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The Practitioner's Role and Responsibility in Residue Avoidance
Dairy Practice Management
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The Practitioner's Role and Responsibility in Residue Avoidance Keith E. Sterner, DVM *
It is a sign of the times that my opening paragraph is a disclaimer. By the time this article is in print, some or all of the recommendations may be outmoded or superseded by events unforeseen at this writing. This article constitutes a sincere effort on my part to make recommendations to the practitioner that will help to assure a wholesome, safe food product. With this in mind, an explanation about the format and intent of the article is in order. The first few pages deal with specific recommendations for practitioners to employ in order to attempt to comply with current laws and regulations. They are purposely brief and without explanation to allow quick assimilation of the technical information. More detailed explanations and background information follow on subsequent pages.
FIVE POINTS OF COMPLIANCE Recommendations in order for practitioners to comply with government laws and regulations are as follow:
1. Establish and maintain valid veterinarian/client/patient relationships (VCPR). Be able to document or support evidence of such relationships. 2. As extralabel drug use occurs, maintain and keep records that allow for identification of treated animals and appropriate extended times for drug withdrawal, based on the compound(s) used - know the pharmacology of the drugs you are using. 3. Ensure that clients have some means of positively identifying and segregating treated animals as well as complying with drug labeling, storage, and treatment requirements. 4. Select and recommend appropriate supplemental residue tests ·President, American Association of Bovine Practitioners; Owner/Operator, Sterner Veterinary Clinic Professional Corporation, Ionia, Michigan
Veterinary Clinics of North America: Food Animal Practice-Vol. 5, No.3, Nov. 1989
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to be run before milk or animals are cleared for shipment. Keep in mind that many current on-farm or in-clinic residue tests do not detect violative drug residues from extralabel use. For milk, when in doubt, clear individual samples with the milk cooperative prior to sending the milk. 5. Familiarize yourself and your clinic staff with the AVMA Guidelines for Supervising Use and Distribution of Veterinary Prescription Drugs (a removable insert in the Journal of the American Veterinary Medical Association, Vol. 193, No.7, October 1, 1988; they are also published in the AVMA directory.) (Fig. 1). With regard to the five points of compliance, the following definitions and examples are offered: Reference Point 1 The Food and Drug Administration (FDA) has provided under its rules for extralabel drug use (ELUD), when certain conditions are met. This authority is not a statutory one but one rather allowed by regulatory policy of the FDA; in other words, the practitioner does not have the benefit of a specific law (statute) that allows such use. This ELUD is a policy of the FDA, and therefore subject to change by whatever agency is charged with enforcing the law. The caveat is that the veterinarian must assume liability if extralabel use results in drug residues or adverse reactions. Basic to extralabel drug use is a valid VCPR, which is defined as existing when A. 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 veterinarian's instructions. B. 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 is 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. C. The veterinarian is readily available for follow-up evaluation in the event of adverse reactions or failure of the treatment regimen. It is vital that the practitioner be able to document the VCPR, should there ever be a question with regard to ELUD. This can be best accomplished through client and practitioner record-keeping systems. Practitioners are strongly encouraged to develop and maintain such documentation. Many of the computerized billing systems now available can greatly facilitate the storage and recall of such records. Any practitioner in food animal practice should seriously consider adopting such a system.
617
AVMA Guidelines for Supervising Use and Distribution
of Veterinary Prescription Drugs
Figure 1. American Veterinary Medical Association guidelines for supervising the use and distribution of veterinary prescription drugs. (From J Am Vet Med Assoc 193(7), October 1, 1988; with permission.) (Illustration continued on following page)
618
Preface In an effort to assist practicing veterinarians who supervise the use and distribution of veterinary prescription drugs and over-the-counter drugs that, for clinical effectiveness, must be used in an extra-label manner, the Council on Biologic and Therapeutic Agents has developed the following guidelines. The guidelines were approved by the 1988 House of Delegates and are being published in a pull-out section that may be retained by the practitioner for easy reference. The guidelines were designed to heighten the practitioner's level of awareness on the subject and to promote appropriate animal drug use by practitioners as well as animal owners. The Council emphasizes that the guidelines must not be interpreted as hard and fast rules. Each practitioner must exercise sound clinical judgment as well as common sense when making decisions regarding the use of therapeutic agents, regardless of whether the drugs in question actually are being used or dispensed by the practitioner, or whether they are dispensed on the order of the veterinarian and used by the animal owner or his agent. The Council acknowledges the extensive efforts of Dr. Jack Morse, Turlock, Calif, who as a member of the Council, was a principal author of these guidelines. Fred W. Scott, Chairman Council on Biologic and Therapeutic Agents
2 Figure 1.
(Continued)
(Illustration continued on opposite page)
619
Table of Contents INTRODUCTION Nonprofessional Staff. . . . . . . . . . . . . . . . . . . . .. 4 Client Relationships . . . . . . . . . . . . . . . . . . . . . .. 4 Veterinary Prescription Drugs . . . . . . . . . . . . . . . .. 5 GUIDEUNES Veterinary Prescription Drugs Dispensed or Used by Veterinarians in Private Practice . . . . . . . . . . . Veterinary Prescription Drugs Delivered to Clients by Drug Distributors on the Order of a Veterinarian. . Veterinary Prescription Drugs Obtained from a Pharmacist on the Order of a Veterinarian . . . . . .
6 7 8
DEFINITIONS AND BACKGROUND Veterinary Prescription Drugs . . . . . . . . . . . . . . . .. 9 Extra-Label Use of Drugs . . . . . . . . . . . . . . . . . . . . 9 Veterinarian-Client-Patient Relationship . . . . . . . . . . . 10 Concept of a Veterinary Practice . . . . . . . . . . . . . . . 10 Dispensing Labels . . . . . . . . . . . . . . . . . . . . . .. 10 Veterinary Drug Orders . . . . . . . . . . . . . . . . . . . . 11
3 Figure 1.
(Continued)
(Illustration continued on following page)
620 INTRODUCTION Society is pressing for changes in the way animal drugs are distributed and used, because consumers are concerned that meat, milk, and eggs may contain harmful drug residues. Although food animal products of US origin are among the most wholesome and safe in the world, the perception of hazardous residues still exists in the minds of consumers because contaminants are occasionally detected. Unless the livestock industry, the pharmaceutical industry, drug distributors, and the veterinary profession work together to eliminate harmful residues, the possibility exists that, eventually, few drugs will be available for use in food animals. Despite health management techniques and disease prevention programs, there will always be a need for therapeutic drugs. Failure to act could result in further erosion of public confidence in the wholesomenE1ss of food animal products. I The veterinary profession should take the leadership in assuring a supply of meat, milk, and eggs that is free of harmful residues. Veterinarians can assume this responsibility if their proper role in supervising use and distribution of drugs used in food animals is recognized and supported by regulatory agencies, livestock owners, and pharmaceutical distributors. The veterinary profession must adhere to high ethical and scientific standards to merit this support. Nonprofessional Staff The guidelines for supervising veterinary prescription drugs dispensed by veterinarians in private practice are designed to decrease the possibility of inadvertent inappropriate dispensing by clinic staff, and to aid the staff in carrying out the veterinarian's instructions. Methods should be devised to assure that employees comply with instructions in the veterinarian's absence. Staff members authorized to dispense drugs should be properly trained. Because of potential confusion, veterinary prescription drugs labeled "Caution: Federal law restricts the drug to use by or on the order of a licensed veterinarian" should be segregated and identified with an easily noticed mark or sticker. Client Relationships Parts of these guidelines relate to the relationship between the veterinarian and the client and the client's employees. Of
4 Figure 1.
(Continued)
(Illustration continued on opposite page)
621 necessity, this relationship requires honesty, openness, and a commitment to a common cause. Owner treatment records decrease the possibility of violative residues, and comply with the FDA guide for preserving the identity of food animals treated with drugs used in an extra-label manner. Drug storage recommendations are made to protect children and unauthorized persons from access to potentially dangerous drugs. The additional set of instructions for veterinary prescription drug use will provide the client with another source of reference on proper drug usage. Labels on containers may become dirty and blurred through repeated use. Suggested ways to accommodate these additional instructions are clear plastic covers for instruction inserts that can be posted in the drug room area, loose-leaf notebooks for instructions, and computer printouts or farm or ranch visit reports posted under plastic.
Veterinary Prescription Drugs By FDA's definition, veterinary prescription drugs are those drugs restricted by federal law to use by or on the order of a licensed veterinarian. Any other drugs used in animals in a manner not in accordance with their labeling (extra-label uses) should be subjected to the same supervisory precautions that apply to veterinary prescription drugs. In this document, when the term "veterinary prescription drug" is used, the precautions noted apply to all drugs used for extra-label purposes as well as those defined by FDA to be veterinary prescription drugs. There are vast differences among types of practices, species of animals treated, and production-management circumstances. These guidelines provide a basis for responsible professional decisions. Each veterinarian must use clinical judgment, current medical information, good sense, and high ethical standards when applying them to practice situations. Veterinarians should be responsible for supervising use of veterinary prescription drugs that are dispensed or administered in the course of private practice, delivered to a client by drug distributors upon the veterinarian's order, or obtained from a pharmacist on the prescription of a veterinarian. For clarity, these guidelines are restated for each of the above situations.
