Source: EURLEX
Language: en
Format: md

*|*

# 52014SC0273

**COMMISSION STAFF WORKING DOCUMENT IMPACT ASSESSMENT Accompanying the document Proposal for a Regulation of the European Parliament and of the Council on veterinary medicinal products /\* SWD/2014/0273 final \*/**

  

TABLE OF CONTENTS

1..... Procedural
issues and consultation of interested parties 6

1.1.     Overview........................................................................................................... 6

1.2.     Stakeholder consultation................................................................................... 6

1.3.     Inter-service Steering Group.............................................................................. 7

1.4.     Scrutiny by the Commission's
Impact Assessment Board................................. 7

2..... Problem
definition......................................................................................... 8

2.1.     Background....................................................................................................... 8

2.2.     Problem identification....................................................................................... 9

2.3.     Underlying drivers........................................................................................... 10

2.3.1.       A multi-species and
stagnant market................................................. 10

2.3.2.       Costs to place a product
on a pluri-national market.......................... 12

2.3.3.       Complex requirements for
keeping medicines on the market............ 14

2.3.4.       Lack of clarity in the
legislation........................................................ 15

2.4.     Contribution to the fight
against the development of resistance to antimicrobials          17

2.5.     Principles of Conferral,
Subsidiarity and Effectiveness (added value) tests.. 19

3..... Objectives........................................................................................................... 20

3.1.     General objective............................................................................................. 20

3.2.     Specific and relevant
operational objectives.................................................... 20

3.3.     Consistency with other EU
policies and horizontal objectives........................ 21

4..... Policy
options.................................................................................................. 21

4.1.     Baseline scenario – "no
EU action"................................................................. 21

4.2.     Policy options regarding
lack of availability of veterinary medicines............. 23

4.2.1.       Policy options to expand
the market beyond the top four animal species          23

4.2.2.       Policy options to simplify
procedures for obtaining a marketing authorisation in multiple national markets................................................................................. 24

4.2.3.       Policy options to review
data requirements in marketing authorisation procedures       25

4.2.4.       Policy options to simplify
post authorisation requirements............... 26

4.2.5.       Policy options for
breakthrough medicines....................................... 27

4.2.6.       Policy options to clarify
rules on internet retail, on the authorisation of new treatments, on inspections
and on authorisation of medicines for emerging diseases           27

4.3.     Additional policy options to
strengthen the veterinary medicines legislation regarding the authorisation and
use of veterinary antimicrobials in veterinary medicine...... 28

4.4.     Options discarded at an
early stage................................................................. 29

5..... Analysis
of impacts...................................................................................... 29

5.1.     Costs and benefits of
options to expand the market beyond the top four animal species           30

5.1.1.       Option 1 - No new EU
action............................................................ 30

5.1.2.       Option 2 - Improve the
Cascade........................................................ 30

5.1.3.       Option 3 – Expand the
database to cover all veterinary medicines... 30

5.1.4.       Option
4 – Reduced data requirements for veterinary medicines for
limited markets   31

5.1.5.       Option
5 – Reduced data requirements for medicines for bees........ 31

5.2.     Costs and benefits of
options to simplify authorisation procedures................ 31

5.2.1.       Option 6 - No new EU
action............................................................ 31

5.2.2.       Option 7 - Automatic
recognition of a national marketing authorisation           31

5.2.3.       Option 8 - Single
marketing authorisation procedure for all products 32

5.2.4.       Option 9 – Wider scope for
the centralised procedure...................... 32

5.2.5.       Option 10 - Simpler
packaging and labelling..................................... 33

5.2.6.       Option 11 – Allow already
nationally approved medicines to freely circulate across the Union................................................................................................. 34

5.3.     Costs and benefits of
options to review data requirements for marketing authorisation procedures......................................................................................................................... 35

5.3.1.       Option 12 - No new EU
action.......................................................... 35

5.3.2.       Option 13 – Generic
applications may refer to environmental data.. 35

5.3.3.       Option 14 – Harmonisation
of clinical trial procedures across the Union          36

5.4.     Costs and benefits of
options to simplify post authorisation procedures........ 36

5.4.1.       Option 15 - No new EU
action.......................................................... 36

5.4.2.       Option 16 – Risk-based
pharmacovigilance...................................... 36

5.4.3.       Option 17 – Review of
procedures to change a marketing authorisation (variations)    36

5.4.4.       Option 18 – Delete the
obligation to market a product within 3 years of approval (Sunset clause)................................................................................................ 37

5.4.5.       Option 19 – Delete
requirements for renewals.................................. 37

5.4.6.       Option 20 Exempt
homeopathic medicines from pharmacovigilance requirements       37

5.5.     Costs and benefits of options
to review incentives for breakthrough medicines 37

5.5.1.       Option 21 - No new EU
action.......................................................... 37

5.5.2.       Option 22 – Extended data
protection for new veterinary medicines 38

5.6.     Costs and benefits of
options to improve clarity on internet retailing of veterinary medicines,
authorisation of new treatments, inspections, authorisation of medicines for
emerging diseases......................................................................................................................... 38

5.6.1.       Option 23 - No new EU
action.......................................................... 38

5.6.2.       Option 24 – Authorisation
to sell veterinary medicines through the internet in all Member States................................................................................................. 39

5.6.1.       Option 25 – Establish a
framework to authorise new treatments...... 40

5.6.2.       Option 26 – Establish a
basis to harmonise the controls on the veterinary medicines distribution chain............................................................................... 40

5.7.     Additional policy options to
strengthen the veterinary medicines legislation regarding the authorisation and
use of veterinary antimicrobials in veterinary medicine...... 41

5.7.1.       Option 27- No new EU
action........................................................... 41

5.7.2.       Option 28 – Introduction
of legislative measures to allow restrictions to be placed on the authorisation
and use of veterinary antimicrobials............................ 41

5.7.3.       Option 29 - Measures
regarding advertising of veterinary medicines, including antimicrobials..................................................................................... 42

5.7.4.       Option 30 - Measures
regarding retailing of veterinary antimicrobials 42

5.7.5.       Option 31 - Introduction
of a legal basis for the compulsory collection of data on the use of
antimicrobials................................................................................ 43

6..... Comparison
of the policy options....................................................... 43

7..... Monitoring
and evaluation................................................................... 48

8..... annexes................................................................................................................ 51

Annexes || Page

Annex 1 Acronyms || 52

Annex 2 Glossary || 53

Annex 3 Information sources || 58

Annex 4 Background information on the veterinary sector || 65

Annex 5 Overview of the institutional landscape and of the regulatory framework for veterinary medicines || 70

Annex 6 Further information related to the problems identified with the veterinary medicines legislation and on antimicrobial resistance || 79

Annex 7 Availability of veterinary medicines for bees || 106

Annex 8 SMEs and micro-enterprises || 109

Annex 9 Consultation results and stakeholders ‘ views || 111

Annex 10 Discarded options || 154

Annex 11 Comparison tables of policy options || 157

Annex 12 Table providing an overview of problems, specific objectives, operational objectives and preferred policy options regarding the problem of lack availability of veterinary medicines  || 173

1.
Procedural issues and consultation of interested
parties
1.1.
Overview

The legal environment for the
authorisation, production, marketing, distribution and use of veterinary
medicines is set out in Directive 2001/82/EC of the European Parliament and of
the Council (Articles 95 of the Treaty establishing the European Community -
TEC) and Regulation (EC) No 726/2004 of the European Parliament and of the
Council (Articles 95 and 152 (4) (b) of the TEC). Following the entry into
force of the Lisbon Treaty, amending the TEC, Articles 168 (4) (c) and Article
114 of the Treaty on the Functioning of the European Union (TFUE) give the
legal basis for the legislation in the area of veterinary medicines.

Over the years, the regulatory standards
and procedures set out in Directive 2001/82/EC have been adapted through
legislative amendments in response to scientific advances in the pharmaceutical
regulatory environment and the needs of the veterinary sector. However,
stakeholders and Member States have expressed concerns that the legislation as
it stands nowadays does not meet the needs of the Union regarding the
availability of medicines and treatments for veterinary use and does not fully
achieve the realisation of the internal market for veterinary medicinal
products.

In response to the concerns raised by
stakeholders the Commission agreed to conduct an assessment of the problems in
the application of the veterinary medicinal products Directive, in its
declaration under the co-decision procedure concerning the proposal for a
regulation on residue limits of pharmaceutical products in foodstuffs[1]. The
revision of the regulatory framework for veterinary medicinal products is
included in the Commission Work Programme 2013[2].

1.2.
Stakeholder consultation

A wide online public consultation took
place from April to July 2010. A total of 172 responses were received. A
summary report, showing a breakdown of the responses by type of respondent, was
published online, as well as individual responses (unless they were submitted
confidentially).

In addition, qualitative and quantitative
data were collected on the impact of the legislation between February 2011 and
April 2011 through in-depth consultation with the national competent
authorities, the main industry trade association and the main veterinary
association from six countries (Cyprus, Finland, Germany, Poland, Romania and the United Kingdom).

Various specific consultations were also
carried out with key stakeholders in the veterinary sector and the industry,
through questionnaires, meetings and workshops. The consultation exercise was
complemented by a series of targeted meetings with smaller groups of experts on
pharmacovigilance, antimicrobial resistance, and authorisations/data
protection. Another meeting was organised specifically with small and
medium-enterprises and micro-enterprises (SMEs) to discuss their specific views
and needs.

Contact with Third Countries took place
through participation in conferences and through meetings of the International
Cooperation on Harmonisation of Technical Requirements for Registration of
Veterinary Medicinal Products (VICH) (a multinational programme between the EU,
Japan and the USA).  The points discussed at the VICH meetings were taken on
board for the development of the options listed in this impact assessment.

The impact assessment builds on the report
'An assessment of the impact of the revision of veterinary pharmaceutical
legislation' carried out by the European Policy Evaluation Consortium (EPEC).
One EPEC member, GHK Consulting, carried out the study assisted by Triveritas.
This report was commissioned by the European Commission and the study was
carried out from November 2009 to June 2011.

Information collected for the preparation
of the impact assessment is in Annexes 3 and 9.

1.3.
Inter-service Steering Group

A Commission Inter-Service Steering group (ISG)
on the impact assessment of the revision of the legislation was set up in 2009.
Initially the project was led by the Directorate-General Enterprise, but
following organisational changes the area of pharmaceutical veterinary
medicines was transferred to Directorate General Health and Consumers. The ISG
included the following participants: Commission Directorates General
Agriculture and Rural Development, Environment, Industry and Entrepreneurship,
Maritime Affairs and Fisheries, Research and Innovation, Trade and the
Secretariat General. The group met on 9 October 2009, 17 November 2009, 8
December 2009, 11 June 2010, 8 October 2010, 9 June 2011, 16 April 2012, 17
September 2012 and 25 October 2012.

1.4.
Scrutiny by the Commission's Impact Assessment
Board

The impact assessment was scrutinised by the Impact Assessment Board
(IAB) on 18 December 2012. In its initial opinion, the Board requested the
following improvements to the report:

To
better present the main problem, explain its drivers and support it with
evidence;
Improve
the baseline scenario and better demonstrate the need to act;
Improve
the intervention logic and option design;
Better
assess and compare options;
Improve
monitoring and evaluation arrangements.

These points had been taken on board in the
preparation of a new version of the  report. In particular, this report
concentrated on the problem of the lack of availability of medicines and its
main drivers. The baseline scenarios regarding availability of medicines and
the need to act were better explained, for example regarding the harmonisation
of controls, retailing of medicines, novel therapies and antimicrobial
resistance. The option design and intervention logic were modified to provide in
depth analysis only for the more realistic options. The assessment of risk, and
the cost and benefits of the policy options were better explored. The
evaluation and monitoring arrangements were clarified.

The revised Impact Assessment was re-submitted to the
IAB in July 2013 and some further changes were requested. The problem definition was strengthened and the analysis of the problem
drivers streamlined by merging the description of market characteristics with
the corresponding regulatory failures, i.e. merging multispecies market with
legislation not suited to innovation, and pluri-national market with complex
marketing authorisation requirements and procedures. A better explanation on
the problems related to the current use of the Cascade was given under Section
2.3. The report was amended throughout, where relevant, to complement the views
of industry with the views of national authorities and to better demonstrate
the extent to which some of the regulatory requirements may be considered as
unnecessary (as it is for example the case for the submission of periodic
safety update reports).

To better demonstrate the need for harmonisation at the EU
level regarding internet retailing, new treatments and clinical trials, the report
was amended through footnotes 28-31 and in Annex 6. The report was also amended
in section 2.4, footnote 47 and Annex 6 to explain how the current rules
prevent authorities from prohibiting or restricting the use of antimicrobials;
to provide more details on the "disharmonised decisions" (and views)
of Member States and to clarify if the concern that veterinary surgeons can be
"pressurised" to prescribe unnecessary antimicrobials is only a
hypothetical one (footnote 43). Specific and operational objectives were listed
for antimicrobial resistance under section 3.2.

The options were better explained and their impact analysed, 
for example, regarding the more flexible  use of the Cascade  (option 2);  the
basis for reduction of data requirements for certain products and how the
corresponding risks would be managed (option 4); the aspects of harmonisation
for national control systems, new treatments and clinical trials (options 14,
25, 26); how a criteria  to define safety risk of "legacy" medicines
could be defined (option 11), and how the authorisation of certain classes of
antimicrobials could be restricted (option 28). These points were addressed in sections
5 and 6, and Table 11. An indication of the total implementation costs for the
EU budget and the EMA is provided in section 5. The need to address the issue
of medicines for bees is explained in Annex 7.

The report was amended throughout, where
relevant, to better explain how the standards of public and animal health would
be maintained should the preferred options be  implemented and also to indicate
how the concerns of national authorities have been addressed. The views of all
relevant stakeholder groups, including farmers and consumer organisations, are
presented in the Annex 9. The report also links the assessment of the options'
effectiveness to the corresponding policy objectives in table 3. The benchmark
for the suggested monitoring indicators (linked to the specific objectives) is
in page 45.

2.
Problem definition
2.1.
Background

Veterinary medicines are regulated by
Directive 2001/82/EC and Regulation (EC) 726/2004, from their manufacture to
use, to ensure their quality, safety and efficacy and so safeguard animal and
public health, whilst at the same time ensuring the functioning of the internal
market for veterinary medicines[3].

The veterinary pharmaceutical sector is made
of businesses involved in research and development of new veterinary medicines,
manufacturers of veterinary medicinal medicines (including generics),
importers, wholesalers and retailers. The veterinary pharmaceutical industry sales
in Europe are estimated at 4.6 billion euros - 2005 prices (global sales represent
over 13.4 billion euros in 2009). Around 14,600 people are directly employed by
the veterinary medicines manufacturing industry in Europe.

The animal health market is divided into
two sectors - farmed animals and companion animals - which are driven by
different marketing rationales. The farmed livestock industry is a high volume
market driven by economic, competition and food safety concerns, whereas the
companion animal market represents a smaller market, but characterised by high
value and high growth. It is also less prone to sudden market variations (such
as those occurring from a sudden outbreak of disease) and linked to the changes
to the purchasing power of pet owners[4].
More detailed information on the veterinary sector may be found in Annex 4; an
overview of the regulatory framework for veterinary medicines is in Annex 5.

See Annex 2, Glossary, for an explanation
on technical terms used throughout the impact assessment.

2.2.
Problem identification

The private and public sectors have reported an overall lack
of authorised veterinary medicines in the Union, for minor species[5] (in particular for bees
– see Annex 7), for rare or emerging diseases and for the treatment and
prevention of diseases in major species, as illustrated hereafter. There is a
lack of certain veterinary medicines in all countries, but the availability of
a number of medicines is a particular problem to some smaller Member States. This
lack of authorised veterinary medicines poses significant problems for animals,
their owners, farmers, veterinary surgeons, consumers and governments as the
absence of treatments or the use of non-authorised treatments may result in[6]:

–
Poorer animal health and welfare;

–
Increased risk for public health due to the
spread of untreated zoonosis, or through the exposure to residues of medicines;

–
Negative economic consequences such as interruption
of farming, compromised supply of foodstuffs (in case of disease outbreaks), economic
and competitive disadvantage for EU farming, and trade implications when
residues of unauthorised substances are detected[7],

–
Legal implications for veterinary surgeons who
prescribe medicines under the Cascade (e.g. where residues or unexpected animal
losses occur).

See
Annex 6 for further details of the problems with availability of veterinary
medicines.

Examples
of problems with veterinary medicines availability

Lack of veterinary medicines for minor species

FISH
– There are no authorised medicines to treat any conditions in many of the food
fish species farmed in the Union (sturgeons, perch, cod, char, turbot). There
are on average 10 marketing authorisations per Member State (range from 0 to
29) for medicines for more established farmed species such as  trout and
salmon. This is very low compared to the number of marketing authorisations for
medicines for dogs and chickens, for example (average 592 and 198 marketing
authorisations per Member State respectively). There are no authorised vaccines
against viral haemorrhagic septicaemia of salmonids (which can cause up to 80%  mortality
in fish), or medicines to conditions such as fish lice (Argulus sp),
ichthyophthiriosis, fungal diseases (Saprolegnia sp), flatworms
(mongenean infections), ulcerative dermatitis (Uronema sp).

The lack of veterinary medicines for use in
aquaculture is highlighted in the Strategy for the future of the European
aquaculture[8]
as one of the major problems
for the industry. In Europe,
aquaculture accounts for almost 20% of fish production, with a turnover of
roughly EUR 2.9 billion and generating some 65 000 jobs. The sector is
expanding to farming of “new” species such as sea bass, sea bream, cod, sole,
scallops and octopus and the lack of authorised veterinary medicines is
affecting business. Since only seven applications were received for new
marketing authorisation or for extension of existing marketing authorisations
to include fish in the period 2006-2009, it can be assumed that this situation
will not improve in the near future if there are no changes. Fish farmers
indicated that treatment of diseases in fish is done almost completely with
medicines used under the Cascade, but the statutory withdrawal period of 500 0C/days
reduces the availability of some treatments when this is required in proximity
of the harvest.

TURKEYS - Currently there is no treatment against histomoniasis
(blackhead), a disease caused by the protozoan Histomonas meleagridis.
This disease has high morbidity and mortality in turkeys, with serious
consequences to the European turkey farming industry, as most infected birds
die (there are reports that some farmers had to cull entire flocks due to
infection).

Lack of veterinary medicines for emerging diseases

SCHMALLENBERG VIRUS.
This virus is responsible for abortion and foetal deformities in sheep, goat
and cattle and was initially identified in 2011 in Germany and in The
Netherlands. By October 2012 it had been reported in 14 countries.  A vaccine was
authorised in one Member State in May 2013 (2 years after the initial outbreak)
but this vaccine only has a provisional marketing authorisation and therefore
cannot be mutually recognised in other Member States -  to be placed on the
market in the other 28 countries of the Union a marketing authorisation needs
to be sought in each of these countries, resulting in further delays on the
control of the disease.

Lack of veterinary medicines for the treatment of
diseases in major species

PARASITIC WORMS present a significant production
threat to grazing animals; their control is thus vital for animal health but
heavily depends on the effectiveness of medicines (anthelmintics)[9]. Resistance of worms to
the anthelmintics currently authorised in sheep, cattle, goats, horses is
increasing at an alarming rate, and in some regions of Europe multi-resistance
to the three major anthelmintic classes has already been identified.  There are
few anthelmintic products in the pipeline: only one new class of anthelmintic
for sheep has been developed since the 80s, and livestock producers are left
with few options for effective treatment.

2.3.
Underlying drivers

The reasons behind the lack of available authorised
veterinary medicines are various and are discussed below in detail. In summary,
the high cost of developing a regulatory dossier and applying for a marketing authorisation
combined with the constraints existing in the legislation regarding the data
requirements for multi-species deter the development of new, needed veterinary
medicines. In addition, post marketing authorisation requirements (such as
variations and renewals), to maintain a product on the market become decision-points
for keeping or abandoning well-established but low volume sales medicines. This
situation has more profound effects on medicines for less common indications
and for less common animal species (“minor use-minor species”), with virtually
no authorised medicines for “new” food-producing species, such as cod or
ostriches. As a result, veterinary surgeons have to result to extensive use of
the Cascade. When medicines are used under the Cascade in food producing animal
species, specific (statutory) minimum withdrawal periods have to be observed;
in some cases these withdrawal periods are impractical, for example for animals
with a short life span, thereby limiting the possibilities for treatment.

2.3.1.
A multi-species and stagnant market

The veterinary pharmaceutical sector is
driven by commercial returns obtained through the sales of veterinary medicines
on the resources spent (from product development to placing it on the market).
But the market is split between food producing animals and companion animals
and both sub-sectors are multi-species: this results in a fragmented market.

Over 50% of the pharmaceutical market is
based on the agricultural sector which is cost-sensitive, and is under pressure
from global competition. The market can rarely return high prices for
sophisticated medicines (expensive treatments cannot be afforded for routine
use in production animals as the emphasis is on flock or herd health rather
than individual animals). For livestock farmers animal treatment must be cost
effective. For example, meat production is a price-driven market with intensive
international competition[10],
thus livestock farmers aim to reduce the share of the costs of veterinary
medicines of their total operating costs. For companion animals, the purchasing
power of the consumer equally affects the market price of medicines.

The confined, fragmented markets both for
companion and farming animals drive the pharmaceutical sector to concentrate on
larger markets which permit a positive return on investments[11]. The ‘top four’ markets
for veterinary medicines are dogs, cattle, pigs and cats species. This
translates directly into the number of marketing authorisations in the EU - 70 %
of all marketing authorisations are for those species, with dogs having more
veterinary medicines authorised than any other species (as companion animals
provide a better return to investments than farmed species).

In addition, there is a concern, expressed
both by regulators and the pharmaceutical industry, that the current veterinary
pharmaceutical legislation is not suited to innovation. There has been
considerable consolidation of the veterinary medicines industry over the last
twenty years, with fewer than two dozen international companies remaining in
the sector, and with the development of a very strong generic industry. It is
reported that there is a decline in the number of applications for new
veterinary medicines whilst there is a growth in the number of generic
applications.  The development of a generic product is less expensive than that
of a novel product and therefore the potential return to investment for
generics is behind the development of a strong generic pharmaceutical industry.

Another reason behind this shift from
innovation to the manufacture of generic products is that the current data
protection provisions do not take into account the difficulty found by
veterinary sector in recovering investments spent in the development of novel
veterinary medicines. The data protection period currently lasts for 10 years
(13 years for bees and fish) , with an extra year of data protection granted
per new food-producing species added within 5 years of the initial
authorisation. Since 1991 the costs for new product development (total costs
from discovery to first sales, including application procedure) have risen by
229% for food-producing animals, 173% for companion animals and 108% for minor
species. The cost of developing a regulatory dossier which would meet European
requirements for a major species has been estimated at 15-50 million euros,
while for an additional indication it has been estimated at 2-6 million euros.

2.3.2.
Costs to place a product on a pluri-national
market

Prior to placing a veterinary medicine on
the market, the applicant must obtain a marketing authorisation in all the
countries where it intends to market it (Annex 5 describes the EU framework for
authorisation of veterinary medicines). About 80% of the respondents to the
public consultation were dissatisfied with the current regulatory environment.

The veterinary medicines legislation sets
out the provisions concerning the scope and the procedures required for a marketing
authorisation. Although the legislation has been amended[12], [13], [14], [15] to reduce administrative burdens, it still incurs in high costs to
the industry regarding placing a veterinary medicine on the market. The total
annual administrative burden imposed on business by the veterinary medicines
legislation was estimated to be 537.9 million euros per year, which represents
around 13% of the turnover of veterinary medicines sector - twice of that
estimated for the human sector[16]. The
table below summarises the costs incurred by the veterinary pharmaceutical
industry.

Table 1: Break-down of overall
administrative costs (resulting from staff time, overheads, equipment costs and
outsourced costs (e.g. hiring an external expert to prepare a technical report)
per activity per year

Activity || Administrative burden \*[17] || % of the total administrative burden

Application for a marketing authorisation || 91.1 || 17

Packaging and labelling || 184.4 || 34

Applying for a variation to an existing marketing authorisation || 133.5 || 25

Marketing authorisation renewals || 69.5 || 13

Pharmacovigilance || 59.4 || 11

\* million euros per year

The highest burden concerns packaging and
labelling. The requirements are that the text must be written in all the
official languages of the country where the product is to be placed on the
market. This translates ultimately into companies deciding not to apply for
authorisation in some Member States because the costs associated with the
country-specific product labelling and packaging in the relevant national
language(s) represents a too high expense to justify the operation in those
countries. For example, in some countries such as Malta and Finland there are no veterinary medicines authorised for bees[18]. Some Member States such as Luxembourg and Austria have a large number of authorised medicines on their markets because they
benefit from larger markets using the same language, such as France and Germany. But in general, the cost of small manufacturing runs for specific packaging and
labelling outweighs the potential sales in smaller countries.

The cost of obtaining a marketing
authorisation to place a product on the market is also high. Companies, often
SMEs, decide to apply for a national authorisation to initially “test” their
product on a market. To expand beyond those initial national borders, a
re-assessment has to take place to obtain a marketing authorisation in other
Member States even if the nationally marketed product has a record of safe use.
This re-assessment is costly and burdensome both to the pharmaceutical
companies and to the Member States and restrains companies from rolling-out
their product across the EU.

Even the “rolling out” of authorisations
granted in the past through the national route for products that have been on
the market for many years in different Member States is difficult. These
“legacy” products have been authorised with significant differences on the
summary of product characteristics regarding indications and withdrawal period,
for example. Although most of these products have a record of safe use, and
have been on the market in the EU for many years, a scientific reassessment
still has to take place for the product to be marketed in a new Member State. However, this dossier re-assessment (or the evaluation for an application for
a generic, where the reference product is one of these “legacy” veterinary
medicines) often results in referrals to arbitration, when Member States have a
disharmonised view from the initial assessment or regarding the information
placed on the  summary of product characteristics. These referrals are costly -
the pharmaceutical industry estimated the cost of a referral (Article 34
referral) as 445,000 euros.

During the public consultation Member states and the industry
indicated that some  current requirements and procedures (for example regarding
authorisation of antimicrobials) generate unpredictability and disagreements
between Member States and are only resolved through referrals (in particular regarding
the mutual recognised and decentralised procedures); the limited scope of the
centralised procedure and the high administrative burdens. SMEs also indicated
that the current legislation does not set out harmonised procedures and
timelines for the regulation of clinical trials across the EU, and so different
national regulations have been put in place at national level.  This lack of
harmonisation is burdensome and costly for the companies, in particular regarding
the setting up of multi-centric trials. Another area identified by SMEs as
burdensome and unnecessary is the current legal obligation for pharmaceutical
companies to place a product on the market within three years of its approval
(the Sunset clause)[19].

The figure below shows the administrative
burden to the industry incurred in complying with the legislation in order to
place and maintain a veterinary medicine on the market. The decentralised
procedure is the most costly procedure to companies, on average, and the
centralised procedure is the least costly of the three European procedures. The
national procedure generates the lowest administrative burden of all
procedures.

Figure 1 Average administrative burden (in euros) per product per
action, by marketing authorisation procedure

 DCP – decentralised procedure; MRP- mutual
recognition procedure; CP-centralised procedure; NP-national procedure

2.3.3.
Complex requirements for keeping medicines on
the market There are disproportionate costs of
"mandatory defensive research" for keeping a
medicine on the market (that is, the expenditure
necessary to maintain existing products in the market as a result of legal
requirements by the regulatory authorities, through variations, renewals and
pharmacovigilance)[20].
More than 80% of European businesses consulted consider that the EU regulatory
requirements are too burdensome and a barrier to innovation – and the most
negative aspect causing an impact on business is the re-direction of resources for development of new medicines into
defensive research[21],[22],[23]. The average costs
spent on defensive research in the EU was estimated at 35 % of the total global
R&D budget (26% in Canada and 14-16% for Australia, Japan and USA). The industry claimed that the continuing demands for defensive research
have intensified the balancing act between investment in new products and
maintaining existing products on the market[24].

The requirements for variations are cited
as a persistent high cost of defensive research. The veterinary pharmaceutical
industry considers the procedures to introduce variations to the terms of
marketing authorisations very cumbersome, and responsible for around 25% of the
total administrative burden (133.5 million euros per year). Although in recent
years attempts have been made to simplify arrangements for variations, and
since 2009 variations legislation has been harmonised across all four marketing
authorisation procedures, the number of variations to marketing authorisations is
still high[25].

Another factor incriminated as a
disproportionate cost to the industry is pharmacovigilance requirements. Pharmacovigilance
aims to monitor the performance of veterinary medicines placed on the market.
The legislation requires marketing authorisation holders to maintain databases
of all suspected adverse events in animals and humans related to the use of
their veterinary medicines. The marketing authorisation holders are also
required to report adverse events to the competent authorities and prepare
reports on the overall performance of the products (periodic safety update
reports - PSUR). Following the initial placing on the market, PSURs must be submitted
immediately upon request or at the following intervals: 6-monthly for the first
2 years;  annually for the subsequent 2 years; thereafter, at 3-yearly
intervals. This frequency of reporting is considered excessive by both the
pharmaceutical industry and some regulators, in particular those from smaller
countries[26].
The current pharmacovigilance requirements are based on those applied to the
human sector and cost around 59.4 million euros per year[27] to the veterinary
pharmaceutical industry.

It is important to note that although
regulators agree that administrative costs are high, there is a need to 
maintain procedures in place to ensure public and animal health and safety to
the environment.

2.3.4.
Lack of clarity in the legislation

The legislation lacks clarity regarding provisions
on the retailing of prescription and non-prescription veterinary medicines over
the internet or through mail order[28]. As a consequence, some Member States introduced national controls
on online sales of veterinary medicines (e.g.: United Kingdom, Germany, Ireland), and others have no
controls or forbid it (Austria
and Belgium). This fragmentation reduces the potential
benefits that retailers of veterinary medicines (in particular SMEs and
micro-enterprises) could have from operating on a larger, EU-wide market and
developing new services for consumers. In addition, owners of companion animals
and farmers cannot benefit from the growth of the market which could lead to competitiveness
and lower-priced veterinary medicines. It is clear that online sales of
veterinary medicines could benefit substantially these end-users as retail and
wholesale prices of medicines differ up to 50% between Member States[29].

New technologies and therapies for animal
treatment are emerging from developments in the human sector[30],
but the provisions in the veterinary legislation are not sufficiently clear
regarding these treatments. Therefore, some Member States have developed their
own systems at national level to regulate products such as blood and stem cells;
on the other hand, other Member States have no regulation on these areas and
consider these treatments as clinical practice (e.g., Sweden). The current situation creates a fragmentation of the internal market and a problem
of availability of such therapies in some countries, and overall a
disharmonised approach to animal health and welfare in the Union[31].

Effective disease control requires a fast
response, but the current legislation does not allow an effective, rapid
response to a new or re-emerging animal health threat at a pan-European level.
In this situation, veterinary medicines are authorised at national level in
some Member States – those which have developed fast-track procedures to
authorise medicines in exceptional circumstances.  This creates an un-level
playing field in the Union, which is particularly detrimental to farmers.

In addition, no harmonised legal framework
exists at EU level regarding the way controls, including inspections of
wholesale dealers and retailers, are organized and carried out by Member State competent authorities throughout the distribution chain of veterinary
medicinal products.  Consequently there is no uniformity throughout the Union
on the application of such controls, and this generates an un-level playing
field across the Union. For example, some Member States have not fully
implemented or correctly transposed the requirements of the veterinary
medicines legislation[32].
This represents a risk for animal safety and public health and causes distortion
of competition in the Community, detrimental to the operation of the internal
market[33].

Annex 6 provides further information on the
drivers behind the lack of availability of veterinary medicines.

Problem tree: Lack of  availability of
veterinary medicines

2.4.
Contribution to the fight against the development of resistance to antimicrobials

Antimicrobial resistance has increased in
importance worldwide in recent years. It is reported to cause many deaths (25,000
patients die each year in the EU from infections caused by resistant bacteria)
and great financial costs (extra health care costs and productivity losses were
estimated as of at least 1.5 billion euros per year) in the human health care
setting. According to the World Health Organisation, common, yet
life-threatening infections caused by resistant bacteria are becoming difficult
or even impossible to treat. The problem is aggravated by the scarcity of new
antimicrobials being developed, which limits treatment options for patients
with infections caused by multidrug-resistant organisms[34],[35].

The Parliament and the Council have voiced their concerns regarding
the problem of antimicrobial resistance. The Commission considers antimicrobial
resistance a public health threat[36]
and adopted an action plan to address the problem. This action plan list as key
actions (regarding veterinary medicines):

–
Action n° 2: Strengthen the regulatory framework
on veterinary medicines and on medicated feed via the review package foreseen
for 2013;

–
Action n° 7: Promote efforts to analyse the need
for new antibiotics into veterinary medicine;

–
Action n° 10: Strengthen surveillance systems on
antimicrobial resistance and antimicrobial consumption in animal medicine.

Antimicrobial resistance in animals can be
transmitted to humans through zoonotic diseases. The importance of animals and
of food of animal origin in the emergence, spread and persistence of
antimicrobial resistance in humans has not yet been completely established[37] but the inappropriate therapeutic use and the non-therapeutic use
of antimicrobials in animals (such as use of antimicrobials to mask poor farm
management or inadequate zootechnical practise) is considered to be one of the
drivers for the development of resistance in the human sector[38].

Human medicines and veterinary medicines
including antimicrobials are regularly used for non-approved indications and
with non-approved dosages under the Cascade[39].
This ensures animal treatment but there is a concern that this practice, and in
particular the use of last resort human antimicrobials, may contribute to the rise
of antimicrobial resistance in humans.  Another area of concern is the
carry-over of antimicrobials in the production of medicated feed. This is out
of the scope of this impact assessment but is addressed through the revision of
the medicated feed legislation.

It is acknowledged that the current
veterinary medicines legislation does not provide sufficient tools to ensure
that risks to human health arising from the use of antimicrobials in animals
are adequately managed, as the assessment process is based on data presented (product-specific). For example,
there are no legal provisions to allow regulators to prohibit or place
restrictions on the authorisation for animals of certain classes or groups of
antimicrobials that are considered reserved for the treatment of human
infections. As a consequence, these types of antimicrobials may be authorised
in some Member States but not in others, or may be authorised and used under
different conditions. This creates difficulties for the implementation of a
holistic strategy to the control of antimicrobial resistance in the Union. The legislation also does not allow the prohibition or the restriction of the use of
antimicrobials under the Cascade, and this also hampers the prudent use of
antimicrobials in veterinary medicine. In addition, legislative and
non-legislative national measures have been put in place at national level as
an effort to tackle antimicrobial resistance, thus creating disharmonised
decisions in the Member States which generate a constant stream of referrals
for arbitration [40].
Furthermore, the different approaches regarding prescription, use and
distribution of antimicrobials in the Member States hamper efforts to deal with
the problem of antimicrobial resistance in a holistic manner in the EU. There
is also a concern that the advertising of antimicrobials, under the disguise of
informative material, enables or induce farmers and companion animal owners to
pressurise veterinary surgeons to prescribe unnecessary antimicrobials or
prescribe unsuitable (but convenient) antimicrobials, which leads to an overuse
of these medicines[41].

For those reasons, although this is not
directly related to the availability of veterinary medicines, the issue of
antimicrobial resistance will be addressed as part of the revision of the
veterinary legislation, in accordance with the actions of the Commission Action
Plan against the rising threats of antimicrobial resistance.

Further discussion on the issue of
antimicrobial resistance is included in Annex 6.

2.5.
Principles of Conferral, Subsidiarity and
Effectiveness (added value) tests

The primary
purpose of the legislation is to ensure the quality, safety and efficacy of the
veterinary medicines to safeguard public and animal health and safety to the
environment. But this objective must be achieved without hindering the
development of the industry and trade of veterinary medicinal products within
the EU.

Legislation in the area of internal market
(Art 114 TFEU), and regarding common safety concerns in public health matters
and standards of quality and safety for medicinal products (Art 168(4) (c)
TFEU) is a shared competence between Union and Member States. The current EU
legislation on veterinary medicines, Directive 2001/82/EC and Regulation (EC)
No 726/2004, based on Article 95, and Articles 95 and 152 (4)(b) of the TEC
respectively, provide the legal environment on authorisation, production,
marketing, distribution and use of veterinary medicines. The
existing legislation on veterinary medicines brought some harmonisation to the
procedures and rules required to place veterinary medicines on the EU market
but there is evidence that the existing provisions do not completely deliver
the ambition of a functioning internal market and do not match the current
needs of the veterinary sector.

The Communication from the Commission Europe
2010 "A strategy for smart, sustainable and inclusive growth"
identifies the incomplete functioning of the single market as a missing link
and a bottle neck for growth in the Union:

"A stronger, deeper, extended single
market is vital for growth and job creation…. Every day businesses and citizens
are faced with the reality that bottlenecks to cross-border activity remain
despite the legal existence of the single market. They realise that networks
are not sufficiently inter-connected and that the enforcement of single market
rules remains uneven. Often, businesses and citizens still need to deal with 27
different legal systems for one and the same transaction."

To fully achieve a strong internal market on
the area of veterinary medicines, there is a need to simplify and streamline
across the Union the regulatory system for the authorisation of veterinary
medicines, removing inefficiencies and barriers to cross border trade. This
would improve the availability of medicines thus benefiting the veterinary
sector in general, from manufacturers to the end users (farmers and the general
public).

3.
Objectives
3.1.
General objective

In accordance with the Treaty, the objective
of this proposal is to ensure a high level of public health protection, high
standards of quality and safety of veterinary medicines and the optimal
functioning of the internal market.

3.2.
Specific and relevant operational objectives

Increasing the availability of veterinary
medicines would contribute to achieving the overall goal of the proposal. Furthermore,
using this opportunity to contribute to mitigating the risk
of development of antimicrobial resistance would further reinforce the ambition
of a high level of public health protection.

In practice, improving availability of veterinary medicines would
require improving the regulatory environment to:

1)
simplify it and reduce administrative burdens whilst
maintaining safeguards to ensure public and animal health, safety to the
environment and allowing more accessible use of
medicines to fill therapeutic gaps via an improved Cascade;

2)
foster the development
of new medicines, including for minor use-minor species, while keeping those
already on the market;

3)
facilitate the circulation of veterinary
medicines across the EU, through better authorisation procedures, and via new
forms of retail such as internet.

