Medically Important Antimicrobials in Animal Agriculture – Honey Bees

Outline Take Home What Changed? Affected Products Sources of Information I hope to take no more than 15 minutes of your time with some prepared comments, skimming the surface of the issue, then have time for your questions. www.fda.gov

Outline Take Home What Changed? Affected Products Sources of Information www.fda.gov

Take Home Beginning on January 1, 2017 the use of medically important antimicrobials requires an order from a licensed veterinarian to authorize their use. For honey bees, this applies to: oxytetracycline, tylosin, or lincomycin The take home for today is beginning 1 January 2017 an order from a veterinarian authorizing the use of oxytetracycline, tylosin, or lincomycin in honey bees was legally needed. www.fda.gov

Outline Take Home What Changed? Affected Products Medically Important Effective Dates Order Licensed Veterinarian/VCPR Extralabel Use Affected Products Sources of Information I’m going to touch very briefly on 5 subtopics of what changed at the first of the year, then get to the specific drugs used in honey bees. www.fda.gov

What changed? Medically Important Antimicrobial An antimicrobial that is important to human medicine. The regulatory status of Fumagillin is not changed due to this action. Those antimicrobials considered medically important in human medicine and that are also administered to food-producing animals, including honey bees, have changed marketing status. Fumagillin is not important in human medicine and its regulatory status has not changed. www.fda.gov

What changed? Effective Date 1 January 2017: Medically important antimicrobials that were labeled over-the-counter (OTC) now require an order from a licensed veterinarian authorizing their use. Following a 3 year process, the drug sponsors of medically important antimicrobials voluntarily changed the labels on their drugs products as of the end of 2016. www.fda.gov

What changed? Marketing Status VFD Medicated Feed (21 CFR Part 558) Federal Law restricts medicated feed containing this veterinary feed directive (VFD) drug to use by or on the order of a licensed veterinarian. Oral Dosage Forms (Medicated Drinking Water) (21 CFR Part 520) Federal Law restricts this drug to use by or on the order of a licensed veterinarian. You have seen or will see these statements on the medically important antimicrobials, oxytetracycline, tylosin, or lincomycin that you use depending on whether the drug application is approved by CVM as a medicated feed or an oral dosage form drug. www.fda.gov

What changed? Orders Authorizing use Veterinary Feed Directive Prescription On the previous slide we said “by or on the order of” and that “order” is a VFD order for medicated feed or a prescription order for an oral dosage for drug, now in Rx marketing status. www.fda.gov

Veterinary Feed Directive What changed? Order Veterinary Feed Directive Medically Important Antimicrobials regulated by CVM/FDA as new animal drugs for use in animal feeds. (21 CFR Part 558) Authorizes the client to obtain and use the VFD medicated feed. A VFD order authorizes the client ( owner of the animal or animals or other caretaker) to obtain and use the medicated feed to treat their animals only in accordance with the FDA approved indications for use and other label restrictions. These approvals are published in the Code of Federal Regulations in Part 558 – Medicated feed. www.fda.gov

What changed? Order Prescription Medically Important Antimicrobials regulated by CVM/FDA as oral dosage form new animal drugs. (21 CFR Part 520) Just like your physician writes you a prescription to be filled, your veterinarian will be writing a prescription. The approvals are published in the Code of Federal Regulations in Part 520 oral dosage form drugs. www.fda.gov

What changed? Licensed Veterinarian The veterinarian issuing the VFD must: (i) Be licensed to practice veterinary medicine; and My 4th subtopic is the label says by or on the order of a licensed veterinarian. www.fda.gov

What changed? Licensed Veterinarian The veterinarian issuing the VFD must: … (ii) Be operating in the course of the veterinarian’s professional practice and in compliance with all applicable veterinary licensing and practice requirements, including issuing the VFD in the context of a veterinarian-client-patient relationship (VCPR) … 21 CFR Sec. 558.6(b)(1) In addition to being licensed, the veterinarian must be practicing in compliance with the state regulatory requirements for veterinarians. www.fda.gov