5 Figure 1.
(Continued)
(Illustration continued on follOWing page)
622 GUIDELINES Veterinary Prescription Drugs Dispensed or Used by Veterinarians in Private Practice Veterinary prescription drugs should be dispensed only by or on the order of a licensed veterinarian in the presence of a valid veterinarian-client-patient relationship (VCPR). Nonprofessional staff may dispense veterinary prescription drugs only after receiving specific instructions from a veterinarian. Records should be maintained to show the prescription drugs that may be supplied to clients with whom a valid VCPR exists. Such records should indicate the veterinarian(s) who has the animals under his or her care. The dispensing of veterinary prescription drugs should be based on records and medical histories of animals seen or treated. The record of drugs that may be dispensed should not be changed without signed authorization of the responsible veterinarian, who should update each record no less often than on a quarterly basis. The drugs dispensed should be invoiced with the name and address of the client to provide records for follow-up evaluation, if needed. Training for all staff should be regular and effective to assure that veterinary prescription drugs are dispensed only on the order of a veterinarian, and only when a valid VCPR exists. Drugs labeled with the FDA precaution "for use by or on the order of a licensed veterinarian" should be stored separately from other drugs on the practice premises. These drugs should be clearly distinguishable and separated from over-the-counter drugs. They should not be openly displayed or be accessible to the public. Proper labeling should accompany all veterinary prescription drugs dispensed. Quantities dispensed should be no greater than needed for treatment of the animal, herd, or Hock. Clients should be advised that veterinary prescription drugs should be securely stored, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, including identification of animal(s), drug(s) used, routes of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. This could be in the form of a simple table or chart issued by the veterinarian. Instructions for the use of each veterinary prescription drug dispensed should be written by the veterinarian, when applicable. These instructions should be kept in the client's drug storage area.
6 Figure 1.
(Continued)
(Illustration continued on opposite page)
623 Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating. Records should be kept for at least two years when veterinary prescription drugs are dispensed or used in practice. Veterinary Prescription Drugs Delivered to Clients by Drug Distributors on the Order of a Veterinarian Orders issued by licensed veterinarians authorizing drug distributors to deliver veterinary prescription drugs to a specific client should be based on a valid VCPR and should contain the following information: • The veterinarian's name, address, telephone number, and license number (not DEA number) • Name and address of client • Species • Number and quantity of drug(s) to be delivered • Directions for use • Cautionary statements including, if applicable, expiration date and withdrawal time • Date of issue • Number of refills • Veterinarian's signature Drug orders must be initiated by the veterinarian, based on dialogue with the client or his agent. Requests coming directly from drug distributors are not within the bounds of a valid VCPR. Telephone orders require prompt completion and processing of the drug order form. When a drug order is issued, the quantity should be limited to an appropriate usage period. Clients should be instructed that veterinary prescription drugs should be securely stored, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, which would include identification of animal(s), drug(s) used, route of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. Additional instructions for use of each veterinary prescription drug should be written by the veterinarian. These instructions should be kept in the client's drug storage area. Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating.
7 Figure 1.
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624
Veterinarians should keep records of prescription drug orders for at least two years. Veterinary Prescription Drugs Obtained from a Pharmacist on the Order of a Veterinarian Prescriptions/orders issued by licensed veterinarians authorizing pharmacists to dispense veterinary prescription drugs to a specific client should be based on a valid VCPR and should contain the following information: • The veterinarian's name, address, telephone number, and license number (not DEA number) • Name and address of client • Species • Name and quantity of drug(s) • Directions for use • Cautionary statements including, if applicable, expiration date and withdrawal time • Date of issue • Number of refills • Signature of issuer (prescriber) The prescription/order must be initiated by the veterinarian from dialogue with the client or his agent. Requests coming directly from the pharmacist are not within the bounds of a valid VCPR. Telephone orders require prescription/order forms identical to written orders, with identical processing. Quantities prescribed/ordered should be limited to an appropriate usage period. Clients should be instructed that veterinary prescription drugs dispensed by the pharmacist should be stored securely, preferably under lock, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, which would include identification of animal(s), drug(s) used, routes of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. Instructions for use of each veterinary prescription drug dispensed by the pharmacist should be written by the veterinarian, when applicable. These instructions should be kept in the client's drug storage area. Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating. 8 Figure 1.
(Continued)
(Illustration continued on opposite page)
625
Records of prescriptions/orders should be kept for at least two years.
DEFINITIONS AND BACKGROUND Veterinary Prescription Drugs According to FDA, drugs that, because of toxicity or other potential for harmful effect, or because of the method of use, cannot be approved for animal use except under the supervision of a veterinarian are classified as veterinary prescription drugs. The agency requires that such drugs be labeled with the statement "Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian." Phrases such as "For Veterinary Use Only," and "Sold to Veterinarians Only" do not refer to the drug's prescription status. For purposes of these guidelines, when any other drugs are used for extra-label purposes, they should be afforded the same precautions that apply to the FDA definition of a veterinary prescription drug. Extra-Label Use of Drugs Extra-label use means the administration or application of a drug in a manner that is not in accordance with the drug's labeling. Extra-label use of drugs in treating food-producing animals may be considered only in special circumstances. For such usage, the FDA specifies that the following criteria must be met: • A careful clinical diagnosis is made by an attending veterinarian within the context of a valid VCPR • A determination is made that there is no marketed drug specifically labeled to treat the condition diagnosed, or that treatment at the dosage recommended by the labeling has been found clinically ineffective • Procedures are instituted to assure that identity of the treated animals is carefully maintained • A significantly extended time period is assigned for drug withdrawal prior to marketing meat, milk, or eggs; steps are taken to assure that the assigned time frames are met; and no harmful residues occur Certain drugs (chloramphenicol, diethylstilbestrol, and dimetridazole) may not be used in treating food-producing animals even under the cited criteria.
9 Figure 1.
(Continued)
(Illustration continued on following page)
626 Veterinarian-Client-Patient Relationship The 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 veterinarian's 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 in the event of adverse reactions or failure of the treatment regimen. This definition of the VCPR is of necessity broad in scope. Its general terms are intended to apply to many types of practices covering several species of animals. Concept of a Veterinary Practice Veterinary prescription drugs are to be used, ordered, dispensed, or prescribed by the licensed veterinarian within the course of professional practice. This means the veterinarian is licensed or otherwise properly authorized under state law to practice veterinary medicine in the state, and that a valid VCPR exists. Veterinarians who are employees of drug manufacturers or distributors, or veterinarians who operate drug distributorships cannot legally sell veterinary prescription drugs or issue prescriptions or orders for such drugs outside the scope of a professional veterinary practice. Dispensing Labels All veterinary prescription drugs should be properly labeled when dispensed. The label should ordinarily contain information that would appear on a veterinarian's prescription/order to a pharmacist or drug distributor (see page 6). As long as the drug is properly identified, the above information may be supplied separately in writing in lieu of the dispensing label. 10 Figure 1.
(Continued)
(Illustration continued on opposite page)
627 Veterinary Drug Orders Orders authorizing pharmacists to dispense veterinary prescription drugs are called "prescriptions." There is no standard form for the "prescription," but information the prescription should include is specified in each state's pharmacy regulations and rules. Some states have reserved the term "prescription" as an order only a pharmacist may process. Additionally, some states have decreed that instructions to a person other than a pharmacist to dispense a veterinary prescription drug be called a "drug order." These guidelines enumerate the information the prescription or drug order should include, based on the usual requirements of boards of pharmacy, and should be adequate for trained pharmacists. This information may not be adequate for nonprofessionals. For example, Idaho has special requirements for dispensers who are not pharmacists or veterinarians. For any state without stringent qualifications for the nonprofessional processor of the veterinarian's order, a detailed order would be indicated. The veterinarian would retain the third copy, and the drug distributor the original, while the second copy would accompany the drugs delivered to the client. The drug order should be designed to provide the following information: Name and address of the client and evidence that the client understands and will follow directions given. N arne and address of the drug distributor, including evidence of the distributor's commitment that only those drugs listed at the strength and quantity noted on the order will be provided, that drugs will not be delivered after expiration of the order date, and that the drug order will be processed exactly as written by the veterinarian and no substitutions of a different brand or product will be made without consulting the issuing veterinarian. N arne and address of the issuing veterinarian, including his or her signature or other evidence that a valid VCPR exists with the client to whom the drugs are to be delivered, that written instructions on the use of the drugs have been provided to the client, and that the order mayor may not be refilled and, if so, the number of refills. The name of the drug(s) to be delivered, including the strength, unit size, and quantity. This should be a list of only those drugs to be delivered. Written instructions on the use and withdrawal times of the drugs listed. The date of issue and a statement that the order is void in 90 days. 11 Figure 1.
(Continued)
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Since a valid VCPR must exist to dispense veterinary prescription drugs, a sign conspicuously posted in the office may help to avoid problems with clients and non clients seeking to purchase these drugs. Such a sign (see J Am Vet Med Assoc 194:1018, 1989) might read FEDERAL LAW PROHIBITS THE DISPENSING OF CERTAIN MEDICATIONS WITHOUT EXAMINATION OR PRESCRIPTION. YOUR UNDERSTANDING IS APPRECIATED. Reference Point 2 In my experience, the keeping and maintaining of records that identify treated animals is best accomplished at each farm by means of a notebook system. A sample notebook page (Fig. 2) is included, which is designed to be as brief and as easy to follow as possible, allowing all medications and treatments given on the farm to be recorded along with the initials of the person administering the medication. Treatment sheets are subsequently filed by month and year so as to provide a permanent record of medications and treatments. An additional insert sheet is provided with this treatment record book, which lists recommended dosage schedules and the clinic's best estimate of an appropriate withdrawal time for different drugs when they are used in an extralabel fashion. Supplemental residue testing can also be recommended on this sheet when such testing is indicated. (Not all drugs used in an extralabel fashion have valid residue test methods available; therefore, such testing is not always indicated.) This sheet is designed to be replaced as new information and new technologies become available to the practice, with regard to residue avoidance. This sheet is not included here, since at present, there are no guidelines that can be provided without the risk of misinterpretation and subsequent liability. The FARAD (Food Animal Residue Avoidance Databank) is available to those practitioners wishing to obtain withdrawal information on extralabel drug use. This resource can be used to formulate withdrawal recommendations for ELUD and to provide information for making up a clinic guideline. Specific information can be obtained by calling one of three numbers: For eastern and southern regions of the country, the telephone number is (904) 392-4085. For the midwestern region, the number is (217) 333-3611 (this is also the National Animal Poison Control Center). For western areas, the number is (916) 752-7507. Information on both milk and meat drug withdrawal recommendations can be obtained from these FARAD centers. Larger feedlot operations have well-developed computer software available that can provide even more information. At present, I am unaware of any dairy software available for such purposes. Practitioners owe it to themselves and their clients to continually update and familiarize themselves with pathologic conditions and their causes commonly found in practice. Based on this knowledge, sound judgment can be exercised in the selection of pharmaceutical therapy to achieve a favorable therapeutic outcome (Table 1). Tables 1 and 2 provide some insight as to appropriate therapeutic
DATE
COWID#
CONDmON
TREATMENT
TEST yiN
MILK HOLD
yiN
® yiN
MEAT HOLD
® yiN
TEST
Figure 2. Sample table, used to record all medications and treatments given on the farm. The initials of the person administering the medication or treatment are recorded in the first column (INTL).
