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U.S. Department of Health and Human Services

Animal & Veterinary

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MUMS - Swiss Perspective

by Dr. Flurina Stucki


DR. STUCKI:  Good morning, ladies and gentlemen.  First I would like to thank the organizers for arranging this meeting and giving us the opportunity to speak about the MUMS program in our countries and to discuss together later on.  Our institute called Swissmedic is situated in Bern, which is the capitol of Switzerland.  The institute is doing drug authorization and marketing surveillance for human medicine and also for veterinarian drugs.  So we are about 300 people, and the department for the veterinary drugs is only about 10 people.  I can tell you something about the aspects of MUMS in Switzerland.
  (Slide.)

The bear, you can see him on the slide here, is the heraldic animal of Bern.  You can find him everywhere in town, but in his living form he presents a minor species in Switzerland.
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The marketing authorization in Switzerland contains the three minor requirements, quality, efficacy, and safety.  The safety factor for veterinary drugs includes of course the food safety aspect.  The regulation of the authorization is based on the new law of therapeutic products from December, 2000, which includes both human medicines and also veterinary medicines.  Several guidelines are taken into account for that authorization procedure.
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If a drug is already approved in a foreign country with an equivalent medicinal product control it is fixed in our law that this circumstance is considered.  Vice versa, Swiss medic decision are recognized in several countries .
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Last but not least, the increasing requirements for quality, efficacy and safety cause a lack of available veterinary drugs.  Like in other countries, different known reasons are involved in this problem.  The demand of vets to have a wide range of veterinary drugs available, the adoption of the regulation which is demanding MRLs for all active substances applied in food animals, and of course the small market share of veterinary products.  Just to say the most important ones.  You can imagine that this market share is even smaller in Switzerland, and so Switzerland as well is concerned by the MUMS problems.  I will speak to you about our situation and especially about our efforts to handle this problem. 
(Slide.)

The lack of authorized veterinary drugs for MUMS has been recognized to be a major reason leading to misconduct in that field.  As a result of the availability problem there is still observed an increasing off-label use of veterinary drugs.  Legal standards to avoid the procedures are not always followed.  When drugs authorized for small animals are applied in food producing animals the food safety is not granted.  Due to the strong concerns of food safety as well as the requests belonging to animal welfare and animal protection, the Swiss federal authorities decided to act.  Improving the availability of veterinary drugs can actively promote the compliance in this field.
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So what we have done, under the lead of Swissmedic a taskforce group was created in May, 2002, to pay attention to the availability problem, especially in food-producing animals.  In this group were representatives of different federal authorities as well as of cantonal authorities, but also veterinary organizations and various livestock breeding organizations.  The first step was to find resources to deal with the existing situations.  The goal was predicted to work out methods and solutions to minimize the shortage of veterinary drugs.
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One of the first measures was to evaluate the lacking substances.  Together with veterinary organizations and experts, lists have been required with the lacking substances for ruminants, pigs, poultry, farmed fish, horses, and rabbits.  For the selection of this substances in the relation to “must have” -- against “nice to have” the absence of an alternative treatment was an important factor.  A risk assessment took place in the meaning that we stopped going on, with substances without MRLs because there we saw no chance for a solution in the near future because of the high cost.  Some examples, for cattle there is no imidocarb to treat Babesiosis, and there was at this time no Halofugihon  known to treat coccidiosis.  For goats, a short time ago as anthelmintics if there were only benzimidazole substances available.  There was a strong demand for eprinomectin, and further in goats we don’t have any antibiotics to treat mastitis.  In pigs as well as in all other species there is no doxapram available at the moment, and since the loss of phenylbutazone for food producing animals there is no oral NSAID to treat these animals.  In farm rabbits there is no authorized antibiotics at all.  Also in farmed fish there is a strong demand for drugs to treat infectious disease.  Only since several months Bronopol is authorized in our country, but all other drugs are still missing.  For horses doesn’t exist, an authorized penicillinfor intravenous application as well as for example thiobarbiturate for anesthesia.   On the basis of the resulting substances and with quite a large view of the experience of the FDA and of course of the NRSP-7 program and the propositions of the EMEA we heard before, we started to develop some standards in our country.
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The following solutions are either already implemented or are in development.  Since the beginning of September, 2004, we have a new veterinary drug decree which regulates the use of veterinary drugs in food-producing animals.  It has nothing to do with the authorization of drugs.  In this decree the Swiss cascade is implemented.  I will come back to this in the next slide.  Implemented in the same decree is the exceptional rule for horses, but next to that there is still a lot to do.  In progress is the MUMS decree, in a certain way comparable to the FDA bill we heard before.  Other tools underway are the limited permission and a notification requirement for special animals.  There are the five subjects I will talk to you.
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The Swiss cascade is very similar to the cascade in the European Union.  The veterinarian decided in his own responsibility if there is no other treatment in a first step to change to another indication, and then if there is still no drug available on another species.  Then there is a possibility to switch human medicine authorized in Switzerland.  And at last if there is still no product such as referred, a pharmacist can prepare a drug according to a veterinary prescription.  The import from abroad was allowed before the cascade was enforced, and is still possible if there is no other alterative.  For food animals it needs a permission from Swissmedic for each single case.  So it is not a very comfortable way for the veterinarians.  To allow the cascade also for food-producing animals there is a regulation for food safety which is valid for each single step.  Only substances with defined MRLs are allowed to use for this purpose.  That means that either they have MRL or they don’t need anyone because for the protection of the human health it is not necessary to establish an MRL.  Also the withdrawal periods are laid down in this cascade.  The harmonize with the determinations in the European Union.
 
