DATE: 12/12/2023

Case #: 665762

WARNING LETTER

Dear Ms. Flowers:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Omeza LLC, FEI 3019843904, at 1610 Northgate Boulevard, Sarasota, Florida, from July 24-28, 2023.

This warning letter 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 Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

In addition, your Omeza Lidocaine Lavage and Omeza Skin Protectant drug products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a), and are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a). These violations are described in more detail below.

We reviewed your August 17, 2023, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

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

CGMP Violations

1. Your firm failed to maintain the buildings used in the manufacture, processing, packing, or holding of a drug product in a clean and sanitary condition and to keep them free of infestation by rodents, birds, insects, and other vermin (21 CFR 211.56(a)).

You manufacture over-the-counter (OTC) drug products indicated for the temporary relief of pain and itching. Our investigators observed mold-like substance on an air conditioning unit sleeve located directly above your drug product manufacturing area. In addition, insects both alive and dead, and other animal waste, were observed in areas used to store bulk drug products and samples.

Your response included corrective action and preventive action (CAPA) to implement a pest control program. You also included an investigation performed by a third-party consultant for the mold-like substance on the air conditioning unit sleeve.

Your response is inadequate because it did not include a review of environmental monitoring data in your manufacturing areas, an adequate risk analysis of previously manufactured drug product, or testing of reserve samples from impacted batches.

In response to this letter, provide:

• A summary of results from testing reserve samples of all drug product batches within expiry. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients and microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each batch. If testing yields an OOS result, indicate the corrective actions you will take, including notifying customers and initiating recalls.
• A summary of all environmental monitoring data associated with the production of all drug product batches.
• Detailed procedures that demonstrate your firm can maintain buildings free from pests and that they remain in a clean and sanitary state.
• Your risk assessment for all drug products distributed to the U.S. market and within expiry that used raw materials potentially contaminated with insects or other vermin.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. 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)).

You failed to adequately test your incoming components for identity before using the components in your drug products. Additionally, your firm accepted components from suppliers without establishing the reliability of your suppliers’ test analyses.

For example, you failed to perform identity testing of at least one lot of cod liver oil used to manufacture your skin protectant and lidocaine lavage drug products. In addition, the supplier qualification records for the lidocaine used in your lidocaine lavage drug products did not include initial or routine analysis to establish reliability of the supplier’s certificate of analysis (COA).

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

In your response, you provided CAPA stating that the raw materials in your warehouse will be tested for identity, and that your supplier management procedures will be updated to ensure that all suppliers are adequately qualified.

Your response is inadequate because it did not include an adequate retrospective review of previously distributed drug products. Additionally, your CAPA related to supplier qualification did not include detailed testing requirements and frequency for establishing reliability of both
active pharmaceutical ingredient (API) and excipient suppliers.

In response to this letter, provide:

• A comprehensive review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.
• A summary of results obtained from identity testing reserve samples of all API used in previously released drug products within expiry.
• A summary of results obtained from testing all components to evaluate the reliability of the certificate of analysis from each component manufacturer.
• Your updated supplier management procedure that includes detailed testing requirements and frequency for establishing and maintaining reliability of all raw material suppliers.

3. Your firm failed to follow a 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)).

You failed to follow your written stability procedures for your lidocaine lavage and skin protectant drug products. You inappropriately used stability data from a different product to establish a (b)(4) month expiration date for all your drug products.

In your response, you commit to updating your stability study procedure and perform a stability study for your skin protectant drug product.

Your response is inadequate because you did not address the lack of appropriate stability data to support the expiration dates of your drug products that are currently on the market. In addition, it lacked a review of the missing and failing stability data for your lidocaine lavage drug product.

In response to this letter, provide:

• A comprehensive assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:

    o Stability indicating methods
    o Stability studies for each drug product in its marketed container-closure system before distribution is permitted
    o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid
    o Detailed definition of the specific attributes to be tested at each station (timepoint)
    o All procedures that describe these and other elements of your remediated stability program

Unapproved New Drug Violations

Omeza Lidocaine Lavage and Omeza Skin Protectant are “drugs” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are intended for use as an external analgesic and a skin protectant, respectively.

Examples of claims observed on the Omeza Lidocaine Lavage and Omeza Skin Protectant product labels and labeling, including your product website https://omeza.com/, that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the product include, but may not be limited to, the following:

Omeza Lidocaine Lavage:

“Omeza Lidocaine Lavage is the first anhydrous periwound prep with a topical analgesic designed to help during irrigation of debris, reduce irritation, and help prepare the wound for treatment. . . . PERIWOUND TREATMENT . . . HOW IT WORKS . . . HELPS TO RELIEVE PAIN AND ITCH . . . Anhydrous formula promotes a moist healing environment . . . Rich in omega-3s known to help inflammation . . . Lidocaine helps to ease pain before debridement” [from your Omeza Lidocaine Lavage product website, https://omeza.com/omeza-lidocaine-lavage/]

Omeza Skin Protectant:

“OMEZA . . . SKIN PROTECTANT GEL . . . Uses . . . temporarily protects and helps relieve minor skin irritation and itching due to [bullet] rashes [bullet] eczema” [from your Omeza Skin Protectant product label]

Based on the above labeling claims, Omeza Lidocaine Lavage and Omeza Skin Protectant are intended for use as an external analgesic and skin protectant, respectively. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).