INTL
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Aerobic Aerobic Not applicable Anaerobic Facultative anaerobic Facultative anaerobic Facultative anaerobic Not applicable Facultative anaerobic Anaerobic Facultative anaerobic Facultative anaerobic Aerobic
Gram-negative Gram-negative Not applicable Gram-positive Gram-positive Gram-negative Gram-negative Not applicable Gram-positive Gram-negative Gram-negative Gram-negative Weakly gram-negative
Extracellular Extracellular Obligate intracellular Extracellular Facultative intracellular Extracellular Extracellular Attached to host cell membrane Extracellular Extracellular Extracellular Extracellular Extracellular
Bordetella Campylobacter Chlamydia Clostridia Corynebacterium Escherichia coli Enterobacter Eperythrozoon
Erysipelothrix Fusobacterium Hemophilus Klebsiella Leptospira
Facultative anaerobic Not applicable Anaerobic
Rod Rod Rod Rod Spirochete
Rod Rod Rod Rod
Rod Rod
Rod
Rod
SHAPE (IF APPLICABLE)
OXYGEN REQUIREMENTS
Gram-negative Not applicable Gram-negative
STAIN AFFINITY
Extracellular Obligate intracellular Extracell ular
ORGANISM LOCATION
Actinobacillus Anaplasma Bacteroides
BACTERIA
Table 1. Sensitivity Patterns of Bacteria PROBABLE SENSITIVITY
Variable Penicillin Variable Variable Streptomycin, tetracycline, penicillin
Variable Tetracycline Penicillin (except B. fragilis), lincomycin Variable Variable Tetracycline Penicillin Penicillin, • erythromycin Variable Variable Tetracycline, arsenicals
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Facultative anaerobic
Facultative anaerobic
Aerobic Facultative anaerobic Facultative anaerobic Aerobic Facultative anaerobic
Aerobic Aerobic Not applicable
Spirochete
Coccus
Coccus
Rod Rod Rod Rod
Rod Rod
Penicillin (p-hemolytic streptococci) Variable
Variable
Variable Variable Tylosin, lincomycin, erythromycin, tetracycline Variable Variable Variable Variable Variable
1989; with permission.
From Langston VC, Davis LE: Factors to consider in the selection of antimicrobial drugs for therapy. Compend Contin Educ Pract Vet 11:357,
*Organism often resistant in vivo
Treponema
Streptococcus
Gram-positive
Variable Gram-negative Gram-negative Gram-negative Gram-negative
Facultative intracellular Extracellular Extracellular Extracellular Facultative intracellular or extracellular Extracellular or facultative intracellular Extracell ular
Nocardia Pasteurella Proteus Pseudomonas Salmonella
Staphylococcus
Gram-positive Acid-fast Not applicable
Facultative intracellular Facultative intracellular Attached to host cell membrane
Listeria Mycobacterium Mycoplasma
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Common Antimicrobial Drugs SENSITIVITY IN VITRO
DRUG
ACTION
Aminoglycosides (class)
Bacteriocidal
Cephalosporins (first generation) Erythromycin
Bacteriocidal
Lincomycin Nitrofurans Oxytetracycline Penicillin (class) Spectinomycin Sulfonamides Trimethoprimsulfadiazine
Tylosin
SITE OF ACTION
MECHANISM OF ACTION
30s ribosome subunit Protein synthesis; misreading of genetic code Inhibits cross-linkage Cell wall
Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits translocation Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits initiation Breakage of bacterial Bacteriocidal DNA DNA Bacteriostatic 30s ribosome subunit Protein synthesis; inhibits attachment of transfer RNA Bacteriocidal Cell wall Inhibits cross-linkage Bacteriostatic 30s ribosome subunit Protein synthesis; inhibits translocation Bacteriostatic Enzyme Inhibits folate synthesis Sulfadiazine inhibits Bacteriocidal Enzyme folate synthesis; trimethoprim competes for dihydrofolic acid reductase Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits translocation
Cram-Positive
Sensitive Sensitive Sensitive Sensitive Sensitive Sensitive Sensitive Resistant Sensitive Sensitive
Sensitive
*Except B. fragilis fIn vivo efficacy not well established tOther agents usually preferred From Langston VC, Davis LE: Factors to consider in the selection of antimicrobial drugs for therapy. Compend Contin Educ Pract Vet 11:359, 1989; with permission.
regimens and selection of residue avoidance tests. I recommend that practitioners subscribe to and review the FDA Veterinarian for timely information on many drug issues, including new animal drug approvals, revised animal drug approvals, and approval withdrawals; this publication costs $5.00 per year and is available from the Superintendent of Documents, Government Printing Office, Washington DC, 204029371. Food animal practice is in a state of flux, and it is crucial to keep abreast of changes in this important area. The Lactating Cow. With regard to drug therapy in the lactating cow, there are two points to remember: A. There are only five antibiotics and one sulfonamide approved for parenteral administration: Penicillin, dihydrostreptomycin, erythromycin, ampicillin, amoxicillin and sulfadimethoxine. B. Extra-label drug use is often required for effective treatment. Any use of drugs in a dosage or formulation for purposes other than that listed on the label constitutes an extralabel drug usage. This is only allowed if the practitioner has a valid VCPR
633
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
SENSITIVITY IN VITRO
Anaerobes Gram-Negative Clostridial
Other
METABOLISMjExCRETION
Mycoplasmal Leptospiral Rickettsial
Sensitive
Resistant
Resistant
Sensitive
Varies
Sensitive
Sensitive·
Resistant
Sensitivet
Varies
Sensitive
Resistant
Sensitive
Sensitive
Sensitive
Liver
Primary Primary
Sensitivet
Sensitive
Secondary
Primary
Secondary
Primary
Primary
Sensitive
Sensitivef
Varies
Sensitivef
Varies Sensitive
Sensitive
Sensitive· Resistant·
Sensitivef
Sensitive Sensitive
Sensitive Sensitive
Renal
Sensitive
Primary
Secondary
Primary Primary Primary
Sensitivef
Resistant
Sensitive
Primary
Sensitive
Secondary
Primary
and if such extralabel drug usage does not result in residues in food or in adverse reactions. Reference Point 3 Point 3 ensures that the day-to-day procedures for compliance are being followed on the farms. Perhaps the single most common cause of violative residues is the failure of producers to properly identify and segregate treated animals. Periodic review of each client's methods is strongly recommended. The methods of identification employed should be aimed at ensuring that all personnel handling treated livestock can easily identify treated animals so as not to mix them in with the untreated population. The methods used will depend on the length of withdrawal time required. In addition to a recorded list of identifying numbers, items such as colored neck chains, leg bands, marking chalk (NASCO, 901 Janesville Ave, Ft. Atkinson, WI 53538) and marking tape (Professional Tape Co, Inc, 144 Tower Drive, Burr Ridge [Hinsdale), IL 60521) (Fig. 3), should be employed, so that if a segregated animal finds its way into an untreated group or string, it can be readily recognized. Reference Point 4 The selection and recommendation of appropriate supplemental residue tests are probably the biggest problem faced by the practi-
634
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WARNING
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STERNER
WARNING
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THIS ANIMAL HAS BEEN TREATED WITH A MEDICATION THAT ~ PRODUCES A TEMPORARY RESIDUE ""3 > -< 0 DO NOT SELL MILK UNTIL AFTER: ~ ~ t::3 DO NOT SLAUGHTER UNTIL: ~~ -< ~ SUPPLIED BY-STERNER VETERINARY CLINIC P.C. E!; ~
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Figure 3.
Tail tape, to identify treated animals.
tioner attempting to avoid food product residues. First of all, there is no officially validated residue test available to the practitioner at this time. Efforts are under way to develop such validated tests for the producer and the practitioner, but they are some time away from official approval. Table 3 lists most of the currently marketed residue tests in the United States. The two that have found widest application in food animal practices are the Delvo SP test from Gist Brocades and the live-animal swab test (LAST) available from Granite Diagnostics (telephone, toll-free, at 1-800-334-1116). Recommendations to clients regarding the suitability of a cow's milk for shipment may create a significant financial liability for the practitioner if such recommendations cause a contamination of other milk. For that reason, careful consideration should be given before employing such tests for clients. The liability for an individual cull animal is generally much less than that for a tanker or silo of milk. I would, therefore, recommend submission of samples for clearance by the milk cooperative before shipment of a treated cow's milk. Reference Point 5 A reprint of the A VMA Guidelines is included in this article (see Fig. 1), and I suggest that every attempt be made to implement the recommendations in it.
