Update April 12, 2007 (Includes correspondance with FDA/CVM)

Posted to EC List 4/12/2007 Msg #90108

Below is the early stages of an exchange with the FDA. Bottom line
situation here is that the compounded pergolide most of you rely on
is, according to an FDA policy statement, illegal.

http://www.fda.gov/ora/compliance_ref/cpg/cpgvet/cpg608-400.html

The FDA cannot police every compounding pharmacy, but they can more
easily target the wholesalers. The wholesalers know this. No
wholesale shipments, no drug available to the compounders.

The FDA has proposed two solutions which appear below. One is to
convince the prior pill manufacturers to produce the drug for
veterinary use. This hasn't happened yet, and if it does it will be
the ONLY legal source of pergolide and your costs will more than
likely go up. Second option is to have your veterinarian petition the
FDA for an urgent need exemption for use of pergolide in your horse:

http://www.fda.gov/cvm/Policy_Procedures/4170.pdf


Since compounding from bulk is the only available option at the
moment, they would have to grant that permission but so far are
offering it only on a case by case basis. Considering the thousands
of horses that are probably on it, there's a chance that if we get
the ball rolling with these petitions they will quickly see the size
of the need and publish an exemption that allows bulk compounding of
pergolide for horses. This is a link to the process of getting an
exemption for an individual horse:

http://www.fda.gov/cvm/Policy_Procedures/4170.pdf

Urge your vets to do this.

Third thing is that I have sent a letter and background information
to every state's Board of Pharmacy. The FDA Compliance Guidelines
reference two court decisions that upheld the illegality of
compounding from bulk drugs. However, a recent Federal Court decision
in Texas found that it was legal. We can't wait for the courts to
hash it out, but the differences of opinion do leave the door open
for any individual state to make an exception. Susie Gordon found a
roster of state pharmacy boards yesterday. All the e-mails work. I
just put it up as a .pdf file. Anyone with a horse that needs
pergolide should contact your state board and let them know. Ask your
vets to do the same. If we keep the pressure on, there should be some
resolution of this before supplies disappear.

We need to keep the petition Kellie put up rolling too. It's the
documentation of need. Kellie is adding the FDA Ombudsman and all the
state pharmacy boards to her list of people that get copies of the
signatures every few days. Contact your local horse groups, 4-H
clubs, breed organizations - anyone you can think of. Send them to
the library to sign if you have to, but keep the signatures coming.

We can do this!

OK, below is a mail I put up on a vets' list this morning. It has the
exchange with the FDA in it, and what I wrote on that list.

Eleanor

Below is a copy of the first stages of an exchange with the FDA
regarding pergolide. It is important to remember that the pergolide
compounded from bulk drug that most are using is actually an illegal
product. The FDA does not have the manpower to police every
compounding pharmacy, but they can keep track of what goes into and
out of a handful of wholesale supply houses. Now that there is no
longer any legal market for the drug, the supply will dry up.

The first option the FDA suggested was to convince manufacturers of
the pills to resume production. So far, they're not interested in
doing that. Maybe with FDA intervention they will. However, in that
case the only option will be the manufactured pills, likely to
considerably increase the cost to owners.

Their second suggestion was for individual veterinarians to petition
for a medically necessary veterinary drug exemption which, if I am
understanding her correctly, would need to be done on a case by case
basis. This could be an agonizingly slow and laborious process but
if it comes to that I wanted all of you to know there may be hoops to
jump through before you can get pergolide to your clients. Since
there aren't any other options, you could be granted permission to
use bulk compounded pergolide - assuming your compounder could get
it.

I'm hoping that the sheer magnitude of the need will lead to the FDA
publishing a specific exemption for compounding of pergolide from
bulk sources for use in horses with PPID, although that's probably
the last thing they want to do.

Letters and background information have also been sent to each
state's board of pharmacy, to hopefully open the door for exemptions
on a state by state basis. The 1994 AMDUCA legislation permitting
compounding did not specifically mention compounding from bulk drug
one way or the other. The compliance guidelines are FDA policy
statements, not law. They reference two court decisions that upheld
the ban on compounding from bulk drug, but a recent decision in a
Texas federal court ruled that veterinary compounding from bulk drug
was not illegal.

Eleanor M. Kellon, V.M.D.
Equine Nutritional Solutions
58 Maple Farm Road
Ephrata, PA 17522


-----Original Message-----
From: drkellon@aol.com
To: marcia.larkins@fda.hhs.gov
Sent: Thu, 12 Apr 2007 8:35 AM
Subject: Re: Urgent Matter


Dear Dr. Larkins,

Thank you for your reply.

