Voici le rapport final de l'atelier consacré aux médicaments vétérinaires et l'abeille qui a eu lieu en décembre 2009 à Londres. C'est un rapport qui est consultable sur le site de l'EMEA, ainsi que les conférences qui y ont été données. C'est très intéressant.
"19 March 2010
EMA/28057/2010
Workshop on medicines for
bees - What the Agency can do to increase availability
14 - 15 December 2009, London
Executive Summary
The European Medicines Agency, on 14-15 December 2009, held a workshop to
discuss a specific aspect concerning bee health – the availability of medicines
for bees in Europe, in particular what medicines are needed and what the Agency
can do to increase the availability of needed medicines.
It is acknowledged that the problems of the bee keeping sector and
the decline in the bee population all over Europe and the world are complex and
diverse. One of the concerns raised by interested parties and Member States
over the years is the lack of adequate medicines to treat bee diseases.
The
European Medicines Agency has been active since many years in supporting the
availability of veterinary medicines to treat diseases in animals where authorised
medicines are lacking, and initiated or promoted initiatives on EU level in
this respect. Therefore, the Agency organised this workshop aimed to contribute
to the availability of appropriate treatment options for bees.
The workshop brought together experts
from the bee keeping and honey production section, experts in bee diseases and
treatment of bees, representatives from the regulatory authorities of Member
States, the European Commission, the animal health industry and other
interested parties. The aim was to provide the opportunity to discuss possible
approaches forward and to identify most needed treatment options for bees, including
consideration of practical aspects of how to achieve marketing authorisations
for bee medicines.
Following presentations providing comprehensive information of the
existing activities in Europe concerning bee health, identifying the problems that
the bee keeping community and veterinarians are facing, and proposing ideas for
solutions from the viewpoint of the different concerned parties, the meeting
split up in two breakout groups to discuss specific points identified in the
plenary session as key elements towards providing adequate medicines for the
treatment of bees.
One group concentrated on providing an analysis of the
current situation, by identifying the critical diseases in the beekeeping
sector, discussing the options for treatment, and whether the available options
for treatment are sufficient, and identifying possible reasons for any lack of treatment options. The second
group’s task was to consider issues of feasibility and prepare proposals for
actions that could support the availability and use of authorised veterinary
medicinal products for bees. The
proposals should address availability of existing authorised veterinary
medicines as well as development of new medicines.
Following the presentations of the reports and conclusions
of each break-out group, the discussions were consolidated in the plenary.
The overall conclusions and recommendations of the
workshop were:
·
The problem of bee health
and appropriate treatment of bees is much more complex and diverse than simply identifying
some potentially needed medicines.
·
An overall strategy regarding
medicines for bees should be established. Such a strategy should identify for
each bee disease whether medication was appropriate, and if medication is the
choice of treatment, which medication should be applied as well as the
conditions for the appropriate action or treatment be clarified.
- The information available to beekeepers
on good beekeeping practice should be improved. Adequate information or training of beekeepers would
ensure correct use of medicines. This was seen as a role of governments.
- It should also be explored if specialised training on bee diseases
could be provided to veterinarians. [Post
meeting information: DG SANCO is
funding a training programme on bee diseases for official EU vets under
its Better Training for Safer Food initiative, which will start in 2009]
- The use of only authorised veterinary
medicines in beekeeping should be pursued as goal. Chemical substances
currently used for the treatment of bee diseases should be authorised as
veterinary medicines to ensure that they are adequately formulated for the
intended use and correctly applied.
- The proposal was discussed whether certain
veterinary medicinal products for bees could be exempted from prescription
to facilitate access by the bee keepers.
- Better use should be made
of existing marketing authorisations for bee medicines so that the
authorised veterinary medicines would be available in all countries across
the EU and existing legal provisions should be explored to achieve this. For the future revision of the
veterinary legislation further facilitation of the authorisation of
veterinary medicines for bees should
be considered.
- Further research is needed for the
development of new/alternative treatment options and to identify essential
substances. An expert group should be created to prepare a proposal for a treatment
strategy.
- Substances with existing marketing
authorisations for other species and existing MRLs or substances not
requiring an MRL (former Annex II substances) are considered more likely
for achieving a marketing authorisation than an entirely new molecule or
substances without MRL.
- Approaches like the example of oxalic
acid, where several parties worked in cooperation, should serve as model
for future attempts to achieve a marketing authorisation for a veterinary
medicinal product for bees.
·
The veterinary
pharmaceutical industry shows interest in developing medicines for bees. However
the industry also faces obstacles that hinder development and marketing of
medicinal products for bees. In order to develop new medicines for bees incentives,
in particular adequate data protection, would be needed.
· The meeting considered that continued discussions were necessary to find
solutions. It was recognised that many of these aspects of the debate were outside
the scope and mandate of the European Medicines Agency, and the further
discussions would possibly need to involve additional partners. The efforts by
the Agency to organise the meeting and allow these discussions were appreciated
and further activities welcome.
Report of the meeting
Presentations:
1. Medicines for bees
- Introduction to
subject and aim of workshop
I.
Koudouna (EMA) introduced the subject, summarising the potential reasons for
the decline on bee populations discussed by experts and listing the main bee
diseases in Europe. One concern that was repeatedly mentioned over the last
years by interested parties and member states was the lack of adequate
veterinary medicines to treat bee diseases. Not only the lack of medicines may
hinder treatment but the use of unauthorised products or the use of chemical substances
as raw materials give also rise to concerns in respect to potential incorrect
use of products/chemical substances, the absence of knowledge on their efficacy,
the potential for undesired or illegal residues in honey, the safety of the bee
keeper in applying the product and the potential environmental impact. She
explained the role of the Agency to improve the availability of veterinary
medicines in general and the aim of the workshop, i.e. to contribute to the
availability of medicines for bees and to identify any essential substances for
the treatment of bees, for which ultimately veterinary medicines could be made
available.
- Role of the European Medicines Agency, Establishment
of MRLs and authorisation of veterinary medicines in the EU
I.
Duarte (EMA) outlined the Agency’s role and responsibilities and gave an
overview of the authorisation process of medicines for animals, in particular
for food producing animals, which require the setting of a maximum residue limit (MRL) for the
food commodity/species concerned before a marketing authorisation can be granted. Bees are classified
as food producing animals in the EU thus the establishment of an MRL for honey
is necessary before a marketing authorisation for a veterinary medicinal
product can be granted. I Duarte provided particulars in regard to MRLs and
medicines for bees, listing the substances for which MRLs have been established
in the EU for honey and summarising the data required for applications for
setting an MRL for honey bees and for a marketing authorisation for a
veterinary medicinal product.