This would translate in the following specific
and operational objectives below:

Table 2 Framework on veterinary medicines -
drivers and objectives

Lack of availability of veterinary medicines

Drivers || Specific objective || Operational objectives (OO)

Multi-species market || A Expand market beyond the top four animal species || A.1. Improve the use of the Cascade

A.2. Improve information on authorised veterinary medicines available in the Union

A.3. Simplification of application requirements for veterinary medicines for limited markets

E1. Strengthen data protection incentives

Pluri-national market || B. Simplify procedures for obtaining a marketing authorisation in multiple national markets || B.1. Review centralised, decentralised and mutual recognition procedures

B.2. Revision of the situation with “legacy products”

Complex authorisation requirements || C. Review data requirements in marketing authorisation procedures || C.1. Revision of environmental requirements for generics

C.2. Revision of  provisions for authorisation of clinical trials

Complex requirements for keeping medicines on the market || D. Simplify post authorisation requirements || D.1. Simplification of pharmacovigilance

D.2. Simplification of variation requirements

D.3. Revise the Sunset clause

D.4. Abolish renewals

D.5. Simplify requirements for homeopathics

Legislation not suited to innovation || E. Review incentives for breakthrough medicines || E1. Strengthen data protection incentives

Lack of clarity in the legislation || F. Improve clarity: on  rules on internet retailing of veterinary medicines || F.1. Specify rules for internet retailing of veterinary medicines

on the authorisation of new treatments || F.2. Specify rules for new treatments

on inspections || F.3. Harmonise national control systems

on authorisation of medicines for emerging diseases || A.3. Simplification of application requirements for veterinary medicines for limited markets

The issue of antimicrobial resistance,
recognised worldwide as an important public health threat, is not directly
related to the availability of veterinary medicines. However, in response to
concerns raised by the Parliament and the Council, the Commission adopted an
action plan to tackle this problem in a holistic manner. This plan includes
actions related to the authorisation and use of veterinary medicines and,
therefore, it is proposed to address the issue of antimicrobial resistance in
the context of the regulatory framework for veterinary medicines, focusing on
the authorisation and use of antimicrobials in this area. The specific
objective is an overall strengthening of the veterinary medicines' regulatory
framework regarding the authorisation and use of antimicrobials which would
contribute to lowering the risks to public and animal health.  The operational
objectives are the introduction of proportionate measures regarding the
authorisation and use of antimicrobials and of measures to ensure an efficient surveillance
system on the use of veterinary antimicrobials.

3.3.
Consistency with other EU policies and
horizontal objectives

The objectives listed are coherent with the
EU and the Commission's strategic principles, in particular regarding
decreasing administrative burden[42],
simplifying the regulatory environment[43]
and putting in place measures to complete the internal market[44] for
veterinary medicinal products. This assessment is in addition conducted in
parallel to that for the revision of the medicated feed and is consistent with
the proposed revision of the EU system of official controls along the food
chain, and the policies on animal health[45].

4.
Policy options
4.1.
Baseline scenario – "no EU action"

The baseline scenario for this impact
assessment consists of no changes to the current regulatory framework ("no
EU action"). Consultation with stakeholders indicated that, if there is no
EU intervention, the problems described would continue
to exist and the trend towards divergent national
action is likely to continue. Duplication of efforts, the
setting of different standards and the introduction of more administrative
complexity to the regulatory system would remain.

The problem with the availability of authorised
medicines would continue or even worsen, presenting risks to animal health and
welfare from existing and emerging diseases. The continued lack of availability
of authorised veterinary medicines would lead to animal health and welfare
consequences – and public health would also be at risk, as there is a link
between animal diseases and public health. The lack of suitable authorised
medicines,  in particular to minor species, would force veterinary surgeons to resource
more often to using medicines under the Cascade[46], increasing the potential public and animal health risks (as the
use of medicines under the Cascade is not supported by specific safety and
efficacy studies on their effects). No EU action also would mean that the public
health threat of antimicrobial resistance would not be addressed through clear
legal tools and would continue to be tackled by Member States without a
holistic, consistent approach across the Union.

Further innovations are anticipated
regarding the application of new technologies in veterinary medicine, such as
gene therapy. At present these new types of treatment are not clearly defined
within the legislation, causing confusion as to how they should be treated as
part of the authorisation process[47].
If no EU action is taken, it is likely that this uncertainty will remain, with
an uneven approach to animal treatment across the EU.

Due to different interpretations of the
legislation, the rules on internet retailing of veterinary medicines vary widely
in the Member States, leading to legal uncertainty. It also leads to an un-level
playing field for businesses as internet retailers of veterinary medicines can
be established in some but not all Member States; it also impacts on the
pricing of veterinary medicines across the Union through interference with
competition[48].

Control systems related to veterinary
medicines are organised and carried out by Member States, and significant
variations in the level and effectiveness of controls have been noted[49]. No
EU action would mean that this disharmonised situation would remain.

If the option "no EU action" is
adopted, situations like these described would continue to exist. On the other
hand, action at EU level to draw up a harmonised and proportionate system to
regulate the manufacture, distribution, possession, prescription, dispensing,
administration and use of veterinary medicines would create a predictable legal
environment, beneficial to innovation and to the availability of veterinary
medicines. It would also prevent Member States from taking action which would
result in a further fragmentation of the internal market.

The "no new EU action" option has
been taken as the baseline against which the policy options proposed below were
measured to evaluate their potential impacts.

4.2.
Policy options regarding lack of availability of
veterinary medicines

The policy options considered most
realistic are discussed below. For easy of reading, the options are grouped by
specific objectives. Some of the options are alternative and some address more
than one specific objective. “No new EU action” has always been taken into
consideration as a possible option.

4.2.1.
Policy options to expand the market beyond the
top four animal species

The options discussed
here concern the use of the Cascade, provision of information on the veterinary
medicines authorised in the EU, the granting of MAs for limited markets, and innovation
(operational objectives A1, A2, A3 and E1).

Specific objective || Operational objectives (OO) || Options

A. Expand market beyond the top four animal species || A.1. Improve the use of the Cascade || 2 - Improve the Cascade

A.2. Improve information on authorised medicines available in the Union || 3 - Expand database to cover all veterinary medicines

A.3. Simplification of application requirements for veterinary medicines for limited markets || 4 – Reduced data requirements for MA for limited markets

E1. Strengthen data protection incentives || 5 - Reduced data requirements for medicines for bees

Option 1
- No new EU action

This option proposes no regulatory changes.

Option 2 - Improve the Cascade (OO A.1)

Currently veterinary surgeons must follow a
ranking system to choose a medicine for use under the Cascade; the veterinary
surgeons must also follow the withdrawal period set in legislation, if the animal
under treatment is a food-producing species. This policy option proposes to abolish
the ranking system to introduce more flexibility and so allow veterinary
surgeons to choose the best available treatment to the animal under their care.
The option also proposes to modify the way withdrawal periods are determined
for use under the Cascade, so that a system based on multiplication factors is
used taking into account any withdrawal period information available for the
product.

Option 3 – Expand database to cover all veterinary medicines (OO A.2)

This option proposes to create a
legislative requirement for the compulsory uploading of information on all
marketing authorisations into a single, comprehensive EU database. This
database would be linked to the already existing pharmacovigilance database
(Eudravigilance).

Option 4 – Reduced data requirements for medicines for limited
markets (OO A.3)

This
policy option would introduce regulatory changes to allow applicants to submit
applications with reduced data for certain products. The type of data that
could be omitted would be decided on the scientific advice of the EMA, so that
any safety risks are analysed and taken on board. This option aims to fill
therapeutic gaps on the market for limited markets (minor uses and minor
species), and to allow the authorisation of veterinary medicines in case of
urgent need. This option also relates to specific objective F.

Option 5 – Reduced data requirements for
medicines for bees (OO E.1)

This option proposes to reduce the quality and
efficacy requirements for applications for bee medicines. In addition, this
option proposes to allow veterinary surgeons, under their direct personal
responsibility, to treat bees with medicines that are
authorised in certain Third countries during the time
period that no honey flow takes place.  This would only be allowed if no authorised medicine exists in the EU
for the disease and the use of the
Cascade is not appropriate.

4.2.2.
Policy options to simplify procedures for
obtaining a marketing authorisation in multiple national markets

The options discussed
here concern the authorisation procedures and the management of the problem
with “legacy products” (operational objectives B1 and B2).

Specific objective || Operational objectives || Options

B. Simplify authorisation  procedures || B.1. Review CP, DCP and MRP procedures || 7 – Automatic recognition of a national MA

8 – Single MA procedure for all products

9 – Wider scope for the centralised procedure

10 – Simpler packaging and labelling

B.2. Revision of situation with “legacy products” || 11 – Already nationally approved medicines allowed to freely circulate across the Union

Option 6 - No new EU action

This option proposes no regulatory changes.

Option
7 - Automatic recognition of a national marketing authorisation (OO B.1)

This option is to allow an application for
a marketing authorisation to be assessed and issued by a Member State and made valid automatically throughout the Union. Pharmaceutical companies seeking to
have a product authorised would be free to submit an application to any of the
national competent authorities and, if approved, an authorisation would be
granted entitling the product to be marketed anywhere within the EU.

Option
8 - Single marketing authorisation procedure for all products (OO B.1)

This option proposes that a single dossier
is submitted to a committee composed by representatives from the Member States
which then would assign an assessment team to evaluate its scientific contents.
Once the assessment is concluded (and if positive), a single decision would be
adopted by the Commission or an authorisation issued by all Member States. The
pharmaceutical company then would be free to place the product on the market in
all or on some Member States only, depending on its commercial strategy.

Option 9 – Wider scope for the centralised procedure (OO B1)

This option maintains
the mandatory use of the centralised procedure for innovative medicines (as it
is the case under the current legislation) and proposes to extend the scope of
this procedure to make it available, upon choice by the applicant, to all types
of veterinary medicines. To make the centralised procedure more accessible to
SMEs, the option also proposes the introduction of a legal obligation to
national authorities to introduce supportive measures (e.g., a help desk) to
veterinary SMEs which intend to apply for a marketing authorisation through
this procedure.

Option 10 – Simpler packaging and labelling (OO B.1)

This option is to simplify the packaging
and labelling of a veterinary medicinal product, which is part of the marketing
application dossier. The use of pictograms and abbreviations would be allowed
as much as possible to reduce the amount of written text, whilst still ensuring
the safety of the product. Leaflets would still be required and the
pharmaceutical companies would be allowed to provide information to veterinary
surgeons and the public by other means (e.g. barcodes) too. The national
authorities would no longer pre-approve the packaging and labelling layout of
veterinary medicinal products. Under this option, the national authorities
would be able to authorise the use of a non-official language on the packaging
and labelling of the medicines placed on the market in their territory, if they
so wish.

Option 11 – Already nationally approved veterinary medicines allowed
to freely circulate across the Union (OO B.2)

This option proposes the “rolling out” to
other countries of “legacy” veterinary medicines which already have national marketing
authorisations in the EU. This would be carried out through a review, which would
harmonise the summary of product characteristics of these products, allowing
the widest scope possible (that is, taking on board all the indications and
target species granted in all Member States). The decision on which products
would require assessment prior to harmonisation would be carried out by a
scientific committee, to ensure the safety of the product. The proposal also
includes an option for pharmaceutical companies to join efforts to generate
data if necessary, to be compiled in the form of a monograph (to cover gaps on
data regarding environmental safety, for example).

4.2.3.
Policy options to review data requirements in
marketing authorisation procedures

The options discussed
here concern provisions for the authorisation of veterinary medicines (operational
objectives C1 and C2).

Specific objective || Operational objectives (OO) || Option

C. Review data requirements for marketing authorisation procedures || C.1. Revision of environmental requirements for generics || 13 – Generics applications may refer to environmental data

C.2. Revision of  provisions for authorisation of  clinical trials || 14 – Harmonisation of clinical trials procedures across EU

Option 12 - No new EU action

This option proposes no regulatory changes.

Option
13 – Generic applications may refer to environmental data (OO C.1)

This option proposes to allow pharmaceutical
companies applying for generic veterinary medicines to refer to environmental
data as part of the safety dossier package, which already is no longer required
for a generic application. Therefore a generic application would not require
submission of data on environmental safety, as it is currently the case. Instead,
pharmaceutical companies would have the possibility to take advantage of a
system of data sharing between applicants, so that a report (monograph) could
be generated to address environmental risk concerns.

Option 14 – Harmonisation of clinical trials procedures across the Union (OO C.2)

This option proposes to harmonise the timelines
for the authorisation of clinical trials for veterinary medicines in the Union, which currently are not harmonised.

4.2.4.
Policy options to simplify post authorisation
requirements

The options discussed
here concern, variations, the sunset clause, renewals and pharmacovigilance
requirements (including for homeopathics) (operational objectives D1, D2, D3,
D4 and D5).

Specific objective || Operational objectives (OO) || Options

D. Simplify post authorisation requirements || D.1. Simplification of pharmacovigilance || 16 – Risk-based pharmacovigilance

D.2. Simplification variation requirements || 17 – Review  procedures to change a marketing authorisation (variations)

D.3. Revise sunset clause || 18 – Delete the obligation to market a product  within 3 years of approval

D.4. Abolish renewals || 19 – Delete requirements for renewals

D.5. Simplify requirements for homeopathics || 20 – Exempt homeopathic medicines from pharmacovigilance requirements

Option 15 - No new EU action

This option proposes no regulatory changes.

Option 16 – Risk-based pharmacovigilance (OO D.1)

This option proposes a risk-based approach
to pharmacovigilance, where certain requirements (e.g. submission of repeated
period safety update reports) that do not contribute effectively to public
health, animal health or the protection of the environment are abolished.
Pharmaceutical companies would have the responsibility to collect and introduce
adverse event reports into an EU pharmacovigilance database and to analyse these
data at product level through signal detection. This option would also
introduce the concept of a Pharmacovigilance Master File dossier containing
information on the pharmaceutical company's systems.  Therefore, this option
would remove the requirement for the description of the pharmacovigilance
system to be placed on the dossier for each marketing authorisation application.

Option 17 – Review procedures to change a marketing authorisation
(variations) (OO D.2)

This option proposes a risk-based approach
to deal with variations to a marketing authorisation. Those variations which do
not introduce changes that might substantially affect the product safety would not
require scientific assessment. Other changes would still require prior
authorisation by the competent authorities before implementation.

Option 18 – Delete the obligation to market a product within 3 years
of approval (OO D.3)

The option proposes the removal of the
Sunset clause (an existing obligation to market a medicine within three years
of granting the marketing authorisation) from the legislation.

Option 19 – Delete the requirement for renewals (OO D.4)

This proposal is to abolish the general renewal
requirements for veterinary medicines but maintain a renewal for specific
marketing authorisations, granted to veterinary medicines submitted for
assessment without a complete data dossier.

Option 20 – Exempt homeopathic veterinary medicines from
pharmacovigilance requirements (OO D.5)

This option proposes to exempt veterinary
homeopathic medicines from the requirements concerning pharmacovigilance.

4.2.5.
Policy options for breakthrough medicines

The option discussed here concerns data protection
(operational objectives E.1).

Specific objective || Operational objectives || Option

E. Review incentives for breakthrough medicines || E. 1 Strengthen data protection incentives || 22 – Extend data protection period for new veterinary medicines

Option 21 - No new EU action

This option proposes no regulatory changes.

Option 22 - Extend the data
protection period for new veterinary medicines: (OO E.1)

This option proposes an initial period of
data protection of ten years with extensions to a new species receiving an
added period protection of three years. The maximum period of data protection
would be twenty years. The option would also create particular provisions for medicines for minor species, such as fish
(products would receive an initial data protection period of fifteen years). A
provision to particularly benefit the development of medicines for bees would
be introduced: veterinary medicines initially authorised for bees would have an
automatic initial period of data protection of twenty years, and any extension
to a marketing authorisation to add bees as target species would have a data
protection period of five years. To incentivise the development of novel
antimicrobials specifically developed for use in veterinary medicine, these
products could receive an initial data protection for fifteen years, and
extensions to new species could receive five years data protection.

This option also supports the Specific
objective A - Expand the market beyond the top four animal species.

4.2.6.
Policy options to clarify rules on internet
retail, on the authorisation of new treatments, on inspections and on
authorisation of medicines for emerging diseases

These policy options address problems regarding lack
of clarity on the legislation regarding internet retailing of veterinary
medicines, new treatments and treatments in case of outbreaks (operational
objectives F1, F2, F3 and A3).

Specific objective || Operational objectives || Options

F Improve clarity: on internet retailing of veterinary medicines || F.1. Specify rules for internet retailing of veterinary medicines || 24 – Authorisation to sell veterinary medicines through the internet in all MS

on the authorisation of new treatments || F2 Specify rules for new treatments || 25 – Establish a framework to authorise new treatments

on inspections || F3. Harmonise national control systems || 26 – Establish a basis to harmonise the controls on the veterinary medicine distribution chain

on authorisation of veterinary  medicines for emerging diseases || A3. Simplification of application requirements for veterinary medicines for small markets || 4 – Reduced data requirements for veterinary medicines for limited markets

23 - No new EU action

This option proposes no regulatory changes.

Option 24 – Authorisation to sell veterinary medicines through the
internet in all Member States (OO F1)

This option proposes the introduction of a
requirement for the authorisation at national level of internet retailers
wishing to sell prescription and non-prescription veterinary medicines in the Union. This authorisation would be valid across the EU.

Option 25 – Establish a framework to authorise new treatments (OO F.2)

This option proposes to set out in the
legislation a framework for the authorisation of new treatments (e.g. stem cell
treatments), indicating the data requirements and exemptions relevant to the
area. In order to keep flexibility, important in this fast growing area, detailed
scientific and technical requirements drawn out by the EMA would be placed in
guidance.

Option 26 – Establish a basis to
harmonise the controls on the veterinary medicine distribution chain (OO F3)

This
option is to create a harmonised legal framework regarding the way controls on
the distribution chain of veterinary medicine are organised and carried out by
Member States' competent authorities.

Option 4 – Reduced data requirements for
veterinary medicines for limited markets (OO A3)

This
policy option would create the possibility to reduce some data requirements for
certain types of veterinary medicines, to fill therapeutic gaps on the market
for minor uses and minor species, or to allow the authorisation of veterinary
medicines in case of urgent need. This would be done based on scientific advice
from the EMA. This option also relates to specific objective A.

4.3.
Additional policy options to strengthen the
veterinary medicines legislation regarding the authorisation and use of
veterinary antimicrobials in veterinary medicine

27 - No new EU action

This option does not imply any regulatory changes.

Option 28 - Introduction of legislative measures to
allow restrictions to be placed on the authorisation and use of veterinary
antimicrobials

This option is
to introduce specific legislative requirements regarding the authorisation of
antimicrobials and their use under the cascade. These requirements would refer
to the submission and assessment of data for applications for veterinary
medicines containing certain types or classes of antimicrobials, in connection
with antimicrobial resistance. It would allow the competent authorities to
decide, based on scientific advice drawn by the EMA, whether or not a) a class
of antimicrobials of importance for human health may be authorised for use in
animals and b) if it may be authorised, under which specific conditions. This
option would provide that a decision could be taken even if a causal
relationship between the potential use of veterinary antimicrobials and
antimicrobial resistance in humans cannot be fully established at the time of
assessment due to incomplete scientific knowledge in the area. As part of this
proposal, authorities would be also able to prohibit or restrict the use
of certain antimicrobials under the Cascade, based on scientific advice
prepared by the EMA. Veterinary surgeons would be allowed to supply
antimicrobials to animals under their care only.

Option 29 - Measures regarding advertising of
veterinary medicines, including antimicrobials

The option is to
clarify the current provisions on the advertising of veterinary medicines,
including antimicrobials, aiming to ensure that marketing activities would not
lead to the misuse of prescription medicines.

Option 30 - Measures regarding retailing of veterinary
antimicrobials

The option proposes to allow veterinary
surgeons to prescribe antimicrobials to the animals under his/her care but
introduce a prohibition on the supply of these medicines.

Option 31 - Introduction of a legal basis for the
compulsory collection of data on the use of antimicrobials

The proposal is
to establish a harmonised and compulsory European system for collection of data
on the sales and usage of antimicrobials in food-producing animals.

4.4.
Options discarded at an early stage

The following options were discarded, as they were considered
unfeasible, ineffective or would create unacceptable risks to animal or public
health or to the environment:

To completely abolish pharmacovigilance requirements;
To replace the authorisation of low risk and generic veterinary
medicines with a registration system;
To make the centralised procedure compulsory to all veterinary
medicines;
To introduce exemptions to reduce legislative requirements
regarding  authorisation of veterinary medicines by pharmaceutical
companies that are SMEs or micro-enterprises;
To voluntarily harmonise the summary of product characteristics
of the “legacy products;
To standardise the distribution of veterinary medicines across
the Union;
To forbid generic applications for  antimicrobials;
To re-classify bees as non-food animals;
To develop "soft law instruments" to achieve policy
changes.

See Annex 10 for a detailed explanation on the discarded options.

5.
Analysis of impacts

The policy options to address the problems
highlighted in the report are largely compatible from the perspective of an
overall policy package (to simplify the regulatory environment, to reduce
administrative burdens and to complete the internal market) but their
simultaneous implementation may impact on costs and savings to stakeholders and
regulators. The options were evaluated for their costs and benefits to the
affected sectors based on the evidence obtained from the consultation
exercises. For each option, consultees’ views are referred to if expressed
during the public consultation (consultees’' views are presented in Annex 9).

Monetised costs and benefits were based on
assumptions; sometimes they were not available or accurate due to lack of key
data. This is indicated in each case. The baseline was "no new EU
action".

See Annex 11 for a table showing a
comparison of the costs and benefits of the policy options, and a table
depicting their effectiveness, efficiency and coherence[50] with EU objectives.

5.1.
Costs and benefits of options to expand the
market beyond the top four animal species
5.1.1.
Option 1 - No new EU
action

As this option would not imply any change
to the provisions already existing in the legislation, costs and benefits are
expected to stay identical.

5.1.2.
Option 2 - Improve the Cascade

It was clear from the consultation that the Cascade is
important in veterinary medicine, and contributes to increase the availability
of medicines in particular for  limited markets (minor uses and minor species).

When medicines are used under the Cascade
in food producing animal species, statutory minimum withdrawal periods must be
observed. In some cases these withdrawal periods are impractical, for example
for animals with a short life span, thereby limiting the possibilities for
treatment. The option to improve the use of the Cascade is based on a CVMP’s
proposal. It would replace the current statutory withdrawal periods with a
system based on safety factors which calculates the minimum withdrawal period that
would still ensure food safety. In addition, the option proposes to abolish the
current ranking system which determines the choice medicine for use under the
Cascade, so that veterinary surgeons would have more freedom to choose the best
medicine for the animal under their care.

Some national authorities and the
pharmaceutical industry remarked that a liberal use of the Cascade, even for
companion animals, might pose a risk to animal health and also lead to an
increase in the inappropriate use of antimicrobials. However, the proposal
allows more freedom to veterinary surgeons to choose the best available
treatment for sick animals, by way of an exception, in the absence of suitably
authorised veterinary medicines. This choice is carried out in accordance with a
veterinary surgeons' professional judgment, and for animals under his/her care,
thus ensuring animal and public health and environmental safety. Therefore the
risks of misuse of the Cascade would not increase from the baseline.  This
policy option has no impact on administrative burdens to the industry.

5.1.3.
Option 3 – Expand the database to cover all
veterinary medicines

This option would introduce a requirement
for the compulsory uploading of data on all marketing authorisations to an EU
database. The major benefit of this option would be an improvement on the
transparency within the authorisation system. The availability of an up-to-date
database of authorised veterinary medicines, readily accessible across the
Union, would help with the effective operation of the Cascade so that veterinary
surgeons in one Member State may identify the needed veterinary medicines available
from other Member States.  Therefore, ultimately this policy option would benefit
the protection of animal and public health in general. A complete and
up-to-date database of authorised veterinary medicines would also be a valuable
tool for the pharmaceutical industry, to map the veterinary medicines on the
market in the Union and therefore better target their  R&D investments. The
implementation of this option would lead to unquantified costs to the national
authorities or pharmaceutical industry concerning the uploading of information on
the marketing authorisations to the database. However, this may be balanced by
a reduction in costs related to informing the EMA about the relevant national marketing
authorisations falling in the scope of a referral, for example. The option
would have a positive impact on the functioning of the internal market.

5.1.4.
Option 4 – Reduced data
requirements for veterinary medicines for limited markets

This proposal would reduce administrative
burdens to the pharmaceutical industry regarding the preparation of a dossier
for a marketing authorisation for medicines aiming to fill therapeutic gaps. 
This would be particularly beneficial to farmers, as medicines, in particular
vaccines, could be quickly placed on the market in the event of emergency. The
proposal would be beneficial to animal health and welfare and to public
health.

5.1.5.
Option 5 – Reduced data
requirements for medicines for bees

This proposal is to allow regulators to wave
some data requirements for the authorisation of medicines for bees, if the data
are not considered essential to the safety of the product.  The option could
benefit the availability of medicines for this species by reducing the costs of
product manufacture and the preparation of the application dossier. The
proposal also envisages to allow the use in the EU of medicines for bees
authorised in some Third Countries, with the treatment being carried out when no
honey production takes place (to avoid the risk of residues in honey).

5.2.
Costs and benefits of options to simplify
authorisation procedures
5.2.1.
Option 6 - No new EU
action

As this option would not imply any change
to the provisions already existing in the legislation, costs and benefits are
expected to stay identical.

5.2.2.
Option 7 - Automatic recognition of a national
marketing authorisation

This option would reduce the administrative
burdens to pharmaceutical companies (estimated savings of 67.9 million euros
per year)[51].
These reduced costs would be particularly beneficial to SMEs/micro-enterprises
as they could start business by placing a product on a national market and then
progressively expand to reach other markets.

The success of this option would depend on
Member States.  The lack of peer review is a concern to some Member States,
which fear a possible reduction in the quality of the current assessment
standards. Although all Member States would be working to the same legislation
and guidelines, differences in resources, expertise, policy context and
geographical animal health status might affect the focus of the assessment of
the data presented in the application dossier, rendering the opinion of a
specific competent authority not acceptable to others. This could lead to a
high number of referrals to the CVMP. Such situation may occur even despite the
existence of a voluntary accreditation programme of the national authorities. This
option would favour the free movement of veterinary medicines in the Union.

5.2.3.
Option 8 - Single
marketing authorisation procedure for all products

This option is estimated to have a positive
impact on the simplification of the regulatory framework, and significantly reduce
the administrative burdens imposed by the legislation. If this option is
implemented it would cut an estimated 67.9 million euros each year to the
pharmaceutical industry[52].
This option is supported by the pharmaceutical industry and other consultees[53].

Unlike the current European centralised procedures,
this policy option does not include any element of peer review for the
assessment of the application dossiers. This peer review process requires
additional resources and is time consuming, but also provides quality assurance
at the level of individual marketing authorisation assessment. As for option 7,
many regulators expressed concerns regarding this lack of peer review, even if
a proposed independent EU body is created to assess the quality assurance
systems of the organisations that are responsible for carrying out scientific assessments.
Member States remarked that this option would not be able to ensure the quality
of the assessment process, which also would not be able to take on board
geographical and policy differences in different countries. This might have a
negative impact on animal and public health, and safety to the environment. However,
it was recognised that this option would improve the functioning of the
internal market.

5.2.4.
Option 9 – Wider
scope for the centralised procedure

This option combines the mandatory use of
the centralised procedure for innovative medicines, as it is currently the case,
and makes this procedure optional to all other types of veterinary medicines. In
the public consultation more than 85% of the respondents favoured extending the
scope of the centralised procedure. The SMEs/micro-enterprises consulted
expressed their support for this proposal, as it introduces flexibility and
choice into the system but indicated that they would still be inclined to use
more the centralised procedure if the procedure is made more SME-friendly, by
for example, the introduction of national helpdesks (see Annex 8 for a further
discussion on SMEs/micro-enterprises).

It is possible that applications currently
submitted through the decentralised and the mutual recognition procedures would
shift to the centralised procedure, and overload the EMA. This concern was
expressed by the regulators. It is difficult to estimate whether a significant
shift would take place, as it would depend on the evaluation of veterinary
pharmaceutical companies regarding what would the most appropriate marketing
authorisation procedure for their products. This evaluation would be affected
by many factors, for example the type of medicine, the way authorities would
implement the marketing authorisation procedures and the fees linked to the
procedure. To minimise a potentially excessive workload to the EMA and the CVMP
from such shift, the handling of submissions for authorisation of
well-established medicines such as generics (which require less expertise and assessment)
could be fast-tracked. It is expected that the costs to the EMA of taking on
new tasks (under this and other options) would be around  1-1,5 million euros
per year, which could be covered by a new fee structure and efficiency
measures, introduced by, for example, taking into account an increase in
applications to the centralised procedure and an optimised use of systems
already developed for human medicines.

This option would benefit human and animal
health and the environment, as there would be a more consistent assessment
across the Union of marketing authorisation applications. It would result in
savings in administrative burdens of 5.6 million euros per year[54] to the
pharmaceutical industry.

No additional resources would be required
for the Commission for the management of marketing authorisations granted by
centralised procedure as less resources would be required to manage variations
of central marketing authorisations.

5.2.5.
Option 10 - Simpler packaging and labelling

This policy option would reduce the costs
of product authorisation to the pharmaceutical industry as the costs of language-specific
packaging and labelling are high. There would be no significant impact on
animal or human health or safety to the environment in terms of information
provided on the safe and efficacious use of the product, as any risks
associated with the reduction on the information provided in the packaging and
labelling would be counterbalanced by placing the information on the product
leaflet and by making the information available through other sources (e.g.,
through compendia, barcodes). The option also offers the possibility for Member
States to allow the use of a non-official language on the packaging and
labelling of the product if they so wish. The pre-approval of the packaging and
labelling layout (but not the text) by the competent authorities would be
abolished.

Having the
packaging and labelling of a veterinary medicinal product prepared in fewer EU
languages would reduce the administrative burden to the
industry. It is difficult to quantify this potential benefit in terms of
availability of medicines, but it is likely that some Member
States considered to be small markets would be the most likely to benefit from
this policy change. The relatively high number of products authorised in Belgium and Luxemburg shows the potential of this option. The risk that the package and
labelling presented in a non-official language would not be understood by the
end users, leading to a safety risk, would be mitigated by the authorities'
assessment of the types of products that can be labelled with non-official
languages (for example, restricting this to prescription only medicines as most
veterinary surgeons can speak one of the major European languages) and the use
of standardised abbreviations and symbols.

National authorities agreed with the
industry that the reduction of the amount of text on outer packaging could be
done without compromising the protection of animal and public health, but
considered that no reductions should be made to the text within leaflets, which
provide essential safety information.

5.2.6.
Option 11 – Allow already nationally approved
medicines to freely circulate across the Union

The estimated reduction in administrative
burdens that this option would bring is 14.2 million euros per year as the
administrative assessment would replace existing and relatively costly
mechanisms for extending marketing authorisations to new national markets
through mutual recognition[55].
The implementation of this option would also have a positive impact on the
functioning of the internal market. Its effect on product availability is
likely to be significant and positive, as the range of products available would
increase: it is expected that pharmaceutical companies would be more inclined
to place their products on smaller markets once the cost of obtaining a
marketing authorisation is reduced.

Only medicines with a record of safe use
would be extended across the EU, but in practice pharmacovigilance systems vary
greatly between countries and may not be able to efficiently detect adverse
reactions. Furthermore, a number of older products in some EU markets may have
not been assessed for environmental safety in accordance with current standards[56]. Therefore, there is a
risk that a purely administrative implementation of the option might have a
negative impact on public and animal health, and the environment. To provide
assurances regarding the safety of these medicines, it is possible to propose a
system to harmonise the existing marketing authorisations to veterinary
medicines through a risk-based review. This would allow the scientific
assessment of those veterinary medicines that present, by their nature, a
higher safety risk to the environment or to public or to  animal health (for example,
antimicrobials) whilst still allowing the granting of a harmonised marketing
authorisation with the widest possible summary of product characteristics. Such
review would lead to an increase in the administrative burden to the
pharmaceutical industry, the EMA and the national authorities in the short
term, but in the long term the administrative burdens would decrease due to the
harmonisation of the authorisations. The collaboration between
pharmaceutical companies to generate data through a monograph to cover missing
data (such as environmental risks, for example) identified during the review, could be
established to decrease the costs of the review to the industry.

In the interest of the availability of
medicines for bees, and considering the nature of these products, it is
proposed that any medicines authorised for honey bees in any Member State be administratively recognised across the EU.

5.3.
Costs and benefits of options to review data
requirements for marketing authorisation procedures
5.3.1.
Option 12 - No new EU
action

As this option would not imply any change
to the provisions already existing in the legislation, costs and benefits are
expected to stay identical.

5.3.2.
Option 13 – Generic applications may refer to environmental
data

The current legislation requires that an
environmental risk assessment (ERA) is provided for each new application,
including applications for generics. This requirement applies, even if it is
logical that the ERA for the generic will reach the same conclusions and
outcome as for the originator product. For certain old veterinary medicines on
the market, no ERA has been carried out in accordance with the current ERA
requirements and this is a potential problem, in particular if these products
are used as originator for a new generic application.  The CVMP expressed an opinion that the current legal provisions
requiring an ERA for each new application for generics is considered not
suitable to address the matter, as it leads to the duplication of the
generation of data and possibly inconsistencies in conclusions. This committee suggested
that a flexible approach could be set up,  using a risk-based approach.

The option presented here aims
to remove this inconsistency in the legislation, so that ERA will be considered
in the same way as any other safety data, and no new ERA data would need to be
provided for each generics application. Instead, a system of data sharing between applicants would be
implemented so that a report (monograph) could be generated on active
ingredients to address environmental risk concerns.

The main beneficiaries of this option would
be the manufacturers of generic medicines, for whom the cost of obtaining a
marketing authorisation would decrease. This in turn might lead to an increase
in the number of generics placed on the market, increasing competition and thus
driving down the prices of veterinary medicines (and therefore increasing
animal holders’ access to medicines). It is expected that there would be no
negative impact on the environment, as environmental data are already assessed
as part of the safety dossier provided with the application for the reference
product and companies would be able to join efforts to carry out supplementary
or missing studies for particular ingredients, to cover any deficiencies
detected. In addition, it is expected that the national competent authorities
would elect to monitor these products more closely through pharmacovigilance.  There
is no significant impact on the functioning of the internal market.

5.3.3.
Option 14 – Harmonisation of clinical trial
procedures across the Union

This option aims to harmonise the
procedures for authorisation of clinical trials for veterinary medicines. It is
expected that it would bring a reduction of administrative burdens to the
pharmaceutical industry and therefore it would potentially benefit the 
development of new medicines. This option would particularly benefit SMEs,
which requested it.

5.4.
Costs and benefits of options to simplify post
authorisation procedures
5.4.1.
Option 15 - No new EU
action

As this option would not imply any change
to the provisions already existing in the legislation, costs and benefits are
expected to stay identical.

5.4.2.
Option 16 – Risk-based pharmacovigilance

This option aims to introduce a risk-based approach for
pharmacovigilance, by for example deleting the requirement of submission of
periodic safety update reports (PSUR) for a product. At
present the first PSUR is often due before the product has reached the

market, having scarce value for the evaluation of the
safety of the product. The administrative burden of PSURs is high, while only
very rarely the PSURs lead to safety findings. It is considered that the establishment
of an electronic reporting system and signal detection are more effective means
to monitor suspected adverse events, including
environmental incidents and withdrawal period violations, and could ensure that
prompt action is taken when needed.

The national authorities agreed that the
simplication of pharmacovigilance requirements, in particular regarding PSURs,
would allow them to concentrate efforts on areas and products of higher risk,
rather than using up resources on routine work. However, the authorities also
indicated that a robust pharmacovigilance system is key to protection of human
and animal health.

The implementation of this option would bring
savings to the pharmaceutical industry worth 47.2 million euros per year, and
allow it to focus their resources towards other areas[57].
SMEs/micro-enterprises were specifically consulted on the impact of the pharmacovigilance
requirements to their business and indicated that they would welcome a
simplification of the current requirements.

5.4.3.
Option 17 – Review of procedures to change a
marketing authorisation (variations)

The introduction of a risk-based approach to
deal with changes to a marketing authorisation could reduce administrative
burdens to the pharmaceutical industry by 10.9 million euros per year[58].
This option proposes that only changes to the marketing authorisation with an
assumed effect on safety of the product would be assessed and approved by the
competent authorities. Other changes would be dealt with as notifications. The
option would reduce costs and resources to the competent authorities, as there
would be fewer variations to be processed and scientifically assessed.  No particular
effect on the internal market is expected.

5.4.4.
Option 18 – Delete the obligation to market a
product within 3 years of approval (Sunset clause)

The removal of the Sunset clause from the
legislation would benefit the whole pharmaceutical industry, but in particular
SMEs/microenterprises which requested this during the consultation.  The option
would be beneficial to the availability of medicines. No particular effect is
expected to occur regarding the functioning of the internal market.

5.4.5.
Option 19 – Delete requirements for renewals

This proposal is to abolish the requirement
for a renewal for marketing authorisations for veterinary medicines (innovators
and generics) with exception of authorisations granted to products when some
data have not been presented in the application dossier. This option would
deliver significant reduction of annual savings to the pharmaceutical industry
(at least 67.5 million euros per year)[59].
It would also reduce costs to competent authorities, which could then focus on
the products which really require a renewal assessment.  It is expected that
the option would not have any significant effect on the operation of the internal
market.

5.4.6.
Option 20 Exempt homeopathic medicines from
pharmacovigilance requirements

This option would deliver a simplification
of the current requirements of the legislation regarding homeopathic medicines.
However, homeopathic medicines are veterinary medicines and already subject to
a simplified registration scheme. Abolishing the requirements to monitor the
performance of such medicines might represent a risk to animal health.

 
5.5.
Costs and benefits of options to review
incentives for breakthrough medicines
5.5.1.
Option 21 - No new EU action

This option implies no changes to the costs
or benefits to any stakeholder.

