WARNING LETTER

Pharmaceutical Care Solutions dba Pharmacy Solutions MARCS-CMS 610201 — August 02, 2021

Delivery Method:: UPS Next Day
Product:: Drugs

Recipient:: Recipient Name

Sahar Z. Swidan; Recipient Title

CEO; Pharmaceutical Care Solutions dba Pharmacy Solutions; 5402 Jackson Road, Suite C
Ann Arbor, MI 48103-1866
United States

Issuing Office:: Division of Pharmaceutical Quality Operations III; United States

August 2, 2021

WARNING LETTER
Case# 610201

Dear Ms. Swidan:

From January 15, 2020, to January 24, 2020, U.S. Food and Drug Administration (FDA) investigators inspected your facility, Pharmaceutical Care Solutions dba Pharmacy Solutions, located at 5204 Jackson Road, Suite C, Ann Arbor, MI 48103. During the inspection, the investigators collected evidence indicating 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. 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 collected evidence indicating that drug products produced by your firm failed to meet the conditions of section 503A. For example, the evidence collected indicates that:

1. Your firm compounded drug products using ammonium tetrathiomolybdate. Drug products compounded using ammonium tetrathiomolybdate are not eligible for the exemptions provided by section 503A(a), because ammonium tetrathiomolybdate is not the subject of an applicable USP or NF monograph, is not a component of an FDA-approved human drug and does not appear on the 503A bulks list.²

2. Your firm compounded drug products using a bulk drug substance manufactured by (b)(4), which is not a registered establishment 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 ineligible drug products 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 letter, dated February 14, 2020, in response to FDA’s inspection of your facility. Regarding issues related to the conditions of section 503A of the FDCA, the following corrective action appears deficient: you have not agreed to cease compounding with ammonium tetrathiomolybdate. In your letter you requested that FDA review ammonium tetrathiomolybdate bulk drug substance for addition to Category 1. Ammonium tetrathiomolybdate was nominated for inclusion on the 503A bulks list, but its nomination was later withdrawn. If you would like FDA to evaluate this bulk drug substance, ammonium tetrathiomolybdate may be renominated for inclusion on the 503A bulks list by submitting a nomination to docket number FDA-2015-N-3534 at www.regulations.gov. For more information on how to submit a nomination, please see the instructions in the Federal Register notice titled, Bulk Drug Substances That Can Be Used To Compound Drug Products in Accordance With Section 503A of the Federal Food, Drug, and Cosmetic Act; Establishment of a Public Docket.⁵

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.

In addition, we also note that during the inspection, the FDA investigators collected evidence indicating that your firm had tranilast in inventory. As noted above, for a compounded drug product to qualify for the exemptions under section 503A of the FDCA, bulk drug substances used to compound it must: (I) comply with the standards of an applicable USP or 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). Tranilast was nominated for inclusion on the 503A bulks list, was evaluated by Pharmacy Compounding Advisory Committee and by FDA and FDA determined not to include tranilast on the list of bulk drug substances that can be used in compounding under section 503A, found at 21 C.F.R. 216.23(a). See 21 C.F.R. 216.23(b)(4). Accordingly, drug products compounded using tranilast are not eligible for the exemptions provided by section 503A(a).

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 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.

Please address your reply via email to: ORAPHARM3_RESPONSES@fda.hhs.gov

Attention: Brian D. Garthwaite, Ph. D.
Compliance Officer
U.S. Food and Drug Administration
Division of Pharmaceutical Quality Operations Division III

Your written notification should refer to the Warning Letter Number above (Case # 610201). If you have questions about the contents of this letter, please contact Dr. Garthwaite at (612) 758-7132.

Sincerely,
/S/

Art O. Czabaniuk
Program Division Director
Division of Pharmaceutical Quality Operations III

__________________________

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 On June 9, 2016, FDA issued a 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. Ammonium tetrathiomolybdate was nominated for inclusion on the 503A bulks list, but its nomination was later withdrawn. 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 Act, [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) [21 U.S.C. 321(p)] of the FDCA 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).

5 See https://www.govinfo.gov/content/pkg/FR-2015-10-27/pdf/2015-27271.pdf.