PRACTITIONER COMPLIANCE In addition to the five points delineated previously, milk presents some unique residue problems for the practitioner at this time. The tolerance levels for nonapproved pharmaceuticals are zero. Zero is defined by our technological ability to define zero. Recent advances have made it possible to detect ever smaller quantities of compounds. Previous tests defined by parts per million (ppm) have given way to sensitivities of parts per billion (ppb), and now some tests are sensitive to parts per quadrillion (ppq)! Obviously, the dilemma here is that such very sensitive methodologies can greatly extend present withdrawal
Cite Delvo SP
N/A
IDEXX Corp. Gist-Brocades
Idetech
18 h 8h
High-pressure liquid chromatography (HPLC) Gas chromatography (GC), mass spectrometry
*Excludes capital equipment; quantity discounts may apply
Instrumental Unknown
Micro inhibition Micro inhibition Micro inhibition Instrumental Instrumental
$2.50
$2.80 $1.00/amp
$2.50 $7.50 $1.65 $1.35
ANTIBIOTIC
Penicillin Chloramphenicol Sulfonamide 7 families of antibiotic compounds Penicillin, sulfonamide Penicillin Sulfonamide Tetracycline Erythromycin Sulfamethazine Sulfamethazine Penicillin Penicillin G, Cephapirin, cloxacillin Sulfamethazine Penicillin Sulfonamide Sulfamethazine
Unknown
5h
Cylindrical plate
Neogen
Proscience
Other Methods 3h
10 ppb Pen/3 ppb Sulfon/500 -1 000 ppb s10 ppb
Immucel
EUSA
13 min
EUSA ELISA Enzyme Latex Agg. EUSA Micro
min min min min
<6 min 3h
30 <10 20 6
Bacillus stearothermophilus Bacillus subttlis
Interested Firms
Angenics
Signal Elisa (Int'I D.) Quik-Card (Env. D.) Penzyme Spot
$3.00 $ .90
Receptor Micro
9 min 3.5 h
Cowside CIA Pen/3 ppb Sulfon/5 - 20 ppb Tetra/250 ppb Eryth/200 ppb Sulfam/l0 ppb Sulfam/IO ppb Pen/5 ppb Pen/5 ppb
$1.80
Receptor
10 min
$1.90
Charm II
Pen/3 ppb Chlor/95 ppb Sulfon/l0 ppb
COST PER TEST·
Receptor
SENSITIVITY
12 min
TECHNOLOGY
TEST TIME
Charm I
TEST NAME
SmithKline
Penicillin Assays
TEST MARKETED BY
Table 3. Currently Marketed Residue Tests
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recommendations of approved compounds and the liability associated with extralabel drug use. When making specific recommendations to dairy clients for drug storage, veterinarians should keep in mind the need to comply with the language of the Pasteurized Milk Ordinance (PMO) under Items lr (Abnormal Milk) and 16r (Protection from Contamination) (see below). These rules are used by state regulatory agencies to enforce compliance with proper drug labeling and storage on dairy farms. Two samples of such labels are included (Figs. 4 and 5). The storage requirements are met by ensuring that all animal drugs that are stored in the milkhouse, parlor, milking barn, or adjacent areas be labeled and kept on separate or separated shelves that are also labeled for lactating cows and nonlactating cows. These labeling requirements apply to products stored in the refrigerator and to the refrigerator shelves as well. In our practice, we customarily label all drugs that we dispense so that they comply with the requirements of Items lr and 16r. The decision to apply a clinic label to drugs obtained elsewhere is a personal one, and I generally will not do it unless the client and I have reached a specific understanding regarding drug use and documentation. It is also a personal preference not to write prescriptions, since I feel it removes me from the VCPR and the treatment decision-making process associated with it. For clients who come into the clinic to pick up prescription products, the clinic staff is instructed to check the computer record file to be certain that they are authorized to receive such items. If clinic personnel are uncertain about any drug item requested by a client, they are instructed to contact one of the clinic veterinarians before dispensing. If no one is available, such products are not to be dispensed. Staff are instructed to apologize to the client but still not dispense the item. Most clients have been extremely cooperative with this policy, even when it has meant an inconvenience to them. If people do not have an account with our clinic, the staff are simply instructed to inform them of the need to first have a VCPR before any prescription products can be dispensed. GOVERNMENT ENFORCEMENT
There is a plethora of reasons contributing to the confusion of practitioners and clients over what should be done to ensure that livestock and their food products reach the marketplace free of residues. Part of the confusion stems from the regulatory process and those federal and state agencies charged with enforcement of the law. At this time, at the national level, there are three separate federal agencies regulating residues in milk and tissues. For tissues, the Food Safety Inspection Service (FSIS) branch of the United States Department of Agriculture (USDA) is the inspection and enforcement agency. For milk, enforcement is primarily overseen by the Center for Food Safety and Applied Nutrition (CFSAN) of the
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
637
Food and Drug Administration (FDA). Since 70 per cent of all milk produced in the United States enters interstate commerce, it is regulated by the National Conference of Interstate Milk Shippers (N CIMS), represented by all 50 states, and its published rules, called the Pasteurized Milk Ordinance (PMO). The Center for Veterinary Medicine (CVM) branch of the FDA is charged with setting the tolerance levels for pharmaceuticals, giving approvals and action levels for lactating cows. CFSAN is the enforcing agency, by means of the PMO. In this document, under the definitions of adulterated milk contained in Items lr (Abnormal Adulterated Milk) and 16r (Protection From Contamination) are found the enforcement authority. Item 1r - Abnonnal Adulterated Milk. cc Animals which show evidence of the secretion of abnormal milk in one or more quarters, based upon bacteriological, chemical, or physical examination, shall be milked last or with separate equipment, and the milk shall be discarded. Animals treated with, or which have consumed chemical, medicinal, or radioactive agents which, in the judgment of the regulatory agency, may be deleterious to human health, shall be milked last or with separate equipment and the milk disposed of as the regulatory agency may direct. Evidence of adulteration shall be predicated upon the presence of medicinals/drugs and chemicals not intended for use in treating dairy animals." Item 16r- Protection From Contamination "Milking and milk house operations, equipment, and facilities shall be located and conducted to prevent any contamination of milk, equipment containers, and utensils. No milk shall be strained, poured, transferred, or stored unless it is properly protected from contamination. " (Definitions from the 1989 proposed draft, NelMS; subject to approval.)
In order for a dairy to pass a Grade A inspection, it must have a score of 90 or more points. The failure of enough dairies to do so can result in the loss of a cooperative's right to interstate marketing of milk. The importance of having as many dairies as possible pass inspection cannot be overstated, and the more milk produced on a particular farm, the greater the importance of that particular farm's passing inspection. Veterinarians should make specific efforts to instruct their dairy clients on proper drug storage and labeling to ensure compliance with the memoranda of information (MI) from CFSAN. The PMO further reads as follows: "Medicinals/drugs are properly labeled to include (a) the name and address of the manufacturer, distributor, or veterinary practitioner dispensing the product; (b) directions for use and prescribed withholding times; (c) cautionary statements, if needed. Note: Topical antiseptics, 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 Sub Items 7 and 8 above."
It should be noted that proper labeling of drugs/medicines as defined by the PMO is slightly less detailed than those suggested in the AVMA guideline. Two sample labels that meet the requirements of the PMO are shown in Figures 4 and 5. They are usually printed on self-adhering labels and placed on all prescribed or dispensed medica-
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STERNER VETERINARY CUNIC PC 527 -3320 R#2 Ionia MI 48846 D a t e - - / - - / - - Exp_ __ Owner/Farm: ID#,_ __ MEDICATION: ___________________________________________ DIRECTIONS: Give cC's/holus/oz _ _ _ _ _ _times each day for days. _ _ _day Milk Hold/send sample Y / N _ _ _day Slaughter HoldjLAST TEST Y/N
Figure 4. Sample dispensing label, used to identify prescription or ELUD drugs stored on a dairy farm.
tions. Almost any computer/word processing software can be used to produce these labels. We must all recognize that while the primary focus of residue avoidance for the dairy practitioner is on milk, an equally important area of concern must be drug residues in tissue, since most dairy animals are marketed sooner or later. This concern extends from the neonatal veal calf to the dilapidated dairy cow. The same basic suggestions apply for tissue drug residue avoidance. Know and document what conditions exist and establish withdrawal recommendations based on the pharmaceutical(s) being used as well as the dosages administered. When withdrawal recommendations are in question, owing to ELUD, several options can be exercised. First, greatly extend the "hold" time before slaughter. Second, call the pharmaceutical manufacturer's technical services representatives. Occasionally, they can be of help in estimating reasonable tissue depletion timetables. Third, call FARAD and request information on the specific agent(s) used. Fourth, knowing the routes of excretion (see Table 2), run an appropriate
Lake Region Veterinary Center, Ltd. Elbow Lake, MN 56531 * 112 N. Cascade, Fergus Falls, MN 56537 Client/Town: Date: _ _/ _ _/ _ _ Animal(s) to be treated: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Medication: Expiration Date: _ _/ _ _ DOSAGE: Give cc· s IH SQ IV / oz / bolus / packets _ _ _ _ _ _times each day for consecutive days. DRUG WITHDRAWAL TIMES: Milk from treated animals must not be sold hours following the last treatment, nor can these during nor for animals be slaughtered for human food for days TEST FOR RESIDUES BEFORE PRODUcr MARKETING: Yes-/ No_ _/
Figure 5. Sample dispensing label, used to identify prescription or ELUD drugs stored on a dairy farm.
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
639
residue detection test. Although factors in the urine such as pH and osmolality can influence the positive or negative results to a signincant extent, these tests, nevertheless, represent responsible effort at residue avoidance. Recent articles in the Journal of the American Veterinary Medical Association (Vol. 194, No.7, April 1, 1989, pp 911-921) have raised concerns over the ability of the LAST test to detect certain compounds at the level of tissue tolerances set for them. At present, however, such tests represent the only means practically available to the practitioner for tissue avoidance recommendations. There is the promise of numerous residue avoidance tests being readied for marketing; unfortunately, few, if any, have been marketed yet or been subjected to critical neld evaluation. The food animal industry in the United States is at a crossroads; many interest groups have put agriculture under attack on many fronts, with agendas covering everything from animal rights to converting the entire population to vegetarianism. The intent of this article has been to address specinc practices and recommendations, with regard to residue avoidance in both tissues and milk of animal origin. At present, consumer concern over possible meat and milk contamination is exceeded only by the lack of understanding about production agriculture techniques. Perhaps, ultimately, the most effective role the veterinarian can play in assuaging these fears is to educate clients. This will help ensure that the livestock under our care are treated with the correct medication when necessary and the resulting food products appropriately withheld from market. We must be part of the solution, not the problem. Sterner Veterinary Clinic PC R #2, 821 N. Jefferson Street Ionia, MI 48846
0749-0720/89 $0.00
+ .20
The Practitioner's Role and Responsibility in Residue Avoidance Keith E. Sterner, DVM *
It is a sign of the times that my opening paragraph is a disclaimer. By the time this article is in print, some or all of the recommendations may be outmoded or superseded by events unforeseen at this writing. This article constitutes a sincere effort on my part to make recommendations to the practitioner that will help to assure a wholesome, safe food product. With this in mind, an explanation about the format and intent of the article is in order. The first few pages deal with specific recommendations for practitioners to employ in order to attempt to comply with current laws and regulations. They are purposely brief and without explanation to allow quick assimilation of the technical information. More detailed explanations and background information follow on subsequent pages.
