Editor’s note: The following information can help you as a farm or stable owner–and a horse owner–better understand the implications of the recent FDA letters to manufacturers of illegal omeprazole products.
Amidst the usual tide of emails trying to sell something, notification of a $27-million award in the Nigerian National Lottery, and other general inbox litter was a peculiar message from Amazon. In a “personalized” email, the online retail behemoth was offering equine ulcer medications containing the active ingredient omeprazole at discount prices. The drugs were UlcerGard, a Merial product, for $34.95 (list price $38.59), and Gastromax3, at $24.34 (list price $32.99). For cost-conscious horse owners, Gastromax3 sounds like a bargain, a $10.00 saving, no prescription needed.
What Amazon failed to mention was an important distinction between the two products that both veterinarians and consumers should know: of the two advertised drugs, only Merial’s UlcerGard has been approved for use in horses by the federal Food and Drug Administration (FDA). Gastromax3 has not been approved by the FDA for anything and was the subject of an Oct. 29, 2014, warning letter demanding that the manufacturer of the drug come into compliance with the law. Gastromax3 is not the only over-the-counter ulcer drug facing FDA scrutiny. A total of nine warning letters have been issued by the agency this fall, directed at the manufacturers and sellers of:
- Abler Omeprazole
- Abprazole Plus
- Gastro 37 OTC
- Gastroade Xtra
- Lomac Equine
- Omaktive Oral Paste
- Omeprazole Oral Paste
- Omeprazole/Ranitidine Oral Paste
- Omoguard Paste
- UlcerCure OTC
The warning letters are based on determinations by the FDA that the ulcer medications at issue fit the statutory definition of “drugs” that require agency approval as a prerequisite for legal sale. To date, only two medications containing omeprazole have gone through the necessary testing and are approved for use in the prevention and treatment of equine gastric ulcers. Both are Merial prescription products—GastroGard and UlcerGard.
Why Warning Letters were Sent
The warning letters give notice to veterinarians and consumers that the unapproved drugs have not been evaluated by the FDA for either safety or effectiveness. Lack of approval also means that that the manufacturing process has not been evaluated and may not meet industry standards for purity and consistency, and that labeling may be inaccurate. In other words, absent FDA approval, there is no guarantee that an unapproved drug is either safe or effective, or that the manufacturing of the drug is consistent from batch to batch. Lack of approval, on the other hand, does not necessarily mean that a drug is unsafe, only that reliable test results have not been submitted to the FDA.
Samples of some, but not all, of the unapproved drugs were tested by the FDA and found to be “adulterated.” This means that the label was inaccurate and the concentration of omeprazole in the tested samples contained either too little or too much of the active ingredient. Even the untested drugs are, by definition, considered “adulterated” by the FDA
“All of the products that are the subject of the warning letters, regardless of whether they contain higher or lower amounts of the active ingredient than stated on their labels, are adulterated because they are unapproved,” an FDA agency spokesperson explained. “All of these products would need to be approved by FDA in order to be legally marketed. Part of the agency’s pre-market review involves ensuring the drug is properly manufactured and properly labeled.”
Can These Products Become Legal with Label Changes?
The warning letters provided a 15-day window for the drug manufacturers to bring the products into compliance with federal law, or to explain why compliance will be delayed. Advertising for the listed drugs indicating that they could be used to prevent or to treat ulcers was cited by the FDA as justification for the statutory “drug” designation. This raised a question: can a simple change in the wording of ads, possibly promising less about ulcer treatments and cures, bring the drugs into compliance with the law?
The answer, according to the FDA, is no. The issue is not one of semantics.
“These products would need to be approved by FDA in order to be legally marketed. Animal drugs require FDA-approval to ensure they are safe and effective for their intended use. As required by the Food, Drug, and Cosmetic Act, new animal drugs must be reviewed by FDA for safety and effectiveness and obtain legal marketing status before they can be marketed.
“The pre-market review is integral to FDA’s ability to protect public health. During the review, the agency evaluates information submitted by the drug company to make sure the drug is safe and effective for its intended use and that the drug is properly manufactured and properly labeled. The FDA pre-market review is also necessary for the drug to obtain legal marketing status.”
The approval process is lengthy and expensive. The Animal Health Institute estimates that from start to final approval for a new drug by the FDA, the process can take seven to 10 years and cost millions of dollars.
How Can Drugs Get Approved?
The long and winding road to FDA approval of a new drug begins with information gathering, testing and analysis conducted by the drug manufacturer (called the drug’s “sponsor”). Next comes a New Animal Drug Application containing the test results and proposed labeling information submitted to the FDA’s Center for Veterinary Medicine. Approval is granted if the FDA determines that the new drug is safe and effective when used as labeled. Only then can the drug be marketed legally. After an approved brand name animal drug has been on the market for several years, a drug manufacturer may seek approval for a “generic animal drug,” which is a copy of the already approved drug. If the drugs that were subjects of the FDA warning letters qualify as generic drugs, the approval process would be somewhat shorter.
The FDA has a general mandate in fiscal year 2015 to review and act on 90% of new animal drug applications within 180 days of receipt, and 90% of new generic animal drug applications within 270 days of receipt. Either way, approval for the warning letter ulcer drugs almost certainly is years away.
What Does This Mean for Veterinarians?
For veterinarians, the take home message from the FDA warning letters is straightforward: none of the listed drugs has been approved by the agency as being safe and effective in treating or preventing gastric ulcers in horses. Whether using or prescribing an unapproved drug might constitute veterinary malpractice is a legal question beyond the scope of this article, and veterinarians are urged to discuss any concerns with their attorneys or professional liability insurance carriers.
Nor can prescribing an unapproved drug be justified as an “extralabel” use. Since 1994, when the Animal Medicine Drug Use Clarification Act (AMDUCA) was passed by Congress, extralabel use has been regulated by the FDA. According to the American Veterinary Medical Association, extralabel means the use of an approved drug in a manner that is not consistent with the approved labeling for that drug. Use of an unapproved drug does not qualify as an extralabel use.
What Does This Mean for Horse Owners?
For consumers, especially if the unapproved drugs remain available for purchase, the question is more complicated. The FDA does not discuss details of pending cases, and when—or whether—the unapproved ulcer drugs will be taken off the market is a matter for speculation. In the meantime, consumers must balance the benefit of saving a few dollars through using an illegally marketed drug that has not been approved by the FDA as safe or effective against using an approved drug for preventing or treating gastric ulcers in their horses.
Confusion about the status of a particular drug is understandable, because many of the unapproved drugs have names and packaging that are remarkably similar to those of the approved Merial products. Veterinarians and consumers with questions about whether a particular drug has been approved by the FDA can access a searchable database at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name.