5.5.2.
Option 22 – Extended data protection for new
veterinary medicines

This option proposes to keep the initial
period of data protection of ten years but extensions to a new species would
receive an added period protection of three years, leading to a maximum of twenty
years of protection. The option would also create particular provisions for
minor species: veterinary medicines authorised for fish and other minor species.
Extensions to an initial marketing authorisation to include new species would
still be considered as part of the original marketing authorisation.

It is expected that the extension of the data
protection period would increase the ability of pharmaceutical companies to
recover product development and regulatory costs and make return on investments
for novel medicines. The option would therefore benefit innovation and improve
the availability of veterinary medicines, in particular for limited markets
such as medicines for bees and fish.

This option would benefit primarily
research-based pharmaceutical industry and would have some negative impact on
generics manufacturers, as it would delay their access to data from originators
and so their access to the market. On the other hand, the sustainability of the
generic manufacturing industry depends on new medicines being placed on the
market. It is clear that a balance is needed between providing incentives for
innovation and at the same time allowing the generic industry to enter the
market at a point where investments for innovators have been recovered.

The adequacy of the proposed 20 years
maximum period of data protection for a product and its extensions is difficult
to evaluate, as it depends on many factors such as the size of the investment,
the profit margin of a product, the costs of keeping a product on the market,
market competition and macro-economic conditions[60].  This issue was discussed in depth during the consultation with
representatives of the pharmaceutical industry (both innovators and generics),
competent authorities and end users but no specific information was provided.
However, it is estimated that on average 37%, 29%, 12%, 8% and 13% of the
marketing authorisations would contain one, two, three, four and five species[61]. Therefore, less than 20% of the marketing authorisations would
achieve the full 20-years data protection. It can be concluded that for some
veterinary medicines the proposed data protection system may be too long
(because the cost of the development of the product could be recovered in less time)
and for others too short.

5.6.
Costs and benefits of options to improve clarity
on internet retailing of veterinary medicines, authorisation of new treatments,
inspections, authorisation of medicines for emerging diseases
5.6.1.
Option 23 - No new EU action

This option does not imply any regulatory
changes and therefore costs and benefits are expected to remain the same. Regarding
internet retailing of veterinary medicines, if this option is chosen no harmonisation
across EU for internet business will be achieved. Rulings of the European Court
of Justice oblige Member States to allow internet retailing, and taking into
account the different level of implementation of this ruling in the EU, it is
expected that complaints will continue to be submitted to the authorities which
will need time and resources to clarify the situation. It is expected that the
trend for online shopping of veterinary medicines will continue, and the lack
of authorised internet retailers may lead to a higher risk of purchase of substandard
veterinary medicines.

5.6.2.
Option 24 – Authorisation to sell veterinary
medicines through the internet in all Member States

The option would create a harmonised
framework for the internet retailing of veterinary medicines in the Union, which
would be beneficial for the operation of the internal market for both
non-prescription and prescription medicines. During the consultation, a
significant proportion of respondents asked for the issue of internet retailing
of veterinary medicines to be addressed during the revision of the veterinary
medicines legislation. The option received strong support from SMEs.

The option would provide greater
accessibility of products throughout the EU, create new business opportunities,
increase competition and consequently potentially reduce the prices of
veterinary medicines for end-users (both regarding food-producing and companion
animals). Affordable prices, in turn, would lead to better treatment compliance
and therefore benefit animal and human health.

The implementation of this option would
ring-fence legitimate businesses in the Union, as end users would be able to
recognise legal internet retailers (those with a logo) from the rogue ones and
so be able to make an informed choice when deciding to purchase veterinary medicines
in the internet. Member States would also be able to better enforce the
legislation, and identify and pursue illegal internet traders.

A monetised quantification of costs and
benefits of this option could not be made as the market for internet sales of
veterinary medicines is fragmented and there is no detailed information on the
number of retailers selling veterinary medicines across the EU. However, there
are indications that there is a potential for business growth in this area: for
example, since 2005, when on line pharmacies started to develop in a Member
State (UK) the sales of veterinary medicines for non-food producing animals
grew from 2-5% to 8.6% of the total sales of medicines. Regarding prescription
medicines, only 1.4% of these medicines are sold on line (in the UK) although 78% of the overall market revenues are due to prescription only medicines[62]. Considering the difference in prices of medicines between Member
States (up to 50%), this suggests that business could grow and potentially benefits
end-users such as farmers[63], in particular if prescription medicines are retailed online - the
majority of medicines authorised for food producing animals are
prescription-only.

The implementation of this policy would
lead to some costs to the national authorities which would need to put in place
authorisation procedures to regulate the sector. The actual costs of
implementing this policy could not be calculated, but the majority of the
internet retailers are already authorised as an establishment to wholesale or
retail veterinary medicines (veterinary practices, animal health adviser
premises or pharmacies) and so it is expected that the costs would only be
additional to the current ones.  In addition, internet retailing of veterinary
medicines has already some form of regulation in at least five Member States (UK, Ireland, Hungary, Sweden, Germany) and therefore some systems and procedure are already in
place.

Rulings of the European Court of Justice
oblige Member States to allow on-line sales and therefore this policy option
would be in line with these rulings. It is expected that the implementation of
the option would have no impact on environmental safety.

5.6.3.
Option 25 – Establish a framework to authorise
new treatments

There are currently differences in approach
between Member States on this area. Harmonisation would improve animal health
across the Union and the overall operation of the internal market. In the short
term, the implementation of this policy option would increase administrative costs
to both the pharmaceutical industry and national authorities, which would need
to introduce procedures and pay fees for the authorisation of the products.  However,
some Member States already have guidelines, requirements and procedures in
place for this area, and therefore the industry already has costs associated
with these products[64].

In the medium to longer term the
implementation of this choice could provide regulatory predictability to
industry and decrease administrative burden.

5.6.4.
Option 26 – Establish a basis to harmonise the
controls on the veterinary medicines distribution chain

Enforcement is primarily a role of the Member State's competent authorities, and this option seeks to create a legal tool to allow
the Commission to evaluate controls systems applied by Member States on the
distribution chain of veterinary medicines. The main benefits of the option
would be the creation of a level playing field across the Union regarding the
way Member States organise and carry out their control activities, and
therefore provide assurances to the general public and competent authorities
that harmonised standards are in place for veterinary medicines across the Union. The execution of these controls would remain the competence of Member States. It is
expected that some Member States would need to invest in their inspections
programmes to improve them and this would incur in costs. No significant impact
is expected regarding availability of medicines or administrative burdens, and
in principle harmonisation of control systems between countries would be
beneficial to the operation of the internal market.

5.7.
Additional policy options to strengthen the
veterinary medicines legislation regarding the authorisation and use of
veterinary antimicrobials in veterinary medicine
5.7.1.
Option 27- No new EU action

This option would maintain the status quo,
and therefore there would be no additional costs or benefits. Under this
option, the collection of data on the sales and usage of antimicrobials by
Member States would continue to be carried out in a voluntary basis through
the ESVAC project[65] and so there would be still different systems for the collection of
data at national level.

5.7.2.
Option 28 – Introduction of legislative measures
to allow restrictions to be placed on the authorisation and use of veterinary
antimicrobials

This option would introduce legislative
requirements to ensure that the potential effects of the authorisation and use of
veterinary antimicrobials on development of resistance in humans and animals
are specifically assessed during an application for a marketing authorisation (some
evaluation of risk of antimicrobial resistance is already included in the
assessment process to grant a marketing authorisation to a veterinary
antimicrobial). This option  would in the medium to long term lead to a
reduction in the numbers of referrals to the CVMP, and this would realise some
savings to the pharmaceutical industry and the national competent authorities:
a total of 42 (out of 66) cases referred for arbitration to the CVMP between
2001 and 2012 were related with concerns regarding veterinary antimicrobials,
and the cost of dealing with a referral (regardless of its reason) was roughly
estimated as 445,000 euros for the industry and 31,000 euros for a competent
national authority. The implementation of this option would also bring clarity
to the decision-making process on the authorisation of antimicrobials; this
would contribute to a predictable regulatory environment which would be
beneficial to the pharmaceutical industry. However, it is expected that the
implementation of this option would result in some loss of income regarding the
sales of some types of antimicrobials.

The introduction of measures to prohibit or
restrict the authorisation and the use of some antimicrobials in veterinary
medicines (for example, those reserved for human treatment), including under Cascade,
could have a positive impact on the protection of human health. On the other
hand, it would have a negative impact on the availability of medicines for both
food-producing and companion animals and could have animal health and welfare implications.
The magnitude of this impact would depend on the type and number of
antimicrobials affected by the measures, and the time period and resources
available for animal holders to implement management measures to reduce their
dependence on those antimicrobials. Restrictions imposed on the use of the Cascade
are likely to affect mainly minor species, for which there are less authorised
medicines (including products used in preventative medicine such as vaccines).
The implementation of this option might also lead to an increase of illegal
usage of antimicrobials, and therefore the competent national authorities would
need to focus resources on enforcement activities on this area. The costs to
farmers, veterinary surgeons and national authorities associated with possible
restrictions on the use of the Cascade could not be calculated as there are only
limited data on the use of the Cascade across the Union.

5.7.3.
Option 29 - Measures regarding advertising of
veterinary medicines, including antimicrobials

The option aims to clarify that direct-to-
consumer advertising of antimicrobials (and also other prescription medicines) is
forbidden, while advertising to veterinary surgeons is still allowed. The
implementation of this option would be beneficial to public and animal health,
as it would diminish the pressure that farmers and companion animal owners are
reported to place on veterinary surgeons for the prescription of certain types
of “convenient” antimicrobials (for example those which allow a short
withdrawal period or are long acting) even if these antimicrobials are not
appropriate. However, end-users sometimes benefit from the advertising and
marketing materials which are made available to them, when these materials provide
information on animal health issues. In this respect, this option could affect
in particular farmers who could receive less information on veterinary
medicines.

5.7.4.
Option 30 - Measures regarding retailing of
veterinary antimicrobials

The option proposes to
restrict the retailing of veterinary antimicrobials by veterinary surgeons.
Certain Member States already implement this option, based on the principle
that the retailing of veterinary medicines is not consistent with the
independent position of a veterinary surgeon. However, the impact of this
policy on the reduction of antimicrobial resistance in humans is not yet clear
as there appear to be no clear-cut relationship between this restriction and
antimicrobial consumption in Member States. A report prepared for the Dutch[66] government on this
issue concluded that a restriction could remove the income incentive for the
veterinarian but would not sufficiently strengthen the veterinary surgeon'
independence. On the other hand, a French report has been published recently
and concluded that financial incentives for veterinarians may affect their
prescription with regards to quality (type of medicine prescribed) and quantity
(volume of antibiotics prescribed)[67].

The implementation of
this option would have a significant, negative impact on veterinary practices,
for which the income from selling medicines is often important. In some
countries the implementation of this option would require a major change to the
supply chain of veterinary medicines, with associated impact on costs to
national authorities and retailers. It could also negatively affect access to medicines
for farmers in rural areas, who rely on their veterinary surgeons for the
purchase of medicines for their animals (although online sales could mitigate
this effect). On the basis of current knowledge and evidence, it is not yet
completely clear if this option would have a significant positive effect on public
health regarding management of antimicrobial resistance. This option would have
no significant impact on the single market

5.7.5.
 Option 31 -
Introduction of a legal basis for the compulsory collection of data on the use
of antimicrobials

This option
proposes to establish a harmonised and compulsory European system for
collection of data on the sales and usage of antimicrobials in food-producing
animals. It builds upon the current voluntary surveillance programme, ESVAC[68]. The costs of tasks
related to this surveillance project vary from country to country and only
partial data are available across the EU. For example, Sweden and Hungary estimated the costs for these activities at around 8,200 and 1,500 euros
respectively, whereas the Czech Republic estimated that at least 200 000 euros
per year are spend on activities related to antimicrobial resistance[69]. Despite these already existing costs, it is expected that the
administrative costs to the national authorities would increase with the
implementation of his policy, as their systems and procedures would need to be
adapted to achieve harmonisation of data collection (type of data and
collection systems) on antimicrobials across the EU. The implementation of this
proposal would have a positive impact on animal and public health, as it is
recognised that the analysis of reliable data on the use of antimicrobials in
animals is an essential element for the identification and quantification of
the risk of developing and spreading antimicrobial resistance between humans
and animals. The option would have no significant impact on safety to the
environment or on the functioning of the internal
market.

6.
Comparison of the policy options

A comparison of the policy options against the objectives of the
proposal and their impact on stakeholders, and in terms of efficiency, efficacy
and coherence[70]
with the EU policies, was carried out and is summarised in Annex 11.  Based on this
evaluation , the preferred options were compiled in a single package (2, 3, 4, 5,
9, 10, 11, 13, 14, 16, 17, 18, 19, 22,  24, 25, 26, 28, 29, 31), designed to
improve the availability of veterinary medicines without sacrificing standards
to public and animal health and safety to the environment. The measures proposed were developed taking on board the views of
the regulatory authorities and scientific experts through consultations,
workshops and bilateral meetings.

This package contains options which
simplify the regulatory requirements for the authorisation of veterinary
medicines and their maintenance on the market (addressing pre and post
authorisation procedures). The preferred option for a revised authorisation
procedure for veterinary medicines extends the scope of the centralised
procedure (option 9), making it optional to all types of veterinary medicines, whilst
still maintaining the possibility of national authorisations. This option does
not bring the total harmonisation of the authorisation procedure, desired by
the pharmaceutical industry, to the same extent that the option to create a
single, obligatory route of authorisation for all veterinary medicines would.
However, the preferred option introduces a level of flexibility to the
authorisation system (which is beneficial to the SMEs/micro-enterprises in
particular) whilst still allowing the pharmaceutical industry to a) seek an
authorisation to place any type of veterinary medicine on the market throughout
the Union via the centralised procedure if they so desire or b) seek national
authorisations in selected countries if the markets for the product are restricted,
due to national animal health status for example. In addition, the measures to
simplify the requirements regarding packaging and labelling (option 10),
variations procedures (option 17), and pharmacovigilance (option 16) should significantly reduce the
administrative burdens to the industry and bring savings for the competent
national authorities. The implementation of these measures should take on board
the advice from scientific committees, whenever relevant, to ensure that
simplification is not achieved at the cost of product safety.  It is expected
that overall these measures would free resources from the pharmaceutical
industry for re-investment in new product development, therefore indirectly
having a positive effect on the availability of novel medicines for companion
and farmed animals.  These measures are in line with the Commission's
strategies in simplifying the regulatory environment and reducing
administrative burdens in the Union.

The preferred package also introduces
measures to extend the period of data protection for veterinary medicines to a
maximum of 20 years (option 22), to better protect developments efforts leading
to new products. These measures should stimulate innovation and consequently
improve the availability of novel veterinary medicines, including antimicrobials
and medicines for limited markets such as bees (option 5). Keeping the concept
of global marketing authorisation would avoid an excessively long delay in the placing
on the market of generics. This would benefit competition and consequently the
pricing of veterinary medicines to end-users.

The removal of an inconsistency within the
legislation to allow the protection period for safety data to cover
environmental data (option 13) would potentially encourage applications for
generics. This could improve market competitiveness and bring benefits to
animal and public health. It is expected that there would be no negative impact
on the environment, as environmental data are already assessed as part of the
safety dossier provided with the application for the reference product. As part
of the package of preferred options, it will also be possible for companies to
join efforts to carry out studies to generate data  (option 11), to cover any
deficiencies regarding information on safety to the environment that may be
detected. In addition, it is expected that the national competent authorities
would elect to monitor these products more closely through pharmacovigilance.

The option to introduce a legislative
framework to regulate the authorisation of new treatments (option 25) would
bring harmonisation to the area and benefit to animal health across the Union. It would also benefit the operation of the internal market and business growth. The
options to reduce data requirements for limited markets (option 4), improve the
Cascade (option 2) and improve the database for products authorised in the Union (option 3) would benefit in particular animal health and welfare.

The “rolling out” of “legacy products”
already authorised in the EU (option 11) would reduce administrative burdens to
the pharmaceutical industry in the long term and improve the range of
veterinary medicines available across the Union. This would possibly have an
effect on the price of medicines in the Union through competition, therefore
benefiting farmers and the general public through better animal health. In
addition, the introduction of a legislative basis for the regulation of
internet retailing (option 24) would stimulate business growth, and so also provide
greater accessibility of medicines to end-users across the Union. The
circulation of legal veterinary medicines across borders would be improved, in
particular considering the measures proposed to improve the use of the
centralised procedure and to facilitate the labelling of veterinary medicinal
products. An harmonised regulation of internet retailing across the EU would
ring-fence legitimate businesses, allowing end-users to make an informed choice
when deciding to buy veterinary medicines online, and facilitating enforcement
by Member States against rogue traders. The option could potentially bring
benefits to animal and public health.

An improved harmonisation of controls carried
out by Member States would benefit consumers and provide further assurance on
the quality and safety of veterinary medicines throughout the distribution
chain (option 26), improving the trust between competent authorities.  It would
also help to ensure a level playing field in Member States, regarding
enforcement of the legislation.

The package of preferred options also tackles the issue of
antimicrobial resistance and introduces provisions to minimise risks to public
health arising from the use of antimicrobials in veterinary medicine[71] (option 28). These proposals
take on board as much as possible the need to promote the continued
availability of effective antimicrobials for use in veterinary medicine but it
is recognised that they may affect some sectors, such as the farming sector for
example, which relies heavily on the use of antimicrobials as part of normal
husbandry. It is difficult to evaluate with certainty how much the options proposed
would effectively contribute to minimising the risks of developing
antimicrobial resistance. However, it is clear that the prudent and responsible
use of antimicrobials in veterinary medicine should be put in place to contribute
to the management of antimicrobial resistance in humans[72]. The implementation of
the options to harmonise the collection of data on antimicrobial use (option
31) and to incentivise the development of new antimicrobials specific for
veterinary medicine should bring at medium and long term more clarity on this
area and benefit public and animal health[73]. Clarification on the rules regarding advertising of veterinary
medicines (option 29), including antimicrobials, would also support the
responsible use of antimicrobials. The option to completely forbid veterinary
surgeons from retailing antimicrobials (option 30) was discarded because of the
economic impact that this measure would have on veterinarians in rural areas
and of the accessibility of medicines to farmers in isolated regions, without
solid evidence of benefits to public health.

The Union rules apply to all veterinary
medicines, and any safety risks to the target animals, users, consumers and the
environment are the same irrespective of the size of the business working on
the sector. For this reason it is difficult to create exemptions to
specifically benefit SMEs/micro-enterprises. However, most of the proposals
selected simplify the regulatory environment and this is beneficial in
particular to SMEs/microbusinesses, which often struggle to meet the demands of
the current legislation on veterinary medicines. Furthermore, particular care
was taken during the preparation of the impact
assessment to take on board specific concerns raised by SMEs/micro-enterprises
during the consultation. Thus the package of preferred options proposes the
harmonisation of clinical trials across the Union, the removal of the sunset
clause and the introduction of measures to assist these enterprises at national
level (such as introduction of helpdesks). The first two measures would also
benefit larger pharmaceutical companies but the latter may incur in costs to
the national regulatory authorities.

Policy options 4, 5, 9, 10, 11, 14, 16, 17,
19 introduce cost reductions related to administrative burdens to the industry
against the baseline. Options 11 and 25 would give rise to a cost increase to
the industry in the short term but overall the selected options reduce administrative
burdens to the industry. The impact assessment shows that the total estimated
savings of all preferred options to the industry would amount to at least 145.4
million euros per year.  The reduction, depending on the response of relevant
authorities and pharmaceutical companies to the new rules, could be up to 6% of
the total sales of veterinary pharmaceuticals. An overall impact on the
benefits of the proposed package to industry (including
SMEs/micro-enterprises), national competent authorities and end users could not
be accurately quantified, but the package delivers a proportionate set of
measures to simplify the rules concerning the authorisation, placing on the
market, monitoring and use of veterinary medicines whilst introducing
legislative tools to manage emerging threats to animal and public health. These
changes create a clearer and more predicable regulatory environment for
veterinary medicines, conducive to a reduction in the costs of placing a
product on the market. This in turn would remove barriers to innovation, and may
encourage the authorisation of more (new) products and authorisation in more
markets further improving the availability of veterinary medicines in the Union and the functioning of the internal market and competition, with a positive effect on
public and animal health. The simplification changes proposed are efficiency
measures and do not lower the standards of the veterinary medicines placed on
the market in the Union.

Table 3 Effectiveness and efficacy scoring
of the preferred policy options

Options || Main trade-offs and synergies between the options || Efficiency || Effectiveness

Option 2 || More flexibility on the use of Cascade benefits animal and public health. || ++ || ++

Option 3 || Introduces costs to the national competent authorities but improves the level of information on veterinary medicines authorised in the Union to stakeholders, including end users. || ++ || ++

Option 4 || Reduces data requirements for veterinary medicines for small markets and so improves the availability of medicines and animal and public health. || ++ || ++

Option 5 || Decreases administrative burdens to the industry, and so may improve the availability of medicines for bees. || ++ || ++

Option 9 || Introduces more flexibility to the system and improves the functioning of the internal market || ++ || ++

Option 10 || Decreases administrative burdens to the industry, and so may improve the availability of medicines in particular in smaller countries || ++ || ++

Option 11 || Introduces administrative burdens and costs to authorities in the short term but reduces them in the long term; introduces harmonisation on the placing of the market of veterinary medicines and improves animal and public health. || ++ || ++

Option 13 || Removes repeated assessment of data and so reduces administrative burdens. May benefit product availability. || + || +/neutral

Option 14 || Introduces more harmonisation to the procedure and may benefit innovation || ++ || ++

Option 16 || Introduces a risk-based system of pharmacovigilance; delivers cuts to administrative burdens. || ++ || ++

Option 17 || Delivers cuts to administrative burdens. || ++ || ++

Option 18 || Supports SMEs/microenterprises and business in general, decreases administrative burdens. || +++ || +++

Option 19 || Abolish renewals - thus less supervision by national competent authorities - but delivers cuts to administrative burdens. || ++ || +

Option 20 || No new action, relevant to requirements to homeopathic medicines – option does not introduce any regulatory changes. || neutral || neutral

Option 22 || Stimulates innovation but delays entry of generics onto the market || + || +

Option 24 || Introduces administrative burdens and costs to internet retailers and authorities but introduces harmonisation on the sector; improves competition and pricing of veterinary medicines and so benefits animal and public health. || + || +++

Option 25 || Introduces administrative burdens and costs to authorities in the short term but introduces harmonisation on the placing of the market of advanced therapies; improves animal health. || + || ++

Option 26 || Provides further assurance on the safety of veterinary medicines across the distribution chain, supporting changes that introduce risk-based procedures or reduce amount of data submitted for assessment; ensures a level playing field regarding enforcement across the Union. || + || neutral

Option 28 || Introduces some administrative burdens to the industry and authorities but may improve public health; decreases the availability of antimicrobials to animals. || + || +

Option 29 || May restrict information to farmers and other health professionals;  improve public health. || + || +

Option 31 || Introduces some costs to authorities; contributes to better public and animal  health regarding antimicrobial resistance || neutral || +

None of the options proposed conflict with
EU general policies. They link with specific policy
objectives as follows:

Specific policy objective Expand the
market beyond the top four animal species: options 2, 3, 4, 5
Specific policy objective  Simplify
authorisation procedures: options 9, 10, 11
Specific policy objective  Review data
requirements for marketing authorisation procedures: options 13, 14
Specific policy objective  Simplify post
authorisation requirements: options 16, 17, 18, 19
Specific policy objective  Review
incentives for breakthrough medicines: option 22
Specific policy objective  Improve
clarity: on internet retailing of veterinary medicines, on the
authorisation of new treatments, on inspections, on authorisation of
veterinary  medicines for emerging diseases: options 24, 25, 26, 4
Specific objective strengthening of the
veterinary medicines' regulatory framework regarding the authorisation and
use of antimicrobials: options 28, 29,  31

The choice of legal instrument

Analysis of the problems identified with
the current legislation on veterinary medicines and the objectives of the
proposal, in light of the Articles 14 and 168 (c) TFEU leads to the conclusion
that the proposal should take the form of a Regulation. This is the appropriate
legal instrument as it sets out clear and detailed rules which will become
applicable in a uniform manner and at the same time across the Union. Diverging or incomplete transposition of the provisions of the Directive has led to
different levels of public and animal health protection, as reflected in the
numbers of referrals to the scientific committees, for example, and created
obstacles to the functioning of the internal market. The choice of a Regulation
still allows Member States to retain their competence for granting of marketing
authorisations, enforcement, authorisation of clinical trials,
pharmacovigilance monitoring, authorisation of wholesalers and retailers of
veterinary medicines.

7.
Monitoring and evaluation

Monitoring and evaluation will be measured
against the objectives set out in this impact assessment and the benchmark is the current situation. It is proposed
to establish an EU database on marketing authorisation linked to pharmacovigilance
and to have a legal basis for collecting data on the use of antimicrobials in
all Member States. This will facilitate the collection and analysis of data
necessary to evaluate the revision of the legislation. The core indicators and
the data collection strategy are highlighted below.

Table 4 Future monitoring and evaluation

Problem || Indicators Objective: to expand market beyond the top four animal species || Data source

Lack of availability of authorised veterinary medicines || Number of new veterinary medicines authorised (for major and minor species, for small and larger markets) || Commission, EMA and the regulatory network

Numbers of marketing authorisations by animal species || EMA

Objective: to simplify procedures for obtaining a marketing authorisation in multiple national markets ||

Number of existing products authorised by national procedures “rolled out” || Member States

Numbers of marketing authorisations by Member States       || EMA

Number of applications submitted by SMEs || EMA, Member States

Number of complaints || EMA, Member States

Number of referrals || EMA

Time and costs of development of a medicine || Animal health industry

Objective: review data requirements in marketing authorisation procedures ||

Numbers of clinical trials in the EU || EMA, Member States

Objective: to simplify post authorisation requirements ||

Numbers of variations submitted || Commission, EMA, Member States

Number of reported adverse events for food-producing animals and companion animals; number of executed pharmacovigilance inspections || EMA

Percentage of budget spent on defensive R§D to maintain products on the market || Animal health industry

Objective: to review incentives for breakthrough medicines ||

Ratio of number of marketing authorisations for generics and innovative products || EMA

Number of extensions to new species || EMA

Use of the Cascade || Member States

Objective. Improve clarity: on  rules on internet retailing of veterinary medicines, on the authorisation of new treatments, on inspections, on authorisation of medicines for emerging diseases ||

Number of infringements to the veterinary medicines legislation regarding controls on the distribution chain of veterinary medicines || FVO reports

|| Number of internet retailers authorised to sell veterinary medicines || Member States

The following is proposed regarding the
monitoring of the changes introduced regarding the measures to deal with the
problem of antimicrobial resistance:

|| Objective: to strengthen the veterinary medicines' regulatory framework regarding the authorisation and use of antimicrobials ||

Antimicrobial resistance || Number of specific antimicrobials authorised  for veterinary medicines || Commission, EMA and the regulatory network

Sales of antimicrobials used in veterinary medicines || EMA

Number of referrals on veterinary antimicrobials || Commission

 The legal instrument will contain a review
clause concerning the evaluation of the Regulation and the submission of a
report to the European Parliament and the Council. The Commission will consult
national competent authorities, veterinarian' and farmers' associations, the
pharmaceutical industry, SMEs/micro-enterprises, distributors and retailers of
veterinary medicines to prepare the review, which should examine whether or not
the policies implemented achieve their desired effect, and what are the actual
costs and benefits to the sector affected. It is proposed that the review is
carried out ten years after implementation, covering in particular the impact
of the changes to the legislation on availability of medicines, animal health,
public health, environment, internal market and innovation.

8.
annexes

Annex 1 Acronyms

ADI || Acceptable daily intake

AMR || Antimicrobial resistance

CMDv || Coordination Group for Mutual Recognition and Decentralised Procedures (veterinary)

CVMP || Committee for Medicinal Products for Veterinary Use

CoE || Council of Europe

ECDC || European Centre for Disease Prevention and Control

EEA || European Economic Area

EGGVP || European Group for Generic Veterinary Products

ESVAC || European Surveillance of Veterinary Antimicrobial Consumption

EMA || European Medicines Agency

IAB || Impact Assessment Board

MA || Marketing Authorisation

NCA || National Competent Authority

PSUR || Periodic Safety Update Report

SME || Small and Medium-sized Enterprise

SPC || Summary of Product Characteristics

TFEU || Treaty on the Functioning of the European Union

VICH || International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products

Annex 2 Glossary

Acceptable Daily Intake

The amount of a residue that is considered safe for a person to ingest
daily for a life time (see also MRL).

Cascade

The Cascade is a provision in the veterinary medicines
Directive that allows a veterinary surgeon to prescribe medicines in a way that
would not otherwise be permitted. The principle of the Cascade is that, if
there is no suitable veterinary medicine authorised in the Member State to treat a condition, the veterinary surgeon responsible for the animal may, in
particular to avoid causing unacceptable suffering, treat the animal in
accordance with the following sequence, in descending order of priority:

·
A veterinary medicine authorised in the Member State for use in another animal species or for a different condition in the same
species.

· If there is no such product, the next option is either –

o
a medicine authorised in the Member State for human use, or

o
a veterinary medicinal product not authorised in
that Member State but authorised in another Member State for use in any animal
species for the condition in question or for another condition.

·
If there is no such product, the last option is
a veterinary medicine prescribed by the veterinary surgeon and prepared
extemporaneously by a person authorised to do so under national legislation.

Food producing animals may only be treated under the
Cascade with medicines which contain pharmacologically active substances listed
in the Table of Allowed Substances of Commission Regulation EU (European Union)
No 37/2010, in the interest of food safety. A veterinary surgeon prescribing
for, or administering a medicine to, food-producing animals under the Cascade
is required to specify an appropriate withdrawal period to the animal produce.
Unless the medicine indicates a withdrawal period for the species concerned,
this should not be less than 7 days for eggs and milk, 8 days for meat from
poultry and mammals and 500 degree days for meat from fish.

CMDv

The Coordination Group for Mutual
Recognition and Decentralised Procedures (veterinary) (CMDv) is a group set up for the examination of technical questions and
procedures relating to the marketing authorisation of a medicinal product in
two or more Member States in accordance with the mutual recognition procedure
or the decentralised procedure. This group aims to resolve any divergence that
may arise between the Member States in these procedures. The group is composed
of one representative per Member State, including Norway, Iceland and Liechtenstein. Observers from the European Commission and accession countries, where
applicable, also participate in the meetings.The EMA provides the secretariat
of the CMDv.

CVMP

The Committee for Medicinal Products for Veterinary Use
(CVMP) is responsible for preparing the Agency's opinions on all scientific
questions concerning veterinary medicines, and has a legal basis in Regulation
(EC) No 726/2004. This Committee is responsible for conducting the initial
assessment of centralised applications for veterinary medicines, and for
post-authorisation activities, including the assessment of variations to
existing marketing authorisations. The CVMP also arbitrates in cases where
there is an unresolved disagreement between Member States concerning an
application submitted through the mutual recognition or decentralised procedure
(referrals). Other CVMP's functions are the establishment of maximum residues
limits, the provision of scientific advice to the pharmaceutical industry and
the preparation of scientific and regulatory guidelines

The CVMP is composed of a chairperson, elected by serving CVMP members,
one member and an alternate nominated by each Member State and one member and
an alternate nominated by Iceland and by Norway. It may also have up to five co-opted
members, chosen among experts nominated by Member States or the Agency and
recruited, when necessary, to provide additional expertise in a particular
scientific area.

Data protection

This is a period of time during which a veterinary
medicine cannot be used as a reference for an application for a generic
medicine. The current legislation states that an application for a generic
product can be submitted after 8 years of authorisation of the originator
product, but the generic product cannot be marketed until 10 years have passed
from the initial authorisation of the originator (13 years for products
indicated for the treatment of bees and fish).

Veterinary medicines for food production species may
benefit from an extra 1 year protection for each extension to a food producing
species, if the change is authorised within 5 years following the granting of
the initial marketing authorisation. The total maximum protection period is 13
years, for a marketing authorisation for 4 or more food-producing species.

The data protection period should not be confused with
patent protection. Patents protect the invention, not the data required for
pre-market approval. Patents and data protection may run concurrently and so
sometimes the data protection period will expire at the same time as the
patent, but this is not always the case.

Generic veterinary medicinal product

A generic is a veterinary medicinal product which has
the same active substance as a reference (originator) product and whose
bioequivalence with the reference product has been demonstrated. If these
conditions are met, a generic applicant for marketing authorisation is exempted
from the requirement to prove safety and efficacy through pre-clinical tests
and clinical trials, and the competent authority relies on the proof of safety
and efficacy provided by the reference product to authorise the product. According
to the current legislation, the applicant would need to provide an
environmental risk assessment with the application for a generic product and,
depending on the type of product, a user risk assessment. The name of the generic
medicine and its packaging differs from those of the reference medicine.

There is a legislative basis in the veterinary
legislation for hybrid applications for a generic product. Such applications
are required when the applicant is not able to demonstrate bioequivalence to
the reference product through bioavailability studies, or where bioequivalence
can be demonstrated to the reference product, but the applicant desires to
present the medicine as a different strength or a different route of
administration to the reference product  (for example, if the reference product
is an oral medicine for cats and the applicant for the generic medicine wants
to market the product as an injectable - in this case the applicant can refer
to the reference product to cover some of the safety and efficacy data
requirements, but needs to produce its own data to support the change in the
route of administration). The authorisation of this type of generic product relies
in part on the results of data from the  reference medicine and in part on new
data ("hybrid").

Global market concept

When a medicinal product has been granted an initial
marketing authorisation, any additional changes (such as pharmaceutical forms,
administration routes) are included in the initial marketing authorisation. All
these changes are considered as part of the same global marketing
authorisation. So the global marketing authorisation contains the initial
authorisation and all variations and extensions thereof, as well as any
additional strengths, pharmaceutical form, administration routes or
presentations authorised through separate procedures and under a different
name, granted to the marketing authorisation holder of the initial
authorisation – these developments do not  restart or prolong this period and 
have the same end-point of the data and market exclusivity periods, namely 8
and 10 years after the first marketing authorisation was granted, respectively.

Homeopathic veterinary medicinal product

A homeopathic veterinary medicinal product is defined in the Directive
as "Any medicinal product prepared from substances called homeopathic
stocks in accordance with a homeopathic manufacturing procedure described
by the European Pharmacopoeia or, in the absence thereof, by the pharmacopoeias
currently used officially in the Member States. A homeopathic medicinal
product may contain a number of principles."

Companies wishing to place a homeopathic medicinal
product on the market may apply for a marketing authorisation or may take
advantage of the simplified registration procedure, which allows the product to
be placed on the market with no stated therapeutic indications and where there
is sufficient dilution to guarantee the safety of the remedy. Products
authorised by national authorities on or before 31 December 1993 have automatic
rights to be placed on the market. Homeopathic medicinal products intended for
food producing species must comply with the provisions of the legislation on
residues limits of pharmacologically actives substances in foodstuffs of animal
origin.

Marketing authorisations

The legislation requires that before a medicine can be placed on the
market it must be given a marketing authorisation.

There are four routes that applicants can take to obtain a marketing
authorisation, and they all involved the assessment by competent authorities of
the quality, safety and efficacy data submitted by the pharmaceutical company
in accordance with the legislation:

·
National procedure
Each EU Member State has its own procedures for the authorisation of medicines
that fall outside the scope of the centralised procedure.

·
Mutual recognition procedure
In the mutual recognition procedure, a medicine is first authorised in one EU
Member State, in accordance with the national procedures of that country.
Following this, the marketing authorisation holder can seek further marketing
authorisations in other EU countries in a procedure whereby the countries
concerned agree to recognise the validity of the original, national marketing
authorisation following an assessment process.

·
Decentralised procedure
Using the decentralised procedure, companies may apply for simultaneous
authorisation in more than one EU country of products that have not yet been
authorised in any EU country and that do not fall within the mandatory scope of
the centralised procedure.

·
Centralised procedure

In the EU a company may submit a single
application to the EMA for a marketing authorisation that is valid simultaneously
in all EU Member States, plus Iceland, Liechtenstein and Norway. This is called the centralised (or Community) authorisation procedure, and is
mandatory for certain types of medicines and optional for others.
For medicines that do not fall within these categories, companies have the
option of submitting an application for a centralised marketing authorisation
to the EMA if the product is of significant therapeutic, scientific or
technical innovation, or if its authorisation would be in the interest of
public or animal health.

Applications through the centralised procedure are submitted directly
to the EMA, and the evaluation is carried out by the EMA's CVMP. Once the CVMP
adopts an opinion on whether the medicine should be authorised or not, the
opinion is transmitted to the European Commission, which has the ultimate
authority for granting the marketing authorisation in the EU through a
Commission Decision.

Maximum Residue Limits

The maximum residue limit (MRL) is the maximum concentration of residue
accepted by the European Union (EU) in foodstuffs obtained from an animal that
has received a veterinary medicine or that has been exposed to a biocidal
product for use in animal husbandry.

MRLs are determined scientifically. The first step is to identify the
No(A)EL (No Observed Adverse Effect Level) of the substance, which is the
highest dose that does not cause adverse effects.  Then the Acceptable Daily
Intake (ADI) is determined. The ADI is estimated by dividing the No(A)EL level
by an uncertainty level (100-1000 x) to a allow extrapolation between species
and to take into account individual variations between individuals (a margin of
safety). The MRL is set out by dividing the ADI between edible tissues and food
stuffs such as milk, muscle, liver etc so that a limit level for residue is
given to each tissue. The allocation of the ADI takes into account how much a
particular food may be eaten every day (the so called "food basket").

The use of animal medicines in food producing species requires observance
of the withdrawal period – the time period between the last treatment given to
the animal and the time when the level of residues in the tissues (muscle,
liver, kidney, skin/fat or products (milk, eggs, honey) is lower than or equal
to the MRL. Until the withdrawal period has elapsed, the animal or its products
must not be used for human consumption. The withdrawal period for veterinary
medicines is listed in the summary of the product characteristics and on the product
literature.

Minor use and minor species

There is no legal definition for major or minor species. The CVMP
have defined major species based on animal population data and total
consumption figures, using global numbers across the European Union:

Major food-producing species are cattle (dairy and meat
animals), sheep (meat animals), pigs, chickens (including laying hens) and
salmon. Major companion animal species are cats and dogs. All other species are
considered to be minor species.