What changed? Extralabel Use Licensed Veterinarians have limits on orders authorizing the use of approved drugs in animals. Veterinarians have federal, and perhaps, also state restrictions on extra-label use of drugs. www.fda.gov

What changed? Extralabel Use (a) Extralabel use means actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling. … 21 CFR Sec. 530.3(a) Extra-label use is defined in the Code of Federal Regulations. www.fda.gov

What changed? Extralabel Use Limitations of Extralabel use …, the following specific extralabel uses are not permitted and result in the drug being deemed unsafe within the meaning of section 512 of the act: So are the limits to what a veterinarian can order or authorize. www.fda.gov

What changed? Extralabel Use Limitations of Extralabel use … (a) Extralabel use in an animal of an approved new animal drug or human drug by a lay person (except when under the supervision of a licensed veterinarian); One limit is by a lay person except under the veterinarians supervision. www.fda.gov

What changed? Extralabel Use Limitations of Extralabel use … (b) Extralabel use of an approved new animal drug or human drug in or on an animal feed; A big restriction is in or on animal feed. www.fda.gov

What changed? Extralabel Use Limitations of Extralabel use … (c) Extralabel use resulting in any residue which may present a risk to the public health; and There are two restrictions regarding if a residue occurs in the food, in this case honey. www.fda.gov

What changed? Extralabel Use Limitations of Extralabel use … (d) Extralabel use resulting in any residue above an established safe level, safe concentration or tolerance. 21 CFR Sec. 530.11 The second residue restriction. I’ll mention that believe it or not antibiotics have been found in honey. www.fda.gov

Outline Take Home What Changed? Affected Products VFD Medicated Feed (21 CFR Part 558) Rx Oral Dosage Form New Animal Drugs (21 CFR Part 520) Sources of Information OK finally the part you are most interested in. Which products that you use are regulated as feed and which as oral dosage form drugs. www.fda.gov

Affected Products VFD Medicated Feed Oxytetracycline NADA N138-938 (21 CFR Sec. 558.450) Examples: NADA N138-938 N008-804 N095-143 Oxytetracycline is regulated as a medicated feed marketed under three CVM approved applications. You can look up the details for each application at the website in the sources of more information at the end of this talk. I’m going to mention all of them together as they are published in the Code of Federal Regulations. You can also access the CFR at another link in sources of information. I mush emphasize that you should look at the label of the product you are using, the label trumps my summaries here. www.fda.gov

Affected Products VFD Medicated Feed (21 CFR Sec. 558.450) Active Ingredient: Oxytetracycline Indication: For control of American Foulbrood caused by Paenibacillus larvae and European Foulbrood caused by Streptococcus pluton susceptible to oxytetracycline. I read slide www.fda.gov

Affected Products VFD Medicated Feed Amount: 200 mg/colony Limitation: Remove at least 6 weeks prior to main honey flow. Read slide www.fda.gov

Affected Products VFD Medicated Feed By State: VFD Distributor Notification List: http://www.fda.gov/downloads/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/UCM096059.pdf Approved Medicated Feed Mill Licenses: http://www.fda.gov/downloads/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/UCM089534.pdf This Type A is what we call a Category I, so you do not have to be a licensed mill to obtain it legally. Never-the-less I have included links that list by state where the licensed feed mills are and where establishments have notified CVM that they intend to distribute VFD medicated feed, so that might be a place in your state to visit to learn what products they may carry. www.fda.gov

Affected Products VFD Medicated Feed Extra-Label Use: Prohibited You remember from the slides above that extra-label use of a medicated feed is prohibited. www.fda.gov

Rx Oral Dosage Form New Animal Drugs Affected Products Rx Oral Dosage Form New Animal Drugs 21 CFR Sec: 520.1660d: Oxytetracycline 520.2640: Tylosin 520.1260c: Lincomycin Now I’m switching to the second category of drugs – oral dosage form drugs that are now prescription new animal drugs. The three of most interest to you, I believe are oxytetracycline, tylosin, and lincomycin. www.fda.gov

