WARNING LETTER

Apothecary Pharma, LLC MARCS-CMS 717972 — December 01, 2025

Delivery Method:: VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTED
Product:: Drugs

Recipient:: Recipient Name

Priyanka Rana; Recipient Title

President and Chief Pharmacy Officer; Apothecary Pharma, LLC; 1913 Evans Road
Cary, NC 27513-2041
United States

Issuing Office:: Center for Drug Evaluation and Research (CDER); United States

WARNING LETTER
WL # 717972

December 1, 2025

Dear Ms. Rana:

You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]¹ on September 7, 2024, and most recently on January 11, 2025. From May 12, 2025, to May 15, 2025, FDA investigators inspected your facility, Apothecary Pharma, LLC located at 1913 Evans Road, Cary, NC 27513. During the inspection, the investigators noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigators noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.

FDA issued a Form FDA 483 to your facility on May 15, 2025. FDA acknowledges receipt of your facility’s response, dated June 9, 2025, and related attachments received July 17, 2025. FDA acknowledges that your firm ceased sterile drug production as of May 12, 2025, and notified FDA of an intent to resume sterile drug production on August 1, 2025. Based on this inspection, it appears you produced drugs that violate the FDCA.

A. Compounded Drug Products under the FDCA

Under section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.²

An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.

For a compounded drug product to qualify for the exemptions under section 503B, the labeling of the drug must include certain information (section 503B(a)(10) of the FDCA [21 U.S.C. §353b(a)(10)]).

In addition, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b), including the requirement to submit adverse event reports to FDA “in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations)” (section 503B(a)(1), (b)(5) of the FDCA [21 U.S.C. § 353b(a)(1), (b)(5)]).

B. Failure to Meet the Conditions of Section 503B

During the inspection, FDA investigators noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigators noted:

1. Some of your facility’s drug products, such as Tirzepatide Injection 10 mg/mL and Semaglutide Injection 2.5 mg/mL, did not include the following information on the label: a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingredient. Additionally, some of your facility’s drug products did not include the following information on the container: information to facilitate adverse event reporting and directions for use, including, as appropriate, dosage and administration.

2. Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations).³

Specifically, your facility’s procedures for reporting adverse events are inadequate. For example, your documented procedures for reporting adverse events do not include a definition of what constitutes a “serious” and “unexpected” adverse event (21 CFR 310.305(b)).

Because your compounded drug products have not met all of the conditions of section 503B, they are not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.

Specific violations are described below.

C. Violations of the FDCA

Adulterated Drug Products

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:

1. An operator blocked first air by placing gloved hands directly over open sterile containers.

2. An operator placed components within the ISO 5 work area that had the potential to block the movement of first air to critical in-process operations. Specifically, an operator positioned a second row of exposed vials behind a first row in the ISO 5 (b)(4) laminar flow hood, obstructing first air to critical surfaces.

3. An operator rested their arms on the work surface of the hood during aseptic production. This practice may introduce contamination into the ISO 5 work area.

4. 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.

5. Personnel engaged in aseptic processing while exposing skin within the ISO 5 aseptic processing area.

6. 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.

7. Personnel moved quickly in a critical area such that unidirectional airflow is likely to be disrupted.

8. Production areas or equipment have difficult to clean and visibly rusty equipment or surfaces.

9. Lack of disinfection of equipment and supplies at each transition from areas of lower quality air to areas of higher quality air.

10. Failing to disinfect or change gloves frequently enough given the nature of the operations to prevent contamination. More specifically, personnel were observed touching equipment or other surfaces located outside of the ISO 5 area with gloved hands and then proceeding with aseptic processing without changing or sanitizing gloves.

FDA investigators also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:

1. Your firm failed to establish written responsibilities and procedures applicable to the quality control unit and to follow written procedures applicable to the quality control unit (21 CFR 211.22(d)).

2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

3. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).

4. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).

5. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).

6. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).

Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance, Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.

Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, 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.