Minor use medicines are those for intended uses in major species for
diseases that occur infrequently or in limited geographic areas and in only a
small number of animals annually.

Product literature

This term refers to the label,
the immediate packaging, the outer packaging and the package leaflet (if there
is one) of a veterinary medicine. The immediate packaging is the container or
any other form of packaging that is in direct contact with the VMP, e.g. vials,
bottles, blister packs, etc. The outer packaging is the packaging into which
the immediate packaging is placed, e.g. cartons, boxes, packets, etc. The package
leaflet is the leaflet that accompanies the VMP.

Referral

A referral is a procedure used to resolve issues such as
concerns over the safety or benefit-risk balance of a medicine or a class of
medicines. The medicine, or the class of medicines, is ‘referred’ to the EMA's
Committee for Medicinal products for Veterinary Use (CVMP – see above), so that
it can make a recommendation for a harmonised position across the European
Union. The European Commission then issues a decision to all Member States
reflecting the measures they need to take to implement the CVMP recommendation.
The types of referrals are (based on Directive 2001/82):

·
Article 33- Mutual-recognition and decentralised
referral: initiated because of disagreement between Member States within the
framework of the mutual-recognition or decentralised procedure.

·
Article 34 - Divergent decision referral:
initiated in order to obtain harmonisation within the EU of the conditions of
authorisation for products already authorised by Member States.

·
Article 35 - Community interest referral:
initiated in cases involving the interests of the Community or concerns
relating to the protection of human or animal health or the environment.

·
Article 39 and 40 – Follow up referrals.

·
Article 78 referrals - Pharmacovigilance urgent
measures: initiated when, as a result of the evaluation of veterinary
pharmacovigilance data, a Member State considers that a marketing authorisation
should be suspended, withdrawn or varied to restrict the indications or
availability, amend the posology, add a contraindication or add a new
precautionary measure.

Summary of Product Characteristics

The summary of product characteristics (SPC) is a public
document written and updated by pharmaceutical companies and based on the data
submitted for product authorisation and approved by the competent authority. It
is the basis for the preparation of the product literature.

Sunset clause

The Sunset clause is a legal obligation for all
pharmaceutical companies to place a product on the market within three years of
its granting.

Variations

Any changes to veterinary medicines authorisations, for
example, change in the manufacturing process, change in the packaging or change
in the address of the manufacturer.

Withdrawal period

See Maximum Residue Limits.

Annex 3 Information sources

Details of
the consultation carried out for the preparation of this impact assessment

A wide public consultation took place from
April to July 2010 to seek the views of the pharmaceutical industry
representatives, including the generic medicines industry, Member States,
animal health professional organisations, farmers, representatives of internet
retailers of veterinary medicines, non-governmental institutions and
individuals on the legal framework for veterinary medicines. The summary report
on the results of this consultation as well as the individual responses was
published on line (Annex 9). In addition, an evaluation of the European
Medicines Agency concerning veterinary medicines was carried out in 2009 including.
The final report was published January 2010.[74]

Between February 2011 and April 2011,
qualitative and quantitative data were collected on the impact of the
legislation. In-depth consultation with stakeholders  (the national competent
authorities, the main industry trade association and the main veterinary
association) from six countries (Cyprus, Finland, Germany, Poland, Romania and the United Kingdom)  took place – these countries were chosen in order to
achieve a balance between small and large markets, and 'new' and 'old' Member
States. A total of 13 organisations were consulted. Specific consultations were
also carried out with three key stakeholders in the veterinary sector: the
Federation of Veterinarians of Europe, Copa-Cogeca (representing farmers) and
the European Medicines Agency.

A survey listing the policy options was
submitted to all national competent authorities in the EU/EEA, IFAH-Europe and
the FVE, and disseminated to national member organisations. A total of 31
responses were received (12 from industry representatives and individual
companies, 14 from national competent authorities and five responses from end
users groups (national veterinarian organisations, FVE and Copa-Cogeca). In addition, a
questionnaire was sent to the (Coordination Group for Mutual Recognition and Decentralised
Procedure (CMDv) to collect specific information on the costs to the Member
States of work carried out on some specific policy areas, such as antimicrobial
resistance, pharmacovigilance, authorisations.

An industry workshop was organised in March
2011. This workshop was attended by representatives of IFAH-Europe, the
European Group for Generic products, and individuals from 12 animal health businesses,
including a mixture of large and small companies, and manufacturers of novel
and generic medicines.

On 23 September 2011 the Commission
organised a stakeholder meeting to give stakeholders an opportunity to discuss
the outcomes of the public consultation and to discuss key subjects. In
addition, the Commission consulted the Animal Health Advisory Committee[75] on several occasions.

The consultation was complemented by a
series of targeted meetings with smaller groups of experts on
pharmacovigilance, antimicrobial resistance, and authorisations/data
protection. Another meeting was organised specifically with SMEs and
micro-enterprises to identify their specific views and needs.

The review of the legislation on veterinary
medicines was discussed at the meetings of the Standing Committee on Veterinary
Medicinal Products of 29 May 2009, 8 September 2011, 27 September 2012, and the
Veterinary Pharmaceutical Committee of 6 February 2011.

Competent authorities were also consulted
as part of the preparation of the report by the European Policy Evaluation
Consortium (EPEC) (February 2011 to April 2011). The purpose of this exercise
was to collect quantitative and qualitative data, not only from the competent
authorities but also from the veterinary medicines industry, farmers and
veterinary surgeons, on the sector and on the possible impact of the proposed
options.

The use of the 'Cascade' is considered by
stakeholders an essential tool to treat or to prevent diseases if there is no
authorised veterinary medicine on the market. Therefore, a questionnaire was
sent to Member States to obtain specific information from competent authorities
on the implementation of the rules and the use of the 'Cascade' (March 2011). A
questionnaire was also sent to Member States' competent authorities aiming to
collect information on their administrative burdens (September 2012).

List of consultations, communications,
legislation, studies, workshops and other literature relevant to this impact
assessment

Policy documents

(1) COM (2006), 689 and 690 final.
Commission working document measuring administrative costs and reducing
administrative burdens.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2006:0691:FIN:EN:PDF.

(2)
COM (2007), 0023 final. Communication from the Commission to the Council, the
European Parliament, the European Economic and Social committee and the
committee of the regions – Action programme for Reducing Administrative Burdens
in the European Union.

(3)
COM (2008), 394 final. Communication from the Commission to the Council, the
European Parliament, the European Economic and social Committee and the
committee of the Regions “Think Small First” - A “Small Business Act” for
Europe.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0394:FIN:en:PDF.

(4)
Council (2008), Council conclusion of 10 June 2008 on antimicrobial resistance.
http://www.eu2008.si/en/News\_and\_Documents/Council\_Conclusions/June/0609\_EPSCO-AMR.pdf.

(5)
COM (2008), 912 final. Communication from the Commission to the European
Parliament pursuant to the second subparagraph of Article 251(2) of the EC
Treaty concerning the common position of the Council laying down Community
procedures for the establishment of residue limits of pharmacologically active
substances in foodstuffs of animal origin, and repealing Regulation (EEC)No
21377/90. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0912:FIN:EN:HTML.

(6)
COM (2007), 539 final and COM (2008), 545 final respectively. The Animal Health Strategy for the European
Union 2007-2013 "Prevention is better than cure" and it's
implementing Action Plan.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2007:0539:FIN:EN:PDF; and http://eur-         
lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2008:0545:FIN:EN:PDF.

(7)
COM (2009), 162 final. Communication from the Commission to the European
Parliament and the Council: Building a sustainable future for aquaculture, a
new impetus for the strategy for the sustainable development of European
aquaculture.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2009:0162:FIN:EN:PDF

(8)
Council (2009), Council conclusions of 23 November 2009 on innovative
incentives for effective antibiotics. http://register.consilium.europa.eu/pdf/en/09/st16/st16006.en09.pdf.

(9)
Final report. Measurement data and analysis. Pharmaceuticals legislation
priority Area. EU project on baseline and reduction of administrative costs. 5
March 2009.

(10) COM (2010), 714 final.  Communication
from the Commission to the European Parliament and the Council on Honeybee
Health. http://ec.europa.eu/food/animal/liveanimals/bees/docs/honeybee\_health\_communication\_en.pdf.

(11)
COM (2010) 245, final. Communication from the Commission to the Council, the
European Parliament, the European Economic and Social Committee and the
Committee of the Regions – a Digital Agenda for  Europe.

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=COM:2012:0009:FIN:EN:PDF

(12)
COM (2011), Commission recommendation of 14 January 2011 establishing guidelines
for the distinction between feed materials, feed additives, biocidal products
and veterinary medicinal products (2011/25/EU).

(13)
European Parliament (2011), European Parliament Resolution of 12 May 2011 on
antibiotic resistance http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+TA+P7-TA-2011-0238+0+DOC+XML+V0//EN.

(14) European Parliament (2011), B7
0538/2011: European Parliament resolution of 27 October 2011 on the public
health threat of antimicrobial resistance. http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+TA+P7-TA-2011-0473+0+DOC+XML+V0//EN.

(15)
COM (2011), European Commission Communication of 15 November 2011 to the
European Parliament and the Council - Action plan against the rising threats
from antimicrobial resistance http://ec.europa.eu/dgs/health\_consumer/docs/communication\_amr\_2011\_748\_en.pdf.

(16) COM (2011), 777 final. Communication
from the Commission to the European Parliament, the Council, the European
Economic and Social Committee and the Committee of the Regions - Commission
Work Programme 2012, Delivering European renewal http://ec.europa.eu/atwork/programmes/docs/cwp2012\_en.pdf.

(17)
European Parliament (2011), European Parliament resolution of 15 November 2011
on honeybee health and the challenges of the beekeeping sector.

http://www.europarl.europa.eu/sides/getDoc.do?type=TA&reference=P7-TA-2011-0493&language=EN.

(18)
Council (2011), Council conclusions on the Communication from the Commission to
the European Parliament and the Council on Honeybee health

http://www.consilium.europa.eu/uedocs/cms\_data/docs/pressdata/en/agricult/122023.pdf

(19) Council (2012), Council conclusions on
the impact of antimicrobial resistance in the human health sector and in the
veterinary sector – a “One Health” perspective. http://www.consilium.europa.eu/uedocs/cms\_data/docs/pressdata/en/lsa/131126.pdf.

(20)
COM (2012), 629 final. Communication from the Commission to the European
Parliament, the Council, the European Economic and Social Committee and the
Committee of the Regions, Commission Work Programme. http://ec.europa.eu/atwork/pdf/cwp2013\_annex\_en.pdf.

(21)
European strategy for smart, sustainable and inclusive growth (Europe 2020). ftp://ftp.cordis.europa.eu/pub/etp/docs/europe2020\_en.pdf.

(22) 2012 - Motion for a Parliamentary
resolution on the microbial challenge – Rising threats from antimicrobials
(2012)

Binding legislation

(1)
Council (1990), Directive of 26 March 1990 laying down the conditions governing
the preparation, placing on the market and use of medicated feedingstuffs in
the community. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31990L0167:EN:HTML.

(2)
COM (1991), Commission Directive of 23 July 1991 laying down the principles and
guidelines of good manufacturing practice for veterinary medicinal products. http://ec.europa.eu/health/files/eudralex/vol-5/dir\_1991\_412/dir\_1991\_412\_en.pdf.

(3)
Directive 2001/82/EC of the European Parliament and of the Council on the
Community code relating to veterinary medicinal products came into force on 18
December 2001. http://faolex.fao.org/docs/pdf/eur36747.pdf.

(4)
Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31
March 2004 laying down Community procedures for the authorisation and
supervision of medicinal products for human and veterinary use and establishing
a European Medicines Agency. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32004R0726:EN:NOT

 (5)
Commission Directive 2006/130/EC of 11 December 2006 implementing Directive
2001/82/EC of the European Parliament and of the Council as regards the
establishment of criteria for exempting certain veterinary medicinal products
for food-producing animals from the requirements of a veterinary prescription. http://ec.europa.eu/health/files/eudralex/vol-5/dir\_2006\_130/dir\_2006\_130\_en.pdf.

 (6)
Commission Regulation (EC) No 1950/2006 of 13 December 2006 establishing, in
accordance with Directive 2001/82/EC of the European Parliament and of the
Council on the Community code relating to veterinary medicinal products, a list
of substances essential for the treatment of equidae. http://ec.europa.eu/health/files/eudralex/vol-5/reg\_2006\_1950/reg\_2006\_1950\_en.pdf.

(7)
Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the
examination of variations to the terms of marking authorisations for medicinal
products for human and veterinary medicinal products. http://ec.europa.eu/health/files/eudralex/vol-1/reg\_2008\_1234/reg\_2008\_1234\_en.pdf.

(8)
Commission Regulation (EC) No 470/2009 of the European Parliament and of the
Council of 6 May 2009 laying down Community procedures for the establishment of
residue limits of pharmacologically active substances in foodstuffs of animal
origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive
2001/82/EC of the European Parliament and of the Council and Regulation (EC) No
726/2004 of the European Parliament and the Council. http://ec.europa.eu/health/files/eudralex/vol-5/reg\_2009-470/reg\_470\_2009\_en.pdf.

(9)
Commission Regulation (EC) No 37/2010 of 22 December 2009 on pharmacologically
active substances and their classification regarding maximum residue limits in
foodstuffs of animal origin. http://ec.europa.eu/health/files/eudralex/vol-5/reg\_2010\_37/reg\_2010\_37\_en.pdf.

(10) Consolidated
versions of the Treaty on European Union and the Treaty on the Functioning of
the European Union
Official Journal C 83 of 30.3.2010. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2010:083:0013:0046:EN:PDF.

References, studies, papers from stakeholders:

(1) OECD (2000), OECD report on competition
and regulation issues in the pharmaceutical industry, DAFFE/CLP(2000)29.

(2) HMA Task Force on Availability of
Veterinary Medicines (2007), Report of HMA Taskforce on the Improvement of
Veterinary Pharmaceutical Legislation. http://www.hma.eu/74.html.

(3) Business Decisions Limited (2007),
Benchmarking the competitiveness of the European animal health industry, a
report by Business Decisions Limited for IFAH Europe.

(4) WHO (2007), Critically important
antimicrobials for human medicine. Report of the second WHO expert meeting, Copenhagen, 29-31 May 2007. http://www.who.int/foodborne\_disease/resistance/antimicrobials\_human.pdf;

2nd
revision (2009): http://www.who.int/foodborne\_disease/resistance/cia/en/.

(5)
OIE List of antimicrobials of veterinary importance (2007): http://web.oie.int/downld/Antimicrobials/OIE\_list\_antimicrobials.pdf

(6) Agence Française de Sécurité Sanitaire des
Aliments (2008), Conference of 30 September 2008 on Legislation on veterinary
medicinal products: improvement opportunities.

(7) EGGVP (2008), Position paper of EGGVP
on the review of legislation, December 2008.

(8)
ECDC/EMA (2009), ECDC/EMA joint technical report – the bacterial challenge,
time to react, 2009.  http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2009/11/WC500008770.pdf

 (9) Scientific Committee on
Emerging and Newly Identified Health Risks (2009), Joint Opinion on
antimicrobial resistance (AMR) focused on zoonotic infections (Scientific
Opinion of the European Centre for Disease Prevention and Control; Scientific
Opinion of the Panel on Biological Hazards; Opinion of the Committee for
Medicinal Products for Veterinary Use. http://www.efsa.europa.eu/it/efsajournal/doc/1372.pdf

(10)
CVMP (2010), CVMP Strategy on antimicrobials 2011-2015. http://www.ema.europa.eu/docs/en\_GB/document\_library/Other/2011/01/WC500100649.pdf

(11) Summary of the responses to the public consultation
(April-July 2010). http://ec.europa.eu/health/veterinary-use/pubcons\_frame\_index\_en.htm.

(12)
EMA (2011), Outcome of SME office survey on the implementation of the SME
regulation – Commission Regulation (EC) no 2049/2005 – 19/12/2011.http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119946.pdf.

(13)
SME Initiative (2011), Report on the SME Initiative 2006-2011.  http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119970.pdf.

(14)
EMA (2011), European Medicines Agency roundtable with small and medium-sized
enterprise (SME) stakeholder organisations, 19/12/2011. http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119945.pdf.

(15)
Transatlantic taskforce on antimicrobial resistance (2011),  Report, 2011. http://ecdc.europa.eu/en/activities/diseaseprogrammes/TATFAR/Documents/210911\_TATFAR\_Report.pdf.

(16) Scientific Opinion on the public health risks of
bacterial strains producing extended-spectrum β-lactamases
and/or AmpC β-lactamases in food and food-producing
animals. EFSA Journal, 2011, 9 (8): 2322.
http://www.efsa.europa.eu/en/efsajournal/pub/2322.htm.

(17)
Report of the response of Member States and EFTA countries to the questionnaire
on the use of legal provisions of Directive 2001/82 as amended, which are
intended to improve availability of veterinary medicines. 4 April 2011. http://www.hma.eu/fileadmin/dateien/Veterinary\_medicines/00-HMA\_Vet/02-HMA\_Task\_Force/02\_Availability/2011\_04\_TF\_Legislation\_Report\_of\_MS\_Responses.pdf.

(18) EFSA (2012), Technical specifications on the
harmonised monitoring and reporting of antimicrobial resistance in
methicillin-resistant Staphylococcus aureus in food-producing animals and
food.   http://www.efsa.europa.eu/en/topics/topic/mrsa.htm.

(19)
EMA (2012), Sales of veterinary antimicrobial agents in 19 EU/EEA countries in
2010 (EMA/88728/2012). http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2012/10/WC500133532.pdf.

(20) Report from the Task Force on Zoonoses Data
Collection including guidance for harmonized monitoring and reporting of
antimicrobial resistance in commensal Escherichia coli and Enterococcus spp.
from food animals http://www.efsa.europa.eu/en/efsajournal/pub/141r.htm

(21)
IFAH-Europe Impact assessment data package report.  http://www.ifaheurope.org/upl/4/default/doc/IA%20data%20pack.pdf.

Main studies requested by the Commission

(1) Questionnaire on the activities of
competent authorities related to the Directive 2001/82.

(2) GHK Consulting (2011), Study conducted
by GHK Consulting on behalf of the Commission to assess the impact of the
revision of Directive 2001/82- EPEC Report Assessment of the impact of the
revision of veterinary pharmaceutical legislation, July 2011. http://ec.europa.eu/health/files/veterinary/11-07-2011\_final\_report\_.pdf.

(3) Questionnaire directed to Member States
regarding specifically the use of the prescribing cascade in veterinary
medicine. 2011

(4) Questionnaire directed to the CMDV on
specific points regarding the revision of the veterinary medicines legislation
(internet, novel technologies, pharmacovigilance, antimicrobial resistance,
borderline products). 2012

Discussions, workshops, conferences
(major events from which feedback could be collected on issues related to the
revision of the Directive):

Event || Participants

Targeted in  depth-consultation || FVE, Copa-Cogeca, EMA

Industry workshop || Large and small pharmaceutical companies representatives

IFAH Europe/EMA Global Animal Health Conference on availability of medicines || EU and Third Countries pharmaceutical industry, regulators, veterinarians (8-9/3/11)

Stakeholders' consultation meeting || Pharmaceutical industry, Member States, EMA (23/9/11)

Veterinary Pharmaceutical Committee  || Member States, EMA (6/2/ 2012)

Targeted Workshop\_ Pharmacovigilance || pharmaceutical industry, Member States, veterinarians, EMA (29/5/12)

Targeted Workshop-  Antimicrobial Resistance || pharmaceutical industry, Member States, veterinarians, academics, Copa-Cogeca, EMA (8/6/12)

Targeted Workshop-  Authorisations/data protection || pharmaceutical industry, SMEs, Member States,  EMA (22/6/12)

Targeted workshop -  SMEs || SMEs, Member States,  EMA, veterinarians

Workshop on bees || Member States,  EMA, veterinarians, bee keeping organisations (14-15 December 2009)

List of legislation related to
veterinary medicines

· Commission Directive of 23 July 1991 laying down the principles and
guidelines of good manufacturing practice for veterinary medicinal products.

· Regulation (EC) No 178/2002 of the European Parliament and of the
Council of 28 January 2002 laying down the general principles and requirements
of food law, establishing the European Food Safety Authority and laying down
procedures in matters of food safety.

· Regulation (EC) No 1831/2003 of the European Parliament and of the
Council of 22 September 2003 on additives for use in animal nutrition.

· Regulation (EC) No 726/2004 of the European Parliament and of the
Council of 31 March 2004 laying down Community procedures for the authorisation
and supervision of medicinal products for human and veterinary use and
establishing a European Medicines Agency.

· Regulation (EC) No 882/2004 of the European Parliament and the
Council of 29 April 2004 on official controls performed to ensure the
verification of compliance with feed and food law, animal health and animal
welfare rules.

· Commission Directive 2006/130/EC of 11 December 2006 implementing
Directive 2001/82/EC of the European Parliament and of the Council as regards
the establishment of criteria for exempting certain veterinary medicinal products
for food-producing animals from the requirements of a veterinary prescription.

· Commission Regulation (EU) No 122/2013 of 12
February 2013 amending Regulation (EC) No 1950/2006 establishing, in accordance
with Directive 2001/82/EC of the European Parliament and of the Council on the
Community code relating to veterinary medicinal products, a list of substances
essential for the treatment of equidae.

· Commission Regulation (EC) No 658/2007 of 14 June 2007 concerning
financial penalties for infringement of certain obligations in connection with
marketing authorisations granted under Regulation (EC) No 726/2004 of the
European Parliament and of the Council.

· Commission Regulation (EC) No 1234/2008 of 24 November 2008
concerning the examination of variations to the terms of marking authorisations
for medicinal products for human and veterinary medicinal products.

· Regulation (EC) No 470/2009 of the European Parliament and of the
Council of 6 May 2009 laying down Community procedures for the establishment of
residue limits of pharmacologically active substances in foodstuffs of animal
origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive
2001/82/EC of the European Parliament and of the Council and Regulation (EC) No
726/2004 of the European Parliament and the Council.

· Commission Regulation (EC) No 37/2010 of 22 December 2009 on
pharmacologically active substances and their classification regarding maximum
residue limits in foodstuffs of animal origin.

· Directive 2010/63/EU of the European Parliament and of the Council
of 22 September 2010 of the protection of animals used for scientific purposes.

· At the time of writing the Commission is working on a new EU Animal
Health Law, which aims to create a regulatory framework for animal health in
the EU. There are interrelated areas of policy between this legislation and the
veterinary medicines Directive, in particular regarding animal disease and
animal welfare, which were taken on board when preparing this impact
assessment.

Annex 4 Background information on the
veterinary sector

(a) The farming
sector

Two fifths (an
estimated 40.1 %) of the total land area of the EU-27 is farmed (2007). This
proportion rises to two thirds (an estimated 66.3 %) of the land area of the United Kingdom, but is less than one tenth of the total in Sweden and Finland. Arable land (which
includes cereals and other arable land) accounts for a little less than one
quarter (24.2 %) of the total land area of the EU-27, with permanent grassland
(which is composed of pasture, meadow and rough grazing) accounting for 13.2 %.
During the ten years through until 2007, the make-up of land use in the EU-27
did not change substantially.

There were 7.3
million commercial agricultural holdings in the EU-27 in 2007, with a further 6.4
million small holdings (those below a threshold of one European size unit
(ESU)). Almost half (48 %) of the small holdings in the EU-27, mainly
classified as  subsistence holdings, were found in Romania. A little over one
third of the EU-27’s commercial agricultural holdings greater than one ESU is located
in Poland (15.4 %) and Italy (18.9 %), while Spain (12.9 %), Romania (11.9 %) and Greece (9.7 %) also contribute with about a third of the total commercial
holdings as recorded in 2007.

Among most Member
States and across the EU-27 as a whole, there has been a steady decline in the
number of agricultural holdings during the period between 2003 and 2007. In
this four-year period, the number of agricultural holdings in the EU-27
declined by 1.3 million (or 8.8 %), of which almost half were commercial
holdings. There were particularly fast structural changes in Estonia, where the number of holdings declined by more than one third (-36.7 %), as well as in Bulgaria (-25.9 %), Portugal (-23.4 %) and Hungary (-19.0 %).

In 2007, the
total farm labour force in the EU-27 was the equivalent of 11.7 million
full-time workers, of which 9.0 million worked on commercial holdings.
Agriculture remains a family-oriented activity in the majority of Member
States; almost four fifths (78 %) of the total agricultural labour force were
farm holders or members of their family. The main exceptions were Slovakia (44 %) and the Czech Republic (27 %), where there is a different ownership structure
compared with the majority of Member States. Just over one third (34 %) of the
regular agricultural labour force in the EU-27 was female, although in the
Baltic Member States this share was closer to half, reaching 50 % in Latvia.
There were relatively few (6.1 %) agricultural holders in the EU-27 under the
age of 35 years, but a relatively large proportion (34.1 %) were aged 65 years
or over.

Besides
agricultural activity, other gainful activities were also conducted in the EU
farms. These activities, carried out on the holding itself (camp sites,
accommodation for tourists, etc.) or that use its resources (machinery, etc.)
or products (such as processing farm products, renewable energy production),
have an economic impact on and are carried out by the holder, his/her family
members, or one or more partners on a group holding. Gainful activities were
conducted in about one in every ten (9.9 %) of the EU’s agricultural holdings
in 2007, this proportion being slightly higher (13.5 %) among commercial
holdings.

In 2007, the
total livestock population in the EU-27 amounted to 136 million livestock units
(LSUs), of which cattle represented 47.7 %, followed by pigs (27.6 %), poultry
(13.8 %) and sheep (7.6 %). In 2007, cattle were particularly dominant in Luxembourg (85.0 %) and Ireland (81.0 %), and a majority of the livestock population (in LSUs) were
composed of cattle in 13 of the Member States. In one MS (Denmark), pigs represented 70.6 % of the total livestock population although pigs were the largest
category of livestock in four other Member States (Cyprus, Hungary, Spain and Malta).

There is some
evidence that the number of livestock in Europe is decreasing, with a more
noticeable declined in cattle although there is some stabilisation of the swine
population.

Table 5 Cattle
and swine population in the EU (in thousands)

|| 2005 || || 2008 || || 2009 ||

|| Cattle || Swine || Cattle || Swine || Cattle || Swine

EU (15 Member States) || 76,210 || 122,235 || 75,536 || 122,994 || 75,207 || 122,897

Germany || 12,919 || 26,989 || 12,988 || 26,719 || 12,897 || 26,841

France || 18,930 || 15,123 || 19,366 || 14,796 || 19,199 || 14,552

United Kingdom || 10,545 || 4,726 || 9,910 || 4,550 || 9,901 || 4,601

The principal
meat produce in the EU 27 is pig meat (21.3 million tonnes produced) and
beef/veal production (7.7 Million tonnes). In comparison, sheep meat production
is small (0.7 million tonnes).

A quarter (24.7
%) of the EU-27’s pig meat production is from Germany, the next highest
contributions coming from Spain (15.5 %) and France (9.4 %), while 7.6 % is
produced by Poland and 7.4 % by Denmark. A little under one fifth (19.0 %) of
the beef/ veal produced in the EU-27 originated from France in 2009. Ireland reported a relatively high share of the EU-27’s production of cattle meat.

Dairy
production has a diverse structure across the Member States, in terms of farm
and dairy herd sizes, as well as milk yields.  The total collection of cows’
milk in the EU-27 in 2009 amounted to 133.5 million tonnes. Germany recorded the highest share (21.1 %) of
EU-27 milk collected in 2009 and also accounted for the highest proportions of
EU-27 butter (25.2 %) and cheese (22.8 %) production.

Aquaculture is
the farming of aquatic organisms including fish, molluscs, crustaceans and
aquatic plants. Farming implies some form of intervention in the rearing
process to enhance production, such as regular stocking, feeding and protection
from predators. Farming also implies individual or corporate ownership of, or
rights resulting from contractual arrangements to, the stock being cultivated. The
level of aquaculture production in the EU-27 remained relatively stable between
1.2 million tonnes and 1.4 million tonnes during the period 1998 to 2007. The
five largest aquaculture producers among the EU Member States were Spain, France, Italy, the United Kingdom and Greece, which together accounted for around three
quarters of total aquaculture production in 2007. Aquaculture production was
extremely large in Norway – higher than the combined output of the three
largest Member States. The development of aquaculture production between 1998
and 2007 followed different patterns across the EU Member States. Production in
the Netherlands more than halved and there were also large percentage
reductions in aquaculture output in Germany and Denmark, whereas, among the
larger producers, aquaculture output rose by 90 % in Greece.

Source: Eurostat
yearbook 2011

http://epp.eurostat.ec.europa.eu/cache/ITY\_OFFPUB/CH\_08\_2011/EN/CH\_08\_2011-EN.PDF

(b) The
companion animal sector

Around 70 million European households own at least 1 pet. The pet
population is distributed as follows (2010):

Table 6 Pet
population in the EU

Species || Population || Largest populations in:

Cats || 64 448 500 || France (11 M); Germany (8.2 M)

Dogs || 60 226 400 || UK (8 M); France (7.6 M)

Birds || 39 215 000 || Italy (13 M); France (6 M)

Small mammals || 24 614 000 || Germany (5.3 M); Spain (3.8 M)

Aquaria || 8 272 000 || Germany (2 M); UK and Italy (1.5 M)

There is
evidence that the dog and cat population in the EU is increasing, at least in
some Member States:

Table 7
Population of cats and dogs (millions) in some Member States[76]

Member State || Dogs || Cats

|| 2009 || 2010 || 2009 || 2010

Germany || 5,300 || 5,400 || 7,900 || 8,200

France || 7,800 || 7,570 || 10,700 || 11,480

United Kingdom || 7,300 || 8,024 || 7,200 || 10,490

There are
approximately 200.000 veterinarians in Europe, and an estimated 60.000 pet
specialist stores.

The estimated
annual value of pet related services, including those offered by breeders,
groomers, dog trainers, and veterinarians and related to sales of pet
accessories, insurances, medication, vaccination is around  10.5 billion euros.

There are no
definitive statistics on the equine sector, but it is estimated that there are
around 6 million horses in Europe, and that the total impact of equine
activities are around 100 billion euros a year. This takes into account the
direct economic impact of all horse industry activities (breeding, industrial
companies and services linked to horses, education, research etc) and also the
indirect and induced impact of horse activities such as organisation of events
and betting (30 billion euros/year).

It is estimated
that the equine sector in Europe represents around 400 000 full time jobs
equivalent. There are some economic clusters of horse businesses in EU regions,
such as those in Basse-Normandie in France, Kecskemét, Hungary and Newmarket in the UK, where around a third of the jobs are related to the horseracing
industry. The yearling sales alone in Deauville in August 2010 have generated
26 million euros.

Sources:

The European Pet Food Industry Facts and Figures
Report, 2010

http://www.fediaf.org/facts-figures/

The European Horse Network

http://www.europeanhorsenetwork.eu/index.php?page=horse-industry-in-europe

The Federation of Veterinarians of Europe

http://www.fve.org/about\_fve/index.php

Eurostat

(c) The
veterinary pharmaceutical sector

The veterinary
pharmaceutical sector is formed by businesses acting in the areas of Research
and Development, manufacture of veterinary medicines (originators and
generics), importation of medicines, wholesaling and retailing. The veterinary
pharmaceutical industry responsible for developing and placing on the market
veterinary medicinal products is largely composed by stand alone, self-funding
subsidiaries of larger human companies and independent specialist companies. It
creates around 50,000 direct jobs in Europe. The
consensus is that there are strong growth opportunities for development of
veterinary medicines for food producing species outside Europe (USA, China, India, Russia and Brazil), as the growth is driven by the world's demands for milk, meat
and eggs. The prospects for the companion animal sector are linked with the
general economic performance of a country, and it is expected that emerging
markets will also offer opportunities for growth in this sector[77]. Therefore, it is likely that corporate strategic decisions will be
strongly influenced by market forces and regulatory approaches existing outside
the EU.

A rough
estimate from the industry and analysis of Member States' databases suggests
there are around 108 manufacturers of veterinary medicines in Europe. Data
collected for the assessment of the impact of the revision of veterinary
pharmaceutical legislation suggest that the animal health industry in Europe consists of a small number of companies that hold marketing authorisations in multiple
national markets, and a larger number of companies that only hold marketing
authorisations on one national market. The former group includes high-profile
large multinational pharmaceutical companies, which typically hold large
numbers of marketing authorisations. Companies that are present on one national
market make up the majority of the animal health sector in terms of the number
of companies, but the minority in terms of its share of total EU-wide marketing
authorisations. These companies in average each hold six marketing
authorisations. Of the 463 companies that held a marketing authorisation as at
of May 2010, 101 companies (22% of the total) held a single marketing
authorisation on a single national market.

In 2009, the
global sales of veterinary medicines were estimated at approximately 13.4
billion euros. The sales in the European market were estimated at around 4.6
billion euros (at 2005 prices). Between 2005 and 2008 the size of the European
market increased by 23 % compared to an increase of 18 % globally but dropped
back to its 2007 levels in 2009. The animal pharmaceutical industry is
estimated to be around 2.4 % of the size of the human pharmaceutical industry.
The total sector sales for veterinary medicines in 2008 were estimated to be
4.3 billion euros.

In 2004 generic
products had a share of 45% of the total global sales of animal health
products. Generic animal health products are very prevalent in Latin American,
African and Asian countries with a market share of two thirds or more. In North America and the EU the share is approximately one third. It is expected that generics
will become a more dominant factor in the future. This is confirmed by the EU
data on MRP/DCP procedures showing that most procedures concern generic
products.

Eurostat data indicate that in 2007 a total
of 606,500 people were employed in the pharmaceutical manufacturing industry in
Europe. As the animal pharmaceutical industry is estimated to be 2.4% of the
human pharmaceutical industry, this suggests that around 14,600 people are
directly employed by the veterinary medicinal products manufacturing industry
in Europe.

Sources:

EPEC Assessment of the impact
of the revision of veterinary pharmaceutical legislation report, 2011
IFAH-Europe Impact assessment
data package report, 2010
Research and Markets, Generics
in the Animal Health Industry.

Annex 5 Overview of the institutional
landscape and of the regulatory framework for veterinary medicines

Overview of the marketing authorisation procedures

The legislation requires that before a veterinary medicine may be
placed on the market it must have been granted a marketing authorisation. There
are four routes that applicants can take to obtain a marketing authorisation,
and they require assessment by competent authorities of the quality, safety and
efficacy data submitted by the pharmaceutical company in accordance with the
legislation:

Centralised procedure

In the EU a company may submit a single application to the EMA for a
marketing authorisation valid simultaneously in all EU Member States,
plus Iceland, Liechtenstein and Norway. This centralised (or Community)
authorisation procedure is mandatory for certain types of medicines and
optional for others.
The centralised procedure is compulsory for veterinary medicines that are for
use as growth or yield enhancers and medicines derived from biotechnology
processes,. For medicines that do not fall within these categories, companies
have the option of submitting an application for a centralised marketing
authorisation to the EMA if the product is of significant therapeutic,
scientific or technical innovation, or if its authorisation would be in the interest
of public or animal health at community level. Applications through the
centralised procedure are submitted directly to the EMA, and the evaluation is
carried out by the EMA's CVMP, a board of Member States' experts chosen by
their qualifications and expertise regarding evaluation of veterinary
medicines. Once the CVMP adopts an opinion on whether the medicine should be authorised
or not, the opinion is transmitted to the European Commission, which has the
ultimate authority for granting the marketing authorisation in the EU through a
Commission Decision.

A detailed description of the centralised procedure can be found  in
the guidance Notice to Applicants, Veterinary Medicinal Products, Volume 6A,
Procedures for Marketing Authorisations, chapter 4 – Centralised procedure:

http://ec.europa.eu/health/files/eudralex/vol-6/a/vol6a\_chap4\_2006\_05\_en.pdf

Mutual recognition procedure

In the mutual recognition procedure, a medicine is initially authorised
in one EU Member State in accordance with the national procedures of that
country. Following this, the marketing authorisation holder can seek further
marketing authorisations in other EU countries in a procedure whereby the
countries concerned agree to recognise (following assessment of an application
dossier) the validity of the original, national marketing authorisation.

A detailed description of the mutual procedure can be found in the
guidance Notice to Applicants, Veterinary Medicinal Products, Volume 6A,
Procedures for Marketing Authorisations, chapter 2 – Mutual Recognition and Decentralised
procedures: http://ec.europa.eu/health/files/eudralex/vol-6/a/vol6a\_chap2\_2005-11\_en.pdf.

Decentralised procedure

Using the decentralised procedure, companies may apply for simultaneous
authorisation in more than one EU country of products that have not yet been
authorised in any EU country and that do not fall within the mandatory scope of
the centralised procedure.

A detailed description of the decentralised procedure can be found
in the guidance Notice to Applicants, Veterinary Medicinal
Products, Volume 6A, Procedures for Marketing Authorisations, chapter 2 –
Mutual Recognition and Decentralised procedures: http://ec.europa.eu/health/files/eudralex/vol-6/a/vol6a\_chap2\_2005-11\_en.pdf.

National procedure

Each EU Member State has its own procedures and timelines
for the authorisation of medicines through a national procedure. Currently a marketing authorisation issued in one Member State through the national procedure is valid only in that Member State. To place the
product on the market in other Member States the marketing authorisation holder
has to submit an application to the desired countries through the mutual
recognition procedure with a dossier for assessment. Each national competent
authority will assess the dossier and approve the contents of the summary of
product characteristics and product literature.

Description of the steps involved in each procedure:

Centralised procedure

Day 1 Start of the procedure

Day 70 Rapporteur’s assessment report sent to the Co-rapporteur,
CVMP members and EMA Secretariat.

Day 85 Co-rapporteur’s critique of the Rapporteur’s assessment report
sent to Rapporteur, CVMP members and EMA Secretariat. The Rapporteur’s assessment
report and the Co-Rapporteur’s critique are sent to the applicant by the EMA
Secretariat

Day 100 Rapporteur, Co-rapporteur, other CVMP members and EMA receive
comments from Members of the CVMP. Between Day 70 and Day 100, a quality check
on the English version of the Product Information is carried out.