During
the discussion it was questioned why the CVMP had indicated that in principle only
medicinal products requiring a “0 day” withdrawal period should be authorised
for bees. It was explained that in
view of the lack of metabolism in the beehive an elimination of residues over a
certain period of time as defined for other food producing species would not
occur. It was however stressed that a decision was always taken on a case by
case basis considering the data available to assess the residues resulting from
the use of the product in practice.
2. European
Initiatives
-
Bee Surveillance Programmes and Bee Mortality in
Europe
Dr. J. Richardson (European Food Safety Authority (EFSA)) gave an overview
of the tasks of the EFSA and their activities regarding bee health. One ongoing
activity concerns risk assessment guidance on ecotoxicology and environmental
risk assessment and will include a tiered risk assessment approach for bees.
Another activity, which goes back to the initiative by the French AFFSSA,
concerned the bee surveillance
programmes and monitoring of the bee mortality in Europe. The survey conducted
in 2008 confirmed a general weakness of national surveillance systems. Although
in 2003 and 2008 some countries indicated consistently higher bee losses than
in other years, there were insufficient data to analyse a trend. Harmonisation
of surveillance systems across Europe was needed. Literature research also
indicated the multifactorial origin of colony losses and insufficient knowledge
of the underlying factors for this. EFSA concluded therefore the need for more
harmonisation of the European surveillance systems and its parameters/methodology.
In the following discussions Dr Richardson encouraged participants
to send any comments they would have on the report or any findings to EFSA for
consideration for future surveys.
-
Recent actions by the European Commission concerning
bee health
Dr. E. Soto (European Commission, DG Health and
Consumers) gave an overview of the intra-
and intercommunity trade with bees and bee products and explained the
legislation for live bee imports. Import of live bees is restricted to queen bees
and a restricted number of attendants. In addition, specific requirements
regarding the health certification and packaging materials have to be respected.
Legislation with regard to the import of certain live animals, including bees, is
currently revised to be simplified into one single Regulation rather than having
several legal documents, as it is at present.
Dr
Soto also reported of an inter-departmental co-ordination group that has been set
up within the European Commission aimed to improve cooperation and communication
within the different Directorates General. Future policies within the Commission
would include regular scientific expert meetings to discuss emerging threats
and topical issues and the drafting of safeguard measures for Member States for
bee diseases not yet observed in the EU. The inter-service group is also proposing
to set up a pilot study for a more harmonised surveillance in Member States.
3. Overview of bee diseases and available
treatment options
Dr. V. Jenčič (Veterinary
Faculty, University of Ljubljana, Slovenia) gave an introduction into
the structure and life of a honeybee colony, explained the criteria for the
health of a bee colony, the defence mechanisms of bees and the colony and the
reasons of the breaking up of the defence mechanisms. The diseases and pests in
honey bees can be divided in infectious diseases (viral, bacterial, fungal and
parasitical), pests and non infectious diseases. Diseases of a honey bee colony are brood diseases, adult bee diseases,
pest and colony collapse disorder. She mentioned that the OIE Terrestrial
Animal Health Code lists a number of bee diseases and hygiene and disease
security measures are given. As main diseases and available treatment
options Dr Jenčič identified:
·
Brood diseases: The main brood diseases are American
foul brood and European foul brood. The American foul brood is a disease
requiring notification. No treatment options were available for the American foul
brood and treatment with antibiotics is not allowed, as they do not kill the
highly resistant spores. For American foul brood the destruction of infected
colonies is compulsory. Also for the European Foul Brood there were no real
treatment options. In some countries the use of antibiotics was permitted under
certain circumstances, i.e. under veterinary supervision and applying long
withdrawal periods. Therefore, usually the infected colonies were destroyed.
Other
brood diseases are Chalkbrood, Stonebrood and Sacbrood. No specific medical treatment
is available for these. For Chalkbrood good beekeeping hygiene was the best
prevention measure. For Stonebrood, which is a zoonosis, urgent destruction of
infected colonies and honey was compulsory. For Sacbrood hygiene measures and
replacement of the infected queen were recommended.
·
Adult bee diseases: There are several viral diseases,
for none of them a specific medical treatment is available and hygiene measures
were the method of prevention. Nosemosis (Nosema
cerana, Nosema apis) is a parasitic disease in adult bees, for which fumagillin
is highly effective for treatment. However, as no MRL could be established due
to the inadequacy of data available to ensure consumer safety, the use of the
substances is not allowed. Prevention procedures need to be applied.
·
Varroasis: Varroasis is caused by the mite Varroa
destructor. Several treatment options available – biotechnical methods like
drone brood removal, comb trapping and use of chemical substances, however none
was perfect. The best results were
achieved with a combined treatment (“integrated varroa control”) and also if
all beekeepers in a region were to treat bees at same time with same method to
keep resistance low. The chemicals/veterinary medicines are applied by different
routes of administration (spray, smoke, contact). Not all chemical substances
that are/could be used have MRLs/ are authorised as medicines.
·
Other bee diseases, which are however not (yet) in
Europe, are infestation with mites from Tropilelaps, Acarapis wood as well as small
hive beetle. For the latter the treatment was similar to varroa.
·
Colony Collapse Disorder (CCD) is observed worldwide.
It is a multifactorial disease resulting in disappearance of bees. No treatment strategies are yet
available.
Dr Jenčič concluded that a different beekeeping strategy
was needed with more research in honeybee biology and physiology and research
in bee medicines, such as alternative treatments (e.g. pheromones).
4. Medicines for bees: current situation and
future aspects
Dr. W. Ritter (OIE
Reference Laboratory at CVUA, Freiburg (Germany)) outlined the problems with medicines for bees, the current
situation and future aspects. The current perception of many beekeepers
would be that any treatment that helps to fight diseases is allowed. However,
the safety profile of the medicines, ensuring safety of the user, consumer
safety, effectiveness and low side affects to the bees should be the choice.
He pointed out that treatment might result in
residues of hydrophilic substances in honey, while lipophilic substances would accumulate
in the wax, which due to the process of wax recycling and comb foundation could
eventually lead to contamination of the honey.
He reviewed the different application routes (feeding,
trickling, strips, vaporization and evaporation, spraying and dusting) and the
pros and cons in respect to their risk for the applicant, their risk for food
contamination and their extent of efficacy or tolerance in the bee or their
brood.
