Questions and Answers: FDA Approved Free-Choice Feeding Options for Anaplasmosis Control in Cattle
In January 2017, the FDA and animal drug sponsors completed the voluntary transition of antimicrobial drugs of medical importance used in animal feed to Veterinary Feed Directive (VFD) marketing status under Guidance for Industry (GFI) #213. As these medically important antimicrobial drugs have come under veterinary oversight, FDA has received questions from some stakeholders relating to the use of chlortetracycline (CTC) for control of active infection of anaplasmosis in cattle.
Anaplasmosis is an infectious disease of cattle, sheep, and goats. The disease can be acute or chronic. The disease is transmitted in cattle by the organism “Anaplasma marginale,” a member of the Rickettsia family of disease-causing agents. Anaplasmosis is spread by the bite of the common horsefly, other biting insects, or any instrument that can transmit blood (e.g., syringe). Anaplasmosis caused by Anaplasma marginale does not infect humans.
This Question and Answer document is intended to assist with the appropriate selection and use of approved VFD free-choice medicated feed for the control of active infection of anaplasmosis in cattle.
1. Why is the use of chlortetracycline in free-choice feed of concern to the FDA?
After chlortetracycline transitioned to VFD marketing status, veterinarians have had questions about whether they are allowed to issue a VFD for a free-choice medicated feed that does not conform with an approved formula. The FDA understands that supplemental nutrition and the ability to medicate animals through supplemental nutrition can be important to animal health. However, when medicating animals through free-choice mineral supplements, only approved free-choice medicated feed formulations may be used legally, to assure safety and effectiveness.
2. How can producers and veterinarians address anaplasmosis concerns in cattle?
We realize that anaplasmosis in cattle is a significant animal health issue and would like to remind all affected parties that the following FDA-approved therapeutic options for treatment and control of anaplasmosis are currently available:
- Treatment: A number of oxytetracycline injectable drug products are approved for the treatment of anaplasmosis. A summary of the approved use conditions for such products can be found in 21 CFR 522.1660a and 522.1662a.
- Control: A number of applications for use of chlortetracycline (CTC) in Type C medicated feeds (including complete medicated feeds and several free-choice medicated feed formulations) are approved for control of active infection of anaplasmosis. A summary of the approved use conditions for such medicated feeds can be found at 21 CFR 558.128.
Note that chlortetracycline Type C medicated feeds are only approved for the control of active infection of anaplasmosis. Currently, such medicated feeds are not approved for the treatment or prevention of anaplasmosis. We encourage producers to work with their veterinarian if they are concerned that anaplasmosis is something they need to address in their herd health plan.
Information about specific approved animal drugs can be found in the FDA’s searchable database, Animal Drugs @ FDA.
3. What are free-choice medicated feeds and why does the FDA approve individual free-choice medicated feed formulations?
Free-choice medicated feeds are products that contain one or more animal drugs and are placed in feeding or grazing areas for animals to freely consume. Therefore, it is especially important that the product’s composition and consumption rate of the feed are consistent with the approval. The rate determined during the approval process is the consumption rate at which the drug is safe and effective for the intended use and would not result in violative drug residues in human food.
4. Where can feed manufacturers find information about the formulation of free-choice medicated feed?
The sponsor of an approved free-choice medicated feed could choose either to keep the formula proprietary or have it published. The FDA is allowed to post the Blue Bird labeling with the approved formulation for published formulas. Blue Bird labels are sponsor-provided labels that describe the conditions under which a drug or a drug combination is safe and effective and include specific mixing or feeding directions. Accordingly, the FDA has posted two Blue Bird labels with the formulation for Type C Medicated Cattle Free-Choice Mineral Feed containing 6000 g/ton CTC. This labeling is for an approved free-choice salt-mineral mix containing CTC from one of two specific Type A medicated articles (either Aureomycin®, NADA 048-761 or Deracin®, ANADA 200-510) that are indicated for use in beef and non-lactating dairy cattle as an aid in the control of active infection of anaplasmosis caused by Anaplasma marginale susceptible to CTC. Publicly available formulations of CTC free-choice feed may be manufactured at any feed mill.
The FDA has also approved several proprietary (unpublished) formulations for the use of CTC in free-choice medicated feeds for control of anaplasmosis. Only the sponsors of proprietary formulations or the entities with access to them are able to manufacture such free-choice medicated feeds. Proprietary formulations may only be manufactured at a licensed feed mill (21 CFR 510.455(f)).
5. What are Blue Bird labels and what information do they provide?
Blue Bird labels are representative medicated feed labels and are an integral part of an approved new animal drug application for use of a drug in or on animal feed. These representative medicated feed labels are created by Type A medicated article sponsors and describe the conditions under which a drug or a drug combination is safe and effective.
Blue Bird labels specify conditions of use of a drug or drug combination in medicated feed, which often include examples that further illustrate mixing or feeding directions. For example, if a drug level (or range) in a particular medicated feed is not clearly specified on the approved labeling, the examples on a Blue Bird Type C medicated feed label effectively provide the boundaries of the drug level in feed within which the drug should be used.
Following the Blue Bird labels for a particular VFD drug helps to ensure that you are using the drug and the resulting medicated feed according to an approved use.
6. A number of chlortetracycline medicated feed products are approved for control of active infection of anaplasmosis. How would a veterinarian write a VFD for “control of active infection”?
Once a veterinarian has determined that anaplasmosis infection exists within a herd, whether or not clinical signs are apparent yet, he/she may write a VFD to direct the use of CTC for controlling the progression of the disease in that herd.
