---

---

---

WARNING LETTER

November 30, 2023

Re: CMS 664583

Dear James Curtiss:

This letter concerns your firm's distribution of veterinary products for use in aquarium fish and birds.

In August 2023, the U.S. Food and Drug Administration (FDA) reviewed your website (https://aquanestbiotic.com), where you take orders for Fish Amoxi, Fish Kef, Fish Cip, Fish Clinda, Fish Dox, Fish Ethro, Fish Met, Fish Peni, Bird Azith, and Bird Dox. The claims on your website establish that these products are intended for use in the cure, mitigation, treatment, or prevention of diseases in animals, which makes them drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) [21 U.S.C. § 321(g)(1)(B)]. In addition, these animal drugs are misbranded under section 502(o) of the FD&C Act [21 U.S.C. § 352(o)] because they have not been drug listed with FDA, nor have they been manufactured in a facility that is registered with FDA in accordance with sections 510(b) and (j) of the FD&C Act [21 U.S.C. § 360(b), (j)]. As discussed below, introducing or delivering these unapproved and misbranded new animal drugs for introduction into interstate commerce violates section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].

UNAPPROVED NEW ANIMAL DRUGS
Examples of claims observed on your website (https://aquanestbiotic.com) that establish the intended use of your products as drugs include, but may not be limited to, the following:

Fish

• Fish Amoxi, Amoxicillin, 250 mg, 500 mg, capsules, which, as described on your website, “exerts a bactericidal action on gram-positive and some gram-negative bacteria. Amoxicillin is a broad spectrum bacterial antibiotic. It is effective against a number of pathogentic [sic] bacteria associated with marine and freshwater ornamental fish diseases. Can use for infected eyes, pop-eye, fin or tail rot, skin ulcerations, columnaris disease, and gill disease.”
• Fish Kef, Cephalexin/Keflex, 250 mg, 500mg, capsules, described on your website as “a broad-spectrum antibiotic used in the treatment of a wide range of bacterial infections. It is effective against a number of pathogentic [sic] bacteria associated with ornamental fish diseases.”
• Fish Cip, Ciprofloxacin, 500 mg, capsules, described on your website as “a synthetic broad spectrum antibiotic that is effective against gram-negative and some gram-positive bacterial pathogens of fish, e.g. aeromonads, flexibacteria, vibrios. Use for: Columnaris infections (Fin Rot, Saddleback, and Black Patch Necrosis Syndromes), Freshwater and Saltwater Furuncolosis [sic] (skin ulcers, systemic disease). Because it inhibits unique target enzymes needed for bacterial replication and DNA repair, it may be effective against bacteria unresponsive to other antibiotics.”
• Fish Clinda, Clindamycin, 150 mg, capsules, which, as described on your website, “Exerts a bactericidal action on gram positive and some gram negative bacteria. Useful for control of some common bacterial fish diseases including aeromonas, pseudomonas genera and mycobacterial group (gill diseases, chondrococcus).”
• Fish Dox, Doxycycline, 100 mg, capsules, which, according to your website, “exerts a bactericidal action on gram positive and gram negative bacteria. Use for control of some common bacterial diseases of fish including septicemia, mouth rot, and fain and tail rot.”
• Fish Ethro, Erythromycin, 250 mg, capsules, which is, according to your website, “useful for the control of some common bacterial diseases of fish including aeromonas and pseudomonas genera and mysobacterial group (gill diseases, chondrococcus).”
• Fish Met, Metronidazole, 500 mg, capsules, which is, as described on your website, an “antibacterial medication used to control and treat bacterial infections such as eye infection, fin or tail rot, skin ulcerations, pop-eye, columnaris disease, and gill disease. It also works against gram-positive and some gram-negative bacteria, including Aeromonas, Pseudomonas, and Mycobacteria by using bactericidal action while additionally controlling some parasitic diseases.”
• Fish Peni, Penicillin, 250 mg and 500 mg, capsules, described on your website as “an effective treatment for pop-eyes, infected eyes, fin or tail rot, gill disease, columnaris disease, and skin ulcerations and other bacterial diseases in ornamental fish.”

Birds

• Bird Azith, Azithromycin, 250 mg, capsules, which is, according to your website, “a bird antibiotic that is used for systemic and local infections in pigeons, pet birds, and exotic birds. This antibiotic is effective against gram-positive bacteria, as well as some gram-negative bacteria, spirochetes, anaerobic bacteria, and other types of microorganisms. Bird Azith is also effective against Chlamydia psittaci in cockatiels. The active ingredient in this medication works by inhibiting the growth of bacteria, which helps to eliminate the bacteria and the infection.”
• Bird Dox, Doxycycline, 100 mg, capsules, which, according to your website, “Exerts a bactericidal action on gram positive and gram negative bacteria. Useful for treatment of systemic and local infections in exotic and pet birds.”

