- Delivery Method:
- VIA Electronic Mail
Recipient NameRob Kilgore
- Belmar Pharma Solutions, Drug Depot, LLC., dba APS Pharmacy
12860 W. Cedar Drive, Suite 211
Lakewood, CO 80228
- Issuing Office:
- Division of Pharmaceutical Quality Operations II
March 31, 2023
CMS Case #653740
Dear Mr. Kilgore:
From June 6, 2022 to June 17, 2022, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Drug Depot, LLC dba APS Pharmacy, located at 34911 US Highway 19 N Ste 600, Palm Harbor, Florida 34684. During the inspection, the investigators noted that drug products you produced failed to meet the conditions of section 503A of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353a] for exemption from certain provisions of the FDCA.
FDA issued a Form FDA 483 to your firm on June 17, 2022. FDA acknowledges receipt of your facility’s responses, dated July 12, 2022, August 15, 2022, and September 30, 2022. Based on this inspection, it appears that you produced drug products that violate the 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)].1 Receipt of valid prescriptions for individually-identified patients is one of the conditions for the exemptions under section 503A.
In addition, for a compounded drug product to qualify for the exemptions under section 503A, bulk drug substances used to compound it must: (I) comply with the standards of an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph exists, and the USP chapter on pharmacy compounding; (II) if such a monograph does not exist, be components of drugs approved by the Secretary; or (III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, appear on a list developed by the Secretary through regulation (“503A bulks list”) (section 503A(b)(1)(A)(i) of the FDCA).
Further, each bulk drug substance used to compound a drug product must be manufactured by an establishment that is registered under section 510 of the FDCA [21 U.S.C § 360] (section 503A(b)(1)(A)(ii) of the FDCA).
B. Failure to Meet the Conditions of Section 503A
During the inspection, the FDA investigators noted that drug products produced by your firm failed to meet the conditions of section 503A. For example, the investigators noted:
1. Your firm compounded drug products using bulk drug substances, including (b)(4) and (b)(4), that are not eligible for the exemptions provided by section 503A(a), because the bulk drug substances are not the subject of applicable USP or NF monographs, are not components of FDA-approved human drugs, and do not appear on the 503A bulks list.2
2. Your firm compounded drug products using bulk drug substances manufactured by establishments, including (b)(4), which are not registered establishments under section 510 of the FDCA.
Therefore, you compounded drug products that do not meet the conditions of section 503A and are not eligible for the exemptions in that section, including the FDA approval requirement of section 505 of the FDCA, the requirement under section 502(f)(1) of the FDCA that labeling bear adequate directions for use, and the requirement of compliance with CGMP under section 501(a)(2)(B) of the FDCA. In the remainder of this letter, we refer to your drug products that do not qualify for exemptions under section 503A as the “ineligible drug products.”
Specific violations are described below.
C. Violations of the FDCA
Unapproved New Drug Products
You do not have any FDA-approved applications on file for the ineligible drug products that you compounded.3 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
The ineligible drug products you compounded 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.4 Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA. The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. 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 firm’s responses to the Form FDA 483.
Regarding issues related to the conditions of section 503A of the FDCA, you have not addressed the compounding of drug products using ineligible bulk drug substances, including (b)(4) and (b)(4). As explained above, drug products compounded using these bulk drug substances are not eligible for the exemptions provided by section 503A(a) because they are not the subject of applicable USP or NF monographs, are not components of FDA-approved human drugs, and do not appear on the 503A bulks list. In addition, you have not addressed your use of bulk drug substances from establishments that are not registered under section 510 of the FDCA. As stated above, to qualify for the exemptions under section 503A of the FDCA, only bulk drug substances manufactured by an establishment that is registered under section 510 of the FDCA may be used in compounding.
Should you continue to compound and distribute drug products that do not meet the conditions of section 503A, the compounding and distribution of such drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the drug CGMP regulations.
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.
Your written notification should refer to the Warning Letter Number above (Case #653740). Please electronically submit your signed reply on your firm’s letterhead to Ronda R. Loyd-Jones, Director, Compliance Branch, at Ronda.Loyd Jones@fda.hhs.gov and email@example.com.
If you have questions regarding the contents of this letter, you may contact Mr. Thao Ta, Compliance Officer, via phone at 214-253-5217 or e-mail at firstname.lastname@example.org.
Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
cc: VIA ELECTRONIC MAIL
Andrew M. Vukadinovich
Director of Operations
Drug Depot, LLC dba APS Pharmacy
34911 US Highway 19N Ste 600
Palm Harbor, Florida 34684-1921
1 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 503A of the FDCA.
2 These substances are also not eligible for the policy applicable to certain bulk drug substances described in the final guidance titled, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act. This guidance describes FDA’s interim regulatory policy for State-licensed pharmacies, Federal facilities, and licensed physicians that compound human drug products using bulk drug substances that do not otherwise meet the conditions of section 503A(b)(1)(A)(i) while the 503A bulks list is being developed. Specifically, the guidance sets out the conditions under which FDA does not intend to take action against a State-licensed pharmacy, Federal facility, or licensed physician for compounding a drug product using a bulk drug substance that is not the subject of an applicable USP or NF monograph or a component of an FDA-approved drug, until the substance is identified in a final rule as included or not included on the 503A bulks list. These conditions include that the substance may be eligible for inclusion on the 503A bulks list, was nominated with adequate support for FDA to evaluate it, and has not been identified by FDA as a substance that appears to present significant safety risks pending further evaluation. For additional information, see the guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM469120.pdf.
3 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.
4 Your ineligible 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).