Now the regulations for the horses.  This exceptional rule for horses, and horse -are in our country also fixed in the law as food animals -this rule means that horses can be kept for non-food purposes.  But then the passport has to signed: “with this horse is not intended for human consumption.”  For these horses the range of veterinary drugs is of course wider.  These sport horses are considered as pet animals and can be treated also with substances without an MRL, including the forbidden substances for food animals.  All the horses which are still considered as food animals can be treated with substances without established MRLS, but then except for the forbidden substances.  But this requests a withdrawal period of six months.  In these horses all treatments have to recorded in an individual file.
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Now to the MUMS degree itself.  The next three subjects I talk about are suggestions, we are only at the beginning it is in development.  It is not implemented yet.  It will take some time for it.  As we know, the cascade can’t solve all availability problems, and additional, the long withdrawal periods after using the cascade are not feasible for all situations.  The goal has to be that the missing drugs can be authorized one day.  That is our idea.  At the moment we are working out a simplified marketing authorization for MUMS drugs.  This MUMS decree is from the idea similar to our human orphan drug regulation.  

The three main points have to be discussed.  What is the definition of MUMS?  That means which products are considered to profit for such a simplified authorization; and in which field and in which extent are simplifications available, and what can be the grant of the authority?
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Some words to the definition of MUMS.  We don’t have the same problems like in the European Union of course because we are only one country.  It is much more easier for us to do this.  So which animals are considered as minor species?  Also we define only our major species.  It is proposed that cattle, dairy and meat animals; pigs; sheep, but only the meat animals; chicken; horses; dogs; and cats are major species.  All other species are minor species.  This is in particular, for example, goats; sheep, but then without the meat animals; laying hens; rabbits; fish; honey bees, and so on.  This list of the minor species of course can’t be final.
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So what is our definition of minor use?  Seldom occurring indications or limited applications in major species.  What means that?  As a minor use are regarded special applications in major species for diseases which are occurring rarely or which are treated in a circumscribed scope.  That can be, for example, a geographical limited incidence of a disease like babesiosis, or a treatment which is reserved to a specialized clinic.  Also this definition is in discussion.  What is sure is that the applicant of such a marketing authorization has to demonstrate the minor use of his product when it comes to an authorization.
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Now some key words to this MUMS decree.  The attainment of the food safety requirement is a high goal which assumes the existence of defined MRLs.  Especially in these products, the possibility of the pharmaceutical industry to put money into research is very limited as we all know.  For us that means that nearly only substances with an established MRL are possible candidates for a marketing authorization.  That means further that an enlargement or an extension of an already-existing product for MUMS application is one of the most important ways to go for us.  Or at least it should be a product with a known substance respectively with a known MRL.  The extrapolation of MRLs from major to minor species is a tradition in Switzerland and is therefore not a limiting factor for MUMS authorization.  The simplifications we are planning concern mainly the part from the efficacy and sometimes the part of the safety.  Whenever possible, data from literature can replace our studies.  But this decision will be done case-by-case.  Swissmedic will provide its knowledge.  It can give advice and evaluate special study designs or extrapolations before the submission of an application.  The fees for the authorization will be waived.
  (Slide.)

