Food and Drug Administration (FDA)
Center for Veterinary Medicine
December 7, 2000

NOOH FOR POULTRY FLUOROQUINOLONES -- Background Information

What is FDA/CVM proposing?

FDA's Center for Veterinary Medicine (CVM) is proposing to withdraw approval of the new animal drug application for use of the fluoroquinolone antimicrobial drug enrofloxacin in poultry. If the approval is withdrawn, this drug would no longer be legally marketed for this indication. Other approved uses of fluoroquinolones in cattle, dogs, and cats would not be affected by this withdrawal.

What drug is involved and which company is the sponsor?

The drug subject of this proposed withdrawal is New Animal Drug Application (NADA) 140-828, Baytril^® 3.23% Concentrate Antimicrobial Solution -- enrofloxacin -- approved 10/4/96. The sponsor is Bayer Corporation, Agriculture Division, Animal Health, Shawnee Mission, KS.

How is CVM proposing this withdrawal?

If a sponsor decides to seek a hearing, it must file a written notice of appearance and request for a hearing and the data, information, and analyses relied on to demonstrate that there is a genuine and substantial issue of fact to justify a hearing. The Bayer Corporation filed a request for a hearing by the required date (11/30/00.) The firm must submit all data and analysis upon which the request for a hearing relies by 1/2/01.

A request for a hearing must set forth specific facts showing that there is a genuine and substantial issue of fact that requires a hearing. If it conclusively appears from the data, information, and factual analyses in the request for hearing that there is no genuine and substantial issue of fact that precludes the withdrawal of approval of the applications, or if a request for hearing is not made in the required format or with the required analyses, the Commissioner of Food and Drugs will enter summary judgment against the person who requests a hearing, making findings and conclusions, and denying a hearing. If a hearing is requested and is justified by the sponsor's response to the NOOH, the issues will be defined, an administrative law judge will be assigned, and a written notice of the time and place at which the hearing will commence will be issued as soon as practicable.

Why is CVM proposing to withdraw approval of this drug?

CVM is proposing to withdraw the approval of enrofloxacin in poultry because of new evidence that shows that this product is not shown to be safe. Enrofloxacin belongs to the class of antimicrobial drugs called fluoroquinolones. Fluoroquinolones also are approved for use in humans, and they are considered to be one of the most valuable antimicrobial drug classes available to treat human infections because of their spectrum of activity, safety, and ease of administration. This class of drugs is effective against a wide range of human diseases and is used both in treatment and prophylaxis of bacterial infections in the community and in hospitals. Fluoroquinolones are used routinely by physicians for the treatment of foodborne disease. These diseases have a major public health consequence in the United States.

Specifically, CVM has determined that:

Yes, CVM carefully considered the resistance issue when it approved the drug. At the time, CVM believed that enrofloxacin could be used safely in poultry, and that resistance development could be limited by certain restrictions placed on the use of the drugs. However, resistance has developed such that CVM now believes that its only option to protect human health is withdrawal of approval for this NADA.

What is the legal basis for approving or withdrawing approvals for NADAs?

The requirement for approval of NADAs are set out in section 512 of the Federal Food, Drug, and Cosmetic Act (the Act). That section requires that a new animal drug must be shown to be safe and effective for its intended uses. In determining safety, CVM must consider the safety to humans of substances formed in or on food as a result of the use of the new animal drug.

Under Section 512(e)(1)(B) of the Act, the approval for a NADA must be withdrawn if:

"...new evidence not contained in [an approved] application or not available to the Secretary until after such application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when such application was approved, evaluated together with the evidence available to the Secretary when the application was approved, shows that such drug is not shown to be safe for use under the conditions of use upon the basis of which the application was approved...."

Where can interested parties obtain additional information about the NOOH and the basis for CVM's proposed withdrawal?

Further information is included in the October 31, 2000, Federal Register and from Dr. Linda Tollefson, CVM (HFV-200), FDA, 7500 Standish Place, Rockville, MD 20855 (301-827-6647.) Press inquires should be directed to Jon Scheid on 301-827-6514.

Was enrofloxacin the only fluoroquinolone approved for use in poultry?

No, CVM has also approved sarafloxacin hydrochloride in poultry. Abbott Laboratories, North Chicago, IL, is the sponsor of two NADAs for sarafloxacin hydrochloride. NADA 141-017, Sara Flox WSP, was approved August 18, 1995, for the control of mortality in growing turkeys and broiler chickens associated with E. coli organisms. NADA 141-018, Sara Flox Injection, was approved October 12, 1995, for the control of early chick mortality associated with E. coli organisms in chickens and turkeys. Abbott Laboratories has requested withdrawal of these NADAs, that by doing so, the company has waived its right to a hearing and therefore, these NADAs are not covered by the NOOH.