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WARNING LETTER

November 30, 2023

Re: 667410

Dear Elizabeth Field:

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

In November 2023, the U.S. Food and Drug Administration (FDA) reviewed your website (https://www.calvetsupply.com/), where you take orders for Aquarium Amoxicillin, Aquarium Amoxicillin Clavulanate, Aquarium Azithromycin, Aquarium Cephalexin, Aquarium Ciprofloxacin, Aquarium Clindamycin, Aquarium Doxycycline, Aquarium Levofloxacin, Aquarium Metronidazole, Aquarium Minocycline, Aquarium Penicillin VK, and Aquarium Sulfamethoxazole/Trimethoprim. 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://www.calvetsupply.com/) that establish the intended use of your products as drugs include, but may not be limited to, the following:

• Aquarium Amoxicillin, 250 mg capsules, 500 mg capsules, “Amoxicillin is a semisynthetic broad spectrum antibiotic. For treatment against many gram-positive and gram-negative microorganisms.”
• Aquarium Amoxicillin Clavulanate, 875 mg/125 mg tablets, “Amoxicillin/Clavulanate Potassium is a semisynthetic antibiotic. For treatment against many gram-positive and gram-negative microorganisms.”
• Aquarium Azithromycin, 250 mg tablets, “Azithromycin is a semisynthetic broad spectrum antibiotic. For treatment against many gram-positive and gram-negative microorganisms”
• Aquarium Cephalexin, 250 mg capsules, 500 mg capsules, “Cephalexin is a broad spectrum antibiotic. For treatment against many gram-positive and gram-negative microorganisms.”
• Aquarium Ciprofloxacin, 250 mg tablets, 500 mg tablets, “Ciprofloxacin is a synthetic broad spectrum antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”
• Aquarium Clindamycin, 150 mg capsules, “Clindamycin is a semisynthetic antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”
• Aquarium Doxycycline, 100 mg tablets, 100 mg capsules, “Doxycycline is a broad spectrum antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”
• Aquarium Levofloxacin, 500 mg tablets, “Levofloxacin is a synthetic broad spectrum antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”
• Aquarium Metronidazole, 250 mg tablets, 500 mg tablets, “Metronidazole is a synthetic broad spectrum antibiotic. For treatment against many gram-positive and gram-negative microorganisms.”
• Aquarium Minocycline, 100 mg capsules, “Minocycline is a semisynthetic broad spectrum antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”
• Aquarium Penicillin VK, 250 mg tablets, 500 mg tablets, “Penicillin VK is a broad spectrum antibiotic. For treatment against many gram-positive and gram-negative microorganisms.”
• Aquarium Sulfamethoxazole/Trimethoprim, 800 mg/160 mg tablets, “Sulfamethoxazole/Trimethoprim is a synthetic antibiotic. For treatment against many gram-negative and gram-positive microorganisms.”

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, 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 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 all of your 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, 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

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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