|
Bulk Drug Use in Veterinary
Prescription Compounding
Island Pharmacy Services specializes in the
preparation of custom, compounded prescriptions. By definition, a
compounded drug is a unique formulation that is medically necessary because
commercial drugs either do not exist, or do not exist in the correct dosage
size or form. Often, one of the hardest parts of preparing a
compound is securing a source of the drug.
IPS is a licensed human pharmacy, and many of
the drugs we compound for pets are based on commercially available human
medications. Typically, a compound for a pet is a tiny fraction of the
human dose. After receiving the prescription, IPS uses its experience
and technology to precisely compound the exact dosage required in the form
that is easiest to administer. For pets, this may be a capsule, a
flavored liquid, or a transdermal gel. Human medications are most often
used in cases where the drug is patented, thus limiting our source to a single
manufacturer. In some other cases, generic drugs are used to lower the
final cost to the consumer.
However, in many cases there is NO manufactured
drug on which to base the compounded prescription. For example, IPS
routinely compounds many sizes of doses of potassium bromide. This drug
(also known as KBr) has not been used in humans for over 100 years.
There are NO manufactured doses of KBr available in the
US
. Yet it is extremely effective in controlling seizures in dogs, and is
routinely prescribed by veterinarians for this reason. Therefore, ALL of
the compounded prescriptions filled by IPS for KBr are prepared using
pharmaceutical-grade powder.
Another example is a liquid preparation of
metronidazole. This drug is readily available in large tablets. When a
patient needs a tiny dose in a liquid form IPS will compound it to match the
prescription. IPS does not use the inexpensive generic tablets
when compounding liquid doses of metronidazole because the drug is terribly
bitter. Instead, we use a variation called metronidazole benzoate.
This alternative (after we make the appropriate potency conversions here in
our lab) is an effective substitute and has the benefit of being insoluble –
meaning that the drug does NOT have the bitter taste of the base chemical.
Metronidazole benzoate is NOT used in any manufactured drugs; therefore ALL of
the compounded prescriptions filled by IPS for metronidazole liquid are
prepared by using pharmaceutical-grade powder.
All the above information is provided as
background to counter discrepancies in FDA regulations. In years past,
the FDA took the position that compounded prescriptions were “unapproved new
drugs”. The FDA is charged with controlling the release of new
drugs in the
US
, and the lengthy and expensive process that drug manufacturers must submit to
before having their new drugs approved actually finances the operation of the
FDA to a large extent. The FDA is then responsible for monitoring drug
manufacturers. The FDA, by its charter, has NO jurisdiction over
the practice of pharmacy. That responsibility belongs to the individual
states (Boards of Pharmacy.)
However, if the FDA can “reclassify” a pharmacy
as a manufacturer then it can assert jurisdiction. And in the past, all
the FDA had to do was accuse a compounding pharmacy of marketing an
“unapproved new drug” to claim this jurisdiction. It should
be obvious that a pharmacy that compounds a special dose for an individual
patient has not submitted this drug to the new drug application process (nor
invested tens of millions of dollars.) In the case of small fractions of
existing drugs, the compounded dose is not a new drug, but only a new
(and unique to that patient) dose of the drug. If the special dose was
available anywhere else there would be no reason for the doctor to
prescribe a special (and usually more expensive) compounded version.
In 1997, a law was passed by the US Congress
named the FDA Modernization Act (FDAMA.) This law had wide bipartisan
support, yet it still took many years to make its way through the legislative
process. Among many other things, this law corrected some outdated and
unenforceable policies of the FDA. It also recognized officially,
for the first time, the importance of compounded drugs to the practice of
medicine. The FDA was told by Congress in effect to “keep their noses
out of pharmacy”. A compounded prescription was defined to be
equally valid with a prescription for a drug “off the shelf”.
Compounding prescriptions did not make a pharmacy a manufacturer.
Compounding prescriptions was validated as a legitimate (if rarely practiced)
function of pharmacy. AND, compounding was legitimate as long as the
chemicals used in the preparations were obtained from FDA approved sources.
