Drug use regulations and legislation affecting your practice (Proceedings)

I. Critical Legislation in the U.S. House and Senate

The most critical bill related to the practice of veterinary medicine on the date these proceedings were prepared is HR 1549 - The Preservation of Antibiotics for Medical Treatment Act of 2009. The companion bill in the Senate is S 619

Thomas.gov is a government site for reading and tracking bills introduced in the U.S. Senate and House. By searching on the Bill Number you can find the available information on the text of the bill, related bills, all congressional actions and other information.

H.R. 1549 SUMMARY AS OF 3/17/2009–Introduced.

Preservation of Antibiotics for Medical Treatment Act of 2009 - Amends the Federal Food, Drug, and Cosmetic Act to require the Secretary of Health and Human Services to deny an application for a new animal drug that is a critical antimicrobial animal drug unless the applicant demonstrates that there is a reasonably certainty of no harm to human health due to the development of antimicrobial resistance attributable to the nontherapeutic use of the drug. Defines "critical antimicrobial animal drug" as a drug intended for use in food-producing animals that contains specified antibiotics or other drugs used in humans to treat or prevent disease or infection caused by microorganisms.

Requires the Secretary to withdraw approval of a nontherapeutic use of such drugs in food-producing animals two years after the date of enactment of this Act unless certain safety requirements are met. Directs specified congressional committees to hold hearings on the implementation of such a withdrawal of approval.

So where is this bill today (Summer, 2011)? The bill sponsor (Slaughter, D-NY) is no longer chair of the House Rules Committee, which was used (against the House rules) as the venue for a hearing on the bill. The Rules Committee is intended to address issues related to House rules (hence the name) and not hearings on the content of legislation. Now the bill would have to move through legitimate channels, where fair questioning and hearing of the bill would happen. Some version of this bill has been in circulation for quite a few years now, one of the originals with Brown when he was in the House and Kennedy and Snowe in the Senate.

The PEW Foundation has been an aggressive supporter of this bill. Their full report on industrial farm animal production and executive summary may be accessed at http://www.ncifap.org/. The AVMA response to the report may be accessed at http://www.avma.org/advocacy/PEWresponse/.

II. State legislative activity related to antibiotics

Most Recent – New York state, from the text of the bill….

     10 (b)"Non-therapeutic use of antimicrobial agents" shall mean any use of

     11 antimicrobial agents, including without limitation as a feed or water

     12 additive, for an animal for growth promotion, feed efficiency, weight

     13 gain, routine disease prevention, or other routine purpose, in the

     14 absence of any clinical sign of disease in the animal.

     15 2. (a) No person shall engage in the non-therapeutic use of antimicro-

     16 bial agents in cattle, poultry, sheep, swine, or any animal raised for

     17 the purpose of providing food for human consumption, including animals

     18 that provide non-meat food products such as eggs and milk.

     19 (b) No person shall sell, expose for sale, or transport for sale with-

     20 in this state, regardless of place of origin, any food product derived

     21 from an animal that has been subject to non-therapeutic use of antimi-

     22 crobial agents.

     23 3. Violation of this section shall constitute a class A misdemeanor.

III. At the time of writing these proceedings, we await the final rule on the extralabel use of cephalosporins in food animals.

The original order of prohibition put out for comment was issued on July 2, 2008. It was revoked November 25, 2008 due to over 200 substantive comments. The FDA Center for Veterinary Medicine had another call for input and numerous discussions with stakeholders in the Spring of 2009. The final rule is under review within the agency at the time of this writing, and has been since fall of 2009.

IV. Guidance 209 was put out on June 28, 2010 by the FDA/CVM to get input on two proposed directions. The input was given by the end of 2010, and the CVM is currently evaluating comments and preparing a response. There are extensive review comments related to previous evaluations, but the key components of the guidance are the two principles and the conclusion, which are reproduced here as excepts of the document.

"Principle: The use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that are considered necessary for assuring animal health.

In light of the risk that antimicrobial resistance poses to public health, FDA believes the use of medically important antimicrobial drugs in food-producing animals for production purposes (e.g., to promote growth or improve feed efficiency) represents an injudicious use of these important drugs. Production uses are not directed at any specifically identified disease, but rather are expressly indicated and used for the purpose of enhancing the production of animal-derived products. In contrast, FDA considers uses that are associated with the treatment, control, or prevention of specific diseases, including administration through feed and water, to be uses that are necessary for assuring the health of food-producing animals.