Day 115 Receipt of draft list of questions (including overall
conclusions and overview of the scientific data) from Rapporteur and
Co-Rapporteur by CVMP members and EMA.

Day 120 CVMP adopts the list of questions as well as the overall
conclusions and review of the scientific data to be sent to the applicant by
the EMA. Clock stop. At the latest by Day 120, adoption by CVMP of request for
GMP inspection, if necessary ( the inspection procedure starts).

Day 121 Submission of the responses, including revised summary of
product characteristics, labelling and package leaflet text in English and
restart of the clock.  After receipt of the responses, the project manager will
prepare a revised timetable in consultation with Rapporteur and Co-Rapporteur
for the evaluation of the responses. In general the following standard
timetable will apply:

Day 160 Joint response assessment report from Rapporteur and
Co-Rapporteur received by CVMP members and EMA. EMA sends joint response assessment
report to the applicant, making it clear that it only sets out their
preliminary conclusions and that it is sent for information only and does not
yet represent the position of the CVMP. Where applicable, inspection to be
carried out.

Day 170 Deadline for comments from CVMP Members to be sent to
Rapporteur and Co-Rapporteur, EMA and other CVMP members.

Day 180 CVMP discussion of the draft opinion (summary of product
characteristics, labelling and package leaflet) and decision taken on the need
for an oral explanation by the applicant. If oral explanation is needed, the
clock is stopped to allow the applicant to prepare the oral explanation. Submission
of final inspection report to EMA, Rapporteur and Co-Rapporteur by the
inspections team (at the latest by day 180).

Day 181 Restart of the clock and oral explanation (if needed). The project
manager sends updated summary of product characteristics and product literature
in English to the applicant.

By 210 Adoption of CVMP Opinion + CVMP assessment report.

Day 211 Transmission to applicant of CVMP Opinion + CVMP assessment report

Day 215 at the latest Applicant provides the EMA with summary of product
characteristics, Annex II, labelling, package leaflet and Annex A in all EU
languages and Norwegian.

Day 232 Applicant provides the EMA with summary of product
characteristics, Annex II, labelling, package leaflet and Annex A in all EU
languages, taking account of comments received from Member States by Day 229.

By Day 237 EMA Transmission of Opinion and Annexes in all EU
languages to the applicant, Commission and Members of the Standing Committee, Norway and Iceland.

Mutual recognition procedure

Before day -14 Applicant discusses the application with the
Reference member state (RMS)

The RMS updates the assessment report and inform the Concerned
Member States (CMS) of proposed start date

Submission of the dossier to the CMS (and RMS if necessary)

Circulation of the assessment report to CMS

-14 Days Automatic validation of the application

Day 0 Start of the procedure

Day 54 CMS send comments to RMS and applicant (via RMS)

Day 57 RMS circulates the List of Questions (LOQ) to the applicant
and CMS

Day 65 Applicant sends response to LOQ to RMS, who forwards this to
CMS

Day 70 RMS circulates assessment of response to LOQ to applicant and
CMS

Day 77/78 CMD(v) meeting -RMS informs applicant of outcome of
discussions after the meeting

Day 82 Applicant sends new drafts of SPC, product literature and
labelling (with translation) to RMS, who forwards them to CMS

Day 85 If necessary, final drafts of SPC, product literature  and
labelling are prepared

Day 88 CMS send final comment to RMS

Day 89 RMS circulates final assessment report, SPC, product
literature and labelling to CMS and applicant

Day 90 If consensus is reached, the RMS will close the procedure; if
consensus not reached, a  referral is initiated to CMD(v).

Start of national phase

Day 95 Applicant sends translations to all CMS

Day 120 Granting of national marketing authorisation in RMS and CMSs
if no

referral to the Co-ordination group. The national agencies adopt the
decision and issue the marketing authorisation subject to submission of acceptable
translations/mock-ups.

Day 180 Granting of national marketing authorisation in RMS and CMSs
if positive

conclusion by the Co-ordination group and no referral to the CVMP.
National agencies adopt the decision and issue the marketing authorisation
subject to submission of acceptable translations/mock-ups.

Decentralise procedure

At least 3 months before the DCP, the applicant
discusses the application with RMS. The

RMS then inform CMS of proposed start date.

-14 Days Submission of the dossier to the RMS and CMS
and validation of the application (may be extended to 30 days for generics when
the reference product is not authorised in the RMS)

Assessment step I

Day 0 RMS starts the procedure

Day 70 RMS circulates drafts of LOQ, SPC, product
literature and labelling with the preliminary assessment report to CMS

Day 100 CMS send comments to RMS

Day 105 RMS forwards LOQ to the applicant and CMS

Clock-off period – the applicant has 3 (6) months to
submit a response

Day 106 Valid submission of response.

RMS re-starts the clock

Assessment step II

Day 120 (0) RMS forwards to applicant and CMS Draft AR,
and drafts of SPC, product literature and labelling

Start of Assessment step II

If consensus reached, the RMS can close the procedure

Day 145 (25) CMS send comments to RMS and applicant (via
RMS)

Day 150 (30) RMS circulates LOQ to applicant and CMS

If consensus reached, the RMS can close the procedure

Day 170 (50) Applicant sends response to LOQ to RMS

RMS immediately forwards this to CMS

Day 190 (70) RMS circulates assessment of response to
LOQ to applicant and CMS

Day 197/198 (77/78) CMD(v) meeting

The RMS informs applicant of outcome of discussions
after the meeting

Day 202 (82) the applicant sends new drafts of SPC, PL
and labelling to RMS.

Translations may be included. The RMS forwards this to
CMS.

Day 205 (85) If necessary, final drafts of SPC, product
literature and labelling

Day 208 (88) CMS send final comment to RMS

Day 209 (89) RMS circulates final AR, SPC, product
literature and labelling to CMS and applicant

Day 210 (90) If consensus reached, the RMS will close
the procedure

If consensus not reached, a referral to CMD(v) is
triggered.

National phase

Day 125/155/215/275 Applicant sends translations to all CMS

Day 150/180/240 Granting of national marketing
authorisation in RMS and CMSs if no

referral to the Co-ordination group. National agencies
will adopt the decision and will issue the marketing authorisation subject to
submission of acceptable translations/mock-ups.

Day 300 Granting of national marketing authorisation in
RMS and CMSs if positive conclusion by the CMD (v) and no referral to the CVMP.
National Agencies adopt the decision and issue the marketing authorisation
subject to submission of acceptable translations/ mock-ups.

Analysis of the
number of marketing authorisations per type of process[78]

Information on the numbers of applications for marketing
authorisations received by the competent authorities through the four
authorisation procedures are analysed below.

Applications for the centralised procedure were received by the EMA
whilst national competent authorities received applications for either the MRP
or DCP. The HMA provided information on those types of applications. There is
no comprehensive information across the EU for applications received by the
national competent authorities through the national procedure. The UK was the only competent authority that provided these data, which is therefore used here
as an example.

Applications
processed through the Mutual Recognition procedure

The Heads of Medicines Agency (HMA) provided data on marketing
authorisation applications received through the Mutual Recognition Procedure. 
These data covered applications for new marketing
authorisations, line extensions[79], variations,
and renewals received between 2006 and 2009.  A total of 2,235 applications were received in
this period, of which 330 (15 %) concerned new marketing authorisations or line
extensions.

Figure 2 Number of applications received through the MRP, by type of
application (2006-2009)

Applications processed through the
Decentralised procedure

The HMA provided data on marketing authorisation applications received through the decentralised
procedure. These data covered applications for new marketing
authorisations, line extensions, variations, and renewals
received between 2006 and 2009.  A total of 597
applications were submitted, of which 210 applications concerned new MAs or
line extensions.

Figure 3 The
number of applications received by the competent authorities through the DCP,
by type of application (2006-2009)

Applications processed through the
Centralised Procedure

The figure below shows the total number of
applications received by the EMA through the Centralised Procedure between 1997
and 2009. There were 145 applications for new marketing
authorisations. The most common form of Centralised procedure application was
for a Type II variation to an existing marketing authorisation (214).

Figure 4 Number of applications received
through the Centralised Procedure, by type of application (1997-2009)

Applications processed through the National Procedure

Data on MA applications received through
the national procedure were requested from the competent
authorities in the Member States during the consultation but only UK data
became available. The data provided by the UK authorities cover the period 2000
to 2009, and shows applications received for: new marketing
authorisations, renewals, and certain types of
variations.

The figure below
shows the total number of applications received by the competent authority in
the UK between 2000 and 2009. A total of 7,895
applications were received, of which 7% were applications for new marketing
authorisations and 33 % applications for renewals.  The majority (61%) of applications received were for variations.

Figure 5 Number of applications received, by type of application (2000-2009)

Authorisation of antimicrobials for use in
veterinary medicine

There are no particular restrictions in the current veterinary
medicines legislation regarding the authorisation or use under the Cascade of
antimicrobials in animals. However, there is a requirement for submission of
data on potential emergence of resistant bacteria as part of the application
dossier. Decisions on the authorisation of veterinary antimicrobials are
product-related, made on a case-by-case basis and based on the data presented
in the dossier.

Clinical trials
Applications for marketing authorisations for
veterinary medicines require data from clinical trials to demonstrate their
safety and efficacy under normal conditions of use. The data requirements for
clinical trials are set out in Directive 2001/82/EC but EU
Member States have their own procedures and timelines to authorise clinical
trials, as these are not set in legislation.

Product literature (packaging and labelling)

The Directive 2001/82 sets out that mock-ups of
immediate and outer packaging of the veterinary medicines must be submitted for
approval by the competent authorities as part of the application process. The
product literature of veterinary medicinal product must be in the official
language or languages of the country where the product is to be placed on the
market.

Placing veterinary medicines on the market in the
event of an emergency

The current legislative provisions in the Directive
2001/82 allow the placing of a veterinary medicine on the market without a
marketing authorisation if the health situation in the country so demands and
the medicine has already been authorised in one Member State. It also
regulates, in the event of a serious epizootic disease, the provisional use of
an immunological veterinary medicine without a marketing authorisation, after
informing the Commission. Member States have their own national procedures and
timelines to streamline the authorisation of veterinary medicines when there is
an urgent need.

Placing on the market of homeopathics

Homeopathic veterinary
medicinal medicines may be placed on the market if they hold a marketing
authorisation or have been registered in accordance with a simplified procedure
for homeopathics. Homeopathic medicinal products intended for food producing
species need to comply with the provisions of the legislation on residues
limits in foodstuffs of animal origin in order to be placed on the market. For
homeopathic immunologicals, the same rules for regular immunologicals apply.

Maintenance of marketing authorisations
Pharmacovigilance

Directive 2001/82/EC sets out the arrangements for pharmacovigilance
for veterinary medicines. Marketing authorisation holders must report serious
suspected adverse events within 15 days to the competent authorities and
prepare periodic safety update reports on the overall performance of the
product at set intervals for all veterinary medicines. Marketing authorisation
holders must submit the details of their pharmacovigilance systems as part of
every application for a marketing authorisation. Any changes to this system
require a variation. There is a requirement for the inspection of marketing
authorisation holders by the competent authorities for compliance with the
legislation regarding pharmacovigilance.

Renewals

Directive 2001/82/EC sets out the requirements for ensuring the
continued quality and safety of a veterinary medicine once marketed. Under the current legislation, marketing authorisations are valid
for five years and then may be renewed on the basis of a re-evaluation of the
risk-benefit balance. Once renewed, marketing authorisations are valid for an
unlimited period unless there are justified grounds relating to pharmacovigilance
to proceed with one additional five-year renewal.

Variations

The legislation requires that any
amendments to a marketing authorisation require the submission of a variation. Variations are categorised according to
their complexity, ranging from Type 1A variations (the least complex), through
Type 1B variations, to Type 2 variations (the most complex).  Some variations
concerning purely administrative changes (such as changes to the address of the
marketing authorisation holder, for example) may be implemented before the
competent authorities are notified, but other equally simple changes will still
require assessment by the competent authorities.

Provisions regarding data protection and authorisation of generic
veterinary medicines

The legislation sets out the provisions regarding data protection
for new veterinary medicines and the requirements for the authorisation of
generics. A generic medicine may only be placed on the
market 10 years (13 years, if the product is for bees or fish) after the initial
authorisation of the originator medicine. Veterinary medicines for food
producing species benefit from an extra 1 year protection for each extension to
a food producing species, if the extension is authorised within 5 years
following the granting of the initial marketing authorisation ("window of
opportunity"). There is a requirement for environmental safety data to be
submitted with a generic application, but other safety data are not required.

The legislation sets out that any extensions to a veterinary
medicine are "rolled back" into the initial marketing authorisation
(the global marketing concept), and therefore developments of the product do
not restart or prolong the data protection period of the marketing
authorisation.

Other provisions

The wholesale dealing and retailing of veterinary
medicinal products activities are regulated under Directive 2001/82/EC, as well
as the advertising of veterinary medicines. The legislation also sets out the
requirements for inspections of manufacturing sites for Good Manufacturing
Practice, and of sites of marketing authorisation holders regarding compliance
with pharmacovigilance obligations.

Annex 6 Further information related to the problems identified with
the veterinary medicines legislation and on antimicrobial resistance

Some facts and figures concerning the availability of
medicines in the Union are presented below:

Authorisation issues

Smaller countries tend to have fewer authorised
medicines

There is considerable variation
between countries in terms of the number of authorised products – from 296
products in Iceland to
2,944 products in France.  Smaller
countries tend to have fewer authorised veterinary medicinal products.

Figure 6 Number of authorised products and authorised
‘brands[80]’
on national markets, as at May 2010

High proportion of products authorised in small
countries are not placed on the market

Commercial decisions regarding return on investiments
drive actual product availability, even where a marketing authorisation holder
has spent resources obtaining a marketing authorisation. This is particularly
true of the centralised procedure, where companies are granted a pan-european
authorisation but may decide not to market the product in non-profitable
markets. From the point of view of the farming sector,
some EU farmers are at a competitive disadvantage within the EU (and indeed
with the world) regarding optimal opportunities for animal treatment and
consequently productivity.

Data from the consultation
showed that products authorised through the national procedure were most likely
to be marketed (on average 80 % of marketing authorisations were marketed).  In
contrast, on average 56 % of products authorised through the Centralised
Procedure were marketed, though in Romania the proportion was as low as 34 %. [81]

The use of a national route to place a veterinary medicine on the
market is widely used. Data obtained through the consultation[82] indicate that the majority of the pharmaceutical companies
operating in the veterinary pharmaceutical sector hold marketing authorisations
(brands) only in a single national market (67 %)[83]. Most of the veterinary medicines available in the Member States
historically have been authorised through the national procedure. This creates
a barrier to the single market as a veterinary medicine must have a marketing
authorisation in the Member State before it can be placed on the market in that
Member State, and the current Mutual recognition procedure leads to the
re-assessment of products that already have a marketing authorisation in at
least one Member State.

Figure 7 Proportion of a sample of marketing
authorisations which are marketed in selected countries, as at January 2011

There are few authorised veterinary medicines for
minor species[84]

The analysis of marketing authorisations for eleven ‘case study’ species[85]
demonstrated that there are considerable variations in the number of products
authorised for use per
species.  More products are authorised for use in dogs than any other species.  The ‘top 4’
species in terms of the number of authorisations (dogs, cattle, pigs and cats)
on average accounted for 70 % of all authorisations.

Figure 8 Number of products authorised for use per species, as at May 2010. Note that
products can have multiple target species.

There are few authorised products for therapeutic
categories

Using the Anatomical Therapeutic Chemical (ATC) (vet)
classification system[86],
it was possible to examine the therapeutic categories of veterinary medicinal
products authorised in Europe.  The ATCvet classification system categorises
products according to their therapeutic use, starting with 15 categories
labelled QA to QV (the ATCvet classification systems does not enable the
analysis of the distribution of medicines for particular conditions (e.g.
diseases), only broad therapeutic categories).

 Certain therapeutic categories appear to
be relatively unimportant within animal health, whilst
others – e.g. QB (blood products) – are considered to be emerging areas where
developments may take place in the future.

Antiparasitics (ATCvet
categories QP), anti-infectives (QJ)) and immunologicals (QI) accounted for the
largest numbers of authorised products, on average making up 63% of the total
number of medicines.  In smaller markets in particular there were very few
authorised products (typically under 5) within many therapeutic categories.

Figure 9 Therapeutic categories (ATCvet system) for all authorised
products on national markets, as at May 2010.

The number of applications for new authorisations
submitted each year is low, and few applications concern minor species

The graph below shows that the EMA typically
receives around 20 applications for a new marketing authorisation/line
extension (that is, innovative products) through the centralised procedure each
year.  Data as regards applications through the mutual recognition and
decentralised procedures are limited, but do show that both routes are used
more frequently by businesses than the centralised procedure.  In the UK (the only Member S tate that that provided data regarding applications received through the
national procedure) applications received through the national procedure have
declined in number in recent years.

Figure 10 Number of applications for new marketing
authorisations/line extensions received by the
authorities through the centralised
(1997-2009), mutual recognition (2006-2009), decentralised (2007-2009) and national (UK only, 2000-2009) procedures
each year:

The number of applications for
new marketing authorisations/line extensions is low.  Of all the applications
concerning minor species plotted in the figure below, 62 % involved horses and
just 4 applications (2 %) involved bees.

Figure 11 Number of applications for new marketings/ line extensions involving
horses, goats, turkeys, bees, or salmon, trout or other fish received by the
authorities through the centralised
(1997-2009), mutual recognition (2006-2009), decentralised (2007-2009) and national (UK only, 2000-2009) procedures each year

The lack of innovation for products for food-producing species is
also, to a certain extent, reflected in the number of applications to establish
Maximum Residue Limits (MRLs). For example, whilst an increase of 50% in the
number of applications for the extension of MRL to new species was reported in
2011 in comparison to 2010, the number of applications for MRL for new molecule
remained low (3 applications in 2010; 1 application in 2011)[87]. Changes to
the legislation were made to permit the extrapolation of MRLs to minor species,
but this has not yet generated the expected benefits for minor species.

Defined medicine availability problems in various species

Several lists of needed veterinary
medicines have been produced along the years. The
European Technology Platform on Global Animal Health[88], a
technology platform led by the pharmaceutical industry, has prepared an action
plan which includes a gap analysis of available products required to deliver new and improved tools for the control of major diseases. The Federation of European Veterinarians identified the following as
most needed in the Union[89]

Species || Conditions

Turkeys || Histomoniasis

Rabbits || Scabies enterocolitis

Fish || Kidney disease, anaesthetics

Bees || American fowlbrood, nosemosis

Dairy sheep and goats || Coccidiosis, nematode and trematode infections

Dairy goats || Mastitis

Pigs || Anaesthetics

A discussion on the reasons behind the
problem with the availability of medicines is presented here.

Complexity of the authorisation system

The current system for authorisation of veterinary
medicines offers four different routes of application: the centralised (CP),
the decentralised (DCP), the mutual recognition (MRP) and the national
procedures. This framework has become very complex and introduced a high level
of bureaucracy both for industry and regulators. A further problem is the
existence of various legal bases for applications. This complex structure seems
to lead to ever new aspects and possibilities in using the legislation posing
increasing regulatory demands and disharmonisation. Furthermore, the mutual
recognition and decentralised procedures often leads repeated evaluations of
dossiers and discussions over the acceptable level of documentation provided by
the applicants and the interpretation of data. This has often led to costly
referrals to CMDv and CVMP to arbitrate over disagreements.

Case study – the cost of a referral A generic company applied for a marketing authorisation in various countries through the decentralised procedure. One of the Member States calls a referral on the basis of divergent opinion during the procedure. The referral is accepted and the pioneer company is requested to harmonise the SPC across all the Member States: Costs to the marketing authorisation holder of the originator product Activity || Costs\*

Compilation and publication of the dossiers || 6,000

Resources for internal and external experts || 15,000

Translations || 20,000

Preparation of variations to amend SPC and product literature || 9,000

Regulatory national fees for variations ||

Write off of label inventory, packaging || 120,000

Cost of new labels, label development || 120,000

Total || 308,000

 Man days = 137 \* || 137,000

Overall cost || 445,000

Overall timeline || 18-24 months

\* man cost estimated as 1,000 Euros per day

Costs for the two Member States leading on the assessment work for
the referral was estimated by the UK: 375 hours (appr  31,500 Euros). The
costs to the EMA and CVMP members and their experts considering the
assessment reports produced by the leading Member States have not been
estimated.

\* Euros

There have been 66 referrals from 2001-2013. More than half of the
cases concern antimicrobials (42 / 66). Nearly half of the cases are Art. 33
referrals (30/66) (concerning mutual recognition/decentralised procedures).

This complexity in the regulatory environment makes it difficult
for smaller companies to make applications for marketing authorisations and to
maintain products on the market once an authorisation has been issued. The
pharmaceutical industry also indicated that the changes over time of the
regulatory framework increased product development time[90] and this is of crucial importance to them, as minimising
time-to-market is an important factor in successful innovation.

Administrative burdens

Stakeholders have reported that the costs and the time needed for
new product development in Europe has significantly increased over recent
decades. The administrative burdens vary with the marketing authorisation
procedures[91]:

Table 8 Administrative burden associated
with the current marketing authorisation procedures

Marketing authorisation procedure || Total cost per product  year \*

Centralised || 243,729

Decentralised || 291,568

Mutual recognition || 269,799

National procedure || 151,408

\*Euros

The centralised procedure is the least
costly of the three European procedures. The
decentralised procedure is the most costly option to the companies, and the
national procedure generates the lowest administrative burden. The majority of
the marketing authorisation holders (62%) only hold marketing authorisations in
a single national market, and just 4 % marketing authorisation holders hold
marketing authorisations within 18 national markets (for which data were
available for the consultation).

A break down of the costs of administrative
burdens to the industry is shown in the figure below[92].

Figure 12 Administrative burdens imposed on
business

These costs are equivalent to a high proportion of the industry
turnover: and it is estimated to amount to 537.9 million per year across the Union. Considering that the total sales of veterinary medicines industry in Europe were estimated as 4.3 billion (2008), the administrative burden associated with
meeting legislative requirements is equivalent to 13 % of the annual turnover
of the sector:

Table
9 Estimated value of the annual administrative burdens imposed by the
legislative framework for veterinary medicinal products

Information Obligation || Administrative burden (million euros p.a.) || % of total administrative burden

Applying for a new MA || Sub-total || 91.1 || 17%

Applying for a variation to an existing MA || Type 1A || 19.7 || 4%

Type 1B || 20.6 || 4%

Type 2 || 93.1 || 17%

Sub-total || 133.5 || 25%

Renewing a MA || Sub-total || 69.5 || 13%

Pharmacovigilance reporting || Suspected Adverse Reactions || 4.3 || 1%

Serious Adverse Reactions || 8.0 || 1%

PSURs[93] || 47.2 || 9%

Sub-total || 59.4 || 11%

Packaging & labelling || Sub-total || 184.4 || 34%

Grand total || || 537.9 || 100%

Source: GHK calculations based surveys
& engagement with industry and regulators

Use of the Cascade

The European Commission consulted Member States on the use of the Cascade
by means of a questionnaire (March to June 2011). Twenty replies were received.
More than half of the respondents indicated that they have a procedure for importation
of medicines for use under the Cascade. Most respondents could not provide any precise
data on the extent of the usage of the Cascade. Four respondents indicated that
1-5% of total use of medicines for food producing species and 2-40% for
companion animals.is under the Cascade Three respondents provided data suggesting
that all veterinary surgeons make use of the Cascade. The use of the Cascade is
reported to be particularly frequent in pet animals (dogs, cats, horses) and
minor species.

Packaging and labelling

The legislation sets out that the mock ups of immediate and outer
packaging of veterinary medicines should be submitted as part of the
application process for approval.  The legislation also requires that the
product literature of the veterinary medicinal product should be in the
language of the country where the product is placed on the market. The cost of
complying with the legislative requirements for packaging and labelling is
cited as the single largest administrative burden for the industry.

Case study: Costs to the industry of the packaging activities required for a product consisting of blister packs of tablets, contained in a carton with a leaflet (multilingual pack, with texts in 13 different languages for 17 countries)[94]: Activities || 13 individual presentations (pallet load of 1920 packs) costs\*

Artwork: creation/preparation || 23,000

Costs of the printed materials (blister, folding box, package leaflet) and costs of packaging operations (for example, labelling, boxing per packaging line and line clearance) || Blister: 106,640 Folding box: 84,000 Package leaflet: 18,800 Total: 209,440

Warehousing || 0.0032 per pack

Total || 253,775

Write offs (expired or soon to be expired material) || 21,335

Batch release by QA/QC || 13 batches \*\*

\*Euros

\*\* Cost not specified

The pharmaceutical industry indicated that the manufacture of small
batches of veterinary medicines to supply small markets is expensive and the cost
of labelling such medicines with the national languages is too high to justify
the operation. The adoption of multi-lingual packaging could overcome this
problem by making a larger batch of product available in several markets, but
the current legal requirements for extensive written information to be present
on the product literature hinder the use of multi-lingual labels.

For this reason not all products that are authorised via the
centralised procedure (that is, have a pan-European marketing authorisation and
therefore could be put on the market in all Member States) are actually
available in smaller markets in the EU. As discussed above, in Romania, for example, only 34 % of centrally authorised medicines are on the market[95]. Some small markets such as Luxembourg and Austria do have a large number of centrally authorised medicines in their markets, but this could be
because they benefit from larger markets with the same language, such as France and Germany[96].

There is a provision in the Directive 2001/82 (Art 61 (1)) which
allows Member States' authorities to exempt labels and package leaflets for
small containers from the obligation to have the text in the official language
of the Member State where the product is authorised. This provision is used in
particular for immunological products, for example for single dose vaccine
vials, but it is considered by the pharmaceutical industry and some Member
States as insufficient to alleviate the administrative burden on packaging and
labelling in general.

Data protection

The legislation is based on the granting of 10 years data protection
for the first application for a medicine. Any extension by a food producing
species would add a further year to this period up to a maximum of 13 years. 
Below are provided the estimated costs for development of a veterinary medicine
and extending it to a new animal species.

Table 10  Estimated average development costs for generic medicines
(source: EGGVP):

|| Food producing animal || Companion animal

Standard generic application || €0.4-0.95 M || €0.15-035 M

Hybrid generic || €0.6-1.25 M || €0.35-0.05 M

Well-established use || €0.5-1.25 M || €0.35-0.75 M

Table 11. Average of direct costs of product development based on
figures of nine pharmaceutical companies (source: IFAH-Europe)

New medicine || Extension to another species || Extension to new species with new formulation

€6.3 M-€ 9.6 M || €1.9 M-€ 3.5 M || €2.6 M-€ 4.8 M

Table 12 Estimated costs by a contract
research organisation for costs of product development (source: IFAH-Europe)

|| New medicine || Extension to another species || Extension to new species with new formulation

Companion animal (non-antibiotic) || €4.3 M || €1.1 M || €1.4 M

Companion animal (antibiotic) || €4.4 M || €1.2 M || €1.5 M

Food-producing animal (non antibiotic) || €5.4 M || €1.6 M || €2.0 M

Food-producing animal || €5.5 M || € 1.7 M || €2.1 M

Variations to an existing marketing
authorisation

The legislation sets out that any amendment
to the formal documentation and/or underlying data submitted in support of a
marketing authorisation requires the submission by the marketing authorisation
holder of a variation application to the relevant competent authorities.  The
number of competent authorities to whom variation applications have to be
submitted depends on the procedure followed, and ranges from one (the EMA in
the case of the centralised procedure), up to all EU/EEA countries in the
(unlikely) event that a veterinary medicine was authorised through individual
national procedures.

Variations are categorised according to
their complexity, ranging from Type 1A variations[97] (the least
complex), through Type 1B variations, to Type 2 variations (the most complex). In recent years attempts have been made to
simplify arrangements for variations, and since 2009 variations legislation has
been harmonised across all four marketing authorisation procedures[98].

Table 13 Number of variations for different
marketing authorisation procedures in the period 2006-2009

|| Type IA || Type IB || Type II

Centralised procedure || 104 || 112 || 164

Mutual recognition procedure || 628 || 420 || 534

Decentralised procedure || 109 || 162 || 98

However, the costs to the industry are
still high as a large number of variations concerns the most complex variations
type II (27% for mutual recognition procedure, 34% for decentralised procedure
and 43% for centralised procedure).  For example, the estimated cost of
applying for a Type 1A variation (e.g., a change to the address of the
marketing authorisation holder) through the centralised procedure is 8,354
euros.  As it is likely that multiple applications for Type 1A variations would
be submitted over the life time of a marketing authorisation, the
administrative burden per product is high. The amendments of the variation
legislation did not decrease the number of variations per application.

Table 14 Ratio of variations per valid
marketing authorisation procedure for centralised procedure in period 1997-2011

|| Number of variations || Number of valid marketing authorisations || Variations ratio || || Number of variations || Number of valid marketing authorisations || Variations ratio

1997 || 4 || 5 || 0.8 || 2006 || 56 || 65 || 0.9

1998 || 8 || 10 || 0.8 || 2007 || 103 || 76 || 1,4

1999 || 19 || 17 || 1,1 || 2008 || 102 || 88 || 1,2

2000 || 39 || 27 || 1,5 || 2009 || 119 || 100 || 1,2

2001 || 50 || 29 || 1,7 || 2010 || 162 || 114 || 1,4

2002 || 39 || 35 || 1,1 || 2011 || 287 || 128 || 2,2

2003 || 64 || 40 || 1,6 || || || ||

2004 || 65 || 51 || 1,3 || || || ||

2005 || 69 || 52 || 1,3 || || || ||

It is estimated that variations can account
for 50% of the workload of regulatory staff, and represent a large portion of
the overall post marketing administrative burdens to the industry.

Marketing authorisation renewals

Marketing authorisation holders are required
to apply for a renewal five years after the initial granting of an
authorisation. No further renewals are required, unless the competent
authorities determine that a renewal is needed based on pharmacovigilance data.
The industry argues that the requirements for a mandatory renewal provide
regulators with a formal opportunity to seek new, additional test data, even if
the products have been on the market for many years with a good
pharmacovigilance record (in order to comply with new guidelines for example).
According to the pharmaceutical industry, this forces the industry to direct a
significant proportion of the research and development budget (around 35 %[99]) into "defensive research", instead of concentrating
their efforts on the development of new medicines.  The industry claims that,
in contrast, companies outside the EU spend much less resources[100] in this area.  As a consequence of the transfer of resources from
the innovative research into defensive research, there is a negative impact on
the availability of new veterinary medicines in the EU, and a reduction of the
attractiveness of the EU markets for product development. Post-marketing costs
such as those described above have been cited by SMEs as particularly
challenging to that sector of the industry[101].

Pharmacovigilance

Pharmacovigilance aims to monitor the
performance of veterinary medicines placed on the market and involves the
collection of data on suspected adverse events and their reporting to the
competent authorities. It is a key area for animal and
public health safety. The legislation requires that marketing authorisation holders
maintain databases of all suspected adverse events in animals and humans
related to their veterinary medicines.  The marketing authorisation holders are
also required to report serious suspected adverse events within 15 days to the
competent authorities and prepare reports on the overall performance of the
product at set intervals (periodic safety update reports, PSUR). The current
system requires a PSUR every 6 months for the first year of a product's life,
then every year for the next 2 years, and then every 3 years thereafter. Taking
into account that a small company may have up to 100 product authorisations and
a large company 1000 (the largest animal health company may have 5000
authorisations), the estimated total work days per year dedicated to dealing
with this task is large. The pharmaceutical industry estimated that the average
number of PSURs is 50 per year, representing around 500 workdays (involving many
staff across the company) per PSUR.[102] The inspection of manufacturers for compliance with the legislation
regarding pharmacovigilance also adds to the overall cost: The pharmaceutical
industry estimated that tasks related to inspections take 30 days work per
year.

In addition to these post authorisation
activities, applicants also need to submit, at application stage, details of
their pharmacovigilance systems together with each new application.

The pharmaceutical industry estimated that
on average 4.3 full time staff per company work on pharmacovigilance per year
(pharmacovigilance managers, dealing with inspections, case handling, report
writing, gathering information on Third Country reports)[103].  The current system is based on that applied in the human sector,
and the industry argues that the investment needed to maintain this system is
not justifiable in terms of animal health.

Table 16. Pharmacovigilance data for
centrally authorised products.

Year || Submitted reports on adverse reactions || Submitted Periodic Safety Update Reports || Initiation of pharmacovigilance referral (Art 78 of Directive 2001/82/EC)

2004 || 187 || 45 ||

2005 || 354 || 42 ||

2006 || 738 || 52 || 1

2007 || 1424 || 81 ||

2008 || 1943 || 95 ||

2009 || 3129 || 112 ||

2010 || 4474 || 118 || 1

2011 || 4888 || 132 || 1

Homeopathic medicines

Homeopathic veterinary medicinal products
fall within the scope of the legislation on veterinary medicines[104].
Stakeholders working in the area of homeopathic medicines raised a concern
regarding the regulatory burdens existing in this sector and indicated that
they are disproportionate in relation to the risks involved.

Internet retailing of veterinary
medicines

Internet retailing of veterinary medicines
is a sector that is growing[105]. Internet pharmacies have estimated that from 2005 to 2011, the
sales of non-prescription medicines through the internet in the UK (a Member
State that allows sales of prescription and non-prescriptions medicines on
line), have increased to take from 2.5% to 8.6% of the total sales of
medicines, and now [106]around 48% of non-prescription medicines (such as spot on external
anti-parasitic medicines for pets) are bought through the internet in the UK. 
On the other hand, although prescription-only medicines represent 78% of the
market in revenue in that country, only 1.4 % of these medicines are bought
online. In comparison with Third Countries, data from the consultation
indicated that the market penetration of a leading online veterinary pharmacy
in the US, for example, grew from 3.1% in 2004 to 6.3% in 2010, and around 38%
of their sales are prescription medicines (2011)[107]. The whole
sale price differences between Member States and the price level of online
medicines compared to recommended retail prices in Member States indicate the
scope for reducing the costs of animal health for end users by internet
retailing.

Table 17A Available
information from consultation with Member States on internet retailing of
veterinary medicines in the Union:

Situation in the Union || Comments

Countries where internet retailing of veterinary medicines  is not allowed or not regulated: Austria, Belgium, Czech Republic, France ||

Countries which allow or regulate internet retailing of veterinary medicines: ||

Hungary  || Allowed for wholesalers and distributors having licence to sell veterinary medicines in their stores and maintain a web-shop.

Ireland || Licences are granted under national legislation to holders of a Merchant Licence (Retailers) to sell certain categories of animal remedies within the State via a specified website (only products classified as Licensed Merchant medicines or Companion Animal Medicines). The cost of an internet Licence is €76 and is of unlimited duration, subject to compliance with the Animal Remedies Regulations. Compliance is monitored via an inspection programme. The cost to the NCA is not known.

Sweden || Only allowed through pharmacies with authorisation. The authorisation for a pharmacy is 20 000 SEK and thereafter 11 500 SEK every year.

UK || Allowed. There is no specific legislation on internet retailing of veterinary medicines in the UK. The retail supply of veterinary medicines through internet channels is covered by the relevant general national legislation on retail supply. The VMD introduced a voluntary scheme in May 2012 which facilitates self-regulation by UK-based internet retailers supplying veterinary medicines. Following accreditation, on-site inspections of accredited internet retailers' premises (if they have not been inspected already) are carried out, to check on-going compliance with the legislation. There is no cost to the industry as the scheme is voluntary but the internet retailers must be approved as a wholesale dealers or as retailers of veterinary medicinal products (and as such would have already been approved and inspected by the VMD and paid the appropriate fees).The fees for various inspection types can be found in Schedule 7 of the Veterinary Medicines Regulations 2011. http://www.vmd.defra.gov.uk/public/vmr.aspx The cost to the NCA of administering the system is not known.

Germany || Prescription and non-prescription medicines for pets allowed.

Table 17B. Price
difference between online retail price of some veterinary medicines in relation
to recommended retail price in Germany and France (source MedicAnimal).

Table 17C 
Wholesale price comparison between United Kingdom, Germany and France (source MedicAnimal)

Antimicrobial resistance

Background information

Organisms resistant to antimicrobials are
found in humans, animals and the environment and may be transferred from
animals to humans and between species of bacteria. Antimicrobial resistance is
resistance of a microorganism to an antimicrobial medicine to which it was
previously sensitive. According to World Health Organisation common, yet
life-threatening infections by resistant bacteria are becoming difficult or
even impossible to treat[108]
and it is a serious, growing, and global threat to health[109].
Replacement treatments are more costly, more toxic, need much longer durations
of treatment, and may require treatment in intensive care.  In the EU 25000
patients die each year from infections caused by resistant bacteria and causes
great financial costs (extra health care costs and productivity losses were
estimated as of at least 1.5 billion euros per year) [110] ,[111],[112].  The problem of antimicrobial resistance is aggravated by the
scarcity of new antimicrobials being brought to the market by pharmaceutical
industry. The lack of a new supply of new effective antibiotics limits
treatment options for patients with infections caused by multidrug-resistant
organisms.

The Food and Agriculture Organisation
concluded that antimicrobial resistance has profound impacts on animal health
and production. It means that essential veterinary medicines may no longer be
available for the treatment of animal diseases, the failure of disease control
programmes, increased severity and longevity of diseases, increased mortality,
reduced productivity, and increased risk of disease spread in animal
populations[113].

The causes of antimicrobial resistance are
various and complex. Antimicrobial resistance in humans is often caused by
inappropriate use, poor infection prevention and control practices, and through
the constant exposure of bacteria to antimicrobials in healthcare settings.
These important drivers of antimicrobial resistance are outside the scope of
the revision of the legislation on veterinary medicines.

Animals and humans are often susceptible to
the same microorganisms causing infections, and in the EU the same classes of
antimicrobials are being used in human medicine and veterinary medicine to
treat these infections. Therefore the use of antimicrobials in animals will
generate resistance to the same classes of antimicrobials as being used in
human. Indications exist that antimicrobial resistance in animals is
transmitted to humans through zoonotic bacteria, by direct contact or through
the food chain. The importance of animals and of food of animal origin to the
emergence, spread and persistence of antimicrobial resistance in humans has not
yet been completely established[114].

