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July 22, 2021

Case #: 610679

WARNING LETTER

Mr. Mougeot:

From December 12, 2019, to December 20, 2019, a U.S. Food and Drug Administration (FDA) investigator inspected your facility, Matthew 7:25, Inc. dba Thrive Pharmacy, located at 2683 Saint Johns Bluff Rd S, Suite 135, Jacksonville, Florida 32246. During the inspection, the investigator 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. In addition, the investigator noted deficiencies in your practices for producing drug products.

FDA acknowledges that on March 10, 2020, your firm initiated a voluntary recall of Buprexone Banana Cream 6-0.6 mg Troche, Buprenorphine Watermelon 8 mg Troche, and Buprenorphine Black Cherry 2 mg Troche due to subpotency of the products. 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.

B. Failure to Meet the Conditions of Section 503A

During the inspection, the FDA investigator noted that drug products produced by your firm failed to meet the conditions of section 503A. For example, the investigator noted that your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced, including phentermine 37.5 mg capsules.

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

Adulterated Drug Products

The manufacture of the ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigator observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations included, for example:

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).

2. Your firm failed to establish an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).

3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).

During the inspection, the FDA investigator collected samples from three separate lots of troches produced by your firm. FDA analysis of these samples determined that they were subpotent of the declared label claim. Specifically, your Buprexone Banana Cream 6-0.6 mg Troche, Buprenorphine Watermelon 8 mg Troche, and Buprenorphine Black Cherry 2 mg Troche drug products contained 85.7% (80.2% for Naloxone), 92.5%, and 89.4%, respectively, of the labeled concentrations of Buprenorphine. Under section 501(b) of the FDCA [21 U.S.C. § 351(b)], a drug is deemed to be adulterated if it purports to be or is represented as a drug the name of which is recognized in an official compendium and its strength differs from, or its quality or purity falls below, the standard set forth in such compendium. The strength of your Buprexone Banana Cream 6-0.6 mg Troche, Buprenorphine Watermelon 8 mg Troche, and Buprenorphine Black Cherry 2 mg Troche drug products differed from the labeled amount of product it was purported to possess, causing it to be adulterated under section 501(b) of the FDCA.

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.

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.² Accordingly, these ineligible drug products are misbranded under section 502(f)(1) of the FDCA.

In addition, under section 502(a) of the FDCA [21 U.S.C. § 352(a)], a drug product is misbranded if its labeling is false or misleading in any particular. As noted above, analyses showed that your Buprexone Banana Cream 6-0.6 mg Troche, Buprenorphine Watermelon 8 mg Troche, and Buprenorphine Black Cherry 2 mg Troche drug products contained 85.7% (80.2% for Naloxone), 92.5%, and 89.4%, respectively, of the labeled concentrations of Buprenorphine. Because the labeling of these drug products was false, the drug products were misbranded under section 502(a) of the FDCA. It is 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 acknowledge your voluntary recall, initiated on March 10, 2020, of Buprexone Banana Cream 6-0.6 mg Troche, Buprenorphine Watermelon 8 mg Troche, and Buprenorphine Black Cherry 2 mg Troche due to subpotency of the products. However, it is unclear if your firm has evaluated all other batches produced under similar processes or if your firm has implemented appropriate corrective actions to prevent recurrence of sub-potent product.

In addition, regarding issues related to the conditions of Section 503A, you have not addressed the compounding of drug products for office stock.

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. Before doing so, you must comply with the requirements of section 505 and 502(f)(1) and fully implement corrections that meet the minimum requirements of the CGMP regulations.³

We also note that during the inspection, the FDA investigator collected evidence indicating that your firm compounded drug products that might be considered essentially copies of commercially available drug products (e.g., phentermine hydrochloride 37.5 mg capsules and buprenorphine hydrochloride 8 mg troches). For your awareness, we note that under section 503A of the FDCA, a drug product is not eligible for certain exemptions if it is prepared by a pharmacist or physician who compounds “regularly or inordinate amounts” any drug products that are essentially copies of a commercially available drug product (section 503A(b)(1)(D) of the FDCA). The term “essentially a copy of a commercially available drug product” does not include a drug product in which there is a change, made for an identified individual patient, which produces for that patient a significant difference, as determined by the prescribing practitioner, between the compounded drug and the comparable commercially available drug product (section 503A(b)(2) of the FDCA).⁴

In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b)].

FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. A third-party consultant with relevant drug manufacturing expertise should assist you in conducting this comprehensive evaluation.

E. Conclusion

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 adequately address this matter 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. 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 complete corrective action within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction.

Your written notification should refer to case # 610679.

Please electronically submit your reply, on company letterhead, to Jamillah Selby, Compliance Officer, at [email protected]. In addition, please submit a signed copy of your response to [email protected] and [email protected].

If you have questions regarding the contents of this letter, you may contact Jamillah Selby via phone at 214-253-5218 or email at [email protected].

Sincerely,
/S/

Monica R. Maxwell
Program Division Director
Office of Pharmaceutical Quality Operations,
Division II

Cc: Renee Alsobrook
Chief Compliance and Enforcement
Division of Drugs, Devices and Cosmetics
Department of Business and Professional Regulation

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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 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).

3 In this letter we do not address whether your proposed corrective actions would resolve the CGMP violations noted above.

4 See FDA’s guidance, Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act (“503A copies guidance”), available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM510154.pdf.