Affected Products Rx Oral Dosage Form New Animal Drugs Oxytetracycline hydrochloride (21 CFR Sec. 520.1660d) Examples: A/NADA N008-622 A200-026 A200-146 A200-247 * As before I’ve listed the approved application numbers, but will give the CFR summaries. www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs Active Ingredient: Oxytetracycline Indication: * For control of American Foulbrood caused by Paenibacillus larvae. Read slide www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs Amount: 200 milligrams per colony, administered via either a 1:1 sugar syrup (equal parts of sugar and water weight to weight) or dusting with a powdered sugar mixture. Limitation: … Remove at least 6 weeks prior to main honey flow. Read slide www.fda.gov

Rx Oral Dosage Form New Animal Drugs Affected Products Rx Oral Dosage Form New Animal Drugs Tylosin tartrate (21 CFR Sec. 520.2640) Examples: A/NADA N013-076 A200-473 * A200-455 * The second drug is tylosin. www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.2640) Active Ingredient: Tylosin tartrate Indication: For the control of American Foulbrood (Paenibacillus larvae). Read slide www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.2640) Amount: Mix 200 milligrams tylosin in 20 grams confectioners/powdered sugar. Use immediately. Apply (dust) this mixture over the top bars of the brood chamber once weekly for 3 weeks. Read slide www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.2640) Limitation: The drug should be fed early in the spring or fall and consumed by the bees before the main honey flow begins, to avoid contamination of production honey. Complete treatments at least 4 weeks before main honey flow. Read slide www.fda.gov

Rx Oral Dosage Form New Animal Drugs Affected Products Rx Oral Dosage Form New Animal Drugs Lincomycin powder (21 CFR Sec. 520.1263c) Examples: A/NADA N111-636 There are no generic approvals for this drug product due to the honey bee claim being protected under marketing exclusivity. The third drug is lincomycin www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.1263c) Active Ingredient: Lincomycin powder Indication: For the control of American Foulbrood (Paenibacillus larvae). Read slide www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.1263c) Amount: Mix 100 milligrams lincomycin with 20 grams confectioners'/powdered sugar and dust over the top bars of the brood chamber once weekly for 3 weeks. Read slide www.fda.gov

Oral Dosage Form New Animal Drugs Affected Products Oral Dosage Form New Animal Drugs (21 CFR Sec. 520.1263c) Limitation: The drug should be fed early in the spring or late in the fall and consumed by the bees before the main honey flow begins to avoid contamination of production honey. Complete treatments at least 4 weeks before main honey flow. Read slide www.fda.gov

Affected Products May be Allowed, Oral Dosage Form New Animal Drugs ExtraLabel Drug Use: May be Allowed, If in compliance with 21 CFR Part 530. The oxytetracycline, tylosin, and lincomycin drug I just mentioned have all transitioned to prescription status, and would be potentially eligible for ELU. www.fda.gov

Outline Take Home What Changed? Affected Products Sources of Information www.fda.gov

Sources of Information Approved Applications: AnimalDrugs@FDA: https://animaldrugsatfda.fda.gov/adafda/views/#/search BlueBird labels: http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/BlueBirdLabels/ucm081795.htm eCFR: http://162.140.57.127/cgi-bin/ECFR?page=browse VFD Distributors & Licensed Feed Mills: http://www.fda.gov/downloads/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/UCM096059.pdf http://www.fda.gov/downloads/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/UCM089534.pdf www.fda.gov

Sources of Information OMUMS: http://www.fda.gov/animalveterinary/resourcesforyou/animalhealthliteracy/ucm189540.htm AskCVM@FDA.HHS.GOV http://www.beevets.com/Index.php www.fda.gov

Take Home Use of the Medically Important Antimicrobials, oxytetracycline, tylosin, or lincomycin in honey bees beginning 1 January 2017 required an order from a licensed veterinarian authorizing their use. www.fda.gov