Although some may have concerns that the use of medically important antimicrobial drugs in food-producing animals for disease prevention purposes is not an appropriate or judicious use, FDA believes that some prevention indications are necessary and judicious. Veterinary involvement in the decision-making process associated with the use of medically important antimicrobial drugs is an important aspect of assuring appropriate use, including judicious preventive use. Important factors to consider when determining the appropriateness of a preventive use include whether there is: (1) evidence of effectiveness, (2) evidence that such a preventive use is consistent with accepted veterinary practice, (3) evidence that the use is linked to a specific etiologic agent, (4) evidence that the use is appropriately targeted, and (5) evidence that no reasonable alternatives for intervention exist.

Principle: The use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that include veterinary oversight or consultation.

Most of the feed-use antimicrobial drugs are currently approved for over-the-counter use in food-producing animals for purposes that include the treatment, control, and prevention of disease as well as for production purposes (i.e., for growth promotion uses such as increased rate of weight gain). In addition to instituting measures that would limit use of medically important antimicrobial drugs in food-producing animals to uses that are considered necessary to assure the animals' health, FDA also believes it is important to phase-in the practice of including veterinary oversight or consultation in the use of these drugs. As noted above, FDA believes that this practice is an important mechanism for helping to assure appropriate use. Veterinarians can play a critical role in the diagnosis of disease and in the decision-making process related to instituting measures to treat, control, or prevent disease. FDA recognizes that the nature of veterinary involvement can vary due to numerous factors such as geographic location and animal production setting. In fact, there are limited numbers of large animal veterinarians, which can make consultation or oversight challenging in certain situations.

For example, some animal disease events require immediate attention.. In some cases, veterinarians may be directly diagnosing and administering therapies, while in other cases they are visiting and consulting with producers periodically to establish customized disease management protocols for that producer's herd or flock. Of key importance to FDA is the fact that, in both of these cases, the veterinarian is involved in the decision-making process regarding antimicrobial drug use. FDA recognizes that increasing veterinary involvement in the use of antimicrobial drugs has significant practical implications for animal producers, veterinary practitioners, and the veterinary profession as whole. Therefore, FDA is particularly interested in receiving comments on strategies for effectively phasing-in such a change.

V. For several years, the FDA Center for Veterinary Medicine had withdrawn their compliance policy guideline for compounding (see regulations section below) after legal challenges to the authority of the FDA to regulate compounded products.

A decision by the Fifth Circuit Court of Appeals, filed July 18, 2008, held that the FDA Center for Veterinary Medicine has the authority to regulate compounded drugs as "New Animal Drugs". An excerpt from the court ruling follows (the FDCA is the Federal Food Drug and Cosmetic Act).

"We therefore conclude, in agreement with the two other circuits that have considered the issue,50 that compounded drugs are "new animal drugs" within the meaning of § 321(v)(1) of the FDCA. And unless the compounded drugs are exempt under the FDCA's AMDUCA provisions, § 360b(a)(4) and (5), compounded animal drugs are subject to the FDCA's unsafe, adulteration, and misbranding requirements. As with human drugs, the FDCA contains no blanket "implicit exemption" for animal drugs produced by compounding."

The CPG on compounding is now back on the FDA/CVM website at http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074656.htm.

VI: VCPRs and prescriptions

Much to my surprise I recently learned that the only places where the VCPR requirement is codified federally are in the AMDUCA regulations and the VFD regulations. For label use of prescription drugs, the VCPR is not codified in federal regulations. State requirements may do so, and I would hate to defend extralabel use in the face of adverse reactions or residues without having a documented VCPR. I would suggest the AMDUCA regulations as a good standard for VCPRs established for dispensing or prescribing prescription products for label use. The fine points of establishing a VCPR for extralabel use or VFDs will come down to local standards of practice.

VII: Withdrawal times

The Food Animal Residue Avoidance Database (FARAD) remains the gold standard for setting extralabel use withdrawal times (WDTs). If they aren't able to estimate a withdrawal time from the data they have gathered, I personally wouldn't use the drug in food animals. Whenever you have a chance to talk to an elected official in Washington, DC, be sure to emphasize the importance of continued funding to FARAD.

One practice which is setting the beef and dairy industries up for some significant WDT violations is that of putting Ceftiofur Crystalline Free Acid (Excede®, Pfizer Animal Health) subcutaneously in the neck vs. according to label directions in the ear or at the base of the ear. This results in a greatly extended withdrawal time due to where the injection site now resides. In addition, I have no idea how the pharmacokinetics of the drug are altered. If you are engaging in this practice, contact FARAD for and ELDU WDT; you will be amazed.

You can contact FARAD at http://www.farad.org/ or 1-888-USFARAD.

The FARAD site also has an AVMA-developed ELDU algorithm that you can work through to evaluate a drug use.