- Delivery Method:
- VIA Electronic Mail
Recipient NameWarren C. Gray
- West Coast Nuclear Pharmacy
3906 Cragmont Drive
Tampa, FL 33619
- Issuing Office:
- Division of Pharmaceutical Quality Operations II
October 6, 2020
Case # 604169
From March 19, 2018, to March 23, 2018, U.S. Food and Drug Administration (FDA) investigators inspected your facility, West Coast Nuclear Pharmacy, LLC, located at 3906 Cragmont Drive, Tampa, Florida 33619. During the inspection, the investigators noted serious deficiencies in your practices for producing sterile drug products, which put patients at risk.
FDA issued a Form FDA 483 to your firm on March 23, 2018. FDA acknowledges receipt of your facility’s response dated March 29, 2018, as well as your subsequent correspondence. Based on this inspection, it appears that you produced drug products that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Compounded Drug Products Under the FDCA
Section 503A of the FDCA describes the conditions under which human drug products compounded by a licensed pharmacist in a State licensed pharmacy or a Federal facility, or a licensed physician, qualify for exemptions from three sections of the FDCA: compliance with current good manufacturing practice (CGMP) (section 501(a)(2)(B)); labeling with adequate directions for use (section 502(f)(1)); and FDA approval prior to marketing (section 505) [21 U.S.C. §§ 351(a)(2)(B), 352(f)(1) and 355(a)]. Section 503A does not apply to the compounding of radiopharmaceuticals (section 503A(d)(2)).
In September 2018, FDA issued a guidance titled, Compounding and Repackaging of Radiopharmaceuticals by State-Licensed Nuclear Pharmacies, Federal Facilities, and Certain Other Entities (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/compounding-and-repackaging-radiopharmaceuticals-state-licensed-nuclear-pharmacies-and-federal). This guidance describes the conditions under which FDA generally does not intend to take action for violations of sections 505, 502(f)(1), and 501(a)(2)(B) of the FDCA when a State licensed nuclear pharmacy, Federal facility, or other facility that is not an outsourcing facility and that holds a radioactive materials (RAM) license for medical use issued by the Nuclear Regulatory Commission (NRC) or by an Agreement State compounds or repackages radiopharmaceuticals for human use.
Under current law, radiopharmaceuticals that are compounded by entities that are not registered with FDA as outsourcing facilities, and radiopharmaceuticals that are repackaged, are subject to all applicable provision of the FDCA related to the production of drugs, including section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)] regarding insanitary conditions.
B. Violations of the FDCA
Adulterated Drug Products
The FDA investigators 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 investigators observed the following:
1. Microbial contamination was present in the ISO 5 area during aseptic production without adequate product evaluation and remedial action.
2. Disinfecting agents and materials used within the ISO 5 area are not sterile.
3. (b)(4) are located (b)(4) the ISO 7 buffer room and the unclassified area, potentially allowing an influx of lesser quality air from the unclassified area into the ISO 7 buffer room.
4. Poor practices were observed during aseptic processing. For example, sterile gloves worn by employees came in direct contact with non-sterile objects such as the buffer room door. The same employees then performed aseptic manipulations of radiopharmaceuticals within the ISO 5 hoods without first changing or sanitizing their gloves.
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 responses to the Form FDA 483 as well as your subsequent correspondence. Regarding your response related to the insanitary condition observations, some of your corrective actions appear deficient:
1. In response to our observation that microbial contamination was present within the ISO 5, you stated that you use (b)(4) with a contact time of (b)(4) to inactivate spore-forming Bacillus. However, the manufacturer’s labeling recommends a (b)(4) contact time for sporicidal activity. Your March 29, 2018, response indicated that contaminated areas will not be used until remediation is completed and documented. However, this commitment does not appear in your revised SOPs.
2. In response to our observation that non-sterile disinfectants and materials were used within the ISO 5, you provided your revised SOP 6.0, Cleaning and Maintenance of the Clean Room Facility v1. In your March 29, 2018 letter, you stated that you would revise the SOP to indicate that after disinfecting the ISO 5 hoods with a non‐sterile agent, they should be secondarily sterilized using sterile (b)(4) on sterile lint free wipes. The revised SOP lists non-sterile disinfectants to be used, followed by use of sterile disinfectants. This disinfection practice poses a risk to the sterile drug products produced as the use of sterile (b)(4), following the application of a non-sterile cleaning agent will not kill the spores which may be present in the non-sterile disinfectant. Further, the use of non-sterile cleaning agents has the potential to introduce contamination into the ISO 5 hoods.
3. In response to our observation regarding your firm’s (b)(4) being located (b)(4) the ISO 7 buffer room and the unclassified area, which potentially allows an influx of lesser quality air from the unclassified area into the ISO 7 buffer room, you provided, among additional supporting documents, a video of a smoke study performed on the (b)(4). We acknowledge that your third-party certifier indicated that the results of the study were acceptable. However, the smoke studies performed were static and did not simulate the routine operation of transferring items. In addition, there was not adequate, visible smoke to determine if there is ingress air from the unclassified area into the cleanroom. Furthermore, even if your smoke study shows no ingress, you have no assurance that it will be maintained without continuous pressure monitoring of the ISO 7 buffer room. Moreover, the (b)(4) do not contain HEPA coverage. As such, your remediation is insufficient to adequately mitigate the concerns raised in this observation.
4. In response to our observation that your personnel touched non-sterile objects, such as a door, and returned to aseptic production without changing or sanitizing gloves, you revised SOP 9.100, Required Garb for Clean Room Facility Access, to indicate that gloves should be disinfected or changed frequently, every (b)(4) interval during continuous compounding. In addition, it states that gloves must be routinely inspected for holes and replaced accordingly. Your revisions to the SOP, while improvements, do not appear to address one of the most concerning observations. Specifically, the investigators observed that an operator contacted a door, which is a high touch surface, and then resumed aseptic processing without changing or sanitizing their gloves. Thus, we remained concerned about poor aseptic practices observed within your facility.
The Agency noted that your firm placed non-sterile (b)(4) within the ISO 5 hood during aseptic processing. In your correspondence, your firm indicated that the use of non-sterile (b)(4), which contain (b)(4), helps to contain radioactive spills, thus decreasing personnel exposure to radiation. However, the use of a non-sterile (b)(4) has the potential to introduce contamination into the ISO 5 or product.
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 the violations identified above 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 correct the violations cited in this letter. Failure to promptly correct these 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 correct violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you do not believe that the products discussed above are in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot complete corrective action within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.
Please identify your response with FEI 3010421557 and Case # 604169. Send your electronic reply to Dr. Shawn Larson – Compliance Officer at Shawn.Larson@fda.hhs.gov and ORAPHARM2_Responses@fda.hhs.gov.
If you have questions regarding the contents of this letter, please contact Dr. Larson at 214-253-5216.
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,