This meant that a pharmacy could compound a drug from either a manufactured
dose (brand name or generic) or a pharmaceutical- grade powder obtained from
an FDA approved source at the discretion of the pharmacist.
Unfortunately, this law also placed restrictions
on what a pharmacy could and could not say in advertisements about compounded
prescriptions. For example, pharmacies were prohibited under this new
law from listing any drugs they compounded. The FDA was forced to
grudgingly accept the practice of compounding but didn’t want pharmacies to be
able to tell anyone about it. You can see that this would make it
difficult to effectively advertise our services, and so a group of pharmacies
challenged the law in court and this advertising provision was found to be
unconstitutional. The FDA immediately sought to have this ruling
overturned in appeals court, but the ruling was again found to be valid.
The FDA then appealed to the US Supreme Court (one government bureaucracy
spending our tax dollars while tieing up another branch of government.)
The Supreme Court agreed with the appeals court that the advertising
restriction was unconstitutional. It also ruled that a single provision
of the law could not be removed without invalidating the entire law.
Therefore, the entire FDA Modernization Act was struck down.
Essentially, the Supreme Court threw the whole mess back in the lap of
Congress to pass a new law without the unconstitutional provisions.
Smarting from this rebuke, the FDA has sought to
publicize some of the old, outdated policies of the past. Pharmacies are
currently subject to some of the same unworkable and nonsensical policies of
decades ago, even though the practice of medicine in general (and veterinary
medicine in particular) has advanced dramatically.
One of these outdated policies states that
compounding for animals cannot be done based on “Bulk Chemicals”.
The underlying reason for this law probably has some validity. The FDA,
in addition to regulating drug manufacturers, is also charged with protecting
the safety of our food supply. And the FDA is very aggressive in
protecting this food supply from contamination by chemicals. Ranchers
are responsible for insuring that chemicals are not illegally given to
livestock, which would then pass on to human consumers. Pharmacies are
prohibited from supplying compounded drugs for use in food producing
animals. These regulations are designed to protect consumers from
unscrupulous persons introducing contaminated food products to the marketplace.
And, for these reasons, bulk drugs are prohibited for use in
compounding for animals – the FDA does not want pharmacies making up thousands
of doses of potentially harmful drugs for herds or flocks of animals.
At IPS, we wholeheartedly agree with the
prohibition of compounding for food producing animals. IPS does not
prepare any compounded drugs for food producing animals.
However, if we adhere to “the letter of the
law”, we are also prohibited from using bulk chemicals in compounding for ALL
animals, including your pets. This regulation has not been enforced in
the past and we do not expect it to be enforced in the future for several
reasons:
1. The
compounding that IPS does it primarily for pets and companion animals.
These include dogs and cats, birds and ferrets, rabbits and hamsters, etc.
IPS also compounds medications for zoo animals, pleasure horses, reptiles, and
just about any other type of pet you can imagine. NONE of these animals
have the slightest connection to the human food supply. NONE of the
compounded medications we supply have any chance of reaching the human food
supply. ALL of the compounds we prepare are individual prescriptions –
NOT prepared for mass distribution to herds or flocks of food animals.
For this reason, the FDA has NEVER restricted the compounding of
prescription medications for pets by IPS based on chemical powders.
2. The
term “bulk powders” is misleading. ALL of the hundreds of
chemicals that we keep in stock at IPS are obtained from FDA approved
suppliers. The vast majority of these chemicals are obtained in
quantities of 100 to 500 GRAMS – in other words, less than one pound.
These quantities can hardly be called “bulk”! It is
incorrect to envision our pharmacy buying pharmaceuticals in 500 pound drums.
The definition of a compounded drug is a unique prescription for an individual
patient. Many of these compounds are one of a kind, and contain a few
grams or milligrams of drugs. We obtain the smallest quantity of drug
possible to make the compound economically feasible for the pet owner.
For this reason, the FDA has NEVER challenged the small amounts of
drugs that we purchase and use in compounding for pets. Since nothing
has changed, the restriction of such purchases cannot be defended.
3.
