Pharmedica USA, LLC MARCS-CMS 648269 — April 28, 2023

WARNING LETTER

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• Delivery Method: VIA UNITED PARCEL SERVICE AND VIA E-MAIL
• Product: Drugs

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• Recipient: Mr. Fida M. Abuhmeidan; Chief Executive Officer (CEO); Pharmedica USA, LLC; 4734 E. Mossman Rd.; Phoenix, AZ 85050; United States; osm@pharmedicausa.com

• Issuing Office: Division of Pharmaceutical Quality Operations IV ; United States

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WARNING LETTER

April 28, 2023

Dear Mr. Abuhmeidan:

The U.S. Food and Drug Administration inspected your drug manufacturing facility, Pharmedica USA, LLC., FEI 3015269827, at 2836 W. Deer Valley Road, Building E2, Phoenix, Arizona, from November 1, 2022 to November 7, 2022.

FDA determined that drug products manufactured at your facility are adulterated under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions.

This warning letter also summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

We have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.

Insanitary Conditions

The FDA investigator 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 FD&C Act. For example, the investigator observed that your facility lacked ISO classified areas, including ISO 5, for sterile drug product manufacturing, and your manufacturing facility was in a state of disrepair.

CGMP Violations

During our inspection, our investigators observed specific violations including, but not limited to, the following.

1. 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. Your firm also failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.113(b) & 211.42(c)(10)).

You manufactured a multi-dose, preservative-free, over-the-counter (OTC) ophthalmic drug product for the product owner, Purely Soothing, without adequate facility design, controls, and procedures to ensure sterility of containers/closures and finished ophthalmic drug product. If ophthalmic drugs are not sterile, they pose an unacceptable risk to patients including infection and potential for vision loss.

Furthermore, it is essential that multi-dose ophthalmic drug products contain one or more suitable substances that will preserve a product and minimize the hazard of injury resulting from incidental contamination during use.

During the inspection, you informed us that you were unaware that ophthalmic drug products are required to be sterile, and acknowledged that your facility is not designed and equipped to handle or manufacture sterile drug products, even though your drug products are intended for use as “eye drops.”

To help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing, see FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice at https://www.fda.gov/media/71026/download.

2. 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)).

You failed to adequately qualify the equipment and validate the processes used to manufacture your drug products. You have not performed process performance qualification (PPQ) studies, nor do you have an ongoing program for monitoring process control, to ensure stable manufacturing operations and consistent drug quality for products in U.S. distribution.

Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately to ensure the quality of raw material inputs, (b)(4) materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality are necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.

See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.

3. 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, and conduct for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms. (21 CFR 211.165(a) and 21 CFR 211.165(b)).

Your firm failed to conduct adequate release testing of all your drug products. For example:
• You did not conduct appropriate laboratory testing, including sterility testing, for each batch of drug product (e.g., ophthalmic) that are required to be sterile.
• You did not conduct appropriate laboratory testing of each batch of drug product (e.g., nasal spray) required to be free of objectionable microorganisms.

Full release testing, including for identity, strength, and purity, must be performed prior to batch release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.

4. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).

Your firm failed to conduct adequate testing on the components used to manufacture your finished drug products (e.g., ophthalmic product, nasal spray). Additionally, your firm accepts components from your suppliers without establishing the reliability of your suppliers’ test analyses, and you did not obtain or review the suppliers’ certificate of analysis (COA) for all components (e.g., methylsulfonylmethane (MSM), (b)(4) water).

Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications prior to use in the manufacture of your drug products.

5. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

Your firm failed to establish an adequate quality unit (QU) with the responsibilities and authority to oversee the manufacture of your drug products. For example, you failed to ensure:

• Adequate procedures describing roles and responsibilities of the QU, including but not limited to supplier qualification, batch release, complaints, process validation, equipment cleaning, and CGMP training (21 CFR 211.22(a) and (d)).
• Adherence to a stability program (21 CFR 211.166(a)).
• Consistent and complete batch records (21 CFR 211.188).
• Adequate investigations and deviations (21 CFR 211.192).

Even when a QU consists of one or only a few, those persons are still accountable for overseeing ongoing effectiveness of all systems and procedures, and review of the results of manufacture to ensure that product quality standards have been met.

Drug Recall & Production Ceased

On February 2, 2023, FDA held a teleconference with you. We recommended you consider removing any batches of Purely Soothing 15% MSM Drops and Purely Soothing MSM Nasal Spray drug products currently in distribution from the U.S. market.

On February 14, 2023, you communicated your commitment to cease the manufacturing and distribution of all drug products with no intention of producing drug products in the future and agreed to voluntary recall all drug products manufactured with active ingredient MSM.

On March 3, 2023, you issued a voluntary worldwide recall of Purely Soothing, 15% MSM Drops (i.e., ophthalmic) due to non-sterility. The company announcement was posted to the FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/pharmedica-usa-llc-issues-voluntary-worldwide-recall-purely-soothing-15-msm-drops-due-non-sterility.

We acknowledge your commitment to cease production of all drugs at this facility.

If you plan to resume any operations regulated under the FD&C Act, notify this office prior to resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

If you resume CGMP activities, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPA before you pursue resolution of your firm’s compliance status with FDA.

Conclusion

The violations cited in this letter are not intended to be an all-inclusive list of violations that exist 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.

Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other federal agencies from awarding contracts.

Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

Please identify your response with unique identifier CMS 648269 and send electronically to orapharm4_responses@fda.hhs.gov or by mail to:

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
19701 Fairchild Road
Irvine, CA 92612-2506

If you have questions regarding this letter, please contact William V. Millar, compliance officer, via email at william.millar@fda.hhs.gov or by phone at (503) 671-9711 Ext. 30.

Sincerely,
/S/

CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV

Cc: Mohamed Khalil
Head of Operations
Pharmedica USA, LLC
m.khalil@pharmedicausa.com