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pharm
2/11/98
wilson (dvm, also has a law degree)

Due to a 
conflict, we're moving a lecture from 2/23 10 am to 2/24 10 am

These 
lectures on legal affairs pertaining to drugs are very important. 

He 
gives this lecture twice a year - here and at UCD. It's a vast subject. 
It's really important esp for food animal medicine people, and also b/c 
the FDA is enforcing the food drug and cosmetic act differently these 
days. We'll talk about FDA, DEA, etc.

US News and World Report 11/97: 
"Outbreak: danger in the food supply" re: salmonella in food. A vet in VT 
becomes a hero because he did vigorous testing to figure out why calves 
were dying instead of thinking they just had e.coli.

who is the client 
of the food animal vet? the producer or the consumer? well, both. food 
animal vets have to consider the producer's need and the consumer's 
needs. 

some vet from Iowa got a year in jail, some other vet got 21 mos 
in prison, some other guy got 10 mos - not to mention hefty fines upward 
of 100,000 - 200,000 and these guys all went to jail b/c they thought 
they could prescribe whatever they wanted for food animals. 

UCB 
wellness letter: imagine a world without any drug regulations - 
everything's OTC and you figure out your own doses - estrogen, 
testosterone, etc as well. Melatonin is currently marketed as a wonder 
substance but not regulated, b/c in the US it isn't a "drug." the FDA 
tries to protect us from unscrupulous marketeers selling drugs.


healthfood stores sell all kinds of things that are supposed to treat all 
kinds of illnesses - they're called "nutritional substances" and are not 
regulated by the FDA.

sources of information: handout "fda and the 
veterinarian"; chapter in "law and ethics of the veterinary profession" 
by Dr. Wilson - can get in library or bookstore. 

FDA Veterinarian:


FDA-CVM
Communication and education branch
HFV-12
7500 Standish Place

Rockville MD 2-855
http://www.cvm.fda.gov
301-594-1765 or 1769

310-594-4512 or 1807

the fda website is very useful.
now, the fda does 
want to hear from you re: adverse drug reactions.

we're going to start 
working our way through these issues now, following the outline. 

who 
does what? 

the FDA: regulates animal foods, animal health products, 
drugs. very different from the USDA! doesn't regulate vaccines, 
biologicals.

the USDA: regulates all biological products - vaccines, 
diagnostics, immunizing components of diagnostic kits, antitoxins. 

the 
EPA: regulates all topical medications, insecticides for use on 
animate/inanimate objects. eg, advantage, frontline

the DEA: regulates 
controlled drugs. the FDA regulates their dosages and labelling, and the 
DEA oversees the controls and tracking of use of the controlled drugs.


what is a drug? see p 8 of the booklet: 
article recognized in the 
official US Pharmacopeia, and articles intended for use in diagnosis, 
cure, mitigation, treatment, or prevention of disease in man or other 
animals; and articles other than food intended to affect the structure or 
any function of the body of man or other animals. it also includes 
articles intended for use as a component of a drug.

new animal drug: 
also p 8: any drug intended for use in animals other than man, the 
composition of which isn't generally recognized by experts as safe and 
effective for use under the conditions described under the labelling 

so 
basically everything we use is called a new animal drug.
note that it 
costs these days a minimum of about $200 million to get a drug on the 
market for the human population, and 10-20 mill for a new veterinary 
drug. this is why we don't see drugs for ferrets, rabbits, birds, etc - 
it's too expensive to get approval for those drugs in those spp, and 
return isn't there.
so we use human products, which is risky wrt food 
animals.

adulterated drugs: p 39:
products that are defective, unsafe, 
not shown to be safe, filthy, or made under unsanitary conditions, or 
made under procedures not complying with good mfrng practice regulations. 


so mixing drugs together is adulterating drugs, or compounding, and is 
frowned on by the FDA, because you don't know shelf life, safety, other 
parameters of the new mixture. also, once you've done this, you become 
the pharmacist - you lose the product liability coverage of the 
manufacturer. So, Dr. Wilson isn't a fan of mixing/compounding drugs - 
except for adding things to fluids for IV use. However, many 
practicioners make up their own drugs all the time, which is really a 
violation of federal law.

misbranded drugs: p 14: sale of a veterinary 
rx legend drug product to a layperson, except on an rx or on order of 
licensed practicioner, causes drug to be misbranded, b/c it fails to have 
appropriate instructions for use.