The specific situations regarding certain bee diseases
were analysed.
Nosemosis presents a problem, in particular in
southern Europe. No authorised medicines were available and other control
measures were applied as well as anti-coccidial medicines under off-label use. These
anti-coccidia, which seem to be effective, should be further explored as future
bee medicines.
For the American and European Foulbrood no authorised
medicines are available, some antibiotics show efficacy against the bacteria in
the larvae, however not against the spores, these can only be destroyed by
eradication (e.g. burning).
Varroa infestation remains the currently most
important disease in bees, not only with regard to causing varrosis but also by
introducing viral diseases. While several veterinary medicines were authorised,
there is concern for the future due to observed resistance against synthetic
anti infectious medicines, and the uncertainty of effectiveness of natural anti
infectious substances. Potential
future treatment options include genetic therapy or prophylactic vaccination.
Dr Ritter recommended that authorisation of bee
medicines should be made easier and better harmonised across Europe and innovative
developments should be encouraged.
In the discussion following this presentation the
need for facilitation of authorisations for bee medicines across Europe was
supported, proposals were made for automatic approval of medicines, meaning
that a medicine authorised for bees in one EU country would be automatically
authorised in other EU countries and simplification of distribution of bee
medicines across Europe was recommended.
5. Veterinarians
and Bee health involvement, taking France as an example
Dr N. Vidal-Naquet
Federation of Veterinarians of Europe (FVE) presented proposals regarding the
involvement of veterinarians in bee keeping based on the approach taken in France
and reflections on further actions. While beekeeping is no longer part of the
routine curriculum at the French Veterinary education, a high standard diploma
course has been set up in 2005 on beekeeping and bee keeping pathology. The three
week course enables veterinarians to understand the principles of beekeeping
but also the pathology and management of various conditions. These specialised
veterinarians are/will be able to work with the beekeepers in managing of the
diseases as well as be involved in research and diagnostics development.
The non-availability of effective veterinary
medicines for bees causes challenges for beekeepers, veterinarians as well as
for regulatory authorities and pharmaceutical industry. The problems encountered
were analysed in detail at the example of the treatment of Varroa destructor. A
number of veterinary medicines are authorised in France, with one product allowed
as prescription only. The problems experienced by beekeepers which may lead to
not achieving fully successful treatment can have different causes, e.g.
resistance development, lack of efficacy and non-optimised practices in the
treatment regimen. Further clarification through scientific studies would need
to be achieved on some key questions in order to identify if veterinary
medicines are needed to treat the diseases, and if confirmed, which essential
medicines are lacking.
Experience from the United States would have shown
that widespread use of some of these substances resulted in increased
resistance. A better availability and clearer / easier authorisation of veterinary
medicines for bees and consistency across the EU was encouraged. It would need
to be reviewed and clarified which veterinary medicines are necessary, and then
efforts made to establish MRLs in honey and obtain marketing authorisations. In
particular the use of antibiotics and anti-coccidial medicines should be clearly
regulated in order to limit resistance. The veterinarians would have the
responsibility to define the need for veterinary medicines in honey bee
diseases.
In the discussion following the presentation the
meeting was informed that in the former Middle and Eastern European countries
veterinarians were usually involved in treatment of bee diseases, in particular
advising beekeepers on best treatment options. The European Commission has
recently introduced training courses for veterinarians. From the beekeepers
side it was pointed out that involvement of veterinarians or veterinary
services should be free of charge, otherwise beekeepers would not use such
service.
6. The situation in Member States
An overview
of the bee health situation in EU Member States was given at the
examples of the United Kingdom, France and Greece.
Mr Selwyn Wilkins, on
behalf of Mr Mike Brown, (National Bee Unit (NBU) of the Food and Environment
Research Agency (fera)) and Dr M. Spagnuolo-Weaver (Veterinary Medicines
Directorate (VMD)) presented the situation in the UK. The developments of bee health and
losses in the UK over the last decades were presented based on NBU data. A steady increase of colony losses is
being observed since 2001, for which the causes are assumed to be of multiple
nature. Research projects to better understand the causes for the colony losses
have been initiated and first results are being reviewed.
With regard to the availability of veterinary
medicines for bees the UK has set up an action plan with short, medium and
long-term objectives including fee incentives for licensing of bee products,
research work in residue and efficacy issues for substances needed for bee
disease and proposals for changes in the legislation e.g. prescription of bee
products by qualified professionals (not necessarily veterinarians). It was
clarified that the use of oxytetracycline is allowed in the UK under the cascade
for the treatment of the European Foulbrood with the withdrawal period of at
least 6 months.
Dr
Marie-Pierre Chauzat (French Food Safety Agency (AFSSA)) summarised the
situation for France. In France, use of some authorised bee medicines
indicates that efficacy appears to be decreasing, and e.g. due to observed resistance
development, fluvalinate would no longer be recommended for varrosis treatment.
Beekeepers were asking urgently for
medicines against varroa, nosema and foulbroods. In absence of effective
medicines, beekeepers would use alternative “homemade” treatments to treat
disease, in particular for varrosis, with unclear and inconsistent conditions of use. According
to recent studies it was concluded that colony winter mortalities are largely due
to Varroa deleterious effect caused by inappropriate treatments. Dr Chauzat
considered that in light of resistance developments,
uncertain efficacy of existing treatment options and frequent use of home made
treatments there would be an urgent need for the development of new treatments against
varrosis.
In France, the treatment of
American foulbrood is acceptable provided that the disease is not yet largely
developed. Honey and wax would be destroyed.
Dr A. Tsigouri (National
Organization for Medicines (EOF)) gave a summary of the situation in Greece.
She presented statistical data on the Greek apiculture and surveillance results
on be diseases. The most prevalent disease is Nosemosis (over 40% of samples
positive to some pest or disease were Nosema positive) followed by Varroosis,
European Foulbrood and American foulbrood, as well as other bee diseases
(mostly brood diseases). For nosemosis treatment with fumagillin had been used
for the years 2000-2005 under the direct supervision of the State Veterinary
Service with specific prescription for one treatment only and long time away
from honey collection. However, after a recommendation made by DG SANCO
following an inspection visit of FVO in April 2005, to stop using an active
substance not listed in Annex I-III of Reg. 2377/90, this procedure had been
terminated. For varroosis seven products (4 active substances) are
authorised. She called for more
consistency between Member States in authorisation and control of use of
medicines in bees. She pointed out that “cascade” provisions for off-label use
would not be helpful in the case of bees, when no MRLs have been established in
honey resulting in “zero” tolerance. In addition, she noted that while
marketing authorisations are needed for all veterinary medicines containing the
substances allowed for organic beekeeping, this is not clear to all beekeepers.