The risk of antimicrobial resistance grows
in proportion to the amount and frequency of antimicrobial use. In veterinary
medicine, animals are treated either individually or in groups against
infections (so-called mass or herd treatment). Recently
published data[115]
form 19 EU/EEA countries shows that the major proportion of veterinary
antimicrobials sold is for herd treatment.  This may be
required because animals have likely become infected or individual treatment is
not possible in practice (for example for certain diseases on poultry farms),
or for preventive use (in the absence of a disease or clinical signs). However,
some livestock farmers, operating in a heavily
price-driven market with intensive international competition, consider the use
of medicines as a cost-effective management tool[116]. The inappropriate use of herd treatment (such as use of
antimicrobials to mask poor farm management or inadequate zootechnical
practices) provides favourable conditions for microorganisms to emerge and
spread and accelerates the growth of resistance. It is
argued that the low price of antibiotics, related to competition by generic
companies, increase the use of antimicrobials[117]. It should be highlighted that the use of antimicrobials in the EU
requires a prescription by a veterinary surgeon, and so the decision whether or
not herd or preventive treatment is necessary is primarily the responsibility
of a veterinary surgeon.

Farmers and companion animal holders are
reported to put pressure on veterinary surgeons to prescribe antimicrobials
(for example to treat animals preventive with antimicrobials instead of taking
measures to prevent infection) or to prescribe certain types of antimicrobials
(for example those which can deliver a higher profit to farmers by having a
shorter withdrawal period or are long acting respectively). There is evidence
in the US and Australia that direct-to-consumer advertising of human
prescription drugs leads to overprescribing and the prescribing of new
medicines over older, effective ones[118].
No similar data exist in the EU for veterinary medicines, however, it can be
assumed that the same mechanisms take place in the interaction between
veterinarian-farmer and in the relationship between patients and doctor.

The incorrect use of antimicrobials is also
an area of risk for the development of antimicrobial resistance. Veterinary
medicinal products including antimicrobials are regularly used for non-approved
indications and with non-approved dosages under the Cascade[119]. This
ensures the availability of medicines but this practice, and in particular the
use of antimicrobials important in human medicine, may contribute to the
problem of antimicrobial resistance as there are no scientific data supporting
the optimal dosage of medicines used under the Cascade.

Another area of concern is the carry-over
of antimicrobials in the production medicated feed, but this is out of the
scope of this revision[120].
The Commission has already tackled the use of
antibiotics in sub-therapeutic doses as growth promoters[121] in the EU
by introducing a ban on this practice from 1 January 2006[122].  However,
antimicrobials used at low doses in animal feeds are used in certain parts of
the world to improve animal's growth performance. In
the USA it is being discussed whether the use of
antibiotics as growth promoters should be continued[123],[124].

It is possible to reduce the need for
antimicrobials in animal husbandry, for example through improved disease
prevention, good hygiene and management practices which would reduce the
production costs in the long term. This important measure
to reduce antimicrobial resistance is outside the scope of the revision of the
legislation on veterinary medicines, but several organisations are already
promoting the prudent use of antimicrobials. For
example, the European Platform for the Responsible Use of Animal Medicines
(EPRUMA) has issued guidelines promoting best practices and responsible use of
antimicrobials in food producing species. Also, other guidelines have been
prepared or are under preparation at national level, at European level by the
Commission, by veterinary practitioners and by the World Organisation for
Animal Health on how to maximise therapeutic efficacy of antimicrobials and minimise
selection of resistant micro-organisms.

Regardless of the efforts carried out to
improve the effectiveness of antimicrobials in human and veterinary medicine
through guidance, it is recognised that the current veterinary medicines
legislation does not provide sufficient tools both to ensure an adequate supply
of effective antimicrobials in the interests of animal health and at the same
time provide tools for the management of any risks to human health arising from
the use of antimicrobials in animals [125].
In addition, whilst national measures, legislative and non-legislative, are put
in place at national level as an effort to tackle antimicrobial resistance,
this created the opportunity for disharmonised decisions and views in the EU on
this issue. This is shown by the fact that most cases referred for arbitration
(so called referrals) to the veterinary scientific committee of the EMA concern
antimicrobials[126].
The development of new veterinary antimicrobials is reported to have been stalled
because of the uncertainty of future regulatory requirements for
antimicrobials. There is an overall view amongst stakeholders that that this
area needs to be improved.

The role of the veterinary surgeon in
selling antimicrobials is also not harmonised in the Member States.  In six
Member States prescribers of antimicrobials are not allowed to sell them, to
eliminate economic incentives for prescriptions. It is clear that in other
countries veterinarians obtain income from the sale of medicines and therefore
have an economic incentive to prescribe them, but this incentive can be
counterbalanced by personal ethics, peer pressure and the threat of
disciplinary action by veterinary professional boards.

Table 18 Relationship between a restriction
on selling antimicrobials by veterinarians and the use of antimicrobials in a Member State

Member States with a restriction on sales of antimicrobials by veterinary surgeons || || Member States  without a restriction on sales of antimicrobials by veterinary surgeons

Country || Mg/PCU[i] || || Country || Mg / PCU

|| || || Austria || 63

Denmark || 47 || || Belgium || 180

Finland || 25 || || Bulgaria || Unknown

Italy || Unknown || || Czech Republic || 94

Norway || 11 || || France || 132

Portugal || 166 || || Germany || Unknown

Spain || 241 || || Greece || Unknown

Sweden || 15 || || Hungary || 268

[1] ESVAC report 2010: Sales, in tones of active ingredient, of veterinary
antimicrobial agents marketed mainly for food-producing animals1 (including horses), population correction unit (PCU) and sales in
mg/PCU, by country, for 2010.

It is agreed that it is important to
establish a strategy for the containment of antimicrobial resistance in the
veterinary sector, based on the surveillance of antimicrobial resistance
prevalence and trends and antimicrobial use. Data collection on the usage of
antimicrobials in veterinary medicines has already been initiated through the
European Surveillance of Veterinary Antimicrobial Consumption (ESVAC)[127].
This is a voluntary system and therefore not all Member States participate. The
type of data collected differs in the Member States. The information collected
by ESVAC and other bodies such as the European Surveillance on Antimicrobial
Consumption (ESAC), the European Centre for Disease Prevention and Control
(ECDC)[128]
and the European Food Safety Authority (EFSA)[129] is so far
still insufficient to allow a clear identification and quantification of the
risk of developing and spreading antibiotic resistance in the food chain. For
this it is necessary that data should be collected in all Member States in a
similar quality and format.

It needs to be highlighted that
antimicrobial resistance is affected by world trade in food commodities and
travel by humans. The supply of food commodities is a global undertaking, with
food being imported into the EU from numerous third countries and so
potentially being a source of resistant bacteria. Also, travellers bring
resistant bacteria with them from foreign countries[130],[131].
Addressing these factors requires cooperation at regional and global levels and
cannot be dealt with through the revision of the veterinary medicines
legislation.

The
issue of antimicrobial resistance is of great importance in the EU. Recently
(June 2012) the Council adopted its conclusions on the impact of antimicrobial
resistance in the human health sector and in the veterinary sector – a “One
Health” perspective  under the Danish Presidency[132]. In
December 2012, the European Parliament adopted the own initiative "Report
on the Microbial Challenge- rising threats from Antimicrobial Resistance"[133].
Both demonstrate the Council's and the EP’s continued political commitment to
combating antimicrobial resistance.

Contribution of antimicrobial use in
animal sector to the presence of resistant bacteria in humans

The problem of zoonotic bacteria
transmitting antimicrobial resistance is complex. In addition to the use of
antimicrobials there are also other factors linked to bacterial populations,
such as the characteristics of the bacteria under consideration, including
their virulence and their capacity to spread. The current knowledge does not
permit a clear conclusion as to which extent food animal production contributes
to the spread of resistance in humans.  The report Joint opinion on
antimicrobial resistance focused on zoonotic infections [134] states that
there is some evidence available on possible links between the use of
quinolones in animals and emerging/increase of resistance in Salmonella from
humans, and a temporal association between the emergence of quinolone
resistance in the bacterium Campylobacter and its increase in isolates both
from animals and humans following the introduction of quinolones in animal
production has also been shown in several studies.  The report provides an
analysis on the link between the use of antimicrobials in animals and the
development of resistance in humans for four important combinations of group of
bacteria and class of antimicrobials.

Quinolone resistance in Salmonella

Several studies have shown that the use of fluoroquinolones (FQs) in
food producing animals has resulted in the emergence of FQ-resistant isolates.
Such strains have spread from food animals to humans. In order to quantify to
which extent a link between the use of antimicrobials in animals and
emerging/increase of quinolone resistance in Salmonella from human exists, a
quantitative risk assessment is needed. Elements provided in this report in
terms of prevalence of bacteria and prevalence of resistance may help to focus
on specific usages of medicines in different animal species, and highlight
areas where further work is necessary to inform the debate on the link, if any,
between the use of antimicrobials in animals and the emerging/increase of AMR
in humans.

Quinolone resistance in Campylobacter

A temporal association between the emergence of quinolone resistance
and its increase in isolates both from animals and humans following the
introduction of this class of antimicrobial in animal production has been shown
by several studies.

Cephalosporin resistance in Salmonella

Studies in cattle and swine have established a link between
cephalosporin administration, including treatment frequency, and resistance
selection in E. coli. In vivo transfer to, as well as the presence of, many of
these ESBL genes in Salmonella has been demonstrated in several studies.

Macrolide resistance in Campylobacter

In a Canadian study which examined the resistance patterns of
porcine Campylobacter, over 70% of isolates were resistant to macrolides. Risk
analysis revealed a clear association between the (oral) administration of
macrolides and the presence of resistance in faecal isolates. There is
controversy regarding the public health aspects of macrolide resistance in
Campylobacter, with estimates based on a recent risk analysis not exceeding 1
out of 49,000 impaired human treatments in cases of infection with
macrolide-resistant C. coli of porcine origin. The risk for suboptimal
treatment of human cases due to macrolide- resistant C. jejuni infections from
broiler and bovine sources was even lower.

Recently additional interesting information
was released. An article was published demonstrating the relation between the
use of an antimicrobial of the class of cephalosporins and the development of
resistance in humans (" Ceftiofur Resistance in Salmonella enterica
Serovar Heidelberg from Chicken Meat and Humans, Canada,” Dutil et al. 2012, http://wwwnc.cdc.gov/eid/article/16/1/09-0729\_article.htm):“These
events provide evidence that ceftiofur use in chickens results in
extended-spectrum cephalosporin resistance in bacteria from chicken and
humans.”  Leverstein-van Hall MA et al. concluded that
their findings are suggestive for transmission of ESBL genes, plasmids and E.coli
isolates from poultry to humans, most likely through the food chain (Dutch
patients, retail chicken meat and poultry share the same ESBL genes, plasmids
and strains; Clin Microbiol Infect 2011 Jun; 17:873).

In 2011 the Panel on Biological Hazards
(BIOHAZ) delivered an opinion on the public health risks of bacterial strains
producing extended-spectrum beta (β)-lactamases (ESBL) and/or AmpC
β-lactamases (AmpC) in food and food-producing animals (see:
http://www.efsa.europa.eu/en/efsajournal/pub/2322.htm). It was concluded that
there are no data on the comparative efficiency of individual control options
presented in this document in reducing public health risks caused by ESBL
and/or AmpC-producing bacteria related to food-producing animals.
Prioritisation is considered complex, and the effectiveness of measures
discussed based on the best available evidence and expert opinion. As such it
is considered that a highly effective control option to reduce selection of
ESBL/AmpC-producing bacteria at an EU level, would be to stop all uses of
cephalosporins/systemically active 3rd/4th generation
cephalosporins, or to restrict their use (use only allowed under specific
circumstances). Measures intended to minimize off label use should focus on
increased compliance with existing legislation. As co-resistance is an
important issue, it is also of high priority to decrease the total
antimicrobial use in animal production in the EU. Also of importance (more so
after the ESBL/AmpC-producing microorganisms have emerged) are the measures to
control dissemination, for example by implementing increased farm biosecurity
and controls on animal trade (of ESBL/AmpC-carriers), and by improving hygiene
throughout the food chain, and implementing other general post-harvest controls
for food-borne pathogens. Because most evidence is available for high
prevalence of ESBL/AmpC-producing bacteria in the poultry production pyramid,
and their consequent involvement in public health, it is of high priority to
reduce selection pressure imposed by the use of antimicrobials, to prevent
vertical transmission from the top of the poultry production pyramid, and to
prevent local recirculation within subsequent flocks.

Commission’s commitments in the Action plan
against the rising threats from antimicrobial resistance regard veterinary
medicines:

Action n° 2: Strengthen the regulatory framework on veterinary
medicines and on

medicated feed via the
review package foreseen for 2013, in particular:

– To ensure appropriate warnings and guidance on the
labels of veterinary antimicrobials.

– To consider restrictions on the regular or the
off-label use of certain new or critically important antimicrobials for humans
in the veterinary sector.

– To consider amending the rules for the advertisement
of veterinary antimicrobials.

– To revisit the authorisation requirements in order to
sufficiently address the risks and benefits of antimicrobial medicines.

Action n° 7: Promote efforts to analyse the need for
new antibiotics into veterinary medicine

– Establishing request for scientific advice to clarify
in particular whether the development of new veterinary antimicrobials would
reduce AMR.

– Evaluation of the need and possible introduction of
incentives that trigger development in veterinary medicines to increase the
likelihood that innovations reach the market within the review of the rules on
veterinary medicines foreseen in 2013.

Action n° 10: Strengthen surveillance systems on AMR
and antimicrobial consumption in animal medicine

– Inclusion of a legal basis for the monitoring of AMR
in animal pathogens in its forthcoming proposal for a new Animal Health Law.

– Promotion and extension of the European Surveillance
of Veterinary Antimicrobial Consumption (ESVAC) with the collaboration of EMA
to obtain harmonised data on the usage per animal species and production
categories as well as for different indications from all Member States.

– Review of the monitoring of AMR in zoonotic bacteria
and/or indicators.

– With the support of the relevant EU agencies,
establish harmonisation between human and veterinary surveillance to allow
comparison of data.

 Table 19 Detailed Standard Cost
Model Results used to the calculation of administrative burden to the
industry of complying with the legislation on veterinary medicines

(a) Details of
the SCM for the legislative framework for veterinary medicinal products

Activity || MA proc-edure/ details || Staff cost per hour || Staff time hrs || No. actions per entity p.a. || Staff costs per action || Staff costs per entity p.a. || Equip costs per action || Equip costs per entity p.a. || O/S costs per action || O/S costs per entity p.a. || Total no. of entities || Total no. of actions p.a. || Total cost p.a.

Applying for a new MA || CP || 121 || 1,123 || 0.4 || 135,607 || 53,064 || 4,500 || 1,761 || 103,622 || 40,548 || 23 || 9 || 2,193,564

DCP || 121 || 1,160 || 0.9 || 140,093 || 124,659 || 5,662 || 5,038 || 148,591 || 132,221 || 59 || 53 || 15,453,153

MRP || 121 || 902 || 1.0 || 108,974 || 107,028 || 5,662 || 5,561 || 156,799 || 153,999 || 84 || 83 || 22,393,368

NP || 100 || 627 || 0.6 || 62,644 || 35,519 || 4,805 || 2,724 || 84,138 || 47,705 || 594 || 337 || 51,024,658

Sub-total || || || || || || || || || || || || 91,064,743

Applying for a Type 1A Variation || CP || 121 || 38 || 1.0 || 4,604 || 4,433 || 100 || 96 || 3,650 || 3,514 || 23 || 22 || 184,992

DCP || 121 || 47 || 0.4 || 5,629 || 2,080 || 200 || 74 || 6,333 || 2,340 || 59 || 22 || 265,130

MRP || 121 || 45 || 1.5 || 5,397 || 8,070 || 200 || 299 || 5,479 || 8,193 || 84 || 126 || 1,391,180

NP || 100 || 35 || 2.5 || 5,270 || 13,971 || 500 || 1,263 || 5,893 || 14,889 || 594 || 1,500 || 17,883,462

Sub-total || || || || || || || || || || || || 19,724,765

Applying for a Type 1B Variation || CP || 121 || 64 || 1.0 || 7,675 || 7,771 || 100 || 101 || 7,890 || 7,988 || 23 || 23 || 364,780

DCP || 121 || 79 || 0.5 || 9,599 || 5,271 || 500 || 275 || 10,854 || 5,961 || 59 || 32 || 678,886

MRP || 121 || 72 || 1.0 || 8,745 || 8,745 || 500 || 500 || 10,500 || 10,500 || 84 || 84 || 1,658,556

NP || 100 || 55 || 2.5 || 5,529 || 13,971 || 500 || 1,263 || 5,893 || 14,889 || 594 || 1,500 || 17,883,462

Sub-total || || || || || || || || || || || || 20,585,684

Applying for a Type 2 Variation || CP || 121 || 185 || 0.9 || 22,371 || 19,752 || 150 || 132 || 31,095 || 27,455 || 23 || 20 || 1,088,814

DCP || 121 || 238 || 0.3 || 28,692 || 9,532 || 1,175 || 390 || 30,385 || 10,094 || 59 || 20 || 1,180,941

MRP || 121 || 230 || 1.3 || 27,771 || 35,308 || 1,175 || 1,494 || 27,833 || 35,388 || 84 || 107 || 6,063,995

NP || 100 || 164 || 5.3 || 16,378 || 86,204 || 1,175 || 6,185 || 9,588 || 50,467 || 594 || 3,125 || 84,808,648

Sub-total || || || || || || || || || || || || 93,142,399

Applying for a MA renewal || CP || 121 || 302 || 0.3 || 36,447 || 10,483 || n/a || n/a || 7,500 || 2,157 || 23 || 7 || 290,727

DCP || 121 || 244 || 0.1 || 29,411 || 1,795 || n/a || n/a || 16,000 || 976 || 59 || 4 || 163,481

MRP || 121 || 262 || 0.7 || 31,602 || 23,250 || n/a || n/a || 12,833 || 9,442 || 84 || 62 || 2,746,100

NP || 100 || 194 || 5.0 || 19,404 || 96,355 || n/a || n/a || 3,100 || 15,394 || 594 || 2,948 || 66,341,291

Sub-total || || || || || || || || || || || || 69,541,598

Pharmacovigilance reporting || Adverse || 100 || 5 || 13.6 || 474 || 6,458 || 7 || 95 || 40 || 545 || 594 || 8,082 || 4,213,901

Serious adverse || 100 || 8 || 15.1 || 818 || 12,340 || 7 || 106 || 53 || 804 || 594 || 8,953 || 7,866,284

PSUR || 100 || 39 || 17.6 || 3,903 || 68,501 || 335 || 5,880 || 201 || 3,522 || 594 || 10,420 || 46,248,391

Sub-total || || || || || || || || || || || || 58,328,576

Packing & labelling || - || 100 || n/a || 732,578 || 0.01 || 6,889 || 0.40 || 296,157 || 0.01 || 7,482 || 594 || 434,907,365 || 184,350,250

Sub-total || || || || || || || || || || || || 184,350,250

GRAND TOTAL || || || || || || || || || || || || 537,852,751

Notes: All costs are in EUR; n/a means not
available; Equip means equipment costs; O/S means outsourced costs

Source: GHK analysis

Annex 7 Availability of veterinary
medicines for bees

Background
information on the sector

It is estimated
that there are around 700 000 beekeepers in the EU; around 97% of these are
amateur beekeepers (that is, have less than 150 hives). Almost half of the
hives in the EU are concentrated in Spain (17.8 %), Greece (10.9%), France (9.7%) and Italy (8.2%). Honey production in Europe is estimated at around 200 000 tons, and
about 60% of the consumed amount of honey is produced in the EU. Other
commercial activities are also associated with beekeeping - production of wax,
royal jelly and propolis. Apiculture generates an annual value of 1 billion
euros, and also contributes to the total amount of at least 22 billion euros
related to pollination of crops and plants.

Honeybees are
susceptible to a wide range of pests and diseases which, together with other
environmental and agricultural practices and factors, have been incriminated in
the decline in the number of bee colonies and/or higher than normal losses,
especially due to increased winter mortality in the EU and certain parts of the
world. The syndrome "colony collapse disorder (CCD)" results in a
very high rate of honeybee colony losses and has not been observed in the EU
but has been reported in the United States, where it is estimated that less
than 2 million colonies remain. This has great economic impact: for 725.000
acres of almond crops in California alone, 1.4 million of bees are needed for
pollination. The European situation is significantly different both in the
manifestation of the losses and the type and magnitude of negative impacts. So
far scientific studies and data from competent authorities have not been able
to establish either the extent or the exact cause(s) for these losses.
Nevertheless most stakeholders agree that effective pest control in bee
colonies is a cornerstone for the sustainability of the apiculture sector.

The main
parasites and diseases of bees are the mite Varroa destructor, the Nosema
family of fungi, foulbrood bacteria (European and African Foulbrood) and a
number of viruses. European legislation has been put in place to prevent
American foulbrood outbreaks due the trade of bees (Directive 92/62/EEC as last
amended) and on the import of bees and bee products as regards other, exotic
diseases in bees (Regulation(EC) No 206/2010, and Regulation (EU) No 142/2011
adapting earlier similar rules existing since the mid-2000's).

A major concern
regarding the control of bee pests and diseases is the limited availability of
medicines for existing conditions, for example Varroa mite infestations. The number
of active ingredients in authorised veterinary medicines for bees in the EU/EEA
is limited[135]
and resistance of Varroa to standard treatments such as pyrethroids is
of great concern. Nosema infection is also growing in significance but there is
no authorised medicine for this condition.

Information from Discontools identified the
registration procedure ("difficult and not harmonised registration in the
EU") as a challenge for the authorisation of medicines for the control of Varroa
in bees, and pointed out that the due to the relatively small market, an investment into the
beekeeping business represents a high financial risk. The establishment of Maximum Residue Limits (MRLs) for
honey is a particularly challenging step in the development of products for
bees. It is estimated that
development of a new pharmaceutical (new compound) for the treatment of varroa
would take 10-15 years and cost 30-50 million euros. [136]

The cost of preparing a dossier in line with
the quality, safety and efficacy requirements set out in the legislation is not
recovered through the sales of the medicine and the pharmaceutical industry and
beekeeping organisations have expressed their concern that the current
requirements are excessive considering the nature of the target species. This
was discussed at various meetings and in particular at the Workshop on
medicines for bees organised by EMA (December 2009 -http://ec.europa.eu/food/animal/liveanimals/bees/docs/EMA\_conclusions.pdf).

Stakeholders suggested some measures to
incentivise the authorisation of medicines for bees in Europe: reduction of the
data needed for the authorisation, extended data protection, and automatic
mutual recognition of authorisations (that is, once a medicine is authorised in
one Member State it would automatically be authorised in all Member States).

The classification of honeybees as food
producing animals was another area discussed during the consultation. Honeybees fall within the definition of food producing animals
("animals bred, raised, kept, slaughtered or harvested for the purpose of
providing food") in Regulation 470/2009 of the European Parliament and of
the Council on the establishment of residues limits of pharmacologically active
substances of animal origin. This means that veterinary medicines developed for
bees need to comply with the extensive legislative requirements regarding
maximum residues in foodstuff of animal origin. However, the evaluation of
residues of veterinary medicines in honey is complicated by the fact that, due
to the bee physiology as an insect, there is no time-dependent depletion or elimination
of the substance in honey: in contrast to the situation in other food producing
species, where a medicine is metabolised in the animal through a period of
time, medicines are applied or given to bees but if residues are in the honey
they remain there without significant degradation. Therefore, in practical
terms, only substances that do not require a MRL (that is, which will have a
zero day withdrawal period) may be authorised for bees.  Stakeholders proposed
to consider bees as non-food producing animal or as a specific category of food
producing animals (following the example of pet and food producing horses)
because of their specific metabolism as insect and also because only the
collected product made by the animal is eaten (honey) and the animal itself is
not consumed. However, it is not possible to exempt honey from the scope of
regulations on residues of veterinary medicines in animal produce, for food
safety reasons.

It is acknowledged that the problems related
to the decline in honeybee population is complex and multi-factorial, and
effective measures to improve bee health need to concern the development of
novel medicines but also cover farming activities, prudent use of pesticides in
agriculture, habitat and bee species conservation amongst others[137],[138],
[139].

The small size of the market for bee medicines
is the main drive for the lack of available medicines, as ultimately product
development is a decision made by companies based on commercial returns. There
is anecdotal evidence that beekeepers prefer to use "home-made"
preparations instead of authorised medicines to treat their colonies, due to
costs. This activity not only is illegal but also does not help the
authorisation of veterinary medicines for bees. More effective enforcement by
the national competent authorities is encouraged to correct this situation. In
addition, more intensive information campaigns by authorities and beekeepers'
associations on 'good husbandry' and good practice is needed, together with
training of beekeepers, for better and proper management of diseases.

Annex 8 SMEs and micro-enterprises

Background
on the SME/micro-enterprises sector- veterinary medicines

The European Medicines Agency has established
the SME Office following the European Commission's adoption of Commission
Regulation (EC) No 2049/2005. The office promotes innovation and the
development of new medicinal products for human and veterinary use by SMEs. Data on the SME/micro-enterprises environment regarding pharmaceutical medicines is relatively scant,
but information from the EMA's report on the SME initiative 2006-2011  and the
survey on implementation of the SME/micro-enterprises regulation revealed that around 679 companies
registered with the EMA as SMEs in that period. Of these, approximately 6 % are
veterinary companies, 7% are companies developing products for both human and
veterinary use and 14 % are regulatory consultants.

SMEs involved
in the pharmaceutical industry have been profiled as development stage
companies (research/discovery stage), academic spin offs and (bio)
pharmaceutical enterprises developing therapeutic or vaccines and generics
manufacturers. Regarding funding, no specific profiling of
SMEs/micro-enterprises involved in the veterinary sector is available, but in
the human sector, stakeholders are individual private investors (investors
founders and employees/directors - 48%), corporate ownership (venture capital
companies - 42%), public bodies (regional development funds - 96%) and
foundations (4%). It is likely that a similar profile is applicable to the
veterinary sector.

Regarding the
participation of SMEs/micro-enterprises in the pharmaceutical sector, since
2005 there have been 71 centralised applications for marketing authorisations
submitted by SMEs to the EMA. Of these, 12 were for veterinary medicines. The
centralised route is attractive to large multinational companies, but SMEs are
reluctant to use this route due to the high regulatory fees and overall costs
associated with the procedure:  industry data show that the total
administrative cost for a centralised application is estimated as 119 000 euros,
which is equivalent to 119 administrative workload-days. This is often too
expensive to SMEs.

SMEs in the
agricultural sector and health professionals would benefit in general of the
proposed options by an increased availability of veterinary medicines and
reduced administrative burden.

Consultation
with SMEs and micro-enterprises representatives

Consultation
with SME/micro-enterprises took place throughout the following process:

Public consultation which ended on July 2010.
Targeted experts' meeting on Authorisations/Data
protection  (22/6/2012).
Targeted experts' meeting with SMEs (4/10/12).

The attendees
consulted indicated support to the revision of the Directive 2001/82 and
highlighted the following particular points of concern regarding the current
legislation:

Sunset clause

The Sunset
clause is a legal obligation for all pharmaceutical companies to place a
product on the market within three years of its granting.  Companies also need
to avoid not marketing an authorised medicine for a period of three consecutive
years - otherwise they would lose the marketing authorisation for the product.
SMEs have indicated that this provision is challenging to the sector, as
smaller companies often find difficulties in distributing their product.

Clinical trials

There are
already requirements in the veterinary medicines legislation for clinical
trials to be carried out as part of an application for a marketing authorisation.
Member States have, however, created different national procedures and
requirements to implement these provisions as there are no harmonised timelines
or procedures for granting an authorisation for the trial to be carried out. SMEs indicated that this lack of harmonisation across the EU is
particularly burdensome to them, in particular in connection with multicentric
trials for rare diseases, and requested that this issue be addressed through
the revision of the legislation on veterinary medicines.

Support for
SNEs at national level

SMEs indicated
that there is a lack of local, practical support at national level (such as a
local help desk in the language of the country). They also indicated that
financial support, in the form of incentive such as those that already exists
for centralised procedures (90% fee reduction for scientific advice and
inspections and deferral of the fee for marketing authorisations) would be
greatly beneficial to the sector.

Internet
retailing

SMEs indicated
that the lack of harmonisation regarding internet retailing of veterinary
medicines interferes with the development of business in the Union.

References

(1) Outcome of SME office survey on the
implementation of the SME regulation – Commission Regulation (EC) no 2049/2005
– 19/12/2011

(http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119946.pdf)

(2) Report on the SME Initiative 2006-2011

(http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119970.pdf)

(3) European Medicines agency roundtable
with small and medium-sized enterprise (SME) stakeholder organisations,
19/12/2011

(http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2011/12/WC500119945.pdf

Annex 9 Consultation results and stakeholders ‘ views

A Summary of stakeholders' views
on proposals for the amending of the framework on veterinary medicines

Source: EPEC report on the assessment of
the impact of the revision oh pharmaceutical legislation. The average score
awarded by stakeholders to the options was based on a scale where -2 means
‘significant negative impact’ and +2 means ‘significant positive impact’ (base
= 12 responses (industry); 14 responses (regulators); 5 responses (end users).

Policy option A2- Automatic recognition of a marketing authorisation
granted by a Member State

Policy option A3 - Introduction of a single marketing
authorisation procedure for all products

Policy option A4 – Extension of the scope of the
centralised procedure

Policy option A5 - Simplification of the requirements for packaging
and labelling

Policy option A6 Simplification of pharmacovigilance system

Policy option A7 Simplification of requirements for variations to
marketing authorisations

Base = 12 responses (industry); 14
responses (regulators); 5 responses (end users)

Policy option A8 Restriction of marketing authorisation renewals to
specific cases

Policy option A9 Harmonisation of requirements for granting a
marketing authorisation in exceptional circumstances

Survey respondents’ scoring of the policy
option ‘under certain circumstances products are granted authorisations without
the submission of full dossiers’

Survey respondents’ scoring of the policy option ‘data requirements
for product authorisations are reduced’

Policy option A10 Introduction of legislative
measures regarding advanced veterinary therapies

Policy option A11 Enabling existing nationally authorised veterinary
medicines to freely circulate across the Union

Policy option A13 Exclusion of homeopathic veterinary
medicines from the scope of the legislation

Policy option B2 Extension of the data protection
period for new veterinary medicines

Policy option B3 Revision of data protection for
environmental data

Policy option C2 Introduction of legislative measures
regarding internet sales of veterinary medicines

Policy option C3 Enhance the transparency regarding veterinary
medicines authorised in the Union

Survey respondents’ scoring of the policy
option ‘enforcing a European database of authorised products’

Base = 12 responses (industry); 14
responses (regulators); 5 responses (end users)

Policy option C4 Introduction of a
legal basis for the harmonisation of the national control systems

Survey
respondents’ scoring of the policy option ‘national control systems are
required to meet agreed European standards, and the Commission has the powers
to check such systems’

Base = 12 responses (industry); 14
responses (regulators); 5 responses (end users)

Policy option D2 Introduction of legislative measures
to allow restrictions to be placed on the authorisation and use of veterinary
antimicrobials

Survey
respondents’ scoring of the policy option ‘potential impacts on antimicrobial
resistance are addressed as part of the MA process’

Survey respondents’ scoring of the policy
option ‘critical antimicrobials for human use are prohibited for use in the
veterinary sector’

Policy option D3 Clarification on the provisions regarding
advertising and retailing of veterinary antimicrobials

Survey respondents’ scoring of the policy option ‘controls on the
advertising and marketing of antimicrobials to veterinarians’

Policy option D5 Introduction of a legal basis for
the compulsory collection of data on the use of antimicrobials

B Report on the European Commission’s Public Online Consultation:

Better
regulation of veterinary pharmaceuticals: how to put in place a simpler legal
framework, safeguarding public and animal health while increasing the
competitiveness of companies.

Introduction

The European Commission is preparing a
legal proposal on the review of the legal framework for veterinary medicinal
products.

On 13 April 2010 a public consultation was
launched on the key issues of the forthcoming legal proposal. The consultation
document ‘Better regulation of veterinary pharmaceuticals: how to put in place
a simpler legal framework, safeguarding public and animal health while
increasing the competitiveness of companies’ was published on the Commission
website and was available through the ’Commission's IPM tool (Interactive
Policy Making) from 13 April until 15 July 2010. The consultation document is
presented in Annex 1.

Annex 2 contains a full list of the names
of all responding organisations or citizens. The individual responses of those
respondents who did not make a specific request for confidentiality will be
published on the Pharmaceuticals website.

Breakdown of responses

We received 172 responses to the web-based
consultation via the Interactive Policy Making Tool. We received four
additional responses to the consultation by letter or email outside the
Interactive Policy Making Tool. The comments in these additional responses are
included in this report. However, they have not been integrated in the tables
setting out a quantitative analysis of the results. Table 2.1 gives a breakdown
of the responses by type of respondent.

2.1 Category of participants

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (172)

Citizen || 26 || 15,12% || 15,12%

Non-business organisation || 28 || 16,28% || 16,28%

Business organisation / enterprise || 89 || 51,74% || 51,74%

A public authority || 29 || 16,86% || 16,86%

In case of business organisation or enterprise, type of stakeholder

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (172)

Farmer || 7 || 7,87% || 4,07%

Veterinarian || 40 || 44,94% || 23,26%

Manufacturer || 4 || 4,49% || 2,33%

Wholesaler || 1 || 1,12% || 0,58%

Pharmaceutical industry || 35 || 39,33% || 20,35%

Importer || 0 || 0,00% || 0,00%

Researcher || 1 || 1,12% || 0,58%

Other || 4 || 4,49% || 2,33%

Responses to key issues

The statistics of the public consultation
are included in this report. The percentages are calculated on both the total
number of replies to the consultation and total replies to the specific
question.

Key Issues:
Data
exclusivity

Stakeholders’ views differ as to the
appropriateness of the level of data protection provided by the current legal
framework (see table 4.1.1). Overall, the responses can be divided into two
categories. One large group (70 respondents; about 41 %) considers that
the level of data protection is satisfactory without substantiating their
position any further. This group is made up mostly of veterinarians and
farmers. Another group considers that the level of data protection is
unsatisfactory (47 respondents; 27 %) or very unsatisfactory (8
respondents; about 5%). This category is made up entirely of
pharmaceutical companies.

4.1.1 Please indicate your satisfaction with the level of data protection provided by the current legal framework

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

No opinion || 12 || 6.98 % || 8.70 %

Very unsatisfactory || 8 || 4.65 % || 5.80 %

Unsatisfactory || 47 || 27.33 % || 34.06 %

Satisfactory || 70 || 40.70 % || 50.72 %

Very satisfactory || 1 || 0.58 % || 0.72 %

N/A || - || 19.77 % || -

4.1.2 Do you have quantitative or qualitative data showing the impact of the current data exclusivity period on innovation (yes, no)? If so please provide estimate of impact?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (130)

Yes || 27 || 15.70 % || 20.77 %

No || 103 || 59.88 % || 79.23 %

N/A || - || 24.42 % || -

Limited data was provided on the effective
data protection period for the first application of a new veterinary medicinal
product.

4.1.3 Do you have data on effective protection periods of originator products calculated from the authorisation of the originator until the first authorisation of a generic?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (172)

Yes || 13 || 7.56 % || 7.56 %

No || 159 || 92.44 % || 92.44 %

Only six respondents disagree with the
statement that generic companies are conducive to a competitive market (see table
4.1.4). Most respondents (124; 72 %) agreed with this statement.

4.1.4 Do you agree that generic companies provide for a competitive market within the veterinary pharmaceutical industry that is reflected in the pricing structure of veterinary medicines which is passed on to the end user?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

No opinion || 8 || 4.65 % || 5.80 %

Strongly disagree || 6 || 3.49 % || 4.35 %

Agree || 116 || 67.44 % || 84.06 %

Strongly agree || 8 || 4.65 % || 5.80 %

N/A || - || 19.77 % || -

A total of fifty respondents considered the
current data exclusivity period to be unsatisfactory or very unsatisfactory;
nineteen respondents indicated that the current situation was satisfactory or
very satisfactory (see table 4.1.5). Almost all pharmaceutical companies
developing new products consider the current data exclusivity period to be
unsatisfactory.

4.1.5 Do you consider that the current data exclusivity period in the legal framework strikes the appropriate balance between innovation and competition?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (136)

No opinion || 67 || 38.95 % || 49.26 %

Very unsatisfactory || 23 || 13.37 % || 16.91 %

Unsatisfactory || 27 || 15.70 % || 19.85 %

Satisfactory || 15 || 8.72 % || 11.03 %

Very satisfactory || 4 || 2.33 % || 2.94 %

N/A || - || 20.93 % || -

Most respondents (101; 69 %) agree
that the general data protection period of 10 years should be increased (table
4.1.6). The vast majority (109; 63 %) consider that the current additional
data exclusivity period of one year for each extension of the original
authorisation is inappropriate (see table 4.1.7) and would be in favour of
major product developments having their own period of data protection (120; 71 %)
(see table 4.1.8).

4.1.6 Would you agree to increase the general period of data protection of 10 years?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (135)

No opinion || 12 || 6.98 % || 8.89 %

Strongly disagree || 22 || 12.79 % || 16.30 %

Agree || 69 || 40.12 % || 51.11 %

Strongly agree || 32 || 18.60 % || 23.70 %

N/A || - || 21.51 % || -

4.1.7 Do you consider the current additional data exclusivity period of one year for each extension of the authorisation to another food-producing species appropriate?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (135)

No opinion || 10 || 5.81 % || 7.41 %

Very unsatisfactory || 27 || 15.70 % || 20.00 %

Unsatisfactory || 82 || 47.67 % || 60.74 %

Satisfactory || 14 || 8.14 % || 10.37 %

Very satisfactory || 2A || 1.16 % || 1.48 %

N/A || - || 21.51 % || -

4.1.8 Would you be in favour of major product developments (for example extending the authorisation to additional animal species, new formulations of the substance) being subject to their own period of exclusivity (i.e. not being part of the global marketing authorisation for the product containing that active substance)?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (135)

Favour not at all || 4 || 2.33 % || 2.96 %

Favour not || 5 || 2.91 % || 3.70 %

Favour somewhat || 70 || 40.70 % || 51.85 %

Favour clearly || 17 || 9.88 % || 12.59 %

Favour very much || 35 || 20.35 % || 25.93 %

Do not know || 4 || 2.33 % || 2.96 %

N/A || - || 21.51 % || -

Most respondents (63%) would be in favour
of amending the condition whereby it is only in a five-year period following
the granting of the initial marketing authorisation that an extension of the
period of data exclusivity can be obtained (see table 4.1.9).

