Regulatory Aspects of Veterinary Practice without Antibiotics

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Regulatory Aspects of Veterinary Practice without
Antibiotics

• Hubert Karreman, VMD
• Narvon, PA

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Extralabel Drug Use Algorithm for Veterinarians
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Is there a human drug or drug approved for
non-food animals which could be used
extralabelly? YES

• Is there adequate sceintific information to
  determine a withdrawal time? YES
• Proceed with extra-label use of human or non-feed
  animal drug. Establish extended withdrawal time.
  Ensure food safety. Maintain required records.
  Label drug appropriately.

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AVMA algorithm refers to drug choice/use by
veterinarians in context of a valid VCPR

• What is a drug?
• M-I-06-5 3 April 19, 2006 (PMO)
• Drug A drug is defined in section 201(g) of the
  Federal Food, Drug, and Cosmetic Act (FFDCA), as
  amended. For PMO purposes, animal drugs are
  articles intended for use in the diagnosis, cure,
  mitigation, treatment, or prevention of disease
  in man or other animals and articles (other than
  food) intended to affect the structure or
  function of the body of animals.

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However - Extra Label Use (ELU) of drugs refers
only to NADAs via AMDUCA

• Drugs Prohibited for ELU in Food Animals (11)
  (from PMO)
• Chloramphenicol
• Clenbuterol
• Diethylstilbesterol
• Dimetridazole
• Other Nitroimidazoles
• Furazolidine, Nitrofurazone, Other nitrofurans
• Sulfonamide drugs in lactating dairy (except ones
  specifically allowed)
• Floroquinolones
• Glycopeptides (i.e. vancomycin)
• Phenylbutazone in female dairy cattle gt20 months
  or older
• Adamantane and neuraminidase
• Therefore all other compounds are not prohibited
  - IF labeled properly and dispensed used by
  veterinarian within a valid VCPR

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But what about a veterinarians use of a
medicinal that is not explicitly prohibited? The
practice of veterinary medicine is very broad IF
a valid VCPR exists

• Veterinarian/Client/Patient Relationship (VCPR)
  exists when all of the following conditions have
  been met
• The veterinarian has assumed the responsibility
  for making clinical judgments regarding the
  health of the animal(s) and the need for medical
  treatment, and the client has agreed to follow
  the veterinarians instructions.
• The veterinarian has sufficient knowledge of the
  animal(s) to initiate at least a general or
  preliminary diagnosis of the medical condition of
  the animal(s).This means that the veterinarian
  has recently seen and is personally acquainted
  with the keeping and care of the animal(s) by
  virtue of an examination of the animal(s) or by
  medically appropriate and timely visits to the
  premises where the animal(s) are kept.
• The veterinarian is readily available for
  follow-up evaluation, or has arranged for
  emergency coverage, in the event of adverse
  reactions or failure of the treatment regimen.

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COMPLEMENTARY AND ALTERNATIVE VETERINARY
MODALITY(S) CLIENT CONSENT FORM 1. OWNER
IDENTIFICATION Name______________________________
_____ Address_____________________________________
_____________________ 2. ANIMALS
DESCRIPTION Animals Name or Identification
No.___________________________________ Species____
________________ Breed______________________
Age_______ 3. INFORMATION PROVIDED i) I have
been advised by Dr(s).____________________________
______ of the conventional and complementary and
alternative veterinary options for diagnosis and
therapy, and their associated risks, costs and
prognosis. ii) I am aware that the following
complementary and alternative modalities to be
used in the treatment of my animal are not
considered conventional veterinary
medicine. ________________________________________
________________________ 4. I AGREE THAT A) I
have read and fully understand this Client
Consent Form. B) I am the owner of, or the
authorized agent of, the animal described above
and I am of legal age (18 years or older). C) I
consent to the provision of the above listed
complementary and alternative modalities for my
animal by the above-mentioned doctor(s). Client
signature ___________________________________ Vete
rinarian Signature _______________________________
____ Witness Signature Date______________
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HHSPHSFDACFSANOCDCPMSB 5100 Paint
Branch Parkway College Park, MD 20740-3835
M-I-06-5 April 19, 2006
TO All Regional Food and Drug Directors Attn
Regional Milk Specialists FROM Milk Safety
Branch (HFS-626) SUBJECT Current Information
Addressing Item 15r-Drug and Chemical Control Of
The Grade A Pasteurized Milk Ordinance The
purpose of this coded memorandum (M-I) is to
update previously issued guidance on Item 15r of
the Grade A Pasteurized Milk Ordinance (PMO)
addressing drug labeling, use and storage
requirements inspectional areas and follow up
investigations for positive animal drug residues
on Grade A dairy operations.
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Pasteurized Milk Ordinance deals with correct
labeling of drugs found on dairy farms during
regulatory inspections (item 15r)

• PMO page 2
• 4. Drugs shall be properly labeled to include the
  name and address of the manufacturer or
  distributor for OTC drugs, or veterinary
  practitioner dispensing the product for Rx and
  extra label use drugs.
• 5. Drug labels shall also include
• Directions for use, and prescribed withholding
  times
• Cautionary statements, if needed and
• Active ingredient(s) in the drug product.
• 6. Unapproved and/or improperly labeled drugs are
  not used to treat dairy animals and are not
  stored in the milkhouse, milking barn, stable or
  parlor.