She concluded that Greek
beekeepers require urgently more medicines for bees and consistent attitude
through Europe.
7. The beekeeper’s perspective
-
Securing bee
health and honey quality
Introducing his presentation E. Bruneau (COPA-COGECA)
pointed out important specificities of bees that have an impact on bee health
and on honey quality: The differences between bees and other livestock animals,
the specificities of beekeeping in relation to other livestock sectors, veterinary
specificities of beekeeping, which would need to be addressed in the EU animal
health policy and that honey, pollen and royal jelly would not be common
food products. He explained the uniqueness of the bee with the colony being a
”super-organism” with the health status of the colony depending on behavioural
integrity of the individuals who compose it.
He reviewed the situation regarding varroa, which he
considered an emergency situation as highest cause for mortality and a problem
of availability of medicines. While several veterinary medicinal products are
authorised in the EU, they were not available in all countries, in addition
some were difficult to obtain for beekeepers as they are prescription only and
for half of the active substance the varroa mite has developed resistance. He
called for extension of existing authorisations of anti-varroa medicines to all
Member States, more flexibility in the conditions for use of medicines under
the “cascade”, the recognition of the phenomenon of a large-scale resistance,
and the recognition of the importance of two treatments with different active
substances and obligation of alternation of active ingredients over the years.
The development of new active substances – miticides – should be encouraged.
In respect to bacterial diseases - in particular the
American foul brood - he considered the use of antibiotics inappropriate as
they would only camouflage the disease. So far there would be no common
strategy in Europe with some countries using antibiotics other require
destruction of colonies. He proposed a control strategy, with destruction of
bee hives only when clinical signs, and supported possibly genetic selection.
Regarding the control of opportunistic diseases he
pointed out that bees are able to naturally defend themselves except in cases
of disturbances. Therefore, improving the disease control should not only deal
with the treatment of disease but focus on disease prevention and improve the
bee environment. The risk of residues in honey should be minimized in view of
the high number of honey imported from third countries. In respect to the role
of medicines he called for measures to control residues in bee products and for
the adaptation of the EU health policy to beekeeping needs. The procedures for
medicines should be specific for bees/bee products focusing on disease
prevention and aiming to minimise the risk of residues, favouring “natural”
substances. In order to improve disease control, beekeepers and veterinarians should be trained. Also specialized centres
for bee pathology and research regarding the emergence of opportunistic
diseases and improvement of the bee environment (plant diversity) should be
aimed for.
In reviewing the difference
in the production of honey in the EU vs third countries, he pointed out that
honey has in the EU the image of a “natural" and “healthy" product. Antibiotics
were being used in beekeeping of third countries but were not authorised in the
EU. There was also the possibility of contamination through the environment. He
pointed out that 1/3 of
the sanitary alerts due to “residues of veterinary medicine” in food were
residue contaminations of honey and royal jelly. He called for establishing a
level for the control of residues to assure trade and consumer protection; such
level should be sufficiently low
to maintain and protect the quality and positive image of bee products; such
levels could be either reference points for action or an MRL, to be
investigated, under the new MRL regulation.
- The beekeeper’s
perspective on medicines for bees
W. Haefeker (European
Professional Beekeepers Association (EPBA)) presented the beekeepers perspective on medicines for
bees. He pointed out that pathogens would always be present in bee
colonies and that the ability of bees to handle natural pathogens load would
depend on the diversity of food sources and that despite the hives being
infected, bees in a healthy environment were usually without clinical symptoms.
He compared the different types of honey on the
market pointing out that honey in the EU would be mostly regional products, not
highly processed, largely residue free and often organic produced. Beekeepers
would provide free pollination, different to the situation in the USA where
pollination is the main revenue source for beekeepers and honey would be the
by-product.
He considered that availability of medicines as such
would not solve problems with regard to bee health as seen when comparing the EU
situation with the USA, where a wide range of medicines including antibiotics were
easily available to the beekeeper over the counter or via mail order. However, the
USA suffers among the highest rate of colony losses in the world. With regard
to Foul Brood, antibiotics mask the problem and other methods such as shook
swarm method and moving treated hives into an area with good nectar flow appear
good options. Also promoting breeding programmes, e.g. with disease resistant
queens, might be an option. Experience from New Zealand where treatment options
were changed should be noted. Concerning varroa treatment, optimisation of
available treatment options are recommended, e.g. by using stripos that could
be used in hives of different sizes. Development of non-chemical methods might
also be future treatment options e.g. using varroa antagonists (virus) or
molecular vaccines. Presence of pesticides might show more impact on bee health
than previously anticipated.
He concluded that the health
of honey bees is reflective of the surrounding environment and that medicines were
no substitute for making sure the environment does not become hostile to bees
nor were they a substitute for good beekeeping practices. Beekeeping methods
need to take advantage of natural defenses and genetic resources within bee
populations. There is much room for improvement in application of organic acids
to combat varroa, and much room for improvement in the strategy to fight the American
Foulbrood. Additional medicines may be welcome as a last resort but the residue
contamination of bee products was a very important consideration. Many
beekeepers especially the rising number of organic beekeepers would not use
products that may compromise the wholesale image of their bee products.
8. The perspective of the honey trading industry
F. Filodda (European
Federation of Honey Packers and Distributors
(FEEDM)) described the situation of the honey trade and addressed the problem of antibiotic residues in honey, which were
frequently found in honey imported from third countries due to the use of
antibiotics. He remarked that the use of antibiotics was however not restricted
to third countries, but they would also be used by beekeepers in the EU.
Antibiotics would particularly be used in case of
Foulbrood infestations, as beekeepers would fear the loss of their beehives. The
main antibiotics used were streptomycin, sulfonamides, tetra-and
oxytetracycline, tylosin and macrolides. Some of the antibiotics would be
authorised in third countries and their use legal. In the EU the use of
antibiotics was not allowed and no MRLs have been established. The resulting “zero
tolerance” policy of residues would cause significant trade problems as clear,
harmonised rules did not exist with regard to acceptable control methods,
detection limits or sampling methods, resulting in different interpretation by
EU Member States. Applications for
the establishment of MRLs and marketing authorisations for veterinary medicines
in bees would be difficult due to several reasons: to establish MRLs in honey
is often difficult due to the particular residue situation which results in
residues remaining in the bee hive after treatment. This also leads to the
effect that withdrawal periods cannot be established in a similar way as for
other tissues. The concerns that the use of antibiotics may not be helpful were
shared, and other options could be considered, also aimed to maintain the image
that the public has of honey. However, he called for regulatory actions to
overcome the current situation, and recalled the example of oxytetracycline,
where an MRL was not established despite the fact that an MRL application was
submitted and a recommendation was made by the CVMP. He also criticised the
lack of action and consistency of regulators illustrated at the example of a
recent correspondence of FEEDM, with the Commission and the EMA, where MRLs had
been requested for several antibiotics and inconsistent responses had been
received.
