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WARNING LETTER
WL # 713015

November 7, 2025

Dear Mr. Corbin:

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 March 9, 2020, and most recently on November 5, 2024. From March 17, 2025, to March 28, 2025, an FDA investigator inspected your facility, Wells Pharma of Houston, LLC located at 9265 Kirby Drive, Houston, Texas 77054. During the inspection, the investigator noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigator noted serious deficiencies in your practices for producing drug products, which put patients at risk.

FDA issued a Form FDA 483 to your facility on March 28, 2025. FDA acknowledges receipt of your facility’s response, dated May 9, 2025. 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.

In addition, for a compounded drug product to qualify for the exemptions under section 503B, the labeling of the drug must include certain information (section 503B(a)(10) of the FDCA [21 U.S.C. §353b(a)(10)]).

Furthermore, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b), including the requirement to submit adverse event reports to FDA “in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, CFR (or any successor regulations)” (section 503B(a)(1), (b)(5) of the FDCA [21 U.S.C. § 353b(a)(1), (b)(5)]).

B. Failure to Meet the Conditions of Section 503B

During the inspection, the FDA investigator noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigator noted:

1. Some of your facility’s drug products, such as Fentanyl 50 mcg/10 mL in 0.9% Sodium Chloride and Phenylephrine Hydrochloride 800 mcg/10 mL in 0.9% Sodium Chloride, did not include the following statement on the label: “This is a compounded drug.”

2. Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, CFR (or any successor regulations).³ Specifically, your facility’s procedures for reporting adverse events are inadequate. For example, your documented procedures for reporting adverse events do not include a complete definition of what constitutes a “serious” adverse event as it is missing the following language: “Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.” (21 CFR 310.305(b)).

Because your compounded drug products have not met all of the conditions of section 503B, they are not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.

Specific violations are described below.

C. Violations of the FDCA

Adulterated Drug Products

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. An operator placed components within the ISO (b)(4) work area that had the potential to block the movement of first air to critical in-process operations.

2. Your media fills were not performed under the most challenging or stressful conditions. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.

3. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO (b)(4) area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.

4. Cracked plexiglass siding with an appearance of yellowish brown and black discoloration around metal brackets affecting your ISO (b)(4) laminar airflow hoods (LAFHs).

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. 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)).

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

3. 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).

4. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow written procedures applicable to the quality control unit (21 CFR 211.22(d)).

5. Your firm failed to exercise strict control over labeling issued for use in drug product labeling operations (21 CFR 211.125(a)).

6. Your firm 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)).

7. Your firm failed to use equipment in the manufacture, processing, packing, or holding of drug products that is of appropriate design, adequate size, and suitably located to facilitate operations for its intended use and for its cleaning and maintenance (21 CFR 211.63).

8. Your firm failed to establish an adequate system for maintaining 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.

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.

Unapproved New Drug Products

You do not have any FDA-approved applications on file for drug products that you compound.⁴ Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. §§ 331(d)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA

Misbranded Drug Products

You compound drug products that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FDCA.⁵ The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Further, it is also a prohibited act under section 301(k) of the FDCA 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 misbranded.

D. Corrective Actions

We have reviewed your facility’s response to the Form FDA 483.

Some of your corrective actions appear deficient:

1. Regarding your smoke studies, your response stated an outside contractor will perform new smoke studies in May 2025 and other process and procedure updates will be completed in the third quarter of 2025. We have not received the results of your new smoke study and acknowledge procedure updates may be pending. However, your response did not address the risk to current processing and potential impact to distributed product due to the deficient smoke study of your ISO (b)(4) LAFHs not performed under normal dynamic conditions. This is a repeat violation as your firm was also cited for inadequate smoke studies in your ISO (b)(4) LAFH during the 2021 FDA inspection.

2. As it relates to your environmental monitoring (EM) program, your response refers to numerous procedures and corrective and preventative actions (CAPAs) that were either updated or will be revised to address the concerns identified, but deficiencies remain. For example, SOP HOU-QC-018 effective April 7, 2025, provided to “serve as corrections to this observation” still specifies alert (b)(4) CFU and action (b)(4) CFU levels for viable surface samples within your ISO (b)(4) areas. Any microbial contamination in the ISO (b)(4) area is considered an insanitary condition. Any microbial contamination within the ISO (b)(4) area is a serious concern and upon recovery, your firm should immediately assess the impact on drug products produced. This assessment should include a thorough evaluation of how contamination could have entered this critical area, and over what period of time the contamination could have existed, as well as drug products that remain on the market that could be affected.

Your response also stated that modifications to this procedure and others were already in progress as part of change control CC-HOU-2025-005 signed off on March 11, 2025. However, the change control does not address the specific deficiencies found by our investigator. For example, your response did not address the deficiencies regarding when active viable EM process sampling occurs. The timing of this sampling should be based on risk and adequate for the duration of your manufacturing process, not just at the (b)(4) of a batch.

Furthermore, your response does not address the root cause as to why employees are not following proper fingertip sampling technique as outlined in your procedures nor the impact of this practice on lots distributed.

3. You initiated deviation DEV-HOU-2025-002 for not incubating EM plates at the specified time and temperature per your procedure. Your investigation did not assess product impact nor provide adequate justification for release of the batches. We acknowledge you plan to improve your investigation process, but your response did not address the specific issue cited on the Form FDA 483, inadequately incubated EM plates that affected approximately (b)(4) batches of drug product lots intended to be sterile. You determined the root cause was due to short staffing. Your response lacks assurance that your EM testing results are accurate and reliable. In addition, your response failed to address if other tasks that may affect product release have also been missed due to short staffing.

