Right Value Drug Stores, LLC dba Carie Boyd Pharmaceuticals — FDA Warning Letter Findings

Your firm failed to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product (21 CFR 211.46(b)). 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…

Your firm failed to 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)).

Regarding your firm’s failure to establish and follow adequate written procedures for cleaning and maintenance of equipment: a. We acknowledge that your staff were re-trained on the Cleaning and (b)(4) of Glassware SOP. In your response, you stated you are working on a Glassware Hold Study; however, we are unable to review the adequacy of your response until your hold studies are completed and submitted for review.

Regarding your Aseptic Process Simulations, batch records reveal that each operator is required to fill a minimum of (b)(4) units, however, during production an operator can fill up to (b)(4) units. Gowned personnel are the greatest source of microbial contamination in an aseptic process. Operators performing a media fill of less than their typical production volume and duration does not represent the worst-case challenge and stressful condition as it does not take into regard operator fatigue. Your firm failed to provide a robust media fill that mimics an operator’s actual production activity.

Regarding DEV-2023-073 and DEV-2023-074 o, we acknowledge your firm performed an investigation regarding the Total Airborne Particles exceeding the ISO 5 specifications on 12/20/2023 during the filling of Testosterone Cypionate/Testosterone Propionate 200/10 mg/ml with Miglyol R 812N, Lot (b)(4) . However, upon reviewing the production Batch Record (b)(4) , it was noted there were 26 major defects identified during the visual inspection, including dark particulates and filaments in vials. Despite those vials being removed, it appears no further investigation occurred.

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).

Regarding your firm’s failure to provide equipment for adequate control over air pressure, micro-organisms, dust, humidity, and temperature when appropriate for the manufacture, processing, packing, or holding of a drug product: a. You stated you are purchasing additional equipment to control environmental variables, such as temperature and humidity in your DEA Lockup area, however, we are unable to review the adequacy of your response until you submit further details about your proposed corrective actions (e.g., implementation time frame, equipment qualification and written procedures, etc.). b. You stated that you intend to execute process validation for other product families stored in the Lockup area. However, details of your plan, such as the names of the other product families and how you plan to implement these validation protocols were not provided. Some of your corrective actions appear deficient…

We acknowledge that on July 5, 2024, your firm re-executed smoke studies. Some of the smoke studies provided for review demonstrated non-unidirectional, recirculating airflow within the hood. For example, video 19-00133 Transfer of Vials into the Hood, (b)(4) currents were detected from time stamp 00:25 and could be identified throughout the video duration. Video 19-00133 EM Sampler Running and Filling of (b)(4) Vials, (b)(4) currents were identified from time stamp 12:07-12:17 and 13:20-14:54. In both videos, the disruption in airflow appeared to be in the far-right hand side of the BSC hood where empty vials were sitting. The ISO-5 area is critical because sterile drug products are exposed and therefore vulnerable to contamination. Your aseptic manufacturing process should be designed, and operations should be executed to minimize contamination hazards to your sterile drug product.

Regarding the preparation of container closures to remove pyrogenic properties, your firm failed to adequately validate the (b)(4) process for your pellet vial caps and continued to use this process in the manufacturing of drug products. The process validation report, GS-2023-025 (dated 07/03/2023) cited multiple samples failing a (b)(4) in endotoxins. Your firm launched an investigation, IR-2023-036 (dated 09/06/2023) and it was concluded that the rinsing time needed to be…

Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).

Your firm failed to clean and sterilize and process, where indicated by the nature of the drug, container closures to remove pyrogenic properties to assure they are suitable for their intended use (21 CFR 211.94(c)).

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. Specifically, your firm’s media fill vial quantity per technician fails to reflect the most challenging conditions. FDA investigator also noted CGMP violations at your facility, that caused your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example…

Your firm 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, your smoke studies demonstrated disruption in unidirectional airflow in your BSC hood 19-00133.

We acknowledge your initiation of deviations, DEV-2024-046 and DEV-2024-047 and investigation IR-2024-013 in relation to the power outage that occurred on 05/28/2024. However, utilizing visual inspection as your method in identifying the impact of humidity on your in-process pellets is inadequate. Your proposed method of visually inspecting pellets for “swelling” is not scientifically sound, nor data driven.