In the subsequent discussion the chair clarified,
that the response letters from the Commission and EMA had been in fact
consistent. The request to the EMA had been to establish reference points for
actions (RPA) in order to allow for control of honey imported from third
countries. In this respect the response of EMA was to clarify that they are not
responsible for RPAs and therefore such a request would need to be addressed to
the European Commission. In what
concerns requests for the establishment of MRLs for substances used in third
countries, such requests could only be submitted to the EMA by Member States or
the Commission. On the other hand, the Commission, in their response had
considered that RPAs were not appropriate for the case in question, but a
request to the EMA for the establishment of MRLs under specific conditions of Art
9 of the new MRL Regulation should be explored. The Commission representative considered that with the newly
set up co-ordination group any co-ordination issues regarding activities in the
bee health field should be overcome. It was explained that educational measures might be helpful
for the honey suppliers; it was also pointed out that such programmes were
already set up in many countries. In respect to the levels for RPAs proposed by
FEEDM, it was pointed out that these levels were very ambitious to achieve in any
screening method, in particular for fluoroquinolones, as the matrix, honey,
posed challenges for analytical methods.
9. The perspective of the animal health industry
- Why is the availability of
VMP for bees so narrow? What could be done to increase this availability?
Dr Bill Vandaele representing
the Association of Veterinary Consultants (AVC), highlighted the specificities
of bees and their treatments and pointed out the environmental benefits of bees
and their importance for pollination.
He recalled that the issue of inadequate availability of medicines for
bees has been addressed in general at many occasions before in discussion fora and very recently at the worldwide
beekeepers APIMONDIA congress. He
reviewed the situation in some EU countries, using the example of Belgium to
highlight the difficulties beekeepers face. He considered that in Europe the
vast majority of bee treatments with chemical substances are not in line with
legislation due to the lack of authorised medicines, and often pesticides or
bulk chemicals were used. For some substances the first step towards a
veterinary medicine has been done and MRLs were established (or classification
“no MRL necessary”) but no veterinary medicines were authorised or on the
market.
He considered that in order
to find solutions it would be necessary for all parties concerned to work
together. Multiple elements need
to be considered to be successful and he reminded of the FVE guidelines on Good
Veterinary Practice, e.g. regarding varroasis. He supported recent EMA
proposals such as the development of a guideline regarding veterinary medicines
controlling parasitosis in bees and called for consideration of the
environmental impact regarding pollination in the cost-benefit considerations for
medicines. He considered the impact of MUMS requirements in the development of
a veterinary medicine for a minor species too insignificant to provide an incentive
for developing a product for bees.
Therefore, the responsibilities and costs should be shared, between EU
and national regulators, academic and research institutes and industry. Lessons
could b learned from the USA MUMS system. He reminded that the possibilities for
obtaining funding in the context of the ETPGAH or specific EU legislation
regarding bees should be explored.
- Animal Health
Company Experience: Case studies from manufacturers of veterinary medicinal
products
Dr Erik de Ridder and Mr
Guillaume Agede representing the International Federation for Animal Health
Europe (IFAH-Europe) recognised the concerns regarding bee health and honey
quality. They acknowledged that beekeepers were confronted with many challenges
due to diseases and that the lack of therapeutic options was a major concern.
The R&D based animal health companies share the concern from the society as
a whole and see the value for the beekeepers. However, the speakers pointed out
that the animal health companies were confronted with several issues that
hinder bringing medicines for bees to the market: the market is relatively small, the need for MRLs without any
data protection and most of the suitable medicines were old and therefore
equally not eligible for data protection. These difficulties were illustrated with
three case studies involving oxalic acid, fumagillin and tylosin.
Oxalic acid: Following
activities by a consortium to put together an MRL application, an MRL
classification was successfully achieved in 2003. Industry worked with the
competent authorities in Spain to define a veterinary medicinal product for
bees and a marketing authorisation was issued in Spain in 2007 and the product
launched. The sales however were low. Several Member States requested that an MRP
was launched, but as a first step it was proposed to use the cascade system. No use of it really occurred. An import
permission granted by one Member State did also not result in sales. Beekeepers
would continue to use oxalic acid as unauthorised raw material as it is easily
accessible and less expensive. This example would illustrate that even good collaboration
between industry and authorities no return on investment for industry may
result and at the end companies would not keep the product on the market.
Fumagillin:
Fumagillin was on the EU market since 1970 for the prevention and treatment of
nosema disease in bees. In addition later a veterinary medicinal product
containing fumagillin for trout was developed. However, as MRLs could not be
recommended by the CVMP, no marketing authorisation could be maintained or
issued for bees. The CVMP acknowledged that fumagillin would be an essential
substance for veterinary medicine for bees (EMEA/CVMP/411/00). Since then and
in a new regulatory context considering MUMS data requirements to establish
MRLs and having obtained free scientific advice for MUMS, new work on toxicity
studies is ongoing.
Tylosin: Tylosin has been
used in bee-keeping globally and has received approval in the USA from FDA based
on a dossier in which USDA and industry have worked together. The registered
claim is for the treatment of American foulbrood in honeybees. Efficacy, safety
and residue studies were available. In the EU, MRLs have been set for all food
producing species, however, no MRL for honey has been set so far. The UK beekeepers
association has requested the originator to apply for a marketing authorisation
and the company was initially receptive to the idea. However, Dr de Ridder
expressed concerns over what questions might still arise within the evaluation
of the MRL dossier that might lead to further data requirements, even for the
minor species and the minor use, as they have experienced in a similar case previously.
Furthermore, the ‘global marketing authorisation’ concept, as created by Article
5 of Directive 2004/28, would prevent data protection for the dossier:
therefore any work done by the company would immediately be available for the
generic competition. The lack of data protection, preventing return on
investment, was considered the biggest hurdle.