4.1.9 Would you be in favour of amending the condition that only in a time period of five years following the granting of the initial marketing authorisation an extension of the period of market exclusivity can be obtained?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (135)

Favour not at all || 4 || 2.33 % || 2.96 %

Favour not || 14 || 8.14 % || 10.37 %

Favour somewhat || 70 || 40.70 % || 51.85 %

Favour clearly || 8 || 4.65 % || 5.93 %

Favour very much || 30 || 17.44 % || 22.22 %

Do not know || 9 || 5.23 % || 6.67 %

N/A || - || 21.51 % || -

Many respondents refer to the negative
effects which the global marketing authorisation concept has on innovations.
This concept does not take into account the investment and innovation involved
into further developing a product.

Most respondents consider that data
protection rules place a particularly heavy burden on SMEs (see table 4.1.10).
Further analysis shows that the majority of industry respondents do not
consider that there is a specific burden on SMEs (Yes 3 %, No 53 %,
Do not know 27 %, N/A 17 %). Veterinarians, however, hold the
opposite opinion (Yes 75 %, No 2 %, Do not know 11 %, N/A 12 %).

4.1.10 Do you consider that in data protection rules there are particular burdens in relation to the features of SMEs?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (132)

Yes || 70 || 40.70 % || 53.03 %

No || 34 || 19.77 % || 25.76 %

Do not know || 28 || 16.28 % || 21.21 %

N/A || - || 23.26 % || -

Most respondents (65%) would like to
introduce specific intellectual property incentives for small markets (see
table 4.1.11). Only a very small majority (5 %) would not be in favour.

4.1.11 Should specific intellectual property incentives be developed for small markets?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (130)

Yes || 111 || 64.53 % || 85.38 %

No || 8 || 4.65 % || 6.15 %

Do not know || 11 || 6.40 % || 8.46 %

N/A || - || 24.42 % || -

The respondents considered that the current
exclusivity period of 13 years for fish and bees is insufficient (54 %)
and should be extended (56 %) (see table 4.1.12).

4.1.12 Do you consider the current data protection period of 13 years for fish and bees appropriate?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (134)

Yes || 17 || 9.88 % || 12.69 %

No || 93 || 54.07 % || 69.40 %

Do not know || 24 || 13.95 % || 17.91 %

N/A || - || 22.09 % || -

The public were asked to indicate which
species should receive the same approach as bees and fish. Almost all those who
provided comments considered that the same exclusivity period should apply for
all minor species and minor uses.

4.1.13 Should the data period of 13 years for bees and fish be extended to other species?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (134)

No opinion || 11 || 6.40 % || 8.21 %

Very unsatisfactory || 8 || 4.65 % || 5.97 %

Unsatisfactory || 5 || 2.91 % || 3.73 %

Satisfactory || 97 || 56.40 % || 72.39 %

Very satisfactory || 13 || 7.56 % || 9.70 %

N/A || - || 22.09 % || -

Most respondents considered that generics
increase the availability of medicines (see table 4.1.14).

4.1.14 Do you agree that generics increase the availability of veterinary medicines (e.g. in smaller Member States in which the original product was not marketed)?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (136)

No opinion || 8 || 4.65 % || 5.88 %

Strongly disagree || 34 || 19.77 % || 25.00 %

Agree || 35 || 20.35 % || 25.74 %

Strongly agree || 59 || 34.30 % || 43.38 %

N/A || - || 20.93 % || -

About half of the respondents (48 %)
consider that generic veterinary products based on old reference products could
pose a risk for public or animal health (see table 4.1.15).

4.1.15 Generic veterinary products may be based on reference products that have been on the market for a long time, and the approval of these reference products will have taken place not according to current requirements. Do you consider that generic veterinary products based on these ‘’old reference products could pose a risk for public or animal health?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (140)

Yes || 84 || 48.84 % || 60.00 %

No || 50 || 29.07 % || 35.71 %

Do not know || 6 || 3.49 % || 4.29 %

N/A || - || 18.60 % || -

Most respondents (100; 58 %) felt that
an generic should be allowed to use environmental data (see table 4.1.16).
Industry respondents pointed out that environmental safety data requirements
could be adapted if a level playing field was guaranteed for all marketing
authorisation holders.

4.1.16 Do you think an applicant should be allowed to use the data in relation the potential risks posed by medicinal product for the environment (like for the results of safety and residue test or of the pre-clinical and clinical trials?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (128)

Yes || 100 || 58.14 % || 78.13 %

No || 14 || 8.14 % || 10.94 %

Do not know || 14 || 8.14 % || 10.94 %

N/A || - || 25.58 % || -

No clear position emerged on the
establishment of a monograph system for environmental risks: 34 % of the
respondents had no opinion, 18% were not in favour, 10% somewhat in
favour and 18 % clearly or very much in favour.

4.1.17 Would you favour a monograph system for environmental risks?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

Favour not at all || 25 || 14.53 % || 18.12 %

Favour not || 6 || 3.49 % || 4.35 %

Favour somewhat || 18 || 10.47 % || 13.04 %

Favour clearly || 14 || 8.14 % || 10.14 %

Favour very much || 17 || 9.88 % || 12.32 %

Do not know || 58 || 33.72 % || 42.03 %

N/A || - || 19.77 % || -

Authorisation
procedure

About 74% of the respondents are
dissatisfied or very dissatisfied with the current authorisation procedure and
only a minority (23; 13%) appears to be satisfied. This last group of
respondents consists mostly of authorities (11), veterinarians (4) and two
business respondents active in homeopathics.

4.2.1 How do you rank your satisfaction with the current authorisation procedures?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (136)

No opinion || 4 || 2,33% || 2,94%

Very dissatisfied || 4 || 2,33% || 2,94%

Dissatisfied || 105 || 61,05% || 77,21%

Satisfied || 23 || 13,37% || 16,91%

Very satisfied || 0 || 0,00% || 0,00%

N/A || - || 20,93% || -

A majority of respondents (100; 58%)
considered that there is no need for several authorisation procedures in the EU
(see table 4.2.2). However, a substantial minority (35; 20%) believed that
there is a need for several procedures. This minority consisted of authorities
(12), veterinarians (10) and almost all respondents active in aquaculture (3).
Similar results were obtained on the question whether it is necessary that the
number of authorisation procedures should be simplified by reducing it to one
as 62% of the respondents agreed to this position (see table 4.2.3).

4.2.2 Do you consider that there is a need for several authorisation procedures in the EU?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

Yes || 35 || 20,35% || 25,36%

No || 100 || 58,14% || 72,46%

Don't know || 3 || 1,74% || 2,17%

N/A || - || 19,77% || -

4.2.3 Do you consider it necessary that the number of authorisation procedures should be simplified by reducing it to only one?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

No opinion || 4 || 2,33% || 2,88%

Strongly disagree || 27 || 15,70% || 19,42%

Agree || 76 || 44,19% || 54,68%

Strongly agree || 32 || 18,60% || 23,02%

N/A || - || 19,19% || -

A majority of the respondents (71; 41%)
consider that there are parts in the authorisation procedures in particular
burdensome for SMEs. The respondents that did not agree with this statement
(29;17%) consisted mostly of industry (19) and authorities (5).

4.2.4 Do you consider that there are parts in the authorisation procedures in particular burdensome for SMEs?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (124)

Yes || 71 || 41,28% || 57,26%

No || 29 || 16,86% || 23,39%

Do not know || 24 || 13,95% || 19,35%

N/A || - || 27,91% || -

About 59% of the respondents expressed to
be satisfied or very satisfied with the current centralised procedure and about
12% of respondents appear to be dissatisfied or very dissatisfied (table
4.2.5). This last group of respondents consists of industry (8), veterinarians
(5), authorities (3) and food producers (3).

4.2.5 How do you rank your satisfaction with the current centralised procedure?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (133)

No opinion || 8 || 4,65% || 6,02%

Very dissatisfied || 3 || 1,74% || 2,26%

Dissatisfied || 20 || 11,63% || 15,04%

Satisfied || 96 || 55,81% || 72,18%

Very satisfied || 6 || 3,49% || 4,51%

N/A || - || 22,67% || -

There appears to be strong support among
respondents (120; 72%) to extend the scope of the centralised procedure (see
table 4.2.6).

4.2.6 Would you favour extending the scope of the Community procedure (extending the type of products that could be authorised by the Community procedure)?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (136)

Favour not at all || 4 || 2,33% || 2,94%

Favour not || 8 || 4,65% || 5,88%

Favour somewhat || 15 || 8,72% || 11,03%

Favour clearly || 93 || 54,07% || 68,38%

Favour very much || 12 || 6,98% || 8,82%

Do not know || 4 || 2,33% || 2,94%

N/A || - || 20,93% || -

About 64% of the respondents are
dissatisfied or very dissatisfied with the current mutual recognition and
decentralised procedure (see table 4.2.7). A minority (18; 10 %) appeared to be
satisfied. This last group of respondents consisted mostly of authorities (11).

4.2.7 How do you rank your satisfaction with the current decentralised and mutual recognition procedure?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (135)

No opinion || 7 || 4,07% || 5,19%

Very dissatisfied || 5 || 2,91% || 3,70%

Dissatisfied || 105 || 61,05% || 77,78%

Satisfied || 18 || 10,47% || 13,33%

Very satisfied || 0 || 0,00% || 0,00%

N/A || - || 21,51% || -

The reputation for efficiency and scientific
expertise of the competent authority appear the most important criteria for
selecting it as reference member state, followed closely by previous favourable
experience and reputation for communication (see table 4.2.8). The geographical
location seems to be of less importance.

4.2.8 What are your criteria for selecting the reference Member State in the decentralised procedure?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (172)

Previous favourable experience || 34 || 19,77% || 19,77%

Reputation for efficiency || 42 || 24,42% || 24,42%

Reputation for scientific expertise || 38 || 22,09% || 22,09%

Reputation for communication || 28 || 16,28% || 16,28%

Geographical location || 24 || 13,95% || 13,95%

Other || 12 || 6,98% || 6,98%

There appears to be a strong support (68%
of respondents) for a conditional authorisation system (see table 4.2.9).

4.2.9 Do you think a conditional authorisation, similar to the one included in the legal framework for human medicines, would help to mitigate the availability problem?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (131)

No opinion || 9 || 5,23% || 6,87%

Strongly disagree || 4 || 2,33% || 3,05%

Agree || 113 || 65,70% || 86,26%

Strongly agree || 5 || 2,91% || 3,82%

N/A || - || 23,84% || -

Most respondents to the public consultation
(51%) did not favour to include indirect risks in the risk-benefit assessment
of veterinary medicines (table 4.2.10). However, a majority (58%) favoured to
include in the legal framework a basis for restricting a marketing application
in cases where authorisation of a specific medicine would pose an indirect risk
to animal or human health (see table 4.2.11).

4.2.10 Would you favour including in the legal framework a requirement to perform a risk-benefit assessment which also takes into account indirect risks related to the use of the veterinary medicine, for example the development of antimicrobial resistance?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (132)

Favour not at all || 26 || 15,12% || 19,70%

Favour not || 62 || 36,05% || 46,97%

Favour somewhat || 13 || 7,56% || 9,85%

Favour clearly || 15 || 8,72% || 11,36%

Favour very much || 12 || 6,98% || 9,09%

Do not know || 4 || 2,33% || 3,03%

N/A || - || 23,26% || -

4.2.11 Would you favour including in the legal framework a clear basis for restricting a marketing application and/or providing certain indications in cases where authorisation of the specific veterinary medicine would pose an indirect risk to animal or human health?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

Favour not at all || 23 || 13,37% || 16,55%

Favour not || 9 || 5,23% || 6,47%

Favour somewhat || 69 || 40,12% || 49,64%

Favour clearly || 18 || 10,47% || 12,95%

Favour very much || 13 || 7,56% || 9,35%

Do not know || 7 || 4,07% || 5,04%

N/A || - || 19,19% || -

A majority (51%) of respondents favoured not to include in the legal
framework a specific legal basis to restrict the use of antimicrobials which
are critical for human medicines (table 4.2.12).

4.2.12 Would you favour that the legal framework provides a specific legal basis to restrict the use of antimicrobials which are critical for human medicine?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

Favour not at all || 80 || 46,51% || 57,97%

Favour not || 7 || 4,07% || 5,07%

Favour somewhat || 22 || 12,79% || 15,94%

Favour clearly || 13 || 7,56% || 9,42%

Favour very much || 13 || 7,56% || 9,42%

Do not know || 3 || 1,74% || 2,17%

N/A || - || 19,77% || -

Packaging
and labelling

Regarding packaging and labelling
requirements for veterinary medicines the stakeholders were asked six
questions. It can be extracted from their answers, firstly, that the majority
of the stakeholders believe that it is clearly essential or very much essential
to have packaging and labelling requirements at EU level (see table 4.3.1).

4.3.1 Do you consider EU - packaging and labelling requirements essential in terms of providing appropriate information to the users of veterinary medicines?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (142)

Not essential at all || 1 || (0.6%) || (0.7%)

Not essential || 5 || (2.9%) || (3.5%)

Somewhat essential || 11 || (6.4%) || (7.7%)

Clearly essential || 104 || (60.5%) || (73.2%)

Very much essential || 20 || (11.6%) || (14.1%)

Don't know || 1 || (0.6%) || (0.7%)

N/A || 30 || (17.4%) || -

When they were asked if they would be in
favour of reducing the requirement and the information needed in the packages
and labels (see tables 4.3.2 and 4.3.3) most of the participants were positive
about the idea.

Concerning the possibility of having fewer
or non packaging and labelling requirements at all (see table 4.3.2) half of
the stakeholders, mostly consisting of veterinarians, are somewhat in favour.
The authorities answered mostly negatively to this question. Respondents of
industry were clearly or very much in favour.

4.3.2 Would you be in favour of fewer packaging and labelling requirements, or none at all, in the EU legal framework?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (140)

Favour not at all || 14 || (8.1%) || (10%)

Favour not || 17 || (9.9%) || (12.1%)

Favour somewhat || 71 || (41.3%) || (50.7%)

Favour clearly || 9 || (5.2%) || (6.4%)

Favour very much || 29 || (16.9%) || (20.7%)

Do not know || 0 || (0%) || (0%)

N/A || 32 || (18.6%) || -

With regard to the possibility of reducing
the information on the label, most of the participants would be somewhat in
favour of the measure (see table 4.3.3). They are basically veterinarians and
the authorities. Stakeholders from the industry are mainly the ones clearly or
very much in favour of this idea.

4.3.3 Would you be in favour of reducing the information on the label as much as possible and to making it easier for labels to be used in a number of Member States?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

Favour not at all || 5 || (2.9%) || (3.6%)

Favour not || 8 || (4.7%) || (5.8%)

Favour somewhat || 74 || (43%) || (53.6%)

Favour clearly || 9 || (5.2%) || (6.5%)

Favour very much || 42 || (24.4%) || (30.4%)

Do not know || 0 || (0%) || (0%)

N/A || 34 || (19.8%) || -

On the issue about allowing Member States
to decide which language is be used for labelling and packaging (see table
4.3.4), the majority are positive.

4.3.4 Would you favour Member States being allowed to decide which language is to be used for labelling and packaging?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

Favour not at all || 2 || (1.2%) || (1.4%)

Favour not || 5 || (2.9%) || (3.6%)

Favour somewhat || 67 || (39%) || (48.2%)

Favour clearly || 43 || (25%) || (30.9%)

Favour very much || 21 || (12.2%) || (15.1%)

Do not know || 1 || (0.6%) || (0.7%)

N/A || 33 || (19.2%) || -

Regarding the possibility of having
specific requirements for small packs (see table 4.3.5) most the stakeholders
agree or strongly agree with it.

4.3.5 Can you agree to have specific requirements for small packs (small packaging would include ampoules, blister packs and other immediate packs of relative small size), e.g. information being given on the outer packaging of small packs?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (137)

No opinion || 2 || (1.2%) || (1.5%)

Strongly disagree || 1 || (0.6%) || (0.7%)

Agree || 92 || (53.5%) || (67.2%)

Strongly agree || 42 || (24.4%) || (30.7%)

N/A || 35 || (20.3%) || -

About half of the respondents (79 out of
the 172 participants in the public consultation) gave concrete proposals to
amend the legal framework. Two main groups of proposals could be established.

Pharmacovigilance
and monitoring

The majority of respondents agree or
strongly agree that the needs and expectations concerning the safety level of
veterinary pharmacovigilance should be different from those concerning human
medical products (see table 4.4.1). Most of those respondents are veterinarians
and representatives from the industry.

4.4.1 Do you consider that the needs and expectations concerning the safety level of veterinary pharmacovigilance could be different for human pharmacovigilance?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (140)

No opinion || 3 || (1.7 %) || (2.1 %)

Strongly disagree || 20 || (11.6 %) || (14.3 %)

Agree || 83 || (48.3 %) || (59.3 %)

Strongly agree || 34 || (19.8 %) || (24.3 %)

N/A || 32 || (18.6 %) || -

As table 4.4.2 shows, the majority of
respondents are positive about introducing a master file for pharmacovigilance
or any other way of reducing the regulatory burden on authorisation holders. 
At sectorial level, the authorities and industry are very much in favour of
such measures, whereas most veterinarians are merely 'somewhat in favour'.

4.4.2 Would you favour the introduction of a masterfile for pharmacovigilance or any other means of reducing the regulatory burden of authorisation holders?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

Favour not at all || 2 || (1.2 %) || (1.4 %)

Favour not || 2 || (1.2 %) || (1.4 %)

Favour somewhat || 69 || (40.1 %) || (49.6 %)

Favour clearly || 18 || (10.5 %) || (12.9 %)

Favour very much || 46 || (26.7 %) || (33.1 %)

Do not know || 2 || (1.2 %) || (1.4 %)

N/A || 33 || (19.2 %) || -

On the question whether the participants in
the consultation think that there are particular problems in the legislation
for pharmacovigilance for SMEs (see table 4.4.3), it can be seen from the data
that most of the respondents do not have a position on this particular issue.

Among those who have an opinion, the
majority think that there are problems.

4.4.3 Do you think that there are particular problems in the legislation for pharmacovigilance for SMEs?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (130)

Yes || 42 || (24.4 %) || (32.3 %)

No || 11 || (6.4 %) || (8.5 %)

Do not know || 77 || (44.8 %) || (59.2 %)

N/A || 42 || (24.4 %) || -

Finally, as regards the possibility of
establishing a harmonised system for data collection on the sales and use of
medicines in the EU, the majority of respondents are just somewhat in favour of
the measure (see table 4.4.4). They are mainly veterinarians and
representatives from the industry. Those who are clearly or very much in favour
are the authorities and non‑business organisations.

4.4.4 Would you favour the introduction of a specific legal base for establishing harmonised systems for data collection on the sales and use of medicines in the EU?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

Favour not at all || 4 || (2.3 %) || (2.9 %)

Favour not || 2 || (1.2 %) || (1.4 %)

Favour somewhat || 83 || (48.3 %) || (59.7 %)

Favour clearly || 27 || (15.7 %) || (19.4 %)

Favour very much || 18 || (10.5 %) || (12.9 %)

Do not know || 5 || (2.9 %) || (3.6 %)

N/A || 33 || (19.2 %) || -

The
Distribution Channel

A majority of the respondents (66 %)
agree or strongly agree (see table 4.5.1) that there is a need to standardise
and harmonise the conditions for operators in the EU distribution channel. When
the participants were asked if they would be in favour of standardisation by
amending the European legal framework, the same results were obtained: a
majority replied positively (see table 4.5.2).

4.5.1 Do you consider that there is a need to standardise and harmonise the conditions for operators in the EU distribution channel

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (142)

No opinion || 7 || (4.1 %) || (4.9 %)

Strongly disagree || 31 || (18 %) || (21.8 %)

Agree || 83 || (48.3 %) || (58.5 %)

Strongly agree || 21 || (12.2 %) || (14.8 %)

N/A || 30 || (17.4 %) || -

4.5.2 If so, would you favour standardisation by amending the European legal framework?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (138)

Favour not at all || 28 || (16.3 %) || (20.3 %)

Favour not || 5 || (2.9 %) || (3.6 %)

Favour somewhat || 15 || (8.7 %) || (10.9 %)

Favour clearly || 70 || (40.7 %) || (50.7 %)

Favour very much || 16 || (9.3 %) || (11.6 %)

Do not know || 4 || (2.3 %) || (2.9 %)

N/A || 34 || (19.8 %) || -

Most of the participants are very much in
favour or clearly in favour of the prescription of medicines being standardised
in the EU (see table 4.5.3), especially veterinarians, authorities and
non-business organisations. Industry representatives are mainly not at all in
favour.

4.5.3 Would you be in favour of the prescription of medicines being standardised in the EU

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (142)

Favour not at all || 27 || (15.7 %) || (19 %)

Favour not || 5 || (2.9 %) || (3.5 %)

Favour somewhat || 9 || (5.2 %) || (6.3 %)

Favour clearly || 23 || (13.4 %) || (16.2 %)

Favour very much || 76 || (44.2 %) || (53.5 %)

Do not know || 2 || (1.2 %) || (1.4 %)

N/A || 30 || (17.4 %) || -

Most respondents (60 %) consider that
cross-border activities of the sector are hampered by the current rules (see
table 4.5.4).

4.5.4 Do you consider that cross-border activities, for example involving veterinarians active in two Member States, are hampered by the current rules?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (142)

Yes || 103 || (59.9 %) || (72.5 %)

No || 24 || (14 %) || (16.9 %)

Do not know || 15 || (8.7 %) || (10.6 %)

N/A || 30 || (17.4 %) || -

As far as counterfeit veterinary medicines
are concerned, a majority agrees that they have penetrated the veterinary
supply chain (see table 4.5.5). However, it needs to be emphasised that a
number of participants strongly disagree with the above statement, especially
stakeholders from the industry.

4.5.5 Do you agree that counterfeit medicines have penetrated the veterinary supply chain?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (139)

No opinion || 31 || (18 %) || (22.3 %)

Strongly disagree || 25 || (14.5 %) || (18 %)

Agree || 80 || (46.5 %) || (57.6 %)

Strongly agree || 3 || (1.7 %) || (2.2 %)

N/A || 33 || (19.2 %) || -

A lot of the respondents consider that
there are risks to public health from the penetration of counterfeit medicines
into the veterinary supply chain (see table 4.5.6).

4.5.6 If so, do you consider that there are risks to public health from the penetration of counterfeit medicines into the veterinary supply chain?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (132)

No opinion || 6 || (3.5 %) || (4.5 %)

Strongly disagree || 4 || (2.3 %) || (3 %)

Agree || 102 || (59.3 %) || (77.3 %)

Strongly agree || 20 || (11.6 %) || (15.2 %)

N/A || 40 || (23.3 %) || -

When the participants in the consultation
were asked about whether they consider counterfeiting of veterinary medicinal
products to be a problem for animal health and/or public health in the EU, a
large proportion (40 %) said they did not have an opinion (table 4.5.7).

4.5.7 Do you consider counterfeiting of veterinary medicinal products to be a problem for animal health and/or public health in the EU?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (143)

No opinion || 68 || (39.5 %) || (47.6 %)

Strongly disagree || 22 || (12.8 %) || (15.4 %)

Agree || 36 || (20.9 %) || (25.2 %)

Strongly agree || 17 || (9.9 %) || (11.9 %)

N/A || 29 || (16.9 %) || -

Notwithstanding the clear positions on
counterfeit medicines, the great majority of respondents (9578%) indicated that
they had neither quantitative nor qualitative data on counterfeit veterinary
medicinal products (see table 4.5.8). It can be concluded that there is a
consensus among stakeholders (129 out of 131 respondents to this question) that
legislative measures are necessary to tackle counterfeit veterinary medicinal
products (table 4.5.9).

4.5.8 Do you have qualitative or quantitative data on counterfeit veterinary medicinal products?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (140)

Yes || 6 || (3.5 %) || (4.3 %)

No || 134 || (77.9 %) || (95.7 %)

N/A || 32 || (18.6 %) || -

4.5.9 Do you think that legislative measures are necessary to tackle counterfeit veterinary medicinal products?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (145)

Yes || 129 || (75 %) || (89 %)

No || 2 || (1.2 %) || (1.4 %)

Do not know || 14 || (8.1 %) || (9.7 %)

N/A || 27 || (15.7 %) || -

The majority (76 %) of participants in
the consultation agree or strongly agree that issues such as internet trade,
mail order selling or parallel import should be addressed in the revision of
the legal framework for veterinary medicines (table 4.5.10). In this
connection, as we can see from table 4.5.11, most of the participants consider
that the legal framework should be supplemented with specific requirements on
these aspects.

4.5.10 Should the issues of internet trade, mail order selling or parallel import be addressed in the revision of the legal framework for veterinary medicines?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (143)

No opinion || 2 || (1.2 %) || (1.4 %)

Strongly disagree || 9 || (5.2 %) || (6.3 %)

Agree || 53 || (30.8 %) || (37.1 %)

Strongly agree || 79 || (45.9 %) || (55.2 %)

N/A || 29 || (16.9 %) || -

4.5.11 Do you consider that the legal framework should be supplemented with specific requirements on internet trade, mail order selling or parallel import?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (142)

Yes || 129 || (75 %) || (90.8 %)

No || 9 || (5.2 %) || (6.3 %)

Do not know || 4 || (2.3 %) || (2.8 %)

N/A || 30 || (17.4 %) || -

The
use of drugs not in accordance with the summary of product
characteristics (off-label use)

About 86 % of respondents considered
the description in the public consultation accurate (see table 4.6.1). A
minority (34 replies; 19 %) considered that off-label use of medicines was
too common in the EU; the majority (99 replies; 58 %) did not agree with
this statement (table 4.6.2). This last group consisted mostly of veterinarians
and respondents from the pharmaceutical industry.

4.6.1 Is the above an accurate description of the situation?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (151)

Yes || 148 || 86.05 % || 98.01 %

No || 3 || 1.74 % || 1.99 %

N/A || - || 12.21 % || -

4.6.2 Do you consider that off-label use of medicines is too common in the EU?

|| Number of replies to the question || % of total replies to the consultation (172) || % of replies to the question (152)

No opinion || 19 || 11.05 % || 12.50 %

Strongly disagree || 99 || 57.56 % || 65.13 %

Agree || 28 || 16.28 % || 18.42 %

Strongly agree || 6 || 3.49 % || 3.95 %

N/A || - || 11.63 % || -

Respondents clarified that limited data
existed on off-label use (only 14 out of 147 respondents reported that they had
such data) (see table 4.6.3). Some qualitative data were provided on rabbits,
horses, poultry and aquaculture for certain Member States. One authority
provided data on the extent veterinarians had to rely on veterinary medicines
imported from other Member States for use under the cascade. It appeared that
the vast majority of applications for importation were for pets. One
pharmaceutical company stated that 25-30 % of suspected adverse reactions
reported involved off-label use.

4.6.3 Do you have quantitative or qualitative data on off-label use?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (147)

Yes || 14 || 8.14 % || 9.52 %

No || 133 || 77.33 % || 90.48 %

N/A || - || 14.53 % || -

Most of the respondents (115 replies; 67 %)
considered off-label use a potential hazard (see table 4.6.4). However, a
substantial minority (32 replies; 19 %) did not agree with this statement;
these were mainly producers (10 replies), veterinarians (6 replies) or from
industry (5 replies).

4.6.4 Do you consider off-label use a potential hazard for animal and /or public health?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (151)

Yes || 115 || 66.86 % || 76.16 %

No || 32 || 18.60 % || 21.19 %

Do not know || 4 || 2.33 % || 2.65 %

N/A || - || 12.21 % || -

A minority (47 replies; 27 %)
considered it appropriate to exclude certain medicines from off-label use (see
table 4.6.5). These were mainly authorities (17 replies), producers (10
replies), veterinarians (10 replies) and industry (5 replies). Most of the
respondents (104 replies, 69%) did not agree with the statement to exclude
certain medicines from off-label use.

4.6.5 Would you consider it appropriate to exclude certain medicines from off-label use?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (151)

No opinion || 12 || 6.98 % || 7.95 %

Strongly disagree || 92 || 53.49 % || 60.93 %

Agree || 39 || 22.67 % || 25.83 %

Strongly agree || 8 || 4.65 % || 5.30 %

N/A || - || 12.21 % || -

Many respondents (86 replies) took the
opportunity to put forward proposals for amending the legal framework
concerning off-label use.

Harmonisation
of already authorised veterinary products

Regarding this key issue, the vast majority
of the respondents agree with the description of the situation done by the
Commission (see table 4.7.1).

4.7.1 Do you agree with the description of the issue?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (141)

Yes || 139 || (80.8%) || (98.6%)

No || 2 || (1.2%) || (1.4%)

N/A || 31 || (18%) || -

However, when they were asked if they
consider necessary to update and to harmonise the already authorised medicines,
the majority (52%) disagreed (see table 4.7.2), mainly consisting of
participants from the industry and veterinaries. The authorities, even if they
are divided in their opinions, most of them are the ones who agree or strongly
agree with the idea of updating and harmonising the already authorised
veterinary medicines. Respondents from non business organisations are equally
divided between agree and disagree.

4.7.2 Do you consider it necessary to update and to harmonise already authorised medicines?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (142)

No opinion || 5 || (2.9%) || (3.5%)

Strongly disagree || 90 || (52.3%) || (63.4%)

Agree || 36 || (20.9%) || (25.4%)

Strongly agree || 11 || (6.4%) || (7.7%)

N/A || 30 || (17.4%) || -

A majority of respondents agreed to a
risk-based harmonisation (to update and to harmonise already authorised
medicines differently according to the public health risks involved) (table
4.7.3).

4.7.3 If a procedure were established to update and to harmonise already authorised medicines, would you consider it appropriate to apply the procedure differently according to the public health risks involved or to other criteria (e.g. to prioritize the harmonisation of products with high public health concern)?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (142)

Yes || 131 || (76.2%) || (92.3%)

No || 11 || (6.4%) || (7.7%)

N/A || 30 || (17.4%) || -

The majority of the respondents (57%)
preferred a compulsory approach to update and to harmonise already authorised
medicines (see table 4.7.4), consisting mainly of veterinarians, authorities
and non business organisations.

4.7.4 If a procedure were established to update and to harmonise already authorised medicines, would you prefer a compulsory approach?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (143)

No opinion || 10 || (5.8%) || (7%)

Strongly disagree || 34 || (19.8%) || (23.8%)

Agree || 92 || (53.5%) || (64.3%)

Strongly agree || 7 || (4.1%) || (4.9%)

N/A || 29 || (16.9%) || -

New
needs and new challenges

The aim of this last chapter of the public
consultation is to see if the participants perceived that there is a real need
to change the legal framework to better respond to new veterinary needs, new
circumstances and new technologies.

In reply to this, as we can see in table
4.8.1, most of the respondents (81%) agree that this issue needs to be
addressed in the review of the veterinary medicinal legislation.

4.8.1 Should this issue of new needs and new challenges be addressed in the review?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (146)

No opinion || 6 || (3.5%) || (4.1%)

Strongly disagree || 0 || (0%) || (0%)

Agree || 123 || (71.5%) || (84.2%)

Strongly agree || 17 || (9.9%) || (11.6%)

N/A || 26 || (15.1%) || -

Regarding the development and production of
medicines through new technologies, when the stakeholders were asked if they
agree that there are difficulties to assess them, more agree (44%) than
disagree (1%). It is important to note that about 40% of the respondents do not
have a fixed opinion on the subject.

4.8.2 Do you agree that there are difficulties in the assessment of medicines developed or produced by new technologies?

|| Number of replies || % of total replies to the questionnaire (172) || % of replies to the question (146)

No opinion || 69 || (40.1%) || (47.3%)

Strongly disagree || 2 || (1.2%) || (1.4%)

Agree || 65 || (37.8%) || (44.5%)

Strongly agree || 10 || (5.8%) || (6.8%)

N/A || 26 || (15.1%) || -

Not many participants in the public
consultation, just about 20%, had specific proposals how to authorise
veterinary medicinal products urgently in the event of an emergency. Several
participants provided concrete proposals in relation to new needs and
challenges.

Responding
organisations and individuals in alphabetical order

Dr Hans-Jürgen Abmayr || Enterprise

ADS ACUIVAL — Agrupacion de Defensa Sanitaria Acuicultura de la Comunitat Valenciana || Non-business organisation

ADSG — Galician Association of Trout Farmas || Non-business organisation

AEMPS — Agencia Espanola de Medicamentos y Productos Sanitarios Directora || Public authority

Agence Nationale du Médicament Vétérinaire, Agence Nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail, Ministère de la Santé et des Sports, Ministère de l’Alimentation, de l’Agriculture et de la Pêche, France || Public authority

AVEC — Association of European Poultry Processors; EPB — European Poultry Breeders; AEH — Association of European Hatcheries || Enterprise

Chiara Agnoli || Enterprise

Dr Peter Aigner || Enterprise

AHDA — Animal Health Distributors Association || Non-business organisation

Alpharma Animal Health || Enterprise

Andermatt Biovet || Enterprise

Animal and Plant Health Association || Enterprise

ANMVI — Italian National Association of Veterinarians || Non-business organisation

Ann Williams || Enterprise

Associazione Piscicoltori Italiani || Non-business organisation

Brendan Barnes || Citizen

Franz Barth || Enterprise

Burkard Barthel || Enterprise

Bayer Animal Health || Enterprise

Bayerische Staatsministerium für Umwelt und Gesundheit || Public authority

Kirstin Becker || Enterprise

Dr Christian Blaschke || Citizen

Borion || Enterprise

Jean Bouchet || Enterprise

British Trout Association || Non-business organisation

Boehringer Ingelheim Animal Health || Enterprise

Bundesverband für Tiergesundheit || Enterprise

Bundestierärztekammer || Non-business organisation

Bundesverband Praktizierender Tierärzte || Non-business organsisation

Camilla Cammelli || Enterprise

CEVA Santé Animale || Enterprise

Coophavet || Enterprise

CVMP — Committee for Medicinal Products for Veterinary Use || Public authority

European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe || Non-business organisation

Danish Medicines Agency || Public authority

Dr Elke Deus || Citizen

Department of Agriculture, Fisheries and Food, Ireland || Public authority

Barbara Dihlmann || Enterprise

Dociu || Enterprise

ECEAE — European Coalition to End Animal Experiments || Non-business organisation

ECVH — European Coalition on Veterinary Homeopathy || Non-business organisation

Elanco Animal Health || Enterprise

EGGVP — European Group for Generic Veterinary Products || Enterprise

Dr Susanne Elsner || Enterprise

Dr Reinhold Erbing || Citizen

Eurovet Animal Health || Enterprise

Andrea Fabris || Citizen

FAMHP — Federal Agency for Medicines and Health Products, Belgium || Public authority

FEADSA — Federacion Espanola de Agrupaciones de Defensa Sanitaria de Acuicultura || Non-business organisation

FEAP — Federation of European Aquaculture Producers || Business organisation

Federal Ministry of Food, Agriculture and Consumer Protection; Federal Ministry of Health, Germany || Public authority

FEEDM — Féderation Européenne des Emballeurs et Distributeurs de Miel Grosse || Non-business organisation

FFA — Fédération Française d’Aquaculture || Enterprise

FIDIN — Fabrikanten en Importeurs van Diergeneesmiddelen in Nederland || Enterprise

FNOVI — Federiazione Nazionale degli Ordini dei veterinari Italiani || Public authority

Gianluca Fortino || Enterprise

Mirella Fossaluzza || Enterprise

FVE — Federation of Veterinarians of Europe, Belgium || Non-business organisation

FVE — Federation of Veterinarians of Europe, Germany || Non-business organisation

Dr Stefan Gabrie || Citizen

Dr Volker Gerlitzki || Citizen

German Federal Environment Agency || Public authority

Michaela Gambs || Citizen

Bettina Graefenstedt || Enterprise

Dr Frank Hildenbrand || Enterprise

IMB — Irish Medicines Board || Public authority

Icelandic Medicines Agency || Public authority

Ittica Tranquilli || Enterprise

Regierungspräsidium Tübingen || Public authority

Roberto Giavenni || Enterprise

IFAH-Europe — International Federation of Animal Health || Enterprise

Christophe Hugnet || Citizen

Janssen Animal Health || Enterprise

Dr Peter Kellner || Enterprise

Dr Silke Knoll || Enterprise

Dr Thomas Knacker || Enterprise

Dr Heidi Kübler || Non-business organisation

Dott. Vet. Beate Kuhl || Citizen

Laboratorios Ovejero || Enterprise

Dr Stephan Lübke || Citizen

Holger Maschke || Citizen

Matthias Link || Citizen

MedicAnimal || Enterprise

Medical Prducts Agency, Sweden || Public authority

Merial, Belgium || Enterprise

Merial, France || Enterprise

Marian Mestdagh || Enterprise

Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen || Public authority

Ministerium für Ländlichen Raum, Ernährung und Verbraucherschutz, Allgemeine Veterinärangelegenheiten, Germany || Public authority

Ministero della Slute Direzione Generale Sanita Animale e Farmaco Veterinario || Public authority

Ministry of Agriculture, Environment and Consumer Protection, Germany || Public authority

Ministry of Agriculture and Forestry, Finland || Public authority

Ministry of Agriculture, Nature and Food Quality, Department of Food, Animal Health and Welfare and Consumer Policy, The Netherlands || Public authority

Ministry of Environment, Health and Consumer Protection, Department for Consumer Protection, State of Brandenburg || Public authority

Ulrich Möhnle || Enterprise

National Office of Animal Health, UK || Enterprise

National Organisation for Medicines, Greece || Public authority

Niedersächsisches Landesamt für Verbracherschutz und Lebensmittelsicherheit || Public authority

Dr Jo-Ann Lawrence || Enterprise

Dr Ines Ott || Enterprise

Novartis Animal Health || Enterprise

PAN Germany –Pesticide Action Network Germany || Non-business organisation

PEI — Paul Ehrlich Institut || Public Authority

PETA — People for the Ethical Treatment of Animals || Non-business sorganization

Georg Petry || Enterprise

sPfizer Animal Health, UK || Enterprise

PGEU — Pharmaceutical Group of the European Union || Non-business organisation

sPfizer, Italy || Enterprise

Stephan Plank || Citizen

Paky Prenota || Citizen

Annegret Rehrmann || Non-business organisation

Dr Ulrike Quante || Enterprise

Dr Gerd Ricker || Citizen

Richter Pharma || Enterprise

Dr Ulli Rösel || Enterprise

Royal College of Veterinary Surgeons || Public authority

Pier Antonia Salvador || Enterprise

Sebastian Scala || Enterprise

Christoph Schäuble || Citizen

Dr Waltraude Scheffel || Public authority

Julia Scholl || Citizen

Dr Bernd Schulze || Enterprise

Scottish Salmon Producers’ Organisation || Enterprise

SIMV || Enterprise

Slovenia || Public Authority

 Dr Petra Sindern Seevering || Enterprise

SME Ireland || Enterprise

SNVEL –Syndicat National des Vétérinaires d’Exercice Libéral || Business organisation

SNVECO || Business organisation

Société Nationale des Groupements Techniques Vétérinaires, France || Non-business organisation

Dr Mary-Anne Sommer || Enterprise

Dr Martina Spangenberg || Enterprise

Are Thoresen || Enterprise

Tierärztliche Gemeinschaftspraxis WEK Lohe || Enterprise

TVM || Enterprise

Veterinary Council of Ireland || Public authority

VIRBAC SA || Enterprise

VMD — Veterinary Medicines Directorate || Public authority

Rupert Weber || Enterprise

Kai Boris Wiese || Enterprise

Dr Ulrike Zeyen-Blumrich || Citizen

http://ec.europa.eu/health/veterinary-use/pubcons\_frame\_index\_en.htm

C Summary responses of the target consultations:

C1 Pharmacovigilance

|| EUROPEAN COMMISSION HEALTH AND CONSUMERS DIRECTORATE-GENERAL Health systems and products Medicinal products — quality, safety and efficacy

Subject:            Summary report of expert meeting on
pharmacovigilance in the context of the review of the veterinary medicinal
products legislation

On 29 May 2012, an expert meeting took
place on pharmacovigilance. The meeting was held under Chatham House rules and
objective of this meeting was to gather experts’ inputs for the revision of the
legislation on veterinary medicines. Participants were invited based on their
expertise and received a discussion paper on pharmacovigilance shortly before
the meeting.