OTC drugs: P 12: FDA determines 
marketing status based on whether it is possible to prepare adequate 
instructions for use for a layperson to use the drugs safely and 
effectively.  products for which adequate directions for use can be 
written must be labelled for OTC use under existing law.

so that's why 
topical steroids, rogaine, ibuprofen, etc aren't prescription any more. 
so an OTC drug doesn't require a prescription.

legend or rx drugs: drugs 
for which instructions can't be prepared for laypeople are rx drugs. must 
bear legend "caution, federal law restricts this drug to use by or on the 
order of a licensed veterinarian."

now, that's not the same as "sold 
only to licensed veterinarians." also, it's not the same as "for 
veterinary use only." The only real Rx legend is the one quoted above - 
"caution, federal law restricts this drug to use by or on the order of a 
licensed veterinarian."

btw, a big issue in small animal medicine today 
is the request/demand by clients for Rx for heartgard, proban, advantage, 
interceptor, etc. many vets are saying no, not giving out the 
prescriptions. one bullheaded vet in PA refused to write Rx for his 
clients...but the thing is, if you do that, you'll probably lose your 
license. you can't withold a prescription. you have to give a 
prescription if requested. many veterinarians want the sale, or want to 
control the dispensing of the product, but they're not allowed to do that 
- it's unprofessional conduct. 

dispensing Rx products - p 14
defining 
the veterinary-client-patient-relationship - p 15. if you're going to 
prescribe and rx drug, you have to have a valid V-C-P relationship. 
what's that? 1. the vet has assumed responsibility for making medical 
judgement and need for treatment and client has agreed to follow 
instructions. 2. sufficient knowledge of the animals to initiate at least 
a general or preliminary dx. in large animals, that means you've been to 
farm, seen herd, are familiar with them, and so forth. then if the farmer 
calls you next month and says "we hae the same problem again" can you 
prescribe without going back to the farm? yes. you're familiar with them. 
you could go out as far as a year without seeing the herd, but in large 
animals you have to worry about tissue residue, and you have to talk 
about withdrawal times, and you may have to go back sooner to review this 
with management. also keep in mind that horses are food animals - 25% of 
horses slaughtered here get shipped to france as food!! what about in 
small animal practice? you prescribe phenobarb for a seizuring dog. 
client calls for refill after 6 mos. at that point, do you have to see 
the dog again? in general, for small animals, the time frame is 1 yr or 
less. for cytoxan, maybe it's 3 wks. for soloxine, you can maybe give a 
year, without having to see the animal. so those are kind of the rules. 
depends on toxicity and usage of the drug. also 3. practicing vet must be 
readily available for follow-up in case of adverse rxns. what about those 
roving vaccine clinics? they aren't available for follow up. many states 
have enforced rules for these high volume low contact services, so they 
have to give out an 800 number or something. also in many states, 4. you 
must have medical records to support that you have this VCP-R.

q: what 
about town run rabies clinics: well the USDA regulates that. they don't 
require a VCP-R. if a state requires it, you have a vet do a PE, but 
there's no USDA requirement for a VCP-R. 

why is that the case? 
biologicals don't have tissue residues. 

compounding drugs: p 19: hot 
topic for FDA. there was a big case in AZ of a vet who was compounding 
and selling to feedlots 1-2 million bucks worth of stuff a year. they 
were mixing it in tubs by migrant workers or something. this was 
challenged. the FDA was really concerned b/c it was horribly abused by 
food animal practicioners all over the US. the vet lost, big time. every 
calf on this farm was getting abx "preventively" - a whole lot of drugs. 
since then we've seen the whole issue reformulated. it says in the book: 
compounding of drugs is not permitted by the act. courts of appeal have 
held that bulk drugs may not be sold to vets for compounding. practice of 
vet med requires products to treat many species, etc and vets need drugs 
to treat conditions for which there is no FDA approved product


compounding: manipulation of drug formulations to produce a dosage form 
other than that on the label. 