A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling; and with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for these drug products identified above.

Your Omeza Lidocaine Lavage and Omeza Skin Protectant are subject to section 505G of the FD&C Act, 21 U.S.C. 355h, which governs nonprescription drugs marketed without an approved application. Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements.

Omeza Lidocaine Lavage

With respect to OTC external analgesic drug products, Omeza Lidocaine Lavage is subject to the conditions of use set forth in Over-the-Counter (OTC) Monograph M017: External Analgesic Drug Products for Over-the-Counter Human Use (henceforth “M017” or “external analgesic monograph”),¹ encompassed under the final administrative order OTC000033.

However, your Omeza Lidocaine Lavage does not conform to conditions specified in M017. Specifically, its labeling states that the product is intended to be used as a “lavage,” a “periwound” preparation, “designed to help during irrigation of debris” and “to help inflammation.” These intended uses go beyond the general intended uses for an external analgesic, and it does not comply with the applicable final order.

Additionally, the active ingredient, omega-3s, in your product is not an active ingredient included in M017. Although the product labeling does not specifically list this ingredient as an active ingredient, the labeling claims for this ingredient such as “to help inflammation,” demonstrate that this is an active ingredient” as defined in 21 CFR 201.66(b)(2) because it is intended to furnish pharmacological activity.² Omega-3s is not recognized as an active ingredient in M017.

Therefore, as formulated and labeled, your Omeza Lidocaine Lavage drug product does not comply with the external analgesic monograph described above or any other final order.³ Moreover, there is no evident basis under the FD&C Act under which this product would be legally marketed without an approved application. Thus, Omeza Lidocaine Lavage is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Accordingly, this product is an unapproved new drug marketed in violation of section 505(a) of the FD&C Act, 21 U.S.C 355(a). Introduction or delivery for introduction of such a product into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

Omeza Skin Protectant

With respect to OTC skin protectant drug products, your Omeza Skin Protectant is subject to the conditions of use set forth in OTC Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use (henceforth “M016” or “skin protectant monograph”),⁴ encompassed under the final administrative order OTC000005. However, your Omeza Skin Protectant does not conform to conditions specified in M016. Specifically, the indication that the product “temporarily protects and helps relieve minor skin irritation and itching due to [bullet] rashes [bullet] eczema” is not permitted for skin protectant drug products containing cod liver oil as the active ingredient.

Therefore, as formulated and labeled, your Omeza Skin Protectant drug product does not comply with the skin protectant monograph described above or any other final order.⁵ Moreover, there is no evident basis under the FD&C Act under which this product would be legally marketed without an approved application. Thus, Omeza Skin Protectant is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Accordingly, this product is an unapproved new drug marketed in violation of section 505(a) of the FD&C Act, 21 U.S.C 355(a). Introduction or delivery for introduction of such a product into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

Misbranded Drug Violations

Omeza Lidocaine Lavage and Omeza Skin Protectant are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355, and do not comply with the requirements under section 505G of the FD&C Act, 21 U.S.C. 355h.

The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

CGMP Consultant Recommended

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

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 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 electronically submit your reply on company letterhead to Mark W. Rivero, Compliance Officer, at ORAPHARM2_RESPONSES@fda.hhs.gov. In addition, please submit a signed copy of your response to mark.rivero@fda.hhs.gov.

If you have questions regarding any issues in this letter, please contact me by e-mail at ronda.loyd-jones@fda.hhs.gov or by phone at (214) 253 - 5336, or Mr. Mark Rivero by e-mail or by phone at (954) 759 - 7718.

Sincerely,
/S/

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

____________________

1 Section 505G(a)(1) of the FD&C Act specifies criteria under which certain nonprescription drugs without an approved application are deemed GRASE and not "new drugs," notably, conformance with conditions detailed in applicable OTC monograph documents issued by FDA under 21 CFR 330 prior to enactment of the CARES Act. In the case of OTC external analgesic drug products, relevant documents were deemed under section 505G to be a final administrative order, Over-the-Counter Monograph M017: Topical Antifungal Drug Products for Over-the-Counter Human Use. (See Order ID OTC000033, available at FDA’s website OTC Monographs @ FDA, https://dps.fda.gov/omuf.)

2 Under 21 CFR 201.66(b), an active ingredient is a component of a drug intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.

3 FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that Omeza Lidocaine Lavage is GRASE for use under the conditions prescribed, recommended, or suggested in its labeling.

4 In the case of OTC skin protectant drug products, relevant documents were deemed under section 505G to be a final administrative order, Over-the-Counter Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use. (See Order ID OTC000005, available at FDA’s website OTC Monographs @ FDA, https://dps.fda.gov/omuf.)

5 FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that Omeza Skin Protectant is GRASE for use under the conditions prescribed, recommended, or suggested in its labeling.