In summarising the speakers
recognised the interest for society and value for beekeepers for medicines for
bees but pointed out that the lack of data protection and the small market size
are obstacles for developing products. However, industry still sees hope if the
needs of honeybees and their keepers would be seen as critical for agriculture
and society, benefit-risk analysis would allow product development studies to
progress and adequate data protection could be provided.
10. Breakout sessions
Following the presentations and discussions two
break-out groups were formed, which discussed the matter in parallel sessions and
prepared proposals and recommendations for possible solutions / actions. Subsequently
the two groups reported back to the plenary and their considerations and
conclusions were reviewed. The considerations and conclusions, as overall
outcome at the plenary meeting, are summarised below.
Group 1:
chair: Mr E. Bruneau (COPA COGECA), rapporteur I Duarte (EMA)
The group’s task was to
provide an analysis of current situation, identify the critical diseases in the
beekeeping sector, the available options for treatment and conclude whether the options for treatment available are sufficient.
If insufficient, possible reasons for lack of treatment options should be
identified.
In
a second step proposals for possible solutions and actions should be developed, and
where possible the medicines that are
needed to treat bee diseases be identified and proposals for essential substances
made.
- Analysis of current situation
a) Critical diseases in
the beekeeping sector
As critical diseases the following were
identified:
· Varroasis (Varroa destructor)
·
Nosemosis (Nosema
apis Nosema ceranae)
· American foulbrood
(Paenibacillus larvae)
· European foulbrood
(Melissococcus plutonius)
·
Bee virus
New threats are expected
from:
· Tropilaelaps mite
· Small hive beetle
b) Available options for
treatment
c) Are the options for
treatment sufficient?
Varroa
·
Treatment is available
although there are problems of resistance and of efficacy
·
Strategy for control and
treatment is needed – New ways of treatment and new medicines are needed
·
Medicines are available
but not equally at European level
Nosemosis
(Nosema apis and Nosema ceranae)
·
Prophylaxis is essential
·
Good beekeeping is the key
·
Options for treatment are
needed – Antibiotics and coccidiostats are not the solution (no consensus view)
American
foulbrood
·
No treatment is wanted –
destruction of infected colonies, shook swarm method
European
foulbrood
·
No consensus view could be
reached on the approach for treatment. In general it was agreed considered that
prophylaxis is the key. Many considered that antibiotics were not the solution for
the treatment of the European Foulbrood, however this view was not shared by
others.
Tropilaelaps
·
Treatment options available
are considered sufficient at present: the use of treatment as for varroa is
recommended,
Small
hive beetle
·
Veterinary medicines are
available based on coumaphos –
Adequate in the short term
·
More treatment options are
needed in long term, particularly for southern countries
Bee
viruses
·
Essentially linked to the
control of varroa
·
No need for specific
medicines
d) Identify possible reasons for lack of
treatment options
As possible reasons for lack of treatment
options were identified:
• Resistance problems with existing products
• Efficacy problems
• Incorrect treatment
• Lack of harmonised treatment strategy
• Availability of medicines
• Insufficient knowledge of beekeepers
• High costs of veterinary medicines (vs bulk
chemical/homemade product)
- Proposals for possible solutions / actions
The group considered that
an overall strategy has to come first to decide case by case whether medication
should be used, in which conditions e.g. as last resort. Furthermore, the group
considered that:
·
Products should be
authorised as veterinary medicines to ensure that they are adequately formulated
to the intended use.
·
Easier registration of
medicines of substances with MRLs, especially for the ones that do not require
an MRL value (former Annex II substances) – Harmonisation in approach between
Member States was considered essential.
·
Optimising the use of the
substances already available with more flexibility for changing formulation and
conditions of use e.g. organic acids
·
Further research is needed
for development of new/alternative treatments
·
Better instructions for appropriate
use of the products
·
Creation of a group of
experts to propose a strategy for treatment
·
Control programmes are
needed that include good beekeeping practice and medicines
On the reasons described
above no proposals for essential substances were made.
Group 2, chair: Dr
J.-G. Beechinor (Irish Medicines Board), rapporteur: K Grein/I Koudouna (EMA)
Group 2 was asked to consider more issues of
feasibility and to prepare proposals
that would help support the use of authorised veterinary medicines by
beekeepers instead of relying on chemical substances/own preparations, as it is
often current practice. The proposals should address availability of existing
authorised veterinary medicinal products as well as development of new medicines
(entirely new molecules or
substances with MRLs [with or without MRL for honey, substances not requiring
an MRL value (former Annex II
substances)].
The general conclusions of
the group regarding availability of medicines, considering also the concerns identified regarding the access of beekeepers to
authorised medicines (need for veterinary prescription), the
price of medicines and inadequacy of information on existing products, were:
•
Beekeepers must have access
to authorised veterinary medicines and have a choice.
•
Better communication and information of beekeepers of
good beekeeping practice is necessary.
•
Adequate information to
beekeepers and/or training should be provided to ensure correct use of veterinary
medicinal products. This was seen as a role of governments.
• In order to
optimise the use of existing veterinary medicinal products, a strategy on what, when and how to use veterinary
medicinal products should be established, e.g. on national level, and
communicated/published. As example was given that advice on how to alternate
varroa medication in summer vs winter should be prepared and disseminated.
•
It should be further
discussed if countries should provide support, e.g. financial support or
national information centres.
•
It should also be explored if specific training of
veterinarians on bee diseases could be provided.
• It was also considered important that certain veterinary medicinal
products could be exempt from prescription to facilitate access to them for the
beekeepers.
• It was pointed out that at present several important substances for bee
treatment were not available as veterinary medicines, but only available as raw
material (used in “homemade” preparations) and without advice for adequate
treatment, presents a major obstacle for the use of authorised medicines and
development of new ones.
The non-availability of medicines arising from the situation that while a
number of veterinary medicinal products are authorised in the EU, they are not
accessible to beekeepers across the EU as the marketing authorisations exist
only in some countries was further reviewed.
How can existing
marketing authorisations be extended to other countries across EU?
·
In order to make better use of
existing marketing authorisations for bee medicines, it was proposed to explore possibilities under Art 7 of Directive
2001/82/EC, to accept marketing authorisations of other countries.
·
The meeting also called for
a single EU decision on applications (referred to in the discussion as “automatic
mutual recognition”), which is not possible under the current legislation
except for centralised applications, but should be explored for a future
revision of the legislation.
·
Provide incentives to encourage
marketing authorisations for bee medicines, e.g. fee waivers, as already done
in some countries.