FIVE POINTS OF COMPLIANCE Recommendations in order for practitioners to comply with government laws and regulations are as follow:
1. Establish and maintain valid veterinarian/client/patient relationships (VCPR). Be able to document or support evidence of such relationships. 2. As extralabel drug use occurs, maintain and keep records that allow for identification of treated animals and appropriate extended times for drug withdrawal, based on the compound(s) used - know the pharmacology of the drugs you are using. 3. Ensure that clients have some means of positively identifying and segregating treated animals as well as complying with drug labeling, storage, and treatment requirements. 4. Select and recommend appropriate supplemental residue tests ·President, American Association of Bovine Practitioners; Owner/Operator, Sterner Veterinary Clinic Professional Corporation, Ionia, Michigan
Veterinary Clinics of North America: Food Animal Practice-Vol. 5, No.3, Nov. 1989
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to be run before milk or animals are cleared for shipment. Keep in mind that many current on-farm or in-clinic residue tests do not detect violative drug residues from extralabel use. For milk, when in doubt, clear individual samples with the milk cooperative prior to sending the milk. 5. Familiarize yourself and your clinic staff with the AVMA Guidelines for Supervising Use and Distribution of Veterinary Prescription Drugs (a removable insert in the Journal of the American Veterinary Medical Association, Vol. 193, No.7, October 1, 1988; they are also published in the AVMA directory.) (Fig. 1). With regard to the five points of compliance, the following definitions and examples are offered: Reference Point 1 The Food and Drug Administration (FDA) has provided under its rules for extralabel drug use (ELUD), when certain conditions are met. This authority is not a statutory one but one rather allowed by regulatory policy of the FDA; in other words, the practitioner does not have the benefit of a specific law (statute) that allows such use. This ELUD is a policy of the FDA, and therefore subject to change by whatever agency is charged with enforcing the law. The caveat is that the veterinarian must assume liability if extralabel use results in drug residues or adverse reactions. Basic to extralabel drug use is a valid VCPR, which is defined as existing when A. 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 veterinarian's instructions. B. 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 is 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. C. The veterinarian is readily available for follow-up evaluation in the event of adverse reactions or failure of the treatment regimen. It is vital that the practitioner be able to document the VCPR, should there ever be a question with regard to ELUD. This can be best accomplished through client and practitioner record-keeping systems. Practitioners are strongly encouraged to develop and maintain such documentation. Many of the computerized billing systems now available can greatly facilitate the storage and recall of such records. Any practitioner in food animal practice should seriously consider adopting such a system.
617
AVMA Guidelines for Supervising Use and Distribution
of Veterinary Prescription Drugs
Figure 1. American Veterinary Medical Association guidelines for supervising the use and distribution of veterinary prescription drugs. (From J Am Vet Med Assoc 193(7), October 1, 1988; with permission.) (Illustration continued on following page)
618
Preface In an effort to assist practicing veterinarians who supervise the use and distribution of veterinary prescription drugs and over-the-counter drugs that, for clinical effectiveness, must be used in an extra-label manner, the Council on Biologic and Therapeutic Agents has developed the following guidelines. The guidelines were approved by the 1988 House of Delegates and are being published in a pull-out section that may be retained by the practitioner for easy reference. The guidelines were designed to heighten the practitioner's level of awareness on the subject and to promote appropriate animal drug use by practitioners as well as animal owners. The Council emphasizes that the guidelines must not be interpreted as hard and fast rules. Each practitioner must exercise sound clinical judgment as well as common sense when making decisions regarding the use of therapeutic agents, regardless of whether the drugs in question actually are being used or dispensed by the practitioner, or whether they are dispensed on the order of the veterinarian and used by the animal owner or his agent. The Council acknowledges the extensive efforts of Dr. Jack Morse, Turlock, Calif, who as a member of the Council, was a principal author of these guidelines. Fred W. Scott, Chairman Council on Biologic and Therapeutic Agents
2 Figure 1.
(Continued)
(Illustration continued on opposite page)
619
Table of Contents INTRODUCTION Nonprofessional Staff. . . . . . . . . . . . . . . . . . . . .. 4 Client Relationships . . . . . . . . . . . . . . . . . . . . . .. 4 Veterinary Prescription Drugs . . . . . . . . . . . . . . . .. 5 GUIDEUNES Veterinary Prescription Drugs Dispensed or Used by Veterinarians in Private Practice . . . . . . . . . . . Veterinary Prescription Drugs Delivered to Clients by Drug Distributors on the Order of a Veterinarian. . Veterinary Prescription Drugs Obtained from a Pharmacist on the Order of a Veterinarian . . . . . .
6 7 8
DEFINITIONS AND BACKGROUND Veterinary Prescription Drugs . . . . . . . . . . . . . . . .. 9 Extra-Label Use of Drugs . . . . . . . . . . . . . . . . . . . . 9 Veterinarian-Client-Patient Relationship . . . . . . . . . . . 10 Concept of a Veterinary Practice . . . . . . . . . . . . . . . 10 Dispensing Labels . . . . . . . . . . . . . . . . . . . . . .. 10 Veterinary Drug Orders . . . . . . . . . . . . . . . . . . . . 11
3 Figure 1.
(Continued)
(Illustration continued on following page)
620 INTRODUCTION Society is pressing for changes in the way animal drugs are distributed and used, because consumers are concerned that meat, milk, and eggs may contain harmful drug residues. Although food animal products of US origin are among the most wholesome and safe in the world, the perception of hazardous residues still exists in the minds of consumers because contaminants are occasionally detected. Unless the livestock industry, the pharmaceutical industry, drug distributors, and the veterinary profession work together to eliminate harmful residues, the possibility exists that, eventually, few drugs will be available for use in food animals. Despite health management techniques and disease prevention programs, there will always be a need for therapeutic drugs. Failure to act could result in further erosion of public confidence in the wholesomenE1ss of food animal products. I The veterinary profession should take the leadership in assuring a supply of meat, milk, and eggs that is free of harmful residues. Veterinarians can assume this responsibility if their proper role in supervising use and distribution of drugs used in food animals is recognized and supported by regulatory agencies, livestock owners, and pharmaceutical distributors. The veterinary profession must adhere to high ethical and scientific standards to merit this support. Nonprofessional Staff The guidelines for supervising veterinary prescription drugs dispensed by veterinarians in private practice are designed to decrease the possibility of inadvertent inappropriate dispensing by clinic staff, and to aid the staff in carrying out the veterinarian's instructions. Methods should be devised to assure that employees comply with instructions in the veterinarian's absence. Staff members authorized to dispense drugs should be properly trained. Because of potential confusion, veterinary prescription drugs labeled "Caution: Federal law restricts the drug to use by or on the order of a licensed veterinarian" should be segregated and identified with an easily noticed mark or sticker. Client Relationships Parts of these guidelines relate to the relationship between the veterinarian and the client and the client's employees. Of
4 Figure 1.
(Continued)
(Illustration continued on opposite page)
621 necessity, this relationship requires honesty, openness, and a commitment to a common cause. Owner treatment records decrease the possibility of violative residues, and comply with the FDA guide for preserving the identity of food animals treated with drugs used in an extra-label manner. Drug storage recommendations are made to protect children and unauthorized persons from access to potentially dangerous drugs. The additional set of instructions for veterinary prescription drug use will provide the client with another source of reference on proper drug usage. Labels on containers may become dirty and blurred through repeated use. Suggested ways to accommodate these additional instructions are clear plastic covers for instruction inserts that can be posted in the drug room area, loose-leaf notebooks for instructions, and computer printouts or farm or ranch visit reports posted under plastic.
Veterinary Prescription Drugs By FDA's definition, veterinary prescription drugs are those drugs restricted by federal law to use by or on the order of a licensed veterinarian. Any other drugs used in animals in a manner not in accordance with their labeling (extra-label uses) should be subjected to the same supervisory precautions that apply to veterinary prescription drugs. In this document, when the term "veterinary prescription drug" is used, the precautions noted apply to all drugs used for extra-label purposes as well as those defined by FDA to be veterinary prescription drugs. There are vast differences among types of practices, species of animals treated, and production-management circumstances. These guidelines provide a basis for responsible professional decisions. Each veterinarian must use clinical judgment, current medical information, good sense, and high ethical standards when applying them to practice situations. Veterinarians should be responsible for supervising use of veterinary prescription drugs that are dispensed or administered in the course of private practice, delivered to a client by drug distributors upon the veterinarian's order, or obtained from a pharmacist on the prescription of a veterinarian. For clarity, these guidelines are restated for each of the above situations.
5 Figure 1.
(Continued)
(Illustration continued on follOWing page)
622 GUIDELINES Veterinary Prescription Drugs Dispensed or Used by Veterinarians in Private Practice Veterinary prescription drugs should be dispensed only by or on the order of a licensed veterinarian in the presence of a valid veterinarian-client-patient relationship (VCPR). Nonprofessional staff may dispense veterinary prescription drugs only after receiving specific instructions from a veterinarian. Records should be maintained to show the prescription drugs that may be supplied to clients with whom a valid VCPR exists. Such records should indicate the veterinarian(s) who has the animals under his or her care. The dispensing of veterinary prescription drugs should be based on records and medical histories of animals seen or treated. The record of drugs that may be dispensed should not be changed without signed authorization of the responsible veterinarian, who should update each record no less often than on a quarterly basis. The drugs dispensed should be invoiced with the name and address of the client to provide records for follow-up evaluation, if needed. Training for all staff should be regular and effective to assure that veterinary prescription drugs are dispensed only on the order of a veterinarian, and only when a valid VCPR exists. Drugs labeled with the FDA precaution "for use by or on the order of a licensed veterinarian" should be stored separately from other drugs on the practice premises. These drugs should be clearly distinguishable and separated from over-the-counter drugs. They should not be openly displayed or be accessible to the public. Proper labeling should accompany all veterinary prescription drugs dispensed. Quantities dispensed should be no greater than needed for treatment of the animal, herd, or Hock. Clients should be advised that veterinary prescription drugs should be securely stored, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, including identification of animal(s), drug(s) used, routes of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. This could be in the form of a simple table or chart issued by the veterinarian. Instructions for the use of each veterinary prescription drug dispensed should be written by the veterinarian, when applicable. These instructions should be kept in the client's drug storage area.