Finally, the prohibition on compounding for animals using bulk drugs does not
extend to compounding for human patients. This is the crucial reason
this old policy has been unenforceable. Pharmacies can legally
compound for human patients using any FDA approved source of chemical.
In some cases, even if there is a generic drug available, we will use a bulk
powder because it is both less expensive and does not contain any fillers
found in manufactured doses. With so many people allergic to dyes and
fillers, this is an important area of compounding for our human patients.
In the examples cited earlier, we may be called
to compound a liquid suspension of metronidazole. Under the old policies
(which we have reverted back to after the overturning of the FDA Modernization
Act of 1997) we can legally compound this drug for a child with giardia.
As was pointed out previously, this compound is only possible using the bulk
metronidazole benzoate powder. However, we would be prohibited from
preparing the same compound for a cat.
It is also important to note that the grade of
chemicals used at IPS for compounding for animals is actually HUMAN GRADE.
In other words, we are required to use the same quality of drugs for pets as
for humans.
Obviously, there is something wrong with any
regulation that says compounding a drug for a child is not a problem, but
using the same drug for compounding a veterinary prescription is prohibited.
Because of this discrepancy, in the past, whenever the FDA has inspected IPS
we were assured in every instance that the FDA had NO interest
in any compounding we performed for pets. IPS keeps meticulous records
of every ingredient in every compound and NONE are “mass quantities” that
could be diverted to food animals.
The FDA acknowledges that this policy is
nonsensical, as well. The FDA’s “unofficial, unwritten” policy is
that they will use “regulatory discretion to allow compounding from bulk
chemicals when there is no drug in an FDA-approved formulation for the desired
route of administration. This applies to non-food animals alone”.
Note: As of October 2003, the Texas Board of Pharmacy has gone on record
stating that bulk chemicals are only restricted in compounding for food
producing animals.
Island Pharmacy Services has specialized in
prescription compounding exclusively since 1990. We want to assure our
patients that every compound is prepared accurately and legally. The
issue of compounding for animals using “bulk chemicals” is a loophole that was
previously addressed in the FDAMA. We are confident that eventually FDA
regulations will catch up with reality and again make logical sense. In
the mean time, the staff at IPS will be happy to answer any questions or
concerns you may have. You can continue to be assured that we use
chemicals obtained exclusively from FDA approved suppliers. These
chemicals ALL have Certificates of Analysis and expiration dates that we
strictly adhere to. Call the Compounding Specialists at IPS at
800-328-7060.
If you would like to make any comments on this
regulatory oversight of the FDA you may contact the following agencies:
Dr. Stephen Sundlof, Director
Center for Veterinary Medicine
U.S. FDA (HFV-1)
7500 Standish Place
Rockville, MD 20855
fax #: (301) 827-4401
You may copy any correspondence to:
Dr. Mark McClellan, MD, Ph.D., Commissioner
U.S. Food & Drug Administration fax #:
(301) 443-3100
Your Senators and Representatives
(Enter your Zip code at:
http://www.congress.org to find the names and fax numbers for your
Representatives and Senators.)
Dr. Michael Chaddock, DVM, Director
American Veterinary Medical Association
Government Relations Division
fax #: (202) 842-4360
Note: As of January 2004, the FDA has
received over 1,600 letters from concerned pharmacists, veterinarians, and pet
owners. In a related issue, Senator John Ensign from
Nevada
presented a vigorous defense of the need for compounding services at a
Congressional hearing to discuss proposed federal oversight of the
compounding pharmacy industry. Senator Ensign is a licensed veterinarian
who understands first hand the need for compounding and used it regularly in
his veterinary practice.
October 2004 update to the FDA policy on
compounding:
The FDA did not realize what a hornet’s nest of
controversy it had stirred up by using heavy-handed tactics against
compounding pharmacies. Both pharmacy groups and organized veterinary
medicine has been very vocal in any opposition to the right of pharmacies to
compound prescription drugs for nonfood-producing animals. The FDA bases
its stance on a CPG (Compliance Policy Guideline) that seeks to limit the use
of bulk drugs in compounding. By definition, a CPG is an internal
reference for FDA agents. A CPG does NOT have the force of law – it is
an internal document that has not received congressional approval. In
addition, CPG’s are also subject to public input before publication.