The group discussed if the use of cascade would
provide the solution to the problem of (inadequate) availability of medicines?
·
The cascade was considered not the preferable solution, as veterinarians need to be consulted, thus
making treatment expensive and impractical.
·
Furthermore, the veterinarian
cannot have the data and knowledge to advise on a withdrawal period.
· Other obstacles: cascade provisions are for exceptional use, it is
required to have an MRL for a substance to be used under the cascade; it is
also necessary to have an MRL in honey
to allow for residue control.
·
Positive: Cascade allows the
use of veterinary medicines for bees authorised in other countries
Regarding the development of
new veterinary medicinal products for bees the group considered that:
•
The development of the medicine would have a better
chance if an MRL is already available or would be based on the extension of
existing MRLs to honey. Such a medicine is considered to have more chance than an entirely new molecule (without
MRL).
•
The example of oxalic acid was
considered a good model to develop a medicine, with MRL as first step.
Recognising that the marketing authorisation had so far no economic success, this
should however not discourage the
application of this model again in the future.
• The review of substances with JECFA/Codex MRLs
was encouraged in order to identify if there are potential candidates for bee
medicines.
•
Regarding new molecules, some
substances used in plant protection could
be potential candidates.
What incentives for the animal health industry would
allow new veterinary medicinal products for bees to be brought on the market?
(in place: fee reduction, 13 years data protection, MUMS requirements)
•
Data protection is key: 13
years protection is considered adequate, must be unique for formulation.
However, this data protection applies only for new products, and is not
applicable for extensions under the current legislation. The 5 year window for
extensions should be omitted in the future legislation. In addition, the
absence of data protection for MRLs is a concern.
•
The access to the medicinal
products for beekeepers should be facilitated, therefore where possible non
prescription medicines should be authorised for bees.
•
As a result, centralised
marketing authorisations are not suitable as they lead to prescription only medicines.
•
It was recognised that the
uncertainty on data requirements can be overcome by scientific advice: this is provided free of charge for MUMS
products by the European Medicines Agency.
•
Another issue considered
difficult: The establishment of a withdrawal period for veterinary medicines
for bees due to the fact that there is no drug metabolism in honey.
11.
Conclusions and
recommendations
The presentations and
discussions confirmed that the problem of bee health and appropriate treatment
of bees is much more complex and diverse than simply identifying some potentially
needed medicines.
The conclusions of the
breakout sessions were in general supported.
It was reiterated that an overall
strategy regarding medicines for bees would need to be established as priority.
Such a strategy should identify for each bee disease whether medication was
appropriate, and if confirmed, which medication should be used and the
appropriate conditions of use clarified.
It was considered essential
to improve the knowledge of beekeepers on good beekeeping practice, and that adequate information and/or training should be
provided to ensure correct use of medicines. This was seen as a role of governments.
It should also be explored if specific training of veterinarians on bee
diseases could be provided. Control
programmes are needed that include good beekeeping practice and medicines.
It was reiterated that the
use of only authorised veterinary medicines for beekeeping should be the goal.
Chemical substances used for the treatment of bee diseases should be authorised
as veterinary medicines to ensure that they are adequate for the intended use
and the correct conditions of use
are specified. It was pointed out that at present several
important substances for bee treatment are not available as veterinary
medicines, but are only available as raw material, used in “homemade”
preparations and without advice for adequate treatment presents a major
obstacle for the use of authorised medicines and development of new ones.
Another major obstacle to
the access to bee medicines by beekeepers was that they are mostly prescription
only, requiring consultation of a veterinarian thus making treatment
complicated and expensive. While the correct diagnosis of the problem was
considered important the proposal was also discussed whether certain veterinary
medicinal products for bees could be exempt from prescription to facilitate
access to them for the beekeepers.
It was recognised that
several veterinary medicinal products are authorised in some Member States in the
EU, however they are not authorised and accessible to beekeepers across the EU
and in all countries. Efforts should be made to make better use of existing
marketing authorisations for bee medicines, and existing legal provisions
should be explored, such as Art 7 of Directive
2001/82/EC, marketing authorisations of other countries can be accepted if ‘the
health situation requires it’. Providing
incentives for marketing authorisations for bee medicines e.g. through fee
waivers, should also be explored. The use of the cascade was not considered
the preferable solution at present due
to the limitations that its use imposes. In the future revision of the
veterinary legislation further facilitation of marketing authorisations for
medicines for bees, e.g. the
possibility for a single EU
decision for authorisation (referred to in the discussions as “automatic mutual
recognition”), should be considered. More flexibility for changing the formulation and conditions of use would
also be helpful.
While further research is
needed for the development of new/alternative treatment options on the reasons
described above no proposals for essential substances were made at this point.
It was proposed that an expert group be created to prepare a proposal for a treatment
strategy.
Regarding the development
of new veterinary medicinal products for bees the meeting considered that in
general substances with an existing marketing authorisation for other species
and substances with existing MRL or not requiring an MRL (former Annex II
substances) would have better chances to reach a marketing authorisation than an
entirely new molecule (without MRL). The model for oxalic acid, in which sorting
out the MRL was the first step and the collaborative approach between several
partners should be further explored for the future.
The animal health industry has
shown interest in developing medicines for bees, however it also highlighted the
obstacles that hinder medicines development and marketing for bees. Experience
has shown that existing veterinary medicines may not be economically successful
to allow further investment, as beekeepers continue using raw material or home
made preparations. In order to develop new medicines incentives, in particular
adequate data protection would be needed.
The meeting considered that
continued discussions were necessary to find solutions. It was recognised
that many of these aspects of the debate are outside the scope and mandate of
the European Medicines Agency, and that further discussions would need to involve
additional partners. The efforts by the Agency to organise the meeting and allow
these discussions were appreciated and further activities welcomed. The chair
thanked the speakers and participants for their contributions and active
participation. The Agency will consider if further meetings aimed to continue
catalysing the dialogue could be organised."
Figure 1.