6 Figure 1.
(Continued)
(Illustration continued on opposite page)
623 Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating. Records should be kept for at least two years when veterinary prescription drugs are dispensed or used in practice. Veterinary Prescription Drugs Delivered to Clients by Drug Distributors on the Order of a Veterinarian Orders issued by licensed veterinarians authorizing drug distributors to deliver veterinary prescription drugs to a specific client should be based on a valid VCPR and should contain the following information: • The veterinarian's name, address, telephone number, and license number (not DEA number) • Name and address of client • Species • Number and quantity of drug(s) to be delivered • Directions for use • Cautionary statements including, if applicable, expiration date and withdrawal time • Date of issue • Number of refills • Veterinarian's signature Drug orders must be initiated by the veterinarian, based on dialogue with the client or his agent. Requests coming directly from drug distributors are not within the bounds of a valid VCPR. Telephone orders require prompt completion and processing of the drug order form. When a drug order is issued, the quantity should be limited to an appropriate usage period. Clients should be instructed that veterinary prescription drugs should be securely stored, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, which would include identification of animal(s), drug(s) used, route of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. Additional instructions for use of each veterinary prescription drug should be written by the veterinarian. These instructions should be kept in the client's drug storage area. Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating.
7 Figure 1.
(Continued)
(Illustration continued on follOWing page)
624
Veterinarians should keep records of prescription drug orders for at least two years. Veterinary Prescription Drugs Obtained from a Pharmacist on the Order of a Veterinarian Prescriptions/orders issued by licensed veterinarians authorizing pharmacists to dispense veterinary prescription drugs to a specific client should be based on a valid VCPR and should contain the following information: • The veterinarian's name, address, telephone number, and license number (not DEA number) • Name and address of client • Species • Name and quantity of drug(s) • Directions for use • Cautionary statements including, if applicable, expiration date and withdrawal time • Date of issue • Number of refills • Signature of issuer (prescriber) The prescription/order must be initiated by the veterinarian from dialogue with the client or his agent. Requests coming directly from the pharmacist are not within the bounds of a valid VCPR. Telephone orders require prescription/order forms identical to written orders, with identical processing. Quantities prescribed/ordered should be limited to an appropriate usage period. Clients should be instructed that veterinary prescription drugs dispensed by the pharmacist should be stored securely, preferably under lock, with access limited to key personnel. Each client should be advised to keep a complete record of all animals treated, which would include identification of animal(s), drug(s) used, routes of administration, amounts used, duration of treatment, and final disposition of the animal(s), ie, date sold, returned to herd, or died. Instructions for use of each veterinary prescription drug dispensed by the pharmacist should be written by the veterinarian, when applicable. These instructions should be kept in the client's drug storage area. Ideally, these instructions, the drug storage area, and the drugs themselves should be examined at least quarterly with the client, to assure cleanliness, orderliness, purity, and nonexpired dating. 8 Figure 1.
(Continued)
(Illustration continued on opposite page)
625
Records of prescriptions/orders should be kept for at least two years.
DEFINITIONS AND BACKGROUND Veterinary Prescription Drugs According to FDA, drugs that, because of toxicity or other potential for harmful effect, or because of the method of use, cannot be approved for animal use except under the supervision of a veterinarian are classified as veterinary prescription drugs. The agency requires that such drugs be labeled with the statement "Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian." Phrases such as "For Veterinary Use Only," and "Sold to Veterinarians Only" do not refer to the drug's prescription status. For purposes of these guidelines, when any other drugs are used for extra-label purposes, they should be afforded the same precautions that apply to the FDA definition of a veterinary prescription drug. Extra-Label Use of Drugs Extra-label use means the administration or application of a drug in a manner that is not in accordance with the drug's labeling. Extra-label use of drugs in treating food-producing animals may be considered only in special circumstances. For such usage, the FDA specifies that the following criteria must be met: • A careful clinical diagnosis is made by an attending veterinarian within the context of a valid VCPR • A determination is made that there is no marketed drug specifically labeled to treat the condition diagnosed, or that treatment at the dosage recommended by the labeling has been found clinically ineffective • Procedures are instituted to assure that identity of the treated animals is carefully maintained • A significantly extended time period is assigned for drug withdrawal prior to marketing meat, milk, or eggs; steps are taken to assure that the assigned time frames are met; and no harmful residues occur Certain drugs (chloramphenicol, diethylstilbestrol, and dimetridazole) may not be used in treating food-producing animals even under the cited criteria.
9 Figure 1.
(Continued)
(Illustration continued on following page)
626 Veterinarian-Client-Patient Relationship The 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 veterinarian's 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 in the event of adverse reactions or failure of the treatment regimen. This definition of the VCPR is of necessity broad in scope. Its general terms are intended to apply to many types of practices covering several species of animals. Concept of a Veterinary Practice Veterinary prescription drugs are to be used, ordered, dispensed, or prescribed by the licensed veterinarian within the course of professional practice. This means the veterinarian is licensed or otherwise properly authorized under state law to practice veterinary medicine in the state, and that a valid VCPR exists. Veterinarians who are employees of drug manufacturers or distributors, or veterinarians who operate drug distributorships cannot legally sell veterinary prescription drugs or issue prescriptions or orders for such drugs outside the scope of a professional veterinary practice. Dispensing Labels All veterinary prescription drugs should be properly labeled when dispensed. The label should ordinarily contain information that would appear on a veterinarian's prescription/order to a pharmacist or drug distributor (see page 6). As long as the drug is properly identified, the above information may be supplied separately in writing in lieu of the dispensing label. 10 Figure 1.
(Continued)
(Illustration continued on opposite page)
627 Veterinary Drug Orders Orders authorizing pharmacists to dispense veterinary prescription drugs are called "prescriptions." There is no standard form for the "prescription," but information the prescription should include is specified in each state's pharmacy regulations and rules. Some states have reserved the term "prescription" as an order only a pharmacist may process. Additionally, some states have decreed that instructions to a person other than a pharmacist to dispense a veterinary prescription drug be called a "drug order." These guidelines enumerate the information the prescription or drug order should include, based on the usual requirements of boards of pharmacy, and should be adequate for trained pharmacists. This information may not be adequate for nonprofessionals. For example, Idaho has special requirements for dispensers who are not pharmacists or veterinarians. For any state without stringent qualifications for the nonprofessional processor of the veterinarian's order, a detailed order would be indicated. The veterinarian would retain the third copy, and the drug distributor the original, while the second copy would accompany the drugs delivered to the client. The drug order should be designed to provide the following information: Name and address of the client and evidence that the client understands and will follow directions given. N arne and address of the drug distributor, including evidence of the distributor's commitment that only those drugs listed at the strength and quantity noted on the order will be provided, that drugs will not be delivered after expiration of the order date, and that the drug order will be processed exactly as written by the veterinarian and no substitutions of a different brand or product will be made without consulting the issuing veterinarian. N arne and address of the issuing veterinarian, including his or her signature or other evidence that a valid VCPR exists with the client to whom the drugs are to be delivered, that written instructions on the use of the drugs have been provided to the client, and that the order mayor may not be refilled and, if so, the number of refills. The name of the drug(s) to be delivered, including the strength, unit size, and quantity. This should be a list of only those drugs to be delivered. Written instructions on the use and withdrawal times of the drugs listed. The date of issue and a statement that the order is void in 90 days. 11 Figure 1.
(Continued)
628
KEITH
E.
STERNER
Since a valid VCPR must exist to dispense veterinary prescription drugs, a sign conspicuously posted in the office may help to avoid problems with clients and non clients seeking to purchase these drugs. Such a sign (see J Am Vet Med Assoc 194:1018, 1989) might read FEDERAL LAW PROHIBITS THE DISPENSING OF CERTAIN MEDICATIONS WITHOUT EXAMINATION OR PRESCRIPTION. YOUR UNDERSTANDING IS APPRECIATED. Reference Point 2 In my experience, the keeping and maintaining of records that identify treated animals is best accomplished at each farm by means of a notebook system. A sample notebook page (Fig. 2) is included, which is designed to be as brief and as easy to follow as possible, allowing all medications and treatments given on the farm to be recorded along with the initials of the person administering the medication. Treatment sheets are subsequently filed by month and year so as to provide a permanent record of medications and treatments. An additional insert sheet is provided with this treatment record book, which lists recommended dosage schedules and the clinic's best estimate of an appropriate withdrawal time for different drugs when they are used in an extralabel fashion. Supplemental residue testing can also be recommended on this sheet when such testing is indicated. (Not all drugs used in an extralabel fashion have valid residue test methods available; therefore, such testing is not always indicated.) This sheet is designed to be replaced as new information and new technologies become available to the practice, with regard to residue avoidance. This sheet is not included here, since at present, there are no guidelines that can be provided without the risk of misinterpretation and subsequent liability. The FARAD (Food Animal Residue Avoidance Databank) is available to those practitioners wishing to obtain withdrawal information on extralabel drug use. This resource can be used to formulate withdrawal recommendations for ELUD and to provide information for making up a clinic guideline. Specific information can be obtained by calling one of three numbers: For eastern and southern regions of the country, the telephone number is (904) 392-4085. For the midwestern region, the number is (217) 333-3611 (this is also the National Animal Poison Control Center). For western areas, the number is (916) 752-7507. Information on both milk and meat drug withdrawal recommendations can be obtained from these FARAD centers. Larger feedlot operations have well-developed computer software available that can provide even more information. At present, I am unaware of any dairy software available for such purposes. Practitioners owe it to themselves and their clients to continually update and familiarize themselves with pathologic conditions and their causes commonly found in practice. Based on this knowledge, sound judgment can be exercised in the selection of pharmaceutical therapy to achieve a favorable therapeutic outcome (Table 1). Tables 1 and 2 provide some insight as to appropriate therapeutic
DATE
COWID#
CONDmON
TREATMENT
TEST yiN
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yiN
® yiN
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® yiN
TEST
Figure 2. Sample table, used to record all medications and treatments given on the farm. The initials of the person administering the medication or treatment are recorded in the first column (INTL).