Unapproved New Drug Products

You do not have any FDA-approved applications on file for drug products that you compound.⁴Under 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

You compound drug products that 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 causing them to be misbranded under section 502(f)(1) of the FDCA.⁵ The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Further, 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 facility's response to the Form FDA 483. FDA acknowledges that your firm ceased sterile drug production as of May 12, 2025, and notified FDA of an intent to resume sterile drug production on August 1, 2025.

Some of your corrective actions appear adequate; however, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:

1. We acknowledge your corrective actions addressing operating with draft procedures and improper visual inspection techniques, including finalization of SOPs for Quality Unit responsibilities, Corrective and Preventive Action (CAPA), batch record review, out-of-specification (OOS) results, and retraining on the visual inspection SOP. However, your response remains inadequate because draft SOPs for Change Control, Deviations, and Risk Assessment were not addressed, and you did not assure that draft versions will not be used. In addition, you did not provide competency verification or supervisory oversight of retrained inspectors, nor a retrospective review of batches inspected under improper techniques.

2. We acknowledge your actions regarding inadequate skin coverage posing a contamination risk to sterile drug products, including internal training to SOP 0003.00 with emphasis on mirror self-inspection. However, the adequacy of your response cannot
be fully evaluated because you did not provide supporting documentation, competency verification, post-retraining assessments, or updates to SOP 0003.00/procedures to enforce mirror checks. Further, although production was halted until August 1, 2025, you did not submit evidence of interim controls or monitoring results demonstrating proper gowning to assure ongoing compliance thereafter.

Some of your corrective actions appear deficient:

1. Regarding your firm’s failure to establish written responsibilities and procedures applicable to the quality control unit, we acknowledge your voluntary halt of production on May 12, 2025, and your commitment to implementing corrective actions by August 1,
2025. However, your response is inadequate for the following reasons:

a. Your response lacks a retrospective review plan for released batches (b)(4), (b)(4) and fails to include a root cause analysis for why incomplete records were initially released. You have not provided training records demonstrating staff understanding of the new SOP 1012.00 procedures or evidence that the enhanced batch record review process addresses all identified deficiencies.

b. While you engaged (b)(4) Air for re-certification, you have not acknowledged (b)(4)' license revocation since 2014 or provided a plan to validate prior certifications. Your response lacks vendor qualification procedures (e.g., revising SOP 1009.00) and certification review processes. There is no assessment of previously released products manufactured in potentially uncertified environments, which compromises patient safety.

2. We acknowledge your engagement of (b)(4) Air and your retraining efforts related to aseptic operations. However, your response is inadequate because:

a. You did not provide detailed protocols to ensure dynamic smoke studies simulate true production with maximum equipment and personnel, nor did you define acceptance criteria or Quality Unit oversight for vendor-conducted studies.

b. You failed to conduct a risk assessment for the (b)(4) Tirzepatide 10 mg/mL batches released without validated airflow studies, or to provide an impact evaluation or justification for their release.

c. Critical validation gaps remain, including no commitment to perform smoke studies in the ISO 7 cleanroom and no methodologies to improve smoke volume, background contrast, or dynamic simulation.

d. Aseptic technique retraining did not address specific behaviors that compromise first air (e.g., blocking critical surfaces, resting forearms on ISO 5 surfaces, leaning into hoods and exposing skin).

e. You proposed no workspace/equipment modifications to ensure all vials receive unidirectional airflow, and you did not evaluate equipment configurations to mitigate this risk.

3. We acknowledge your retraining to SOP 0003.00 with emphasis on mirror self inspection. However, your response is inadequate because:

a. SOP 0003.00 was not updated to reflect the correct gowning sequence or to establish procedures that enforce mirror checks and supervisory oversight.

b. You did not provide supporting documentation or competency verification demonstrating proper gowning technique; no post-retraining assessments were submitted.

c. You did not address observed deficiencies (e.g., use of safety glasses instead of cleanroom goggles, crossing the demarcation line on the “dirty” side, and masks worn upside down).

d. Procedural gaps remain regarding shoe covers over clogs when entering ISO-classified areas.

e. Although operations resumed on August 1, 2025, you did not provide evidence of interim controls or monitoring results demonstrating continued compliance after August 1, 2025, or plans to assure ongoing compliance thereafter.