These products are new animal drugs under section 201(v) of the FD&C Act [21 U.S.C. § 321(v)] because they are for use in nonfood-producing fish and birds, which are minor species as defined by sections 201(nn) and (oo) of the FD&C Act [21 U.S.C. § 321(nn) and (oo)], and are not the subject of a final FDA regulation finding either that the drugs are generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the drug’s labeling, or finding that the exception to the criterion in section 201(v)(1) of the FD&C Act has been met.

To be legally marketed, a new animal drug must be the subject of an approved new animal drug application, a conditionally approved new animal drug application, or a listing on the Index of Legally Marketed Unapproved New Animal Drugs for Minor Species (“index listing”) under section 512, 571, or 572 of the FD&C Act [21 U.S.C. § 360b, 360ccc, and 360ccc-1]. The FDA approval and index listing processes allow FDA to ensure that there is adequate evidence to demonstrate that new animal drugs are safe, properly manufactured, accurately labeled, and meet the relevant effectiveness standard. The animal drugs named above have not been approved, conditionally approved, or index listed.

Animal drugs that lack the required approval or index listing are considered unsafe and adulterated under sections 512(a) and 501(a)(5) of the FD&C Act [21 U.S.C. §§ 360b(a) and 351(a)(5)]. Introduction or delivery for introduction of an adulterated animal drug into interstate commerce is prohibited under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].

FDA is particularly concerned about your unapproved animal drugs because they raise public health concerns. Available as over-the-counter drugs, they contain antimicrobials that are considered medically important in the treatment of human disease.¹ Concern about the development of resistance to antimicrobials important in human medicine has led FDA to promote more judicious use of animal drugs containing medically important antimicrobials, including working toward ensuring that these drugs can be used in animals only under the supervision of a licensed veterinarian.

MISBRANDED NEW ANIMAL DRUGS
Sections 510(b)(1) and (j)(1) of the FD&C Act [21 U.S.C. § 360(b), (j)] require that manufacturers (which includes repackers and relabelers) of drugs, including animal drugs, register their manufacturing establishments with FDA and provide the agency with a list of all the drug products they manufacture. Drugs that are manufactured in unregistered establishments or that have not been listed with FDA are misbranded under section 502(o) of the FD&C Act. None of the animal drugs in this letter are drug listed with FDA, nor have they been manufactured in a facility that is registered with FDA. Accordingly, these animal drugs are misbranded. Introduction or delivery for introduction of a misbranded animal drug into interstate commerce is prohibited under section 301(a) of the FD&C Act.

This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your product(s). 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 and FDA regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may lead to legal or regulatory action, including without limitation, seizure and/or injunction.

You should be aware that if we take enforcement action against any of the drugs named above or other unapproved/unindexed products you market that contain medically important antimicrobials, we may take action against all of your products that violate the FD&C Act at the same time, including but not limited to enjoining the manufacturing and distribution of any unapproved/unindexed products.

We have the following comments:

1. You can legally market the products named above if you obtain an index listing, approval, or conditional approval. Information about the processes and requirements for obtaining an index listing and various types of animal drug approval is available on the FDA website at

• https://www.fda.gov/animal-veterinary/development-approval-process/minor-useminor-species and
• https://www.fda.gov/animal-veterinary/development-approval-process/new-animal-drug-applications

The index listing process was added to the FD&C Act in 2004 as a streamlined alternative process that addresses the challenges of obtaining FDA approval for drugs for minor species (which are any animal species other than horses, cattle, pigs, dogs, cats, chickens, and turkeys). Drugs intended for use in minor species not used for human or animal food are eligible for index listing. Because the above-named products are intended for use in nonfood-producing fish and birds, you may wish to explore the index listing process. The approval process can also be used for drugs for use in these species.

2. Information on establishment registration and drug listing is available on the FDA website at:

• https://www.fda.gov/industry/fda-basics-industry/registration-and-listing

Within fifteen (15) working days of receiving this letter, please notify this office in writing of the specific steps that you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective actions within fifteen (15) working days, state the reason for the delay and the time within which you will complete the correction. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.

Your written response should be sent to Dr. Vic Boddie, United States Food and Drug Administration, Center for Veterinary Medicine, Office of Surveillance and Compliance, Division of Drug Compliance, by emailing CVMUnapprovedDrugs@fda.hhs.gov.

Sincerely,
/S/

Neal Bataller, ME, DVM
Director Division of Drug Compliance
Office of Surveillance and Compliance
Center for Veterinary Medicine

_______________________

1 A list of medically important drug classes of antimicrobials can be found in Guidance for Industry (GFI) # 152, “Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern,” available at https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM052519.pdf