or terminated early. The SOP should be revised to include:

Documentation requirements for all (b)(4) cycle attempts, whether completed or incomplete; and

Explanation for partial or terminated cycles.

6. Regarding the textured panels in your cleanroom suite, the manufacturer’s Technical Data sheet indicates the panels with textured or smooth surface have fire, mold and mildew resistance. However, there is no statement in the Technical Data sheet supporting the panel’s suitability for cleanroom applications, especially for pharmaceutical manufacturing facilities producing products intended to be sterile. Your response is inadequate because you have not evaluated the risk associated with using walls with textured surface in the cleanroom suite, nor have you developed a strategy to mitigate this risk. The photograph below depicts a section of the reconstructed area and wall in the ISO (b)(4) Hallway/Anteroom (b)(4) after the sink removal. The image shows difficult to clean areas such as textured wall surface and the gap in the molding.

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.

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.

All correspondence should refer to the Warning Letter Number above (# 715955) 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.