INTL
STERNER VETERINARY CLINIC P.C. (616) 527·3320 821 N. Jefferson . Ionia, MI 48846
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Aerobic Aerobic Not applicable Anaerobic Facultative anaerobic Facultative anaerobic Facultative anaerobic Not applicable Facultative anaerobic Anaerobic Facultative anaerobic Facultative anaerobic Aerobic
Gram-negative Gram-negative Not applicable Gram-positive Gram-positive Gram-negative Gram-negative Not applicable Gram-positive Gram-negative Gram-negative Gram-negative Weakly gram-negative
Extracellular Extracellular Obligate intracellular Extracellular Facultative intracellular Extracellular Extracellular Attached to host cell membrane Extracellular Extracellular Extracellular Extracellular Extracellular
Bordetella Campylobacter Chlamydia Clostridia Corynebacterium Escherichia coli Enterobacter Eperythrozoon
Erysipelothrix Fusobacterium Hemophilus Klebsiella Leptospira
Facultative anaerobic Not applicable Anaerobic
Rod Rod Rod Rod Spirochete
Rod Rod Rod Rod
Rod Rod
Rod
Rod
SHAPE (IF APPLICABLE)
OXYGEN REQUIREMENTS
Gram-negative Not applicable Gram-negative
STAIN AFFINITY
Extracellular Obligate intracellular Extracell ular
ORGANISM LOCATION
Actinobacillus Anaplasma Bacteroides
BACTERIA
Table 1. Sensitivity Patterns of Bacteria PROBABLE SENSITIVITY
Variable Penicillin Variable Variable Streptomycin, tetracycline, penicillin
Variable Tetracycline Penicillin (except B. fragilis), lincomycin Variable Variable Tetracycline Penicillin Penicillin, • erythromycin Variable Variable Tetracycline, arsenicals
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Facultative anaerobic
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Aerobic Aerobic Not applicable
Spirochete
Coccus
Coccus
Rod Rod Rod Rod
Rod Rod
Penicillin (p-hemolytic streptococci) Variable
Variable
Variable Variable Tylosin, lincomycin, erythromycin, tetracycline Variable Variable Variable Variable Variable
1989; with permission.
From Langston VC, Davis LE: Factors to consider in the selection of antimicrobial drugs for therapy. Compend Contin Educ Pract Vet 11:357,
*Organism often resistant in vivo
Treponema
Streptococcus
Gram-positive
Variable Gram-negative Gram-negative Gram-negative Gram-negative
Facultative intracellular Extracellular Extracellular Extracellular Facultative intracellular or extracellular Extracellular or facultative intracellular Extracell ular
Nocardia Pasteurella Proteus Pseudomonas Salmonella
Staphylococcus
Gram-positive Acid-fast Not applicable
Facultative intracellular Facultative intracellular Attached to host cell membrane
Listeria Mycobacterium Mycoplasma
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Table 2.
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STERNER
Common Antimicrobial Drugs SENSITIVITY IN VITRO
DRUG
ACTION
Aminoglycosides (class)
Bacteriocidal
Cephalosporins (first generation) Erythromycin
Bacteriocidal
Lincomycin Nitrofurans Oxytetracycline Penicillin (class) Spectinomycin Sulfonamides Trimethoprimsulfadiazine
Tylosin
SITE OF ACTION
MECHANISM OF ACTION
30s ribosome subunit Protein synthesis; misreading of genetic code Inhibits cross-linkage Cell wall
Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits translocation Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits initiation Breakage of bacterial Bacteriocidal DNA DNA Bacteriostatic 30s ribosome subunit Protein synthesis; inhibits attachment of transfer RNA Bacteriocidal Cell wall Inhibits cross-linkage Bacteriostatic 30s ribosome subunit Protein synthesis; inhibits translocation Bacteriostatic Enzyme Inhibits folate synthesis Sulfadiazine inhibits Bacteriocidal Enzyme folate synthesis; trimethoprim competes for dihydrofolic acid reductase Bacteriostatic 50s ribosome subunit Protein synthesis; inhibits translocation
Cram-Positive
Sensitive Sensitive Sensitive Sensitive Sensitive Sensitive Sensitive Resistant Sensitive Sensitive
Sensitive
*Except B. fragilis fIn vivo efficacy not well established tOther agents usually preferred From Langston VC, Davis LE: Factors to consider in the selection of antimicrobial drugs for therapy. Compend Contin Educ Pract Vet 11:359, 1989; with permission.
regimens and selection of residue avoidance tests. I recommend that practitioners subscribe to and review the FDA Veterinarian for timely information on many drug issues, including new animal drug approvals, revised animal drug approvals, and approval withdrawals; this publication costs $5.00 per year and is available from the Superintendent of Documents, Government Printing Office, Washington DC, 204029371. Food animal practice is in a state of flux, and it is crucial to keep abreast of changes in this important area. The Lactating Cow. With regard to drug therapy in the lactating cow, there are two points to remember: A. There are only five antibiotics and one sulfonamide approved for parenteral administration: Penicillin, dihydrostreptomycin, erythromycin, ampicillin, amoxicillin and sulfadimethoxine. B. Extra-label drug use is often required for effective treatment. Any use of drugs in a dosage or formulation for purposes other than that listed on the label constitutes an extralabel drug usage. This is only allowed if the practitioner has a valid VCPR
633
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
SENSITIVITY IN VITRO
Anaerobes Gram-Negative Clostridial
Other
METABOLISMjExCRETION
Mycoplasmal Leptospiral Rickettsial
Sensitive
Resistant
Resistant
Sensitive
Varies
Sensitive
Sensitive·
Resistant
Sensitivet
Varies
Sensitive
Resistant
Sensitive
Sensitive
Sensitive
Liver
Primary Primary
Sensitivet
Sensitive
Secondary
Primary
Secondary
Primary
Primary
Sensitive
Sensitivef
Varies
Sensitivef
Varies Sensitive
Sensitive
Sensitive· Resistant·
Sensitivef
Sensitive Sensitive
Sensitive Sensitive
Renal
Sensitive
Primary
Secondary
Primary Primary Primary
Sensitivef
Resistant
Sensitive
Primary
Sensitive
Secondary
Primary
and if such extralabel drug usage does not result in residues in food or in adverse reactions. Reference Point 3 Point 3 ensures that the day-to-day procedures for compliance are being followed on the farms. Perhaps the single most common cause of violative residues is the failure of producers to properly identify and segregate treated animals. Periodic review of each client's methods is strongly recommended. The methods of identification employed should be aimed at ensuring that all personnel handling treated livestock can easily identify treated animals so as not to mix them in with the untreated population. The methods used will depend on the length of withdrawal time required. In addition to a recorded list of identifying numbers, items such as colored neck chains, leg bands, marking chalk (NASCO, 901 Janesville Ave, Ft. Atkinson, WI 53538) and marking tape (Professional Tape Co, Inc, 144 Tower Drive, Burr Ridge [Hinsdale), IL 60521) (Fig. 3), should be employed, so that if a segregated animal finds its way into an untreated group or string, it can be readily recognized. Reference Point 4 The selection and recommendation of appropriate supplemental residue tests are probably the biggest problem faced by the practi-
634
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KEITH
WARNING
WARNING
E.
STERNER
WARNING
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THIS ANIMAL HAS BEEN TREATED WITH A MEDICATION THAT ~ PRODUCES A TEMPORARY RESIDUE ""3 > -< 0 DO NOT SELL MILK UNTIL AFTER: ~ ~ t::3 DO NOT SLAUGHTER UNTIL: ~~ -< ~ SUPPLIED BY-STERNER VETERINARY CLINIC P.C. E!; ~
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Tail tape, to identify treated animals.
tioner attempting to avoid food product residues. First of all, there is no officially validated residue test available to the practitioner at this time. Efforts are under way to develop such validated tests for the producer and the practitioner, but they are some time away from official approval. Table 3 lists most of the currently marketed residue tests in the United States. The two that have found widest application in food animal practices are the Delvo SP test from Gist Brocades and the live-animal swab test (LAST) available from Granite Diagnostics (telephone, toll-free, at 1-800-334-1116). Recommendations to clients regarding the suitability of a cow's milk for shipment may create a significant financial liability for the practitioner if such recommendations cause a contamination of other milk. For that reason, careful consideration should be given before employing such tests for clients. The liability for an individual cull animal is generally much less than that for a tanker or silo of milk. I would, therefore, recommend submission of samples for clearance by the milk cooperative before shipment of a treated cow's milk. Reference Point 5 A reprint of the A VMA Guidelines is included in this article (see Fig. 1), and I suggest that every attempt be made to implement the recommendations in it.