To date, none of the previous manufacturers of pergolide mesylate
tablets has expressed an interest in continued production of the drug
for veterinary use. One of the reasons for the petition at

http://www.ipetitions.com/petition/savepergolide/index.html

which currently has almost 1400 signatures from both owners and
veterinarians, was to document that there is, indeed, a sizeable
market and need. We are periodically sending the previous
manufacturers spread sheet copies of the signatures. That option has
not opened up to us so far, but we will keep trying.

As for your second option, I will notify owners and veterinarians of
this pathway. However, given the number of horses involved and their
need to continue medication without interruption, I have a few
questions.

How long does the case review process take? That is, if veterinarians
were to wait until they actually had no other options, how long could
they expect to be without medication until a solution is achieved?

In the event manufacturers continue to express no interest in
resuming production, there would be no legal options available
according to Sec 608.400, CPG 7125.40 which specifically prohibits
compounding from bulk drug substances. Am I correct in assuming that
if the pharmaceutical industry continues to have no interest that
permission to use pergolide compounded from bulk drug may be granted
on a case by case basis, or does "case by case" actually mean for a
particular drug rather than each individual animal? Is there a way
the veterinary community at large could help expedite this process
for all horses with the need, rather than on an individual basis?
Would publishing a specific exemption for compounding of pergolide
from bulk drug for use in horses with PPID/Cushing's disease be a
viable option?

Use of pergolide in horses, a nonfood animal, poses no threat to
human health, and is of no environmental concern. We feel the
petition, which represents only a fraction of the horses impacted,
establishes the need and with voluntary withdrawal of the drug by
prior manufacturers we have a de facto loss of availability and no
approved avenues for obtaining it. Please advise whether individual
veterinarians/practices should begin the MNVP process for their
patients, or if there is a way this can be resolved on a larger scale.

Thank you.

Eleanor M. Kellon, V.M.D.
Equine Nutritional Solutions
58 Maple Farm Road
Ephrata, PA 17522


-----Original Message-----
From: marcia.larkins@fda.hhs.gov
To: drkellon@aol.com
Sent: Wed, 11 Apr 2007 7:01 PM
Subject: RE: Urgent Matter


Dear Dr. Kellon,

I have spoken with a staff member in the Division of Compliance
concerning the withdrawal of pergolide mesylate from the human market
and your request for clarification of the Center for Veterinary
Medicine's (CVM) position on this product for veterinary use. There
are two options to consider. The first option is for you to contact
(one or all of) the companies that were marketing the drug and ask
them to consider making it available with a label for veterinary
use. They should then contact CVM to find out what information/data
would need to be submitted for review and consideration.

The second option would involve you finding an alternate source for
the drug and requesting that CVM grant you permission to use it under
the Medically Necessary Veterinary Drug Product Shortage Management
policy (see http://www.fda.gov/cvm/Policy_Procedures/4170.pdf).
There is specific information required that can only be provided by
the requesting veterinarian and each request is considered on a case-
by-case basis. You should contact CVM before submitting a request
under this policy.

I hope this information is helpful. If I can be of any further
assistance please contact me by email or by phone.

Marcia K. Larkins D.V.M.
Ombudsman
Center for Veterinary Medicine
Tel: 240-276-9015
Fax: 240-276-9060



----------------------------------------------------------------------
----------
From: drkellon@aol.com [mailto:drkellon@aol.com]
Sent: Tuesday, April 10, 2007 10:12 AM
To: Larkins, Marcia K
Subject: Urgent Matter


Dear Dr. Larkins,
I apologize in advance if your office is not the proper place for
this issue, but since it involves the FDA proper and CVM on several
levels I am not sure where to turn. Please see the attached file. In
brief, the voluntary withdrawal of pergolide mesylate from the human
market is poised to have a disastrous impact on the health, even
survival, of many horses with pituitary dysfunction (pituitar pars
intermedia dysfunction, aka Equine Cushing's Diease). Owners of
horses that were relying on Permax or the generic tablets are already
having difficulty sourcing the drug from remaining supplies on the
market. Wholesalers supplying veterinary compounding pharmacies have
either decided to no longer stock it or are concerned/confused about
legality.
We are in desperate need of a clarification.

Thank you.

Eleanor M. Kellon, V.M.D.
Equine Nutritional Solutions
58 Maple Farm Road
Ephrata, PA 17522