This was also not followed in the case of this “rule”.
After a June 7th meeting with
numerous congressional leaders, Senator Wayne Allard (himself a veterinarian)
issued the following statement, “I am disappointed the FDA didn’t seek any
public comment before issuing this rule. I am hopeful the FDA will
recognize its errors and will be taking the necessary steps to solicit public
comment and make appropriate changes to the guidelines.”
Senator Lindsey Graham and Representative
Charles Bass issued identical letters to FDA Acting Director Lester Crawford
requesting the agency withdraw its latest CPG. The letters included,
“Should the FDA demonstrate a compelling need to update the CPG, it should
first articulate this need and then issue a revised CPG in draft form for
public comment by stakeholders, allowing affected pharmacists and
veterinarians to provide feedback on the policy before it is implemented.
We recognize the vital role compounding plays in animal health and believe
that it is necessary to preserve access to compounded medication options for
animal patients,” the letters added.
Consequently, on July 12th in a
meeting with the FDA’s Center for Veterinary Medicine (CVM), pharmacy groups
received the admission that the CPG should have been first issued as a draft.
It was also indicated that the current CPG should be revised, and then open
for discussion before it is finalized. The CVM does not dispute that
there is some necessity for compounding from pure pharmaceutical ingredients
for non-food animals.
However, this “voluntary” backpedaling is not
sufficient for pharmacy groups. Therefore, on
September 27, 2004 , a
coalition of pharmacies filed suit against the FDA claiming that the agency is
illegally enforcing an arbitrary regulation it never had the authority to
issue. There are several key points to the suit. First, although
the FDA acknowledges that the CPG is not a law, the FDA continues to act as if
the CPG were law. Pharmacies have been inspected and threatened by
numerous FDA inspectors with no jurisdiction. The FDA has unilaterally
reserved for itself the right to attempt enforcement of non-statutory
regulations. Second, federal law specifically exempts any pharmacy that
complies with state regulations from FDA jurisdiction. All pharmacies
are licensed and regulated by their respective Boards of Pharmacy.
Existing FDA regulations specifically EXEMPT pharmacies and pharmacy practice
from FDA jurisdiction. And third, that the FDA’s course of action
directly contradicts the earlier court cases mentioned above. In this
earlier case, the US Supreme Court ruled that compounded drugs could not be
treated as “new drugs”, and thus were completely beyond the jurisdiction of
the FDA.
In fact, the FDA in its testimony before the
Supreme Court made the following statement: “Like certain off-label
uses, compounding in response to individual medical needs may have important
health benefits. It allows physicians and pharmacists to work together
to develop customized therapies for patients for whom commercially
manufactured drugs are not suitable for various medical reasons.”
The FDA also asserted, “However, because obtaining FDA approval of a new drug
is a costly process, requiring FDA approval of all drug products compounded by
pharmacies for the particular needs of an individual patient would, as a
practical matter, eliminate the practice of compounding, and thereby eliminate
the availability of compounded drugs for those patients who have no
alternative treatment.” The FDA also testified that the cost of
developing and obtaining approval of a new drug is “generally estimated to
exceed $200 million dollars.”
The Supreme Court agreed with the FDA and held:
“The Government also has an important interest, however, in permitting the
continuation of the practice of compounding so that patients with particular
needs may obtain medications suited to those needs. And it would not
make sense to require compounded drugs created to meet the unique needs of
individual patients to undergo the testing required for the new drug approval
process.”
Like some other pharmacies that compound for
veterinary patients, the FDA has also inspected Island Pharmacy Services.
NONE of the chemicals that we routinely use for the compounding of
veterinary prescriptions has been restricted. NONE of our
FDA-approved sources of chemicals has been restricted. We intend to
continue to practice pharmacy in the same way we have since 1990. At IPS
we adhere to ALL the regulations of the Board of Pharmacy of the State of
Wisconsin
. We are convinced that our specialty of veterinary compounding will
weather the current regulatory confusion at the FDA, and that we will continue
to be recognized as the leading compounding practice in the
US
.
|