Wells Pharma of Houston, LLC — FDA Warning Letter Findings

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.

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

Your firm 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…

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.

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.

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.

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)).

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…

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)).

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.

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.

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.

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

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)…

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…

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.

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)).

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…

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…

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.

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.

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…

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).

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.

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