compliance policy guide (in notes): the 
agency acknowledges that there has to be compounding. p 1 says that 
adverse rxns and animal deaths have been caused by compounding. there was 
a company compounding an opthalmic ointment for use in humans and it got 
contaminated and people got all these infections. this is a problem. p 2 
of the guide defines compounding in the right hand column. then it says 
in 3rd paragraph right side - compounding not subject to regulatory 
action follows this criteria:  p3: the agency will exercise regulatory 
discretion and ordinarily wouldn't take action against compounding 
unapproved new animal drug if it is necessary and a legitimate medical 
need is identified, animal's life is threatened, or it is suffering; 
there is a need for an appropriate dosage regimen for species, or size; 
and there is no marketed animal drug which when used as labelled or in 
extralabel manner, will fill the need. so: legitimate need, nothing else 
available, etc.

also 1. dispensing should be within a VCP-R, 
professional assistance is required when the compounding is beyond the 
scope of the vet's knowledge and faacilities. this is a red flag. be 
careful! also, the vet has to take measures to avoid food animal 
residues, known incompatibilities, etc. if a vet you work with was 
creating/compounding drugs, and didn't have a textbook on the premises 
about known drug incompatibilities, you'd be in violation. also you must 
minimize people's exposure to these drugs, and you must keep good 
records, and if you do this, all drugs dispensed must bear clear 
labelling instructions -
lots of stuff on label. this is critical in 
large animal practice. 

on p 5 of guide in notes - in general, agency 
places highest regulatory priority on compounding drugs for use in food 
animals - whole bunch of criteria. compounding of medicaments that are 
essentially the same as approved products must be avoided unless 
legitimate need can be shown. 

p 6 part C - high regulatory priority 
given to situations where animals are harmed or safety is compromised - 
as in failing to use sterility where sterility is indicated, like using 
oral meds IV.

right column of p 6 - compounding for nonfood animals or 
minor food animal use - includes common practices (like mixing ket/val, 
IV fluids, creating doses for bedside use eg to tx tiny kitten, etc) is 
acceptable - low regulatory priority. 
compounding from bulk drugs for 
use in nonfood animals, including those in public and private aquaria


guidance: warning letter is usually the first action against an offender. 
unless there's some kind of horrendous violation. 

the FDA Veterinarian 
- newsletter sent out by FDA. they always list regulatory activities - 
publish list of people/companies who got warning letters.
hope you don't 
appear in there!

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someone asked: what's the difference b/w 
compounding and adulteration of drugs? they are similar. they used to 
define only adulteration, not compounding. then, the FDA realized there 
was this overlap. we have to allow for some compounding.

pharmaceutical 
firms won't make drugs if they can't get return on their investment.


extralabel use: use of an FDA approved drug in a manner other than that 
which is approved by FDA to be printed on label or product insert. also 
called "off label" use. 

about 9 yrs ago or 10 yrs ago, when this whole 
extralabel doctrine was created... see p 20 of FDA booklet - discussion 
of this in food producing animals. it says anyone producing or marketing 
food animals who could be shown to have caused drug residues through 
extralabel use is subject to regulatory action. in contrast, in nonfood 
producing animals, vets can consider extralabel use without being subject 
to regulatory action.

for food animals, extralabel use can be considered 
only when: there's a VCP-r, there's no other drug to use (no marketed 
drug out there, or the labelled drug is ineffective at approved dose), 
procedures are instituted to assure that identity of the treated animals 
is carefully maintained, and there is enough time for drug withdrawal, 
and any prescribed or dispensed extralabel drug has labeling information 
as per p 22.

during break someone came up and told dr wilson that she 
was at AVMA gov't relations office, and that half the time there they 
were dealing with all this stuff. the AVMA wishes more people got taught 
this stuff in vet school. note that without the AVMA we'd be lost, their 
office in washington DC is really important. 

p 22 - exempting criteria 
do not include drug use in treating food producing animals by the laymen!


note re: labelling requirements - a lot of state boards have strict 
labelling requirements as well. many vets are not in compliance with 
labelling laws.

moving on.

