Regulatory Brief

 AVMA Response to the FDA Extralabel Drug Use Order of Prohibition


Formal title: Docket Number [FDA-2008-N-0326] New Animal Drugs; Cephalosporin Drugs; Extralabel Animal Drug Use; Order of Prohibition

The Food and Drug Administration (FDA) is issuing an order prohibiting certain extralabel uses of cephalosporin antimicrobial drugs in certain food-producing animals. This order is based on evidence that according to the FDA, certain extralabel uses of these drugs in these animals will likely cause an adverse event in humans and, therefore, present a risk to the public health.

Brief Description:

In the Federal Register (FR) of July 3, 2008, FDA published an order prohibiting the extralabel use of cephalosporin antimicrobial drugs in food-producing animals, with a 60-day comment period and 90-day effective date for the final order. The order, which was to take effect as a final rule on October 1, 2008, would have resulted in listing cephalosporin as prohibited from extralabel use in food-producing animals. In response to publication of this order, the FDA received requests for a 60-day extension of the comment period.

FDA considered the requests and, in the FR of August 18, 2008, extended the comment period for the order for 60 days, until November 1, 2008. Accordingly, FDA also delayed the effective date of the final rule 60 days, until November 30, 2008. FDA received many substantive comments on the July 3, 2008, order of prohibition. Therefore, to allow more time to fully consider the comments, FDA decided to revoke the order so that it would not take effect November 30, 2008. Accordingly, in the November 26, 2008 FR, FDA withdrew the final rule.

After considering the comments and information submitted in response to the July 2008 order of prohibition, FDA has re-examined the basis for the original order. FDA has determined that there is sufficient basis for prohibiting certain extralabel uses of Cephalosporin drugs in food-producing major animal species. Specifically, FDA is prohibiting the extralabel use of cephalosporin antimicrobial drugs (not including cephapirin) in cattle, swine, chickens, and turkeys: (1) For disease prevention purposes; (2) at unapproved doses, frequencies, durations, or routes of administration; and (3) if the drug is not approved for that species and production class.

Thus, with the exception of extralabel uses of cephapirin, the final effect of this order will be to prohibit many extralabel uses of cephalosporin drugs in food-producing major animal species (cattle, swine, chickens, and turkeys) including:

  1. Use for disease prevention purposes;
  2. Use at unapproved dose levels, frequencies, durations, or routes of administration;
  3. Use of products not approved in the major food species

The extralabel uses that are not prohibited by this order include:

  1. Use of approved cephapirin
  2. Use to treat or control an extralabel disease indication as long as such use adheres to a labeled dosage regimen approved for that species and production class
  3. Use in food-producing minor species

The FDA is prohibiting these extralabel uses in food-producing major species because they believe such uses in these animals will likely cause an adverse event in humans and, therefore, present a risk to the public health.

AVMA Response:

The AVMA commends the FDA's thoughtful consideration of stakeholder comments and revision of the original order prohibiting all extralabel use of cephalosporins in food-producing animals with no exceptions. The revised order prohibiting certain extralabel uses of cephalosporin antimicrobial drugs in certain food-producing animals is consistent with AVMA policy in that it is a narrower, targeted order of prohibition to protect public health and balance the needs of veterinary medicine and animal welfare.

The AVMA recognizes that some uses that facilitate mass dosing of large numbers of animals, such as through drinking water or in ovo injections, are unapproved routes of administration and because these uses have not been evaluated for safety and approved by the FDA may pose unknown risks to public health. Yet, the AVMA cautions against broad-based prohibitions on prevention uses of antimicrobials.

The AVMA understands and agrees that veterinarians must have a rational basis, such as in the case of weaned pigs, for determining that the health of the animals is actually threatened. In keeping with this concept, the AVMA believes it may be necessary to prevent infectious diseases, rather than treat them after they occur, to benefit public health as well as animal health and welfare. Prevention of an infectious disease with antimicrobial therapy can potentially impact resistance trends by decreasing the need and use of antimicrobials for herd-level treatment of disease at higher doses, for longer duration, and with higher-potency classes.

The AVMA has consistently advocated for risk management actions commensurate with the level of actual risk. We understand that the FDA is validly concerned with uses "that facilitate mass dosing of large numbers of animals, such as through drinking water" and that the nature of use of a drug through an unapproved route of administration poses unknown risks, but the AVMA disagrees with the premise that an overall reduction in amount of drug used in livestock will likely achieve the intended goal of decreasing resistance trends in human health. As a general concept, the AVMA supports judicious use of antimicrobials in an effort to balance human and animal health. Simply minimizing quantities of drug use without consideration of other factors (eg, exposure) is unlikely to impact antimicrobial resistance transmission and trends.

The AVMA has a strong position underscoring the importance of veterinary access to antimicrobials for preventive use and believes that any regulatory prohibition of extralabel drug use in animals should be science based and as limited in scope as possible consistent with protection of the food supply, public health, and animal welfare. The AVMA encourages a science-based risk analysis before instituting extralabel drug use prohibitions. The AVMA also encourages a plan to monitor the effect of the prohibition on animal and public health after it takes effect, to be sure the prohibition is needed and beneficial.

Background Documents:

Federal Register Notices:

AVMA Comments:

July 16, 2008; Request for 60-day Extension of Comment Period (PDF)

Relevant AVMA Policies:

Limited Prohibition on Extralabel Drug Use