4. We acknowledge your commitment to address the condition of the ISO 5 laminar airflow hood (LAFH) by August 1, 2025. However, your response is inadequate because:

a. You did not provide essential supporting documentation such as photographic evidence, maintenance records, or updated SOPs, while providing only vague commitments to repair rust damage without specifying repair methods. No interim controls or monitoring were described to mitigate contamination risk while the compromised LAFH remained in service, including upon resumption of operations on August 1, 2025.

b. The root cause analysis attributing rust to (b)(4) lacked supporting evidence and did not include revised cleaning protocols, verification, or preventive measures; dents and peeling paint were inappropriately characterized as “cosmetic.”

c. Reliance on media fills, sterility tests, or prior certifications does not address equipment condition defects that can harbor contamination or disrupt airflow pattern.

d. You failed to provide supporting documentation including photographs, maintenance records, engineering assessments, updated SOPs, or qualification protocols, to demonstrate the implementation and effectiveness of your proposed changes. You did not provide an impact assessment for distributed batches compounded on this LAFH or establish a robust preventive maintenance program to prevent recurrence.

5. We acknowledge retraining to SOP 0004 (Ideal Conduct in Cleanroom) and SOP 2001.00 (Cleanroom Material Transfer). However, your response is inadequate because:

a. You did not revise your SOPs to establish specific disinfection protocols with clear responsibilities and acceptance criteria.

b. You did not provide a comprehensive CAPA plan that includes thorough root cause analysis, implementation evidence, or monitoring strategies to verify effectiveness of corrective actions.

c. You failed to provide training documentation and competency assessments demonstrating that personnel can correctly perform material transfer procedures and maintain proper glove hygiene practices. The proposed sanitize-able metal tool for trash handling lacks specificity and does not mitigate immediate contamination risks during aseptic operation.

d. You did not submit an ongoing compliance plan (e.g., routine observation, audit checklists, personnel monitoring targets) or interim controls upon resumption of operations on August 1, 2025.

6. We acknowledge your retraining to SOP 2004 (Visual Inspection). However, your response is inadequate because:

a. You failed to revise batch records and procedures to include proper defect classification (critical/major/minor), Acceptable Quality Levels (AQL) methodology, and acceptance criteria. Additionally, you did not provide an updated Form F-2004.00-01, and AQL documentation continues to be omitted from your quality control processes. You did not submit documentation demonstrating retraining effectiveness (e.g., training curriculum, attendance, competency assessments, completion dates) or supervisory oversight of inspectors.

b. You failed to provide impact assessment or retrospective review of distributed lots AP-202505 through AP-202513 to determine whether visual inspection deficiencies affected product quality.

c. You failed to provide finalized SOP revisions or evidence of implementation; Annexure-1 lacked sufficient detail to verify changes.

d. The referenced CAPA lacked specific corrective actions, milestones, responsible owners, and effectiveness checks.

Given the nature and significance of the violations identified, FDA remains concerned that your firm has not yet demonstrated that adequate correction has been properly implemented to sustain sterile drug product manufacturing in a manner fully consistent with CGMP. 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.

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).]

Should you continue to compound and distribute drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.

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 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.

All correspondence should refer to the Warning Letter Number above (# 717972) and include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.

Sincerely,
/S/

F. Gail Bormel, JD, RPh
Director
Office of Compounding Quality and Compliance
Office of Compliance
Center for Drug Evaluation and Research

______________________

1 See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).

2 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 503B of the FDCA.

3 For more information, see, FDA’s guidance, “Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act,” which can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM434188.pdf.

4 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.

5 Your compounded 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).