prohibited drugs:
p 23 of the little fda 
booklet
there's a list - chloramphenicol, clenbuterol, 
diethylstilbesterol, dimtridazole, ipronidazole, other nitroimidazole, 
furazolidone (except topical), nitrofurazone (except topical), and as of 
may 1997 fluoroquinolones or glycopeptides except as labelled.

now, 
salmonella typhimurium DT 104 is resistant to every antibiotic except the 
fluoroquinolones. the FDA doesn't want to risk creating fluoroquinolone 
resistant animals. 

unapproved drugs: drugs that have never been through 
FDA regulatory process - may have been made in US or overseas. smuggled 
in. used a lot in companion birds :). these drugs my be approved in 
spain, germany, canada, or whatever. they're illegal here. many exotic 
animal vets need to use these drugs, but the only source is illegal. it's 
bad. you can apply to use it under some investigative use thingy. exotic 
animal vets have a big dilemma. 

human labelled drugs p 24 - they work 
fine in humans, haven't been tested in animals for residue 
depletion/withdrawal times. most veterinary use of these drugs occurs in 
nonfood animal practice and the FDA refrains from taking action in these 
cases. but on p 26- if human labelled drug is only one available for use 
in food animals, it has to meet this list of criteria. basically hs to 
ensure there rae no other options, and make sure to ensure no residues, 
and stuff. 

q: what's your liability wrt withdrawal times? if you tell 
your client they have to wait a certain time and they fail to do so, 
what's your liability? what if a whole truckload of milk is contaminated 
because the farmer doesn't follow your instructions, and then claims you 
never told him about it? how do you prove that you told him? usually by 
some written document. that's why it needs to be on the label. proof vs 
truth is always a problem.

label requirements - big section in the law 
and ethics book - p 223. label requirements generally come from state 
veterinary board of examiners and will be in the regulations. most state 
boards, including CA, now test about laws and regional differences in 
diseases. CA has phased out their nearly impossible board exam.

PPPA: 
poison prevention packaging act: textbook p 234
you know those little 
white envelopes to dispense pills that some vets use? that's rediculous, 
unprofessional, you can't label it, there's no protection against anyone 
eating the envelope like a kid or a dog or something. many states require 
using pill vials that are child resistant. liability is huge. if a kid 
eats a packet of lanoxin or something, you're busted. even though PA 
doesn't require childproof containers. yes, it costs more to buy the 
right packaging, but you really should. there are no national laws re: 
packaging of veterinary products, except iron containing products should 
have appropriate packaging. there are some state laws, though. 

adverse 
drug rxns: p 28 of FDA guide - you can even call the FDA collect if you 
have a veterinary adverse drug rxn - they want to know about it. you can 
download a form from the website to send it in to them. the FDA publishes 
in the FDA newsletter all of the known adverse rxns reported to the FDA. 
so you might look at it and see the three reports where 9 dogs where 
treated with acepromazine, and 4 died - prolonged anesthetic recovery, 
etc. 

there was just a big deal with the recall of Phen/Fen - due to 
heart valve problems in humans. see, when you get your drugs approved, 
you haven't tested on such a huge population.

there's also a citation to 
check the JAVMA article that discusses human vs vet reporting of adverse 
rxn.

product liability: p 236-42 of law and ethics book. implied 
warrantees etc. as long as you're using drugs per label, if there's an 
adverse rxn, the manufacturer is the primary liable party. if you used 
DES and your daughter got cervical cancer, the manufacturer is liable. if 
you use it extralabel, you have to argue about it.

nonstandard 
treatments - as animal's condition gets more hopeless, you get more 
leeway wrt providing nonstandard treatments. you can refer to notes from 
school, journal articles, etc. scientific proceedings from seminars, etc. 
some sort of substantiating evidence should be obtained.

client consents 
and use of drugs
use of psychotropic drugs in animals (none of which are 
approved for use in animals) - you should use consent forms. if you are 
concerned about treating an aggressive animal and having owner get bitten 
and then blaming the drug...argh.

factors influencing need for client 
consent re: use of drugs in animal: this means when do you need a form 
filled out or something:

age and physical condition - if animal is 
really old
likelihood of adverse effects - eg, animals on chemo doses of 
pred will pee in the house - you should warn the client so they don't try 
to sue you for cost of carpets.
pu/pd, v/d/allergies, immunosuppression, 
death - all should be red flags
also if patient is used for breeding.