PRACTITIONER COMPLIANCE In addition to the five points delineated previously, milk presents some unique residue problems for the practitioner at this time. The tolerance levels for nonapproved pharmaceuticals are zero. Zero is defined by our technological ability to define zero. Recent advances have made it possible to detect ever smaller quantities of compounds. Previous tests defined by parts per million (ppm) have given way to sensitivities of parts per billion (ppb), and now some tests are sensitive to parts per quadrillion (ppq)! Obviously, the dilemma here is that such very sensitive methodologies can greatly extend present withdrawal
Cite Delvo SP
N/A
IDEXX Corp. Gist-Brocades
Idetech
18 h 8h
High-pressure liquid chromatography (HPLC) Gas chromatography (GC), mass spectrometry
*Excludes capital equipment; quantity discounts may apply
Instrumental Unknown
Micro inhibition Micro inhibition Micro inhibition Instrumental Instrumental
$2.50
$2.80 $1.00/amp
$2.50 $7.50 $1.65 $1.35
ANTIBIOTIC
Penicillin Chloramphenicol Sulfonamide 7 families of antibiotic compounds Penicillin, sulfonamide Penicillin Sulfonamide Tetracycline Erythromycin Sulfamethazine Sulfamethazine Penicillin Penicillin G, Cephapirin, cloxacillin Sulfamethazine Penicillin Sulfonamide Sulfamethazine
Unknown
5h
Cylindrical plate
Neogen
Proscience
Other Methods 3h
10 ppb Pen/3 ppb Sulfon/500 -1 000 ppb s10 ppb
Immucel
EUSA
13 min
EUSA ELISA Enzyme Latex Agg. EUSA Micro
min min min min
<6 min 3h
30 <10 20 6
Bacillus stearothermophilus Bacillus subttlis
Interested Firms
Angenics
Signal Elisa (Int'I D.) Quik-Card (Env. D.) Penzyme Spot
$3.00 $ .90
Receptor Micro
9 min 3.5 h
Cowside CIA Pen/3 ppb Sulfon/5 - 20 ppb Tetra/250 ppb Eryth/200 ppb Sulfam/l0 ppb Sulfam/IO ppb Pen/5 ppb Pen/5 ppb
$1.80
Receptor
10 min
$1.90
Charm II
Pen/3 ppb Chlor/95 ppb Sulfon/l0 ppb
COST PER TEST·
Receptor
SENSITIVITY
12 min
TECHNOLOGY
TEST TIME
Charm I
TEST NAME
SmithKline
Penicillin Assays
TEST MARKETED BY
Table 3. Currently Marketed Residue Tests
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STERNER
recommendations of approved compounds and the liability associated with extralabel drug use. When making specific recommendations to dairy clients for drug storage, veterinarians should keep in mind the need to comply with the language of the Pasteurized Milk Ordinance (PMO) under Items lr (Abnormal Milk) and 16r (Protection from Contamination) (see below). These rules are used by state regulatory agencies to enforce compliance with proper drug labeling and storage on dairy farms. Two samples of such labels are included (Figs. 4 and 5). The storage requirements are met by ensuring that all animal drugs that are stored in the milkhouse, parlor, milking barn, or adjacent areas be labeled and kept on separate or separated shelves that are also labeled for lactating cows and nonlactating cows. These labeling requirements apply to products stored in the refrigerator and to the refrigerator shelves as well. In our practice, we customarily label all drugs that we dispense so that they comply with the requirements of Items lr and 16r. The decision to apply a clinic label to drugs obtained elsewhere is a personal one, and I generally will not do it unless the client and I have reached a specific understanding regarding drug use and documentation. It is also a personal preference not to write prescriptions, since I feel it removes me from the VCPR and the treatment decision-making process associated with it. For clients who come into the clinic to pick up prescription products, the clinic staff is instructed to check the computer record file to be certain that they are authorized to receive such items. If clinic personnel are uncertain about any drug item requested by a client, they are instructed to contact one of the clinic veterinarians before dispensing. If no one is available, such products are not to be dispensed. Staff are instructed to apologize to the client but still not dispense the item. Most clients have been extremely cooperative with this policy, even when it has meant an inconvenience to them. If people do not have an account with our clinic, the staff are simply instructed to inform them of the need to first have a VCPR before any prescription products can be dispensed. GOVERNMENT ENFORCEMENT
There is a plethora of reasons contributing to the confusion of practitioners and clients over what should be done to ensure that livestock and their food products reach the marketplace free of residues. Part of the confusion stems from the regulatory process and those federal and state agencies charged with enforcement of the law. At this time, at the national level, there are three separate federal agencies regulating residues in milk and tissues. For tissues, the Food Safety Inspection Service (FSIS) branch of the United States Department of Agriculture (USDA) is the inspection and enforcement agency. For milk, enforcement is primarily overseen by the Center for Food Safety and Applied Nutrition (CFSAN) of the
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
637
Food and Drug Administration (FDA). Since 70 per cent of all milk produced in the United States enters interstate commerce, it is regulated by the National Conference of Interstate Milk Shippers (N CIMS), represented by all 50 states, and its published rules, called the Pasteurized Milk Ordinance (PMO). The Center for Veterinary Medicine (CVM) branch of the FDA is charged with setting the tolerance levels for pharmaceuticals, giving approvals and action levels for lactating cows. CFSAN is the enforcing agency, by means of the PMO. In this document, under the definitions of adulterated milk contained in Items lr (Abnormal Adulterated Milk) and 16r (Protection From Contamination) are found the enforcement authority. Item 1r - Abnonnal Adulterated Milk. cc Animals which show evidence of the secretion of abnormal milk in one or more quarters, based upon bacteriological, chemical, or physical examination, shall be milked last or with separate equipment, and the milk shall be discarded. Animals treated with, or which have consumed chemical, medicinal, or radioactive agents which, in the judgment of the regulatory agency, may be deleterious to human health, shall be milked last or with separate equipment and the milk disposed of as the regulatory agency may direct. Evidence of adulteration shall be predicated upon the presence of medicinals/drugs and chemicals not intended for use in treating dairy animals." Item 16r- Protection From Contamination "Milking and milk house operations, equipment, and facilities shall be located and conducted to prevent any contamination of milk, equipment containers, and utensils. No milk shall be strained, poured, transferred, or stored unless it is properly protected from contamination. " (Definitions from the 1989 proposed draft, NelMS; subject to approval.)
In order for a dairy to pass a Grade A inspection, it must have a score of 90 or more points. The failure of enough dairies to do so can result in the loss of a cooperative's right to interstate marketing of milk. The importance of having as many dairies as possible pass inspection cannot be overstated, and the more milk produced on a particular farm, the greater the importance of that particular farm's passing inspection. Veterinarians should make specific efforts to instruct their dairy clients on proper drug storage and labeling to ensure compliance with the memoranda of information (MI) from CFSAN. The PMO further reads as follows: "Medicinals/drugs are properly labeled to include (a) the name and address of the manufacturer, distributor, or veterinary practitioner dispensing the product; (b) directions for use and prescribed withholding times; (c) cautionary statements, if needed. Note: Topical antiseptics, 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 Sub Items 7 and 8 above."
It should be noted that proper labeling of drugs/medicines as defined by the PMO is slightly less detailed than those suggested in the AVMA guideline. Two sample labels that meet the requirements of the PMO are shown in Figures 4 and 5. They are usually printed on self-adhering labels and placed on all prescribed or dispensed medica-
638
KEITH
E.
STERNER
STERNER VETERINARY CUNIC PC 527 -3320 R#2 Ionia MI 48846 D a t e - - / - - / - - Exp_ __ Owner/Farm: ID#,_ __ MEDICATION: ___________________________________________ DIRECTIONS: Give cC's/holus/oz _ _ _ _ _ _times each day for days. _ _ _day Milk Hold/send sample Y / N _ _ _day Slaughter HoldjLAST TEST Y/N
Figure 4. Sample dispensing label, used to identify prescription or ELUD drugs stored on a dairy farm.
tions. Almost any computer/word processing software can be used to produce these labels. We must all recognize that while the primary focus of residue avoidance for the dairy practitioner is on milk, an equally important area of concern must be drug residues in tissue, since most dairy animals are marketed sooner or later. This concern extends from the neonatal veal calf to the dilapidated dairy cow. The same basic suggestions apply for tissue drug residue avoidance. Know and document what conditions exist and establish withdrawal recommendations based on the pharmaceutical(s) being used as well as the dosages administered. When withdrawal recommendations are in question, owing to ELUD, several options can be exercised. First, greatly extend the "hold" time before slaughter. Second, call the pharmaceutical manufacturer's technical services representatives. Occasionally, they can be of help in estimating reasonable tissue depletion timetables. Third, call FARAD and request information on the specific agent(s) used. Fourth, knowing the routes of excretion (see Table 2), run an appropriate
Lake Region Veterinary Center, Ltd. Elbow Lake, MN 56531 * 112 N. Cascade, Fergus Falls, MN 56537 Client/Town: Date: _ _/ _ _/ _ _ Animal(s) to be treated: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Medication: Expiration Date: _ _/ _ _ DOSAGE: Give cc· s IH SQ IV / oz / bolus / packets _ _ _ _ _ _times each day for consecutive days. DRUG WITHDRAWAL TIMES: Milk from treated animals must not be sold hours following the last treatment, nor can these during nor for animals be slaughtered for human food for days TEST FOR RESIDUES BEFORE PRODUcr MARKETING: Yes-/ No_ _/
Figure 5. Sample dispensing label, used to identify prescription or ELUD drugs stored on a dairy farm.
THE PRACTITIONER'S ROLE IN RESIDUE AVOIDANCE
639
residue detection test. Although factors in the urine such as pH and osmolality can influence the positive or negative results to a signincant extent, these tests, nevertheless, represent responsible effort at residue avoidance. Recent articles in the Journal of the American Veterinary Medical Association (Vol. 194, No.7, April 1, 1989, pp 911-921) have raised concerns over the ability of the LAST test to detect certain compounds at the level of tissue tolerances set for them. At present, however, such tests represent the only means practically available to the practitioner for tissue avoidance recommendations. There is the promise of numerous residue avoidance tests being readied for marketing; unfortunately, few, if any, have been marketed yet or been subjected to critical neld evaluation. The food animal industry in the United States is at a crossroads; many interest groups have put agriculture under attack on many fronts, with agendas covering everything from animal rights to converting the entire population to vegetarianism. The intent of this article has been to address specinc practices and recommendations, with regard to residue avoidance in both tissues and milk of animal origin. At present, consumer concern over possible meat and milk contamination is exceeded only by the lack of understanding about production agriculture techniques. Perhaps, ultimately, the most effective role the veterinarian can play in assuaging these fears is to educate clients. This will help ensure that the livestock under our care are treated with the correct medication when necessary and the resulting food products appropriately withheld from market. We must be part of the solution, not the problem. Sterner Veterinary Clinic PC R #2, 821 N. Jefferson Street Ionia, MI 48846