Pharmacy Plus, Inc., dba Vital Care Compounder — FDA Warning Letter Findings

An operator used a non-sterile tool on, and manually contacted, the inner surface of the container or closure for sterile drug products.

An operator placed their gloved hands outside the ISO 5 work area to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood.

Regarding Observation 5 in which an operator was observed using non-sterile pads and wipes within the ISO 5 aseptic processing area, your response stated that you ordered sterile cleaning pads for use within the ISO 5; however, the data sheet provided with your response appears to be for sterile mop heads, rather than for sterile cleaning pads. In addition, your response stated that you trained your operators, “to be cognizant of packaging to assure that all wipes, pads, cleaners, and wands used within the ISO 5 classified areas are sterile, lint-free, or non-shedding;” however, training records were not submitted for review. The use of non-sterile wipes within the ISO 5 is a repeat observation from both the 2019 and 2016 inspections.

Your firm used non-sterile pads and wipers within the ISO 5 aseptic processing area.

We acknowledge your commitments to prevent cross-contamination during drug production. Your response does not address the frequency of cleaning (i.e., between each batch), nor does it address the potential for cross-contamination via operator gloves, gowning, and other routes, and how to mitigate them. In addition, your response does not address the appropriate washing of equipment and/or materials used during compounding. Furthermore, your response indicates that your firm will use a dedicated (b)(4) hood and equipment for hazardous compounding; however, you did not provide documentation demonstrating that this requirement was incorporated into your SOP(s), nor did you provide corresponding training records. Therefore, we remain concerned that hazardous, sensitizing, or highly potent drug product residue may be introduced into subsequent products compounded in your pharmacy.

Regarding Observation 7, in which an operator placed their gloved hands outside the ISO 5 work area to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood, your response stated that you re-assessed and re-trained staff on the frequency required for disinfecting and changing gloves during sterile compounding; however, you did not provide documentation such as training records, for review.

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.

We acknowledge that you created a new High Risk Media Fill SOP. The Form FDA 483 observation indicates that a critical aseptic processing step was not assessed during your prior media fill challenge. Specifically, the transfer of the beaker containing sterile product from the (b)(4) to the ISO 5 laminar flow hood was not evaluated. Your revised media fill SOP does not appear to replicate this process. Furthermore, the observation noted that your firm does not perform an…

Regarding Observation 4, in which your laminar airflow hood contained difficult to clean, particle-generating and visibly dirty equipment or surfaces, we acknowledge your response within which you stated that you will remove it; however, you did not provide supporting documentation which demonstrates that the laminar airflow hood has been removed.

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. 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 firm’s response to the Form FDA 483. We acknowledge your recall of multiple lots of drug products on October 7, 2022. Regarding your response related to the insanitary conditions, we cannot fully evaluate the adequacy of the following corrective actions described in your response because you did not include sufficient information or supporting documentation…

We acknowledge your Form FDA 483 response which seeks to address actionable microbial contamination within your ISO 5 classified aseptic processing areas. During the inspection, your firm’s leadership attributed the out- of-specification (OOS) environmental monitoring (EM) results to an error by your certification company, without providing a scientific rationale to support that conclusion. We acknowledge the revision of your Environmental Monitoring for Viable Microbial…

Your firm did not take appropriate corrective action after microbial contamination was recovered within the ISO 5 aseptic processing area.

Regarding Observation 6 in which an operator used a non-sterile tool on, and manually contacted, the inner surface of the container or closure for sterile drug products, your response stated that (b)(4) forceps were purchased for handling sterile container and closures; however, you did not provide sufficient documentation, such as a purchase invoice and/or a package insert, for review. In addition, your response stated that your operators were trained on the requirement and use of sterile tools to contact the container closure of sterile drug products; however, you did not provide documentation, such as training records, for review.

Your firm produced hazardous drugs without providing adequate segregation, cleaning of work surfaces, and cleaning of utensils to prevent cross- contamination.

Regarding Observation 10, in which your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area, your response stated that future smoke studies would closely mimic production (dynamic) operations, including using the representative equipment and materials used during aseptic processing; however, documentation such as a description of the conditions at the time of the smoke studies or a video copy (if available or performed) of the smoke studies to show that these studies have been and will be conducted under dynamic conditions, training records, and a revised standard operating procedure (SOP) were not provided for review. In addition, it is unclear whether your ISO 5 laminar flow hood(s) have been assessed per the revised SOP. Regarding your response related to the insanitary conditions, the following corrective actions appear deficient…

Your laminar airflow hood contained difficult to clean, particle-generating and visibly dirty equipment or surfaces.