List of
Participants
|
Agede,
Guillaume
|
CEVA
Santé Animale
FRANCE
|
|
Beechinor,
J Gabriel
|
Irish
Medicines Board,
IRELAND
|
|
Besana,
Andrea
|
COPA
COGECA
BELGIUM
|
|
Branner,
Sven
|
Danish
Beekeepers Association
DENMARK
|
|
Bruneau,
Etienne
|
COPA-COGECA
BELGIUM
|
|
Cakstina,
Andra
|
Zāļu
valsts aģentūra
LATVIA
|
|
Casimiro,
Ramiro
|
Agencia
Española de Medicamentos y Productos Sanitarios
SPAIN
|
|
Chauzat,
Marie-Pierre
|
Agence
Francaise De Securite Sanitaire Des Produits De Sante
FRANCE
|
|
Chobotová,
Eva
|
Ústav
štátnej kontroly veterinárnych biopreparátov a liečiv
SLOVAK REPUBLIC
|
|
Clayton, Rick
|
International Federation
for Animal Health (Europe)
BELGIUM
|
|
Clayton,
William
|
Volunteer
assisting the Bees for Development organisation
UNITED KINGDOM
|
|
Clemence,
Rick
|
Pfizer
Ltd
UNITED KINGDOM
|
|
Cyrus,
Barbara
|
European
Medicines Agency (EMA)
UNITED KINGDOM
|
|
De
Ridder, Erik
|
Elanco
Animal Health
BELGIUM
|
|
Draghici,
Alina
|
Institutul
pentru Controlul Produselor Biologice si Medicamentelor de Uz Veterinar;
ROMANIA
|
|
Duarte,
Isaura
|
European
Medicines Agency (EMA)
UNITED KINGDOM
|
|
Dubna,
Sona
|
Czech
University of Life Sciences
CZECH REPUBLIC
|
|
Fehervari, Monika
|
Central Agricultural Office
HUNGARY
|
|
Filodda,
Frank
|
Fédération
Européenne Des Emballeurs Et Distributeurs De Miel (FEEDM); GERMANY
|
|
Gisler,
Simon
|
Andermah
Biovet GmbH
GERMANY
|
|
Grant,
James
|
Fédération
Européenne Des Emballeurs Et Distributeurs De Miel
GERMANY
|
|
Grein,
Kornelia
|
European
Medicines Agency (EMA)
UNITED KINGDOM
|
|
Gurgulova,
Kalinka
|
National
Diagnostic & Research Veterinary Medical Institute
BULGARIA
|
|
Haefeker,
Walter
|
European
Professional Beekeepers Association (EBKA)
GERMANY
|
|
Hahn,
Gesine
|
Bundesamt
für Verbraucherschutz und Lebensmittelsicherheit
GERMANY
|
|
Heck,
Thomas
|
British
Honey Association
UNITED KINGDOM
|
|
Hederová, Judita
|
Ústav
štátnej kontroly veterinárnych biopreparátov a liečiv
SLOVAK REPUBLIC
|
|
Ionescu,
Giusepe
|
AMC
Property
ROMANIA
|
|
Jencic,
Vlasta
|
Veterinary
Faculty university of Ljubljana
SLOVENIA
|
|
Jones,
Anne
|
Birch
Garth (Veterinary Consultant)
UNITED KINGDOM
|
|
Kay,
Jack
|
Veterinary Medicines
Directorate (VMD)
UNITED KINGDOM
|
|
Kirke,
David
|
ERA
Consulting
UNITED KINGDOM
|
|
Kryger,
Per
|
Aarhus
University
DENMARK
|
|
Lecompte,
Philipe
|
Reseau
Biodiversite Pour le Abeilles
FRANCE
|
|
Liege,
Philippe
|
Anisteme
Biosciences
FRANCE
|
|
Lovett,
Tim
|
British
Beekeepers Association
UNITED KINGDOM
|
|
Maček,
Laura
|
Javna
agencija Republike Slovenije za zdravila in medicinske pripomočke; SLOVENIA
|
|
Martin,
Peter
|
Honey
International Packers Association (HIPA)
UNITED KINGDOM
|
|
McIntosh,
Liz
|
Food
and Environment Research Agency (FERA)
UNITED KINGDOM
|
|
Neeser,
Rosmarie
|
Swissmedic
- Schweizerisches Heilmittelinstitut
SWITZERLAND
|
|
Orantes Bermejo, Francisco
José
|
CR. Dop Miel de Granada
SPAIN
|
|
Ponte, Maria Helena
|
Direcção-Geral de Veterinária (DGV)
PORTUGAL
|
|
Reybroeck,
Wim
|
ILVO
- T & V
BELGIUM
|
|
Richardson,
Jane
|
European
Food Safety Authority (EFSA)
ITALY
|
|
Rickwood,
Sandra
|
Surrey
Beekeepers Association
UNITED KINGDOM
|
|
Ritter,
Wolfgang
|
OIE
Reference Laboratory at CVUA
GERMANY
|
|
Schuermann,
Annette
|
Bayer
Cropscience AG
GERMANY
|
|
Seinhorst,
Jan Willem
|
Central
Veterinary Institute of Wageningen UR
NETHERLANDS
|
|
Sharman,
Matthew
|
Food
and Environment Research Agency (FERA)
UNITED KINGDOM
|
|
Siefert,
Benoit
|
VETO
PHARMA
FRANCE
|
|
Simón
Delso, Noa
|
Centre Apicole de Recherche et d'Information (C.A.R.I.)
BELGIUM
|
|
Soto,
Emma
|
European
CommissionDG General Health and Consumers
BELGIUM
|
|
Spagnuolo-Weaver,
Martha
|
Veterinary
Medicines Directorate
(VMD)
UNITED KINGDOM
|
|
Stanchev,
Philip
|
Primavet-Sofia
Ltd
BULGARIA
|
|
Tervell,
Margareta
|
Swedish
Board of Agriculture
SWEDEN
|
|
Torres
Fernandes Pinas, Cristina
|
C.R.
Protected Designation Origen Honey of Granada
SPAIN
|
|
Trumpickaitë
Dzekèiorienë, Snieguolë
|
Nacionalinis
maisto ir veterinarijos rizikos vertinimo institutes;
LITHUANIA
|
|
Tsigouri,
Angeliki
|
National
Organisation for Medicines (EOF);
GREECE
|
|
Vandaele,
Bill
|
Klifovet
BVD; Association of veterinary Consultants (AVC)
BELGIUM
|
|
Vernerova,
Eva
|
Ústav
pro státní kontrolu veterinárních biopreparátů a léčiv
CZECH REPUBLIC
|
|
Vidal-Naquet,
Nicolas
|
Federation
of Veterinarians of Europe
FRANCE
|
|
Voichita,
Andrei
|
Tapas
srl
ROMANIA
|
|
Watkins,
Max
|
Vita
(Europe) Limited
UNITED KINGDOM
|
|
Wilkins,
Selwyn
|
National
Bee Unit (NBU)
UNITED KINGDOM
|
Les commentaires récents