DEA:

someone asked dr wilson about some issues - a vet had a history of 
two misdemeanor marijuana charges - once in 1989 in Tuscon AZ where he'd 
been smoking a joint. then, in july 1993, he got arrested in UT with the 
same friend for the same crime. he paid a fine. the UT justice people 
said after 3 yrs they'd expunge the crime. as of october 1993, he stopped 
using drugs. now, he's trying to get his licenses and he's really worried 
that he won't be able to get his veterinary or DEA registration.  you 
have to tell them if you've ever been convicted of a drug related crime. 
if you've been convicted - list your convictions, tell them the whole 
story, explain the whole circumstances, and indicate that you are now 
clean and have been clean for years. don't mess with the DEA. 

law and 
ethics book, chapter 11. 

classifying: p 263-64.

controlled substances 
are those drugs subject to abuse, classed under schedule I to V. I = high 
potential for abuse - peyote, heroin, mescaline - no justified use. 
schedule II: high potential for abuse, morphine, dilaudid, demerol - used 
medically. III: anabolic steroids, winstrol V, testosterone, nandrolone, 
hycodan, tylenol w/codeine. IV: valium, butorphanol, V: lomotil, 
robitussin AC, etc. it's ll based on potential for abuse.

who has to 
register with the DEA? if you dispense controlled drugs you need to 
register. this includes administration - but if you work for someone who 
has registered, you can dispense or administer from their drugs as an 
agent of the employer and not register. registration costs $210 for 3 
yrs. to *prescribe* controlled drugs, you have to have your own DEA 
registration number. 
in your senior year, dr wilson will give you an 
application for a DEA registration number. once you have your license, 
you can apply. 
who can administer? anyone working as an agent of the 
registrant.

note: say you work in a 6 dr practice. you have a patient. 
you want to rx a controlled drug. you do it. now, if you don't have a DEA 
registration number, you get one of the other docs to write the script 
for you. you dispense hycodan, or whatever. you do it as an agent of your 
employer. now, the client calls in for a refill when you're not there. 
another doctor gets stuck with the case. he doens't have a 
vet-client-patient relationship. can he refill it? the DEA rules sort of 
take second place. as long as it's ok under FDA rules, since someone else 
in the practice has seen the animal within a reasonable time frame, then 
it's ok. but, when the client tries to get drugs in excess of actual 
usage, you have problems. 

when you're worried about clients using the 
drugs, you have to talk to the client and explain how many pills per 
months the animals can have, and say that they can only have a certain 
number and that's it. 

ordering these drugs: you get a form with all 
these carbons in it. you check off the schedule boxes, put down your 
license numbers, list your convictions, etc. then you get your DEA 
number.
then to order the drugs, you fill out a special form and you hve 
to have it perfect, because if one thing is wrong, they will reject the 
whole form. it's in triplicate or quadruplicate. you keep a copy, and 
everyone else gets a copy too.

record keeping - a big pain. you can keep 
computer generated records - PSI/Idexx made a really nice module for 
tracking inventory of controlled drugs. most practices don't use this 
right now, but maybe when we're out there...
you also use a controlled 
drug log. the logs show the staff that you're tracking this stuff! vets 
and techs DO abuse drugs. they need to know that the stuff is being 
closely monitored. if you don't do this, a) you're in violation of DEA 
laws, and b) people will steal your drugs. a bottle of valium is worth 
like $100 on the street. dilaudid goes for about - a $38 bottle from a 
pharmacy with 100 tablets will go for $7500 on the street! some people 
prefer it over heroin and cocaine. yikes!

inventories - have to track 
inventory. failure to do this is violation of federal law with penalties


theft/loss- you have to fill out another form, surprise surprise. you 
have to fill out this whole crime report and what drugs were stolen and 
so forth. 

many practices aren't in compliance with recordkeeping rules. 

re: testing: stuff from lecture will be on the test - you don't have to 
get the book. know about DEA registration. don't go read his book.


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