If the veterinarian makes the determination to issue a VFD order, in the “special instructions”section of the VFD order, the veterinarian may include directions identifying when the client should contact them or when they may begin using the VFD medicated feed.
7. What are the approved VFD medicated feeds containing chlorotetracycline that can be authorized?
The veterinarian may select from the approved VFD drugs, including: (1) the multiple approved Type C medicated feeds containing CTC; (2) the proprietary pressed blocks and loose mineral free-choice feeds, or (3) the publicly available formulations for loose minerals.
Currently, a lawful VFD order may provide for the following levels of CTC in approved free-choice medicated feed:
- Any feed mill using the published formulations (specifications in 21 CFR Sec. 558.128) may manufacture free-choice medicated loose mineral feed containing:
Aureomycin® (NADA 048-761) or Deracin® (ANADA 200-510) at 6,000 g CTC/ton (to provide 0.5 to 2.0 mg/lb body weight/day CTC)
- Only licensed feed mills with access to the approved proprietary formulations may manufacture free-choice medicated feeds containing chlortetracycline from the source specified in the approved formulations:
700 g/ton (to provide 0.5 to 2.0 mg/lb body weight/day),
5,000 g/ton (to provide 0.5 to 2.0 mg/lb body weight/day), or
8,000 g/ton (to provide 0.5 to 2.0 mg/lb body weight/day)
Note that all of the approved medicated feeds for free-choice feeding are formulated to deliver a dose of CTC that will fall within the same approved range when consumed in a free-choice manner by the animals. The expected daily intake of each product depends on the specific formulation, which is clearly described on the labeling.
The FDA understands that supplemental nutrition and the ability to medicate animals through supplemental nutrition can be important to animal health. However, when medicating animals through free-choice mineral supplements, only approved free-choice medicated feed formulations may be used legally, to assure safety and effectiveness.
8. What is the FDA doing to address the need for additional approved free-choice medicated feed formulations?
The FDA understands that when a limited number of approved nutritional formulations are publically available as free-choice medicated feeds, this can limit the usefulness of the drug in varied populations of animals with different nutritional needs. If a company wishes to seek approval of a new free-choice medicated feed formulation or approval of modified conditions of use for an existing formulation, it will need to do so through the new animal drug approval process.
Regulations and guidance regarding medicated free-choice feeds are published in 21 CFR 510.455 and GFI #13: Evaluation of Effectiveness of New Animal Drugs for Use in Free-Choice Feeds-Medicated Block, respectively. We encourage current or potential sponsors of new animal drug applications to contact the FDA’s Center for Veterinary Medicine, Office of New Animal Drug Evaluation, for further assistance regarding the process of seeking approval of new medicated feed formulations.
The published formulations contain a statement saying the “Content of vitamin and trace mineral premixes may be varied. However, they should be comparable to those used for other free-choice feeds.” The intent of this statement is to allow the local feed manufacturer to substitute a trace mineral premix that they have on hand and/or that is intended to fit the animal’s trace mineral needs for that locality. This language allows substitution of the trace mineral premix, but does not allow deviation from the published formulas for the other ingredients.
9. How is the FDA addressing concerns regarding appropriate use of free-choice medicated feed containing chlortetracycline?
In conjunction with finalizing the updated VFD regulation and re-designating medically important antibiotics used in feed as VFD drugs, the FDA has stated its intent to employ a phased-in compliance strategy. [See the Executive Summary (80 FR 31708, June 3, 2015) and responses in the VFD Final Rule. https://www.federalregister.gov/documents/2015/06/03/2015-13393/veterinary-feed-directive.] Under this strategy, the agency is placing its initial focus on educating affected stakeholders on the new requirements before taking enforcement action. As part of this initial education phase, the FDA is also working to address challenges that arise in association with VFD implementation.
Consistent with this phased-in compliance strategy, we are willing to exercise flexibility while (1) the FDA works with affected stakeholders to ensure that veterinarians and cattle producers understand what is needed to be in compliance when using currently approved CTC formulations, and (2) drug sponsors and medicated feed manufacturers understand what new CTC formulations may be needed and how to obtain approval for such formulations. In the interim, we would expect that any continued use of CTC for controlling anaplasmosis in cattle be limited to situations where active anaplasmosis is a significant concern and that CTC use is consistent with the approved dose (0.5 to 2.0 mg/lb body weight/day).
The FDA continues to consider options for addressing the current concerns. We acknowledge that anaplasmosis is a significant animal health concern for the cattle industry and that practical control measures are needed, particularly during the vector season. While we understand that CTC administered through medicated feed can be an important tool for controlling this disease, ultimately, we need to ensure compliance with the approved conditions of use.
10. What does the term “hand-fed” mean on FDA-approved labels?
The term “hand-fed” refers to a feeding system in which a medicated feed is fed: (1) to groups of animals, (2) on a daily (24-hour period) basis, (3) for the approved duration of feeding, (4) in amounts that may (but do not necessarily) constitute the animals’ complete diet, which are intended to provide the entire approved daily drug dose over the course of the 24-hour period.
11. What VFD medicated feeds are approved to be “hand-fed”?
Several combination medicated feeds containing CTC with lasalocid are approved for hand-fed feeding to cattle for control of active infection of anaplasmosis.
12. Who should I contact if I have additional questions?
Further questions about these issues may be directed to AskCVM@fda.hhs.gov.
- Veterinary Feed Directive (VFD)
- Blue Bird Labels for Cattle
- General requirements for animal drug applications