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Topicals pg 3 PMO

• NOTE Topical antiseptics and wound dressings,
  unless intended for direct injection into the
  teat, vaccines and other biologics, and dosage
  form vitamins and/or mineral products are exempt
  from labeling and storage requirements, except
  when it is determined that they are stored in
  such a manner that they may contaminate the milk
  or milk product-contact surfaces of containers,
  utensils or equipment.
• Thus if a topical antiseptic were to be labelled
  for direct injection into the teat, it would be
  OK?

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OTHER DRUGS Regulators are reminded that the
following three (3) drugs are either not to be
used or not to be stored on dairy operations or
fed to lactating dairy cattle because of human
food safety concerns 1. NON-MEDICAL GRADE
DIMETHYLSULFOXIDE (DMSO) NOTE There are serious
medical conditions that may occur in dairy cattle
for which the administration of medical grade
DMSO may be a life saving treatment option. It is
permissible for veterinarians to use FDA approved
medical grade DMSO products under AMDUCA in an
extra-label manner to treat food animals. To
align the PMO with AMDUCA and legitimate
veterinary medical practice, the use of medical
grade DMSO to treat life threatening conditions
in dairy cattle of all classes is allowable.
Under no circumstances should the product be
stored on the operation for indiscriminate use by
dairy personnel. The storage of DMSO in any form
or the use of industrial grade DMSO in any form
on a dairy operation is a violation of Item 15r
of the PMO. 2. DIPYRONE (Novine, No Pain, etc.)
3. COLLOIDAL SILVER what about ionized silver?
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MISCELLANEOUS DRUGS Examples of such drugs
include Aloe Vera Homeopathic Drugs Drugs that
are packaged for infusion (intramammary) or
injection but labeled for oral (feed), topical,
or other routes of administration and Drugs used
in foot baths and sprays for application to dairy
animals feet. What about such drugs that are
appropriately labeled by vet within a valid
VCPR?
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1. Aloe vera

• FDA has received complaints of aloe vera being
  promoted for use as a treatment for mastitis, a
  cure for high somatic cell counts, as an aid for
  increasing milk production, and treatment for
  calf diarrhea. FDA is aware that firms are
  selling containers of aloe vera with no drug
  claims on the label to dairy producers and then
  providing the drug use claims either orally or by
  other printed materials or graphics (labeling).
• No aloe vera product has been approved for the
  treatment of these serious disease conditions or
  to increase milk production. Aloe vera products
  for animals bearing these types of claims are
  unapproved new animal drugs. Aloe vera products
  intended for animal use that do not bear adequate
  directions for animal use are misbranded. The use
  of unapproved drugs is considered a violation of
  Item 15r of the PMO.
• Therefore if labelled by a veterinarian within a
  valid VCPR, then OK?
• How can aloe vera be thought of and referred to
  as a new animal drug??

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2. Homeopathic Drugs

• Homeopathy is an alternative therapeutic modality
  developed in the late 1700's by a German
  physician for use in humans. Homeopathic medicine
  is considered an unconventional form of
  veterinary practice. FDA can find no
  justification for regulating veterinary
  homeopathic drugs any differently from other
  drugs subject to the FFDCA. There are currently
  no FDA approved homeopathic drugs for veterinary
  use.
• Homeopathic drugs found on dairy operations must
  comply with the drug labeling and storage
  requirements of Item 15r of the PMO. If these do
  not comply with the drug labeling requirements,
  they are addressed like other unapproved drugs,
  and should not be stored on dairy operations or
  used to treat dairy animals. If homeopathic drugs
  are properly labeled they are subject to the same
  storage requirements as any other drug.
• NOTE A thorough reading of the label for
  homeopathic drugs will often disclose Item 15r
  deficiencies.
• First it states that there are no homeopathics
  for veterinary use but then goes on to say that
  if homeopathics are found they must comply with
  proper drug labeling. ???

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3. DRUGS PACKAGED FOR INJECTION OR UDDER INFUSION
BUT LABELED FOR ORAL OR TOPICAL USE

• FDA has received several complaints about
  products labeled for oral, topical or other
  routes of administration that are packaged in a
  manner customarily considered to be for
  parenteral (injection and udder infusion)
  administration. Among the products packaged in
  this manner are aloe vera products labeled for
  topical use and packaged in sur-jets/squeeze jets
  (squeeze tubes routinely used for intramammary
  infusion) and probiotic and whey blend products
  labeled for oral use packaged in syringes with
  sterile diluent in vials with udder infusion
  cannulas and alcohol pads or packaged in sterile
  vials closed with a metal ring and rubber
  injection stopper.
• FDA's Compliance Policy Guide (CPG) 7125.39
  entitled "Drugs Packaged for Infusion or
  Injection for Food-Producing Animals" is
  available for guidance on this issue.
• FDA is very concerned about the safety of
  products not approved for parenteral use which
  are infused or injected into food-producing
  animals. FDA believes that the packaging and
  labeling of these products is a subterfuge to
  avoid the more stringent regulatory requirements
  for parenteral drugs. Products that are intended
  for oral or topical administration should not be
  packaged to facilitate parenteral (injection and
  udder infusion) administration. Such drugs will
  be considered to be misbranded if they do not
  contain directions for their packaged use.
• In other words, misleading labeling is
  prohibited. But what if something is honestly
  labeled by the veterinarian within a valid VCPR?