4. Your visual inspection (VI) process and VI training program remain deficient. Your response stated CAPA-HOU-2025-003 was initiated on March 1, 2025, and that your VI procedures will be updated. However, your response did not describe how the planned procedural updates will address all the observations noted by our investigator.

5. Your response related to your disinfectant efficacy study referenced an existing CAPA for cleaning validation (CV) requirements and you also noted that an updated study was initiated. You noted that the CV study was not completed as expected, so you opened a new CAPA-HOU-025-004 on March 5, 2025. However, the new CAPA appears to focus on preventing cross-contamination from beta-lactam residues but doesn’t address the findings noted by our investigator.

6. Regarding the (b)(4) totes used to transfer materials from non-classified areas into the ISO (b)(4) cleanroom suite, your response referenced an existing CAPA for CV and you also noted that updated studies were initiated. Your response did not address the (b)(4) bottoms and handles on the totes and how you plan to minimize the potential ingress of microbial contamination.

7. We acknowledge that you replaced the cracked plexiglass panels on the (b)(4) impacted ISO (b)(4) LAFHs. However, it is unknown how long the cracked plexiglass existed on the ISO (b)(4) LAFHs, and you did not perform an investigation or risk assessment to mitigate any potential concerns with distributed product.

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

1. We acknowledge that training on aseptic technique was performed following the FDA inspection. However, the training slides provided did not show how the training documentation will prevent employees from blocking first air, nor did it provide details on how your aseptic pharmacy technicians will fill drug product intended to be sterile and remove air from a syringe in a manner that does not compromise first pass air. You stated that a checklist will be developed under change control CC-HOU-2025-028 and that implementation of routine walkthroughs will provide risk mitigation pending completion of procedural edits. Your response also stated that “aseptic technique is highly behavior based, ongoing monitoring and correction and intensive training and retraining provides a good measure of risk mitigation.” We agree with your statement that “additionally, the risk to the product/patient is that poor aseptic technique could result in product that is potentially microbially contaminated.” However, you did not provide a copy of the checklist nor evidence of completed walkthroughs to review.

2. As it relates to your media fills, your response stated that a matrix, to include “all products, product sizes, container closure systems, etc.,” shall be developed and where significant gaps are identified, a media fill will be executed in June 2025. It is unclear if you have executed new media fills as we have not received an updated response. Your response also stated that CAPA-HOU-2025-010 was initiated to perform an evaluation of all processes related to media fill and process validation, and because of the CAPA investigation corrective actions shall be identified. We acknowledge your tentative completion date for end of the third quarter 2025 for this action. Therefore, we are not able to assess the adequacy of your media fills and corrective actions, nor the impact, if any, to distributed product due to inadequately executed media fills. It is important that your media fills include all equipment used in manufacturing of drug products, represent your actual operations including your various batch sizes and aseptic operators, and simulates your most challenging and stressful conditions of your aseptic manufacturing operations.

3. Your EM procedures do not provide instructions for performing EM sampling of difficult to clean areas. Per your response, you initiated CAPA-HOU-025-009 but did not provide an update detailing your assessment of procedures HOU-QC-005, HOU-QC-009, and HOU-QC-014. Your response stated identification of hardest to reach clean areas shall be provided for each type of equipment, utensil, or other components used in production. Your response also stated that EM procedures will be updated, combined, or modified as necessary and that your corrective actions will be implemented by June 27, 2025. We have not received these procedures to assess the adequacy of your corrective actions.

4. We acknowledge your statement that you performed immediate training of all labeling technicians in response to concerns noted with your control of labeling operations. However, your response did not provide any details regarding the training nor evidence showing training was completed. We acknowledge your commitment that your corrective actions for procedural and possible physical layout updates would be completed by the end of July 2025. We have not received the revised procedures to assess the adequacy of your corrective actions.

5. We acknowledge you have consulted with a third-party firm to provide temperature mapping and qualification of equipment at your facility to include your (b)(4). You stated these activities and validation of the (b)(4) will be completed by May 16, 2025. We have not received any documentation showing these activities were completed. Equipment used for compounding in your ISO (b)(4) areas including goggles may impact product quality if they are not properly sterilized.

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).]

In addition, regarding issues related to the conditions of section 503B of the FDCA, your corrective actions appear adequate: You submitted CAPA-HOU-2025-014 which indicates you will identify process gaps for complaints and revise associated procedures to address identified gaps, including “HOU-QA-041 Pharmacovigilance Procedure for Adverse Events.” Additionally, in CC-HOU-2025-039, you also state that you will “[r]eview all commercial product labels and update to include the phrase ‘This is a compounded drug’ OR ‘This is a repackaged drug’ as appropriate.”

Should you continue to compound and distribute drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.

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.

E. 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 (# 713015) 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/

F. Gail Bormel, JD, RPh
Director
Office of Compounding Quality and Compliance
Office of Compliance
Center for Drug Evaluation and Research

cc: Lisa G. Hawkins
Senior Vice President of Quality
Wells Pharma of Houston, LLC
9265 Kirby Drive
Houston, Texas 77054-2520

___________________

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.

3 For more information, see, FDA’s guidance, “Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act,” which can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM434188.pdf.

4 The specific products made by your firm are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.

5 Your compounded drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).