Just some words to the limited permission.  This, too, will make important veterinary drugs against dangerous disease available in a short time.  It should be also a part of this planned MUMS decree.  This limited permission normally should end up in a MUMS marketing authorization.  It should give the company or the involved groups more time to collect the missing data.
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To the last factor is to say that this notification requirement is not at all an authorization.  It is more a listing of drugs for special exotic species like ornamental fish and birds and so on.  The requests will differ clearly from a simplified authorization.  It will include only a special veterinary products and, for example, no antibiotics.
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In the meantime, that means until the presented tools are enforced, and this will happen approximately in 2006, some projects are in progress.  On the basis of these projects, we can see if our approaches are working.  In goats, as I mentioned at the beginning, the situation with
anthelmintics was worrying because there were only Benzamidazoles available with a rather high resistance rate.  With the extension of an existing drug for cattle, the substance eprinomectin could be made available.  The cooperation between Swissmedic, the Swiss goat association and the pharmaceutical industry was necessary.  With pharmacokinetic data from literature and a monitored release field study -- that means a field study has to be done -- the marketing authorization could be done.
(Slide.)

For farm rabbits there is as I said no authorized antibiotic at all.  There is a strong need for substances to treat pasteurellosis and diarrhea.  Also in this case the basis was the extension of an existing product, but in this case are no data available to define efficacy and target animal safety.  Because of that, the few Swiss farm rabbit breeders and producers we have in Switzerland team up to the first Swiss farm rabbit association to put power and money together and to support the needed studies.  This is so much amazing because they are normally in big competition, and they team up only because of the availability problem.  The study is under the head of a department of our university.  These studies are in progress at the moment, and we hope that it will work.
  (Slide.)

Let me say some critical points at the end.  Is the pharmaceutical industry willing to cooperate?  We will see it only when the MUMS decree is enforced and can be really used.  The funding is a problem for us, because authorities don’t have money to support research and studies.  You might know in Switzerland the money is safely locked up in banks and is not available for our MUMS projects.
  (Laughter.)

Sometimes the money has to come from the user itself or the breeders or the animal owners.  Strongly connected with the funding of money is the problem of the substances without an established MRL.  There we saw nearly no chance for a marketing authorization in the near future.  The example I mentioned before of these motivated Swiss rabbit breeders and producers is unfortunately a single case until now.  We need a stronger cooperation between all the involved groups, especially the veterinarian, the breeding association, and also the university.  Only then there is a chance to make these lacking veterinary drugs available.  Thank you.
  (Applause.)

DR. WEBB:  Well, that brings our first session to a close, but before you know we always have housekeeping comments to make.  The first is that this meeting has been in large part funded by FDA, which is a government organization.  It is a public meeting, and we require and welcome public comments at certain sections of the meeting.  If anyone has a public comment they wish to make that does not relate to MUMS or anything like that, if they let the front desk know so we can a lot them a time in that session, those sessions.  If there is nobody making a public comment, we will make private comments and continue the meeting. 

The second part is those of you who are wondering what NRSP stands for, and I can never quite remember, it is National Research Support Project No. 7.  No. 6 is for potatoes, so you can see how we rank with that.
  (Laughter.)

For members who have badges on, it is not so you can be identified by security.  It is so that any of you who have a question you want to ask about NRSP-7, people who wear this badge should know the answer to that.  

Anyhow, to something much more important, friends of NRSP-7 have sponsored a reception this evening at the end of business from 6:00 until 7:30, and it is the gazebo or whatever you want to call it.  That little house in the middle there on the upper level at that time, and we would really like to see you all there because it allows us to talk and you to talk to each other.

The final thing is you be back on time on you suffer the same fate as the speakers if the run over.  You didn’t see any bloodshed this morning.  We don’t want bloodshed from you.  Thank you.
  (Whereupon, a break was taken.)

DR. CRAIGMILL:  Ladies and gentlemen, we are going to attempt to remain relatively on time.  So if you could please come in and take your seats, we are going to go ahead and get started.  My name is Art Craigmill.  I am from the University of California at Davis and I am one of the NRSP-7 regional coordinators.  I am the only original one left.  When John and I started we were both young men.
  (Laughter.)

Just a little greyer and a little more worn at the edges.  I am delighted that we have so many in attendance as Dr. Beaulieu said.  Once again, in an attempt to remain relatively on time, I am going to introduce our first speaker of the second session this morning, Professor Eric Mitema.  Dr. Mitema received his veterinary degree.  He also holds a PhD in a field near and dear to my heart, pharmacology and toxicology.  He is currently a professor in Nairobi, and he has two other very important distinctions here.  He serves on his country’s pharmaceutical registration panel, so he does drug evaluations, and he has also been a member of JECFA* since 1995.  I introduce Professor Mitema.