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4. MEDICATED FOOT BATHS AND SPRAYS USED TO TREAT
AND CONTROL CATTLE FOOT ROT AND HEEL WARTS

• Veterinarians prescribe and dairy producers
  routinely use medicated foot baths or sprays to
  control hoof disorders in dairy animals. These
  baths and sprays often contain antibiotics, such
  as oxytetracycline. To comply with the PMO, these
  types of baths and sprays must be operated in a
  manner that will not contaminate the milk or milk
  product contact surface of the milking equipment.
  The use of antibiotics for foot baths/sprays
  constitutes ELU. Veterinarians should comply with
  the labeling requirements for ELU of drugs under
  Item 15r of the PMO.
• To prevent milk contamination, foot baths
  generally should be located on the exit side of
  the milking area (walk through after milking).
  Spraying medication onto the dairy animals
  hooves should not occur in the milking area
  during milking time.
• Notice the term should (versus must)

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CHORULON A CASE STUDY OF FLEXIBILITY IN THE NEW
ANIMALDRUG APPROVAL PROCESSFrom FDA
Veterinarian Nov/Dec 2000

• CVM took the unprecedented step of publishing a
  guidance permitting the use of the unapproved new
  animal drug in brood fish under certain
  conditions (Guidance for Industry 71). This
  action provided the use of the unapproved new
  animal drug, chorionic gonadotropin, under
  regulatory discretion. The decision to provide
  this discretion was based on the low human food
  safety and environmental safety, the need of the
  industry for this relief, the food fish status of
• many of the broodstock which would receive
  treatment, and the likelihood of a formal
  approval for this use.

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it was recognized that the worst case dietary
exposure to Chorulon would be the potential
consumption of the tissue into which the drug had
been injected (the injection site) without
allowing any time for the drug to deplete. Even
in this unlikely event, it was determined that as
much as 25,350 I.U. of total gonadotropin would
be safe for a person to consume. It was clear
from the effectiveness data that in nearly all
instances the total amount of Chorulon
administered to the fish would not be sufficient
to cause concern in the human diet. Hopefully
GRAS (Generally Recognized As Safe) products
which are dispensed or administered in the
context of a valid VCPR and labelled
appropriately according to the PMO but are
unapproved - will be accorded the same treatment
by FDA CVM
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INSTITUTE FOR NON-ANTIBIOTIC AGRICULTURE(INAA)
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INSTITUTE FOR NON-ANTIBIOTIC AGRICULTURE(INAA)

• PURPOSE
• The Institute exists to actively study
  agricultural practices and treatments which
  stimulate and augment animals innate immune
  capabilities to be healthy and to resolve disease
  conditions.
• The Institute is to be a consortium of veterinary
  practitioners, clinical researchers and animal
  husbandry professionals who are dedicated to
  studying the art and science of raising animals
  without relying on antibiotics and hormones.
• Emphasis on applied science to benefit the health
  of agricultural food producing species is central
  to the existence of the Institute.

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GOALS of the INAA

• 1) Link veterinary practitioners and academic
  investigators to study non-antibiotic treatments
  of infectious disease (NATID) and non-hormonal
  treatment of infertility (NHTI) in agricultural
  food producing species. Emphasis will be on
  biomarkers to identify health and disease
  resolution.
• 2) The study of naturally acquired disease and
  its treatment should be given priority to
  experimental infection protocols.
• 3) Encourage holistic approaches to problem
  identification and treatment. The concept of
  exchanging one treatment for another (input
  substitution) is discouraged however, it is
  accepted that precision therapies do exist but
  should be used in the context of the entire
  patient or herd picture.
• 4) Create a data base of NATID and NHTI clinical
  studies - double blind randomized, single blind
  randomized, open trial, case series, case
  reports, and clinical impressions from anywhere
  in the world and from any language.

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GOALS of the INAA

• 5) It is accepted by members of the Institute
  that clinical impressions have historically led
  to discoveries of practical importance and will
  continue to do so.
• 6) Disseminate factual, rational, credible
  information that will enable practitioners to
  provide effective non-antibiotic and non-hormonal
  treatments to major agricultural species (cattle,
  swine, avian, etc)
• 7) Work with appropriate regulatory agencies to
  ensure a safer and more wholesome food supply.
  The promotion of valid veterinary-client-patient-r
  elationship is encouraged whenever carrying out
  clinical duties and studies.
• 8) Encourage/support student interest and mentor
  students to ensure future leadership in food
  production without reliance on antibiotics and
  hormones.