Ten experts participated in the meeting.
The discussion focused mostly on the advantages and disadvantages of the
current pharmacovigilance system and possible amendments: the scope of
pharmacovigilance, the different categories of adverse reactions in
pharmacovigilance, the type of reporting and means of providing information,
signal detection, the organisation and implementation of inspections, the
scope, development and maintenance of pharmacovigilance database(s) and access
to them, the sharing of information between parties, the responsibilities and
tasks of actors, regulatory tools for action, and transitional provisions.

The participants agreed to have a
risk-based approach for pharmacovigilance in the future and to develop a
veterinary pharmacovigilance better adapted to the characteristics of the
veterinary sector. However, views differed as to how these principles should
take shape in practice, in particular in relation to the tasks and
responsibilities of the different actors. Another key question discussed was
the level of events or accuracy that the new veterinary pharmacovigilance
system has to detect.

The group agreed that environmental and
residue violation events should be better covered by other systems, but no
EU-wide alternatives appear to exist.

Both the duplication of tasks by actors in
the system and the repetition of providing and collecting similar information
repeatedly surfaced in the discussion. Also frequently mentioned were the
differences in the way European pharmacovigilance requirements are implemented
by Member States. In general the participants favoured a harmonised,
proportionate pharmacovigilance system in the future. The development of an EU
pharmacovigilance database was supported by the participants; it was pointed
out that actors should be able to continue using their own databases for signal
detection. Surveillance should be based in principle on the active substance,
and the establishment of a masterfile should be made possible. There was no
agreement on the access of actors to the new EU database and how the quality of
the input should be ensured.

Clearly different views were expressed on
several items in the discussion paper, for example the organisation and
implementation of inspections and the need to report on events in third
countries.

C2 Authorisation procedures and data
protection

|| EUROPEAN COMMISSION HEALTH AND CONSUMERS DIRECTORATE-GENERAL Health systems and products Medicinal products — quality, safety and efficacy

Subject:            Subject:         Summary
report of expert meeting on authorisation procedures and data protection in the
context of the review of the veterinary medicinal products legislation

On 22 June 2012, an
expert meeting took place on authorisation procedures and data protection. The
meeting was held under Chatham House rules. The aim was to gather experts’
inputs for the revision of the legislation on veterinary medicines.
Participants were invited on the basis of their expertise and received a
discussion paper shortly before the meeting.

The discussion
focused mainly on the advantages and disadvantages of the current marketing authorisation
and data protection system and how it could be amended: the type and scope of
marketing authorisation procedures; ways of increasing the availability of
medicines by introducing specific procedures for marketing authorisation and
targeted data protection measures; the harmonisation of existing products; the
tasks of the scientific committee and the Member States' coordination group;
the definition of  biological medicine; marketing authorisation procedures for
generic medicines; the concept of global marketing authorisation; and the level
of data protection required to ensure sufficient innovation in the animal
health industry.

The participants were
unable to agree whether in the future one or several marketing authorisation
procedures would be appropriate. Most participants were in favour of letting
companies choose whether to use the centralised, national or decentralised
procedure.

The group agreed on
the need to harmonise existing products. However, views differed as to how this
should be carried out in practice, particularly in relation to the tasks and
responsibilities of the various players.

Generally speaking,
the group were in favour of updating the system for generics, particularly with
respect to the reference products that may be used. For environmental risk
assessment, the same rules would apply as for other safety data requirements.

The participants were
in favour of developing a data protection system that would provide better
support for innovation in the animal health industry. Opinions differed on the
appropriate duration of data protection and whether it should be linked to the
global marketing authorisation concept.

C3 Antimicrobial resistance

|| EUROPEAN COMMISSION HEALTH AND CONSUMERS DIRECTORATE-GENERAL Health systems and products Medicinal products — quality, safety and efficacy

Subject:            Summary report of expert meeting on
antimicrobial resistance in the context of the review of the legislation on
veterinary medicinal products

An expert meeting on antimicrobial resistance
took place on 8 June. The aim of the meeting, held under the Chatham House
rules, was to get input from experts for the revision of the legislation on
veterinary medicines. Before the meeting, the experts received a discussion
paper.

Twenty experts attended the meeting. They
discussed whether or not the current evidence-based evaluation of an
application for a marketing authorisation for an antimicrobial product was
still appropriate, or whether it would be better to take a precautionary
approach. They agreed that any policy measure should be science-base, however,
it was acknowledged the fact that data on use of antimicrobials as a risk to
public health due to antimicrobial resistance is limited. It was emphasised
that a precautionary approach would impact negatively on innovation.

They also discussed the effect any changes
to the legislative requirements on the authorisation of antimicrobials could
have on the availability of medicines. It was argued that regulatory
unpredictability may discourage companies from investing in the development of
new antimicrobials. Some experts were in favour of developing a regulatory
framework, with more detailed guidance from the European Medicines Agency,
claiming that it would be a good idea to define some terms in the legislation,
such as ‘antimicrobial’, ‘antibacterial’, ‘metaphylaxis’ and ‘prophylaxis’.

The issue of ‘conditional authorisations’
was discussed. Although some experts were in favour of them, others were
concerned that they could lead to uncertainty and even interfere with the
availability of products. 'Conditional authorisations' would work if it is
possible to respond appropriately to the conditions imposed.

The experts discussed imposing restrictions
on the authorisation of antimicrobials that are last resort medicines for the
treatment of infections in humans in case there is a possible link between use
of the compound in animals and resistance in humans.  There was support for
this proposal, provided the restrictions were not product-specific and provided
that the need for these antibiotics to protect animal health is recognised and
taken into account. They also discussed whether or not to include a list of
restricted categories of antimicrobials in the legislation. Many of them
expressed concern that this would not allow flexibility to change the list in
the light of scientific progress. Others stressed the fact that experience
showed that such lists are being changed frequently and therefore creating a
high degree of uncertainty. They discussed the sale of antimicrobials by
veterinarians. Some experts thought that veterinarians should be allowed to
sell antimicrobials to treat the animals under their care.

All the experts agreed that the legislation
should clarify that all antimicrobials should be classified as prescription
only-medicines, including those for pets.

They said that it would be a good idea to
make the collection of data on sales of antimicrobials per species compulsory.

C4 Small and medium enterprises

|| EUROPEAN COMMISSION HEALTH AND CONSUMERS DIRECTORATE-GENERAL Health systems and products Medicinal products – quality, safety and efficacy

Subject:            Summary report of experts' meeting with SMEs to
discuss the review of the veterinary medicinal product legislation

On 4th October 2012 a targeted
expert meeting took place with SMEs. The meeting was held under the Chatham
House rules and aimed to gather experts' input for the revision of the
legislation on veterinary medicines. Participants were invited based on their
expertise and received a discussion paper on points for discussion before the
meeting.

There have been fifteen participants. The
following topics were discussed: (i) authorisation procedures, (ii) packaging
and labelling requirements, (iii) rules on advertising, (iv) pharmacovigilance,
(v) "sunset clause", (vi) renewals, (vii) referrals, (viii)
variations, (ix) data protection and (x) clinical trials.

The group agreed that the current
authorization procedures do incur large administrative costs to SMEs and
microenterprises, in particular regarding variations and renewals. The issue of
lack of medicines for bees was discussed as an example of problems for minor
species.  It was suggested that mutual recognition should be obligatory and
automatic for medicines for minor species. The centralized procedure was
discussed and attendees indicated that this is potentially attractive procedure
but the fees are expensive for SMEs, and also the application procedure is
difficult for them, which in general do not have a dedicated regulatory
department. Participants indicated that the national procedure is important for
SMEs, which once obtain approval in one Member State then roll the product
authorisation to other countries through mutual recognition. The relevance of
the decentralized procedure was discussed, as it would potentially be ideal
when a company wishes to obtain an authorization in various countries at the
same time, but attendees explained that the decentralized procedure is very
difficult: MS often have different interpretation of the guidelines and
therefore their requirements are disharmonized. SMEs considered that a helpdesk
in the MS to offer support and free advice to SMEs would be very welcome.

Attendees discussed the possibility of
allowing SMEs to obtain a conditional marketing authorization for minor
species, with an incomplete efficacy package, with commitments to provide the
remaining data at a later date. This type of authorization already exists in
some countries but the annual renewal is an administrative burden to the
company.

Attendees explained that the procedures and
requirements to approve a clinical trial differ considerably between MS, and
this hampers the authorization process for SMEs. Some harmonization on this
area would be welcome.

The classification of bees as food
producing species was also raised. It was argued that this current
classification is not appropriate as the bees' husbandry methods differ from
those for cattle or sheep, for example, as well as their metabolism. For these
reasons, it was argued that the technical requirements in Annex I are excessive
for bee medicines.  However, it was agreed that whilst some data requirements
could be reduced for bees, such as quality requirements regarding GMP
compliance, for example, the safety of honey as a produce for human consumption
is important.

There was a discussion about the
requirements for packaging and labeling of veterinary medicines. Attendees
proposed to remove from the legislation the need for approval of mock ups.

During the short discussion about
advertising, experts commented that MS have different opinions about what can
be advertised, in particular regarding what is allowed to appear in the
internet (and searched through online searching engines). It was agreed that
the rules of advertising could be clarified.

The experts agreed that the requirements as
to the pharmacovigilance should be simplified. Periodic reports were found too
costly – even if no adverse reaction occurred, the report must be prepared,
which generates workload. The experts share also the same view on renewals -
unnecessary workload, if no adverse reactions occur.

According to the experts, the sunset clause
should be deleted.

It was highlighted that if, for instance, a
company has a marketing authorization for two types of vaccines – one for
outbreak and the other one for prevention, usually the second one is being
marketed.

SMEs representative were also in favor of
having longer data protection periods, as they argue that it takes longer for
the SME to develop new products and extending the data protection would be
beneficial and rewarding.

The experts would also support simplifying
the variations procedures.

Annex 10 Discarded options

·
Option to completely abolish pharmacovigilance
requirements: This option was discarded because it would introduce risks to
animal and public health and to the environment, as pharmacovigilance data are essential
for the monitoring of authorised veterinary medicines safety. Even though it is
estimated that the implementation of this option could generate savings to the
pharmaceutical industry of around 59.4 million euros per year, neither the
industry nor regulators nor end-users supported this proposal.

·
Option to replace the authorisation of low risk
and generic veterinary medicines with a registration system: Currently all
veterinary medicines must comply with the quality, safety and efficacy
requirements set out in the legislation – the legislation does not distinguish
between low and high risk medicines regarding the scientific data required. This
option considered creating a registration system for generics and lower risk
medicines (e.g. teat dips), which would not be subjected to scientific
assessment. But it was argued that it is wrong to assume that known active
substances are safe, and that the option ignored the risks posed by variable
quality and manufacturing standards of veterinary medicines. The option
received some support from end-users who considered that the proposal would
increase the supply and the level of competition for certain medicines, and
improve the internal market. It would also lead to a significant reduction of
the administrative burdens to the industry, associated with obtaining a
marketing authorisation (it was estimated that the savings to the industry would
be 181.9 million euros per year).[140]
On the other hand, the industry objected to this option on the basis that it
would distort the market by favouring generics and make recently authorised
medicines uncompetitive. For these reasons the option was discarded.

Option to make the centralised procedure compulsory
to all veterinary medicines: This option would make the centralised procedure compulsory for
all new applications, and would abolish the national, mutual recognition
and decentralised procedures. The EMA would be responsible for the
assessment of the applications and their post authorisation maintenance.
Member States would be responsible for maintaining the existing national
marketing authorisations. This option would have a
positive impact on the free movements of veterinary medicines in the EU.
However, it was discarded on the basis that it would increase the
administrative burden to the industry (by an estimated 170.8 million euros
per year) without in fact leading to an increase on the availability of
medicines (just because a product is authorised does not mean it is
actually placed on the market). In addition, SMEs objected to this option,
and regulators and the industry argued that the EMA would not be able to
process the volume of applications that it would receive with the current
capacity and procedures.

·
Option to introduce exemptions to reduce
legislative requirements regarding authorisation of veterinary medicines by
pharmaceutical companies that are SMEs or micro-enterprises: This option was considered in light of the Commission's policy to
support SMEs and micro-enterprises[141].
However, it was discarded because it runs against the fundamental principles of
the legislation on veterinary medicines, which is to safeguard public and
animal health and environmental safety. It is not possible to relax veterinary
medicines standards for a particular business sector.

·
Option to voluntarily harmonise the summary of
product characteristics of the “legacy products”: This option proposed a
programme of voluntarily harmonisation of the summary of product
characteristics (regarding the indications, target species, warnings and
withdrawal periods) and product literature for all veterinary medicines already
nationally authorised in the Union. This could involve scientific assessment of
all products, and a decision would be reached based on a benefit:risk
evaluation. This option was discarded because it would impose a significant
burden on the national competent authorities and on the pharmaceutical
companies and could lead to the withdrawal from the market of many
“unprofitable” products. In addition, a pilot scheme has been already tested by
the CMDv and considered by both competent authorities and pharmaceutical
industry laborious and time-consuming.

·
Option to standardise the distribution of
veterinary medicines across the Union: There was support by stakeholders
regarding the need to standardise and harmonise the EU distribution of
veterinary medicines. However, it was considered that the classification of a veterinary
medicine as prescription or over the counter, and its distribution, is within
the Member States' competence and therefore EU action would represent a breach
of the subsidiarity principle.

Option to forbid generic applications for antimicrobials: It
was argued that the relatively low price of antimicrobials is an incentive
for their excessive use. However, the adoption of this proposal would be
not compatible with the EU objectives of enhancing the internal market and
improving the availability of medicines.

·
Option to re-classify bees as non-food producing
animals: Stakeholders proposed this option as a measure
to improve the availability of medicines for bees, as the data requirements for
non-food producing animals are less stringent than those for food-producing
animals.  Therefore, the classification of bees as non-food producing animals
could theoretically facilitate the authorisation of medicines for bees. This
option was discarded for food safety reasons, as there would be no procedures
in place to ensure that honey from treated hives would be free from residues or
would not enter the human food chain (a system based on the identification of
individual treated from untreated hives, similar to horse passports, cannot be
introduced for the bees).

·
To develop "soft law instruments" to
achieve policy changes:  This option would rely exclusively
on guidance to introduce changes to the regulatory framework. This general
option was discarded as its non-binding nature would not be sufficient to tackle
the differences in the interpretation and implementation of the legislation.
They would be ineffective to achieve the objectives of the revision of the
legislation on veterinary medicines. In addition, informal guidelines do not
provide legal certainty and are considered inappropriate to ensure the free
movement of veterinary medicines within the internal market. The industry and
regulators did not support this option.

Annex 11 Comparison tables of policy
options

Table 13 Comparison
of costs and benefits of policy options:

Specific objective A Expand market beyond the top four species

Options || Stakeholders

|| Industry || End-users || National competent authorities, European Commission, EMA

Option 1 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 2 Improve the Cascade || Benefits: none Costs: no changes || Benefits: more flexibility and so improved availability of medicines Costs: no changes || Benefits: better management of therapeutic gaps Costs: no changes

Option 3 Expand database to cover all veterinary medicines || Benefits: better information exchange within the authorisation system. Costs: none || Benefits: more transparency and information Costs: no changes || Benefits: better information exchange within the authorisation system. Costs: administrative costs to the competent authorities

Option 4 Reduced data requirement  for MAs for medicines for limited markets || Benefits: reduction of administrative burdens Costs: no changes || Benefits: increase on the availability of medicines for limited markets; more harmonised levels of animal and public health and environmental protection levels. Costs: no changes || Benefits: closing of some therapeutic gaps Benefits: closing of some therapeutic gaps Costs: no changes

Option 5 Reduced data requirements for medicines for bees || Benefits: reduction of administrative burdens and indirectly will provide incentive for   innovation Costs: no changes || Benefits: improved availability of new medicines for bees Costs: no changes || Benefits: Benefits: closing of some therapeutic gaps Costs: No changes

Specific objective B Simplify procedures for obtaining a marketing authorisation in multiple national markets

Option 6 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 7 Automatic recognition of a national marketing authorisation || Benefits: reduction of administrative burdens (estimated as savings of 67.9 million euros per year; increase in innovation Costs: possibly increase in referrals || Benefits: better functioning of the internal market; possible increase in the availability of veterinary medicines (innovators and generics); more harmonised animal and public health, and environmental protection levels. Costs: no changes || Benefits: increase in income from fees for assessment  for some national competent authorities; less resource intensive to certain national competent authorities Costs: costs related to work on referrals

Option 8 Single marketing authorisation procedure for all products || Benefits: estimated reduction in administrative burdens of 67.9 million euros each year; increase in innovation Costs: loss of flexibility for SMEs || Benefits: better functioning of the internal market; may increase the availability of veterinary medicines (both innovators and generics) for companion animals and farmed animals and in some smaller Member States; more harmonised animal and public health and environmental protection levels. Costs: concerns that the lack of peer review and Member States' input might be detrimental to animal and public health, and the environment || Benefits: less resource intensive to certain competent authorities Costs: possibly more referrals

Option 9 Wider scope for the centralised procedure || Benefits: estimated reduction in administrative burdens of 5.6 million euros/year; increase in innovation; maintains flexibility and opportunity of choice, important for SMEs Costs: none || Benefits: possibly increase in the availability of medicines for companion and farmed animals: more harmonised animal and public health and environmental protection levels; improved internal market. Costs: no changes || Benefits: more harmonised assessment of applications; less resource intensive to some national competent authorities, improved internal market Costs: increased pressure on the EMA's resources (fast tracking or exclusion of some types of veterinary medicines applications could alleviate this); administrative costs to the Commission (regarding issuing marketing authorisations)

Option 10 Simpler  packaging and labelling || Benefits: reduction of administrative costs; increase in innovation Costs: possible costs associated with product recalls from the market || Benefits: increase in the availability of medicines in particular in smaller Member States Costs: possibly less intelligible product labels and packaging || Benefits: some efficiency measures to national competent authorities from checking product literature Costs: potential need for increase in in-market inspections, therefore  additional costs to the national competent authorities

Option 11 Allow already approved  veterinary medicines to freely circulate across the Union || Benefits: reduction of administrative burdens estimated as around 14.2 million euros per year; indirectly increase in innovation Costs: increase in the administrative burdens in the short term to harmonise the SPCs for some products following assessment by the competent authorities || Benefits: improved functioning of the internal market; increase in availability and price competitiveness (therefore reduction in price of veterinary medicines; increase of product availability in smaller countries). Costs: none || Benefits: efficiency measures to national competent authorities in medium and long term Costs: some administrative costs to the Commission, EMA and national competent authorities in the short term regarding the work needed  to harmonise the SPCs of some products

Specific objective C Review data requirements for marketing authorisation procedures

Option 12 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 13 Generic applications may refer to environmental data || Benefits: decrease to generics manufacturers to the costs of obtaining a marketing authorisation  Costs: none || Benefits: possibly increase on the availability of generics placed on the market and so possibly reduction on price of medicines; potential public and animal health benefits Costs: none || Benefits: less resource intensive to national competent authorities as no new assessment required for data already assessed as part of innovators ' data package and new data assessed within a monograph system Costs:  possibly more national competent authorities' resources for pharmacovigilance monitoring

Option 14 Harmonisation of clinical trials procedures across the Union || Benefits: Reduction of  administrative burdens and indirectly stimulate innovation; particularly beneficial to SMEs Costs: None || Benefits: improve the functioning of the internal market; increase the availability of medicines; growth of the SME sector Costs: none || Benefits: some efficiency measures re assessment of clinical trials data Costs: increase in resources  to some national competent authorities

Specific objective D Simplify post authorisation requirements

Option 15 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 16 Risk-based  pharmacovigilance || Benefits: reduction of administrative burdens of around 47.2 million euros per year; indirectly – increase in innovation Costs: none || Benefits: redirection of resources by industry might lead to increased  availability of medicines; improve internal market Costs: no changes || Benefits: efficiency savings for national competent authorities from assessing period safety updates; Costs: no changes

Option 17 Review  procedures to change a marketing authorisation (variations) || Benefits: reduce administrative burdens to the pharmaceutical industry by 10.9 million euros per year; indirectly – increase in innovation Costs: potential costs associates with referrals if safety risks are raised || Benefits: potentially increase on the availability of veterinary medicines to companion and farmed animals Costs: no changes || Benefits: efficiency savings due more targeted evaluation of variations; reduction of administrative costs to the Commission Costs: potential costs associates with increase in number of referrals if safety risks identified

Option 18 Delete the obligation to market a product within  3 years of approval || Benefits: reduction of administrative burdens to the industry, especially SMEs Costs: no changes || Benefits: possibly more available products Costs: no changes || Benefits: some reduction in costs of dealing with administration of sunset clause Costs: no changes

Option 19 Delete the requirements for renewals || Benefits: reduction of administrative burdens of at least 67.5 million euros per year: indirectly – increase in innovation Costs: no changes || Benefits: possible increase on the availability of veterinary medicines to companion and farmed animals if resources redirected to new product development Costs: no changes || Benefits: efficiency savings due more targeted evaluation of renewals Costs: no changes

Option 20 Exempt homeopathic medicines from pharmacovigilance requirements || Benefits: reduction of administrative burdens Costs: no changes || Benefits: possibly lower price of homeopathics medicines Costs: potentially negative animal health effects || Benefits: none Costs: possibly potentially negative animal health effects

Specific objective E Review incentives for breakthrough medicines

Option 21 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 22 Extend data protection period for new veterinary medicines || Benefits: better return to investments for R&D companies; increase in innovation; novel veterinary medicines on the market ensure sustainability of generic companies in the long term Costs: loss of income to generics industry in the short/medium  term due to delay for application for generics || Benefits: incentives to innovation may improve the availability of new veterinary medicines; development of antimicrobials specifically developed for use in veterinary medicine could benefit public and animal health Costs: in the short/medium term, less generic medicines placed on the market and so high price of novel veterinary medicines || Benefits: more innovative products to fill therapeutic gaps Costs: no changes

Specific objective F  Improve clarity: on  rules on internet retailing, on the authorisation of new treatments, on inspections, on authorisation of medicines for emerging diseases

Option 23 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 24 Authorisation to sell veterinary medicines through the internet in all MS || Benefits: clearer, harmonised and predictable legal environment; benefits SMEs/micro-enterprises Costs: some increase of the administrative burdens || Benefits: greater accessibility of products throughout the EU; improved internal market; increase the competition and reduce the prices of veterinary medicines; public and animal health benefits Costs: no changes || Benefits: clear legal environment implement ECJ-ruling and so less risks of legal disputes Costs: some increase in costs to the national competent authorities regarding administration of the authorisation procedure and enforcement of the legislation

Option 25 Establish a framework to authorise new treatments || Benefits: clearer, harmonised and  predictable legal environment; benefits to  internal market Costs: some increase administrative burdens regarding data production and fees to obtain an authorisation || Benefits: assurance regarding the quality and safety of advanced therapy products; improved animal health, improved internal market Costs: no changes || Benefits: harmonisation of decisions; improved animal health, Costs: increase in costs related to the introduction of procedures for assessment and authorisation of advanced therapy products;

Option 26 Establish a basis to harmonise the controls on the veterinary medicine distribution chain || Benefits: clearer, predictable  and harmonised regulatory  environment Costs: no changes || Benefits: more harmonised public and animal health protection, protection to the environment across the Union || Benefits: harmonised systems across the Union leading to a level playing field; less costs related to infractions Costs: some Member states may need to invest in their inspections programmes

Option 4 Reduced data requirement  for medicines for limited markets || Benefits: reduction of administrative burdens Costs: no changes || Benefits: increase on the availability of medicines for limited markets; more harmonised levels of animal and public health and environmental protection levels. Costs: no changes || Benefits: closing of some therapeutic gaps Benefits: closing of some therapeutic gaps Costs: no changes

Comparison of costs and benefits of policy
options regarding measures to strengthen the veterinary medicines legislation
regarding the authorisation and use of veterinary antimicrobials

|| Stakeholders || ||

Options || Industry || End-users || National competent authorities, European Commission, EMA

Option 27 No new EU action || No additional costs or benefits || No additional costs or benefits || No additional costs or benefits

Option 28 Introduction of legislative measures to allow  restrictions to be placed on the authorisation and use of veterinary antimicrobials || Benefits: savings to the pharmaceutical industry due to reduction in number of referrals to arbitration; more clarity and predictable regulatory environment regarding authorisation of antimicrobials Costs: loss of income regarding the sales of some types of antimicrobials || Benefits:  possible positive impact on the protection of human health regarding antimicrobial resistance; Costs: negative impact on the availability of medicines for both farmed and companion animals || Benefits: savings to the national authorities, the EMA and the Commission  due to reduction in numbers of referrals to arbitration Costs: potential more resources needed by national competent authorities  for enforcement activities to combat illegal use of antimicrobials; administrative costs to the Commission and the competent authorities in preparing guidance

Option 29 Measures regarding advertising of veterinary medicines, including  antimicrobials || Benefits: clearer legal environment Costs: no changes || Benefits: less pressure on veterinary surgeons for prescription of antimicrobials; Costs: possibly less information transmitted by advertising to non-prescribers regarding animal health issues || Benefits: clearer legal environment Costs: potential  more resources needed by national competent authorities  for enforcement of advertising restrictions

Option 30 Measures regarding retailing of veterinary antimicrobials || Benefits: no changes Costs: no changes  || Benefits: possible reduction on the sales of antimicrobials Costs: less income to veterinary surgeons from the sales of antimicrobials; reduced accessibility of veterinary medicines in remote rural areas if not non-veterinarian retail exists || Benefits: no changes Costs: administrative costs to the competent authorities regarding enforcement

Option 31  Introduction of a legal basis for the compulsory collection of data on the use of antimicrobials || Benefits: transparency on the sales and usage of antimicrobials in the veterinary sector Costs: no changes || Benefits: more science-based measures regarding the management of antimicrobial resistance leading to a positive impact on public and animal health Costs: no changes || Benefits: more robust evidence to permit implementation of risk management measures regarding antimicrobial resistance Costs: some costs to the competent authorities regarding adaptation of systems and procedures for collection and analysis of data

Table 14 Comparison of the options
regarding effectiveness, efficiency and coherence[142] with EU
objectives.

Options 1, 6, 12, 15, 21, 23, 27 are
baseline (no new EU action) - neutral

Options || Effectiveness || Efficiency || Coherence with EU objectives

Option 2 Improve the Cascade || ++ || ++ || ++

Option 3 Expand  database to cover all veterinary medicines || ++ || ++ || +++

Option 4 Reduced data requirement for medicines for limited markets || ++ || ++ || +++

Option 5 Reduced data requirements for medicines for bees || ++ || ++ || +++

Option 7 Automatic recognition of a national marketing authorisation || +++ || ++ || +++

Option 8 Single marketing authorisation procedure for all products || +++ || ++ || +++

Option 9 Wider  scope of the centralised procedure || +++ || ++ || +++

Option 10 Simpler packaging and labelling || ++ || ++ || +++

Option 11 Already nationally approved veterinary medicines allowed to freely circulate across the Union || ++ || + || +++

Option 13 Generic applications may refer to environmental data || +/neutral || + || +

Option 14 Harmonisation of clinical trials procedures across the Union || ++ || ++ || +++

Option 16 Risk-based pharmacovigilance || ++ || ++ || +++

Option 17 Review procedures to change a marketing authorisation     (variations) || ++ || ++ || +++

Option 18 Delete obligation to market a product within 3 years of approval || +++ || +++ || +++

Option 19 Delete the requirement for  renewals || ++ || ++ || +++

Option 20 Exempt homeopathic veterinary medicines from pharmacovigilance requirements || + || + || +

Option 22 Extend the data protection period for new veterinary medicines: || ++ || ++ || ++

Option 24 Authorisation to sell veterinary medicines through the internet in all MS || ++ || ++ || ++

Option 25 Establish a framework to authorise new treatments || ++ || + || +

Option 26 Establish a basis to harmonise the controls on the veterinary medicines distribution chain || neutral || + || +++

Option 28 Introduction of legislative measures to allow restrictions to be placed on the authorisation and use of veterinary antimicrobials || + || + || +++

Option 29 Measures regarding advertising of veterinary medicines, including antimicrobials || + || + || +++

Option 30 Measures regarding retailing of veterinary antimicrobials || - - - || - || ++

Option 31 Introduction of a legal basis for the compulsory collection of data on the use of antimicrobials || neutral || + || +++

Annex 12
Table providing an overview of problems, specific objectives, operational
objectives and preferred policy options
regarding the problem of lack availability of veterinary medicines

Options for no new
EU actions: 1, 6, 12, 15, 21, 23, 27

Problem || Specific objective || Operational objective || Options

Lack of availability of authorised veterinary medicines || A Expand market beyond the top four animal species || A.1. Improve the use of the Cascade A.2. Improve information on authorised medicines available in the Union A.3. Simplification of application requirements for veterinary medicines for limited markets E1. Strengthen data protection incentives || 2 Improve the Cascade 3 Expand database to cover all veterinary medicines 4 Reduced data requirements for  medicines for limited  markets 5 Reduced data requirements for medicines for bees

B. Simplify procedures for obtaining a marketing authorisation in multiple national markets || B.1. Review CP, DCP and MRP procedures B.2. Revision of situation with “legacy products” || 7 – Automatic recognition of national MA 8 – Single MA procedure for all products 9 – Wider scope for centralised procedure 10 – Simpler packaging and labelling 11 – Allow already nationally approved medicines to freely circulate across the Union

|| C. Review data requirements in marketing authorisation procedures || C.1. Revision of environmental data  requirements for generics C.2. Revision of  provisions on authorisation of clinical trials || 13 – Generic applications may refer to environmental data 14 – Harmonisation of authorisation for clinical trials procedures across EU

D. Simplify post authorisation requirements || D.1. Simplification of pharmacovigilance D.2. Simplification of variation requirements D.3. Revise Sunset clause D.4. Abolish renewals D.5. Simplify requirements for homeopathics || 16 – Risk based pharmacovigilance 17 – Review  procedures to change a marketing authorisation (variations) 18 – Delete the obligation to market a product  within 3 years of approval 19 – Delete the requirement for renewals

E. Review incentives for breakthrough medicines || E1. Strengthen data protection incentives || 22 – Extend data protection period for new veterinary medicines

Improve clarity: On rules on internet retailing of veterinary medicines on the authorisation of new treatments on  inspections on authorisation of medicines for emerging diseases || F.1. Specify rules for internet retailing of veterinary medicines F.2. Specify rules for new treatments F.3. Harmonise national control systems A.3. Simplification of application requirements for veterinary medicines for limited markets || 24 – Authorisation to sell veterinary medicines through the internet in all MS 25 – Establish a framework to authorise new treatments 26 – Establish a basis to harmonise the controls on the veterinary medicine distribution chain 4 – Reduced data requirements for medicines for limited markets

[1] COM (2008) 912, 8/1/ 2009

[2] COM (2012) 629, 23/10/12.

[3] Directive 2001/82/EC covers the procedures and the data
requirements (on quality, safety and efficacy) for the manufacture and
authorisation of veterinary medicinal products, including clinical trials. It
also covers their monitoring (pharmacovigilance), possession, distribution,
dispensing and advertising. Requirements for inspections of manufacturers,
wholesalers and retailers of veterinary medicines are also set out in this
legislation.

[4] Benchmarking the competitiveness of the global animal health
industry report, 2011.

[5] Annex 2 Glossary.

[6] Report of the Task Force on the Availability of Veterinary
Medicines, 2007.

[7] See the impact assessment for the proposal for
regulation on animal health (http://ec.europa.eu/food/animal/docs/ah-law-impact-assesment\_en.pdf)
for illustrations of the scale of the impacts of recent animal disease
outbreaks.

[8] http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:52009DC0162:EN:NOT

[9] http://www.merckmanuals.com/vet/pharmacology/anthelmintics/resistance\_to\_anthelmintics.html

[10] For example, the market price is 99 dollar cents per pound poultry
(http://www.imf.org/external/np/res/commod/pdf/Commodity\_Market\_Monthly\_February\_2013.pdf).

[11] This price-driven, fragmented market results in an average
operating profit margin of 17% for animal health. The margins for human
pharmaceuticals (prescription), medical devices and consumer healthcare markets
were estimated as respectively 29%, 22% and 20%. Mapping the Healthcare
Landscape: Bring Pharmaceuticals into Focus, Datamonitor, 2009.

[12] Directive
2004/28/EC of the European Parliament and of the Council of 31 March 2004
amending Directive 2001/82/EC on the Community code relating to veterinary
medicinal products.

[13] Commission Directive 2009/9/EC of 10
February 2009 amending Directive 2001/82/EC of the European Parliament and of
the Council on the Community code relating to medicinal products for veterinary
use. OJ L 44, 14.2.2009, p. 10.

[14] Commission Regulation (EC) 1234/2008 of 24/11/2008
concerning the examination of variations to the terms of marketing
authorisations for medical products for human use and veterinary medicinal
products OJ L334, 24/11/2008, p.7.

[15] Directive 2004/28/EC of the European
Parliament and of the Council of 31 March 2004 introduced  provisions on
generics and data protection, simplification of administrative procedures for
supplying medicines for pets and the creation of the sunset clause (to avoid
the administrative burdens associated with maintaining a marketing
authorisation on the market). http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:32004L0028:EN:HTML

[16] EU project on baseline and reduction of
administrative costs, 2008; measurement of administrative burdens generated by
EU legislation, 2009;
http://ec.europa.eu/dgs/secretariat\_general/admin\_burden/index\_en.htm.

[17]The figures were collected based on a
standard cost model (SCM) developed by EPEC, which took into consideration
staff cost per hour, staff time hours, number of actions per entity per annum,
staff cost per action, equipment cost per action, equipment costs per entity
per annum, total number of companies, operational and support costs per action
and per annum and total number of actions per annum to calculate the total cost
per annum for the industry. The data collected to develop the SCM were obtained
through business surveys and analysis of data on marketing authorisations
awarded through various marketing authorisation procedures. The results were
reviewed and validated at an industry workshop attended by representatives of
businesses that responded to the surveys. EPEC Report, Assessment of the impact
of the revision of veterinary pharmaceutical legislation, p. 26, 96-99,
140-141.

[18] Annex
7 presents a discussion on the issue of availability of medicines for bees.

[19] See Annex 8.

[20] Benchmarking the competitiveness of the global animal health
industry report, p 2011, 61.

[21]  EPEC Report, Assessment of the impact of
the revision of veterinary pharmaceutical legislation, 2011, p. 25-26.

[22] Europe and Australia report the highest
average expenditure on R&D (7.7%). Benchmarking the competitiveness of the
global animal health strategy report 2011, p. 11.

[23] The  biggest barriers to innovation
identified were the packaging costs and preparation of the data dossier for a
submission for a marketing authorisation and also the uncertainty in the sector
resulting from unclear policies in the area, re-direction of resources to
defensive R&D (that is, to maintain the product in the market) and
insufficient data protection for novel medicines. It is reported that 87%of
resources are redirected to defensive R&D in Europe, and 33-35% elsewhere
in the world. Benchmarking the competitiveness of the global animal health
strategy report 2011, p. 13,14.

[24]  Benchmarking the competitiveness of the
global animal health industry report, 2011, p. 14-15, 61.

[25] For further details see Annex 6.

[26] EPEC Report,
Assessment of the impact of the revision of veterinary pharmaceutical
legislation, 2011, p. 195-197

[27] For further details see Annex 6.

[28] In the public consultation 90% of the
respondents considered that the veterinary medicines legislation should be
supplemented with specific requirements on internet trade, mail order selling
or parallel trade. The issue of internet retailing is not recent – there has
been a court case regarding the internet retailing of human medicines: Judgment
of the European Court of Justice from 11 December 2003 in Case C-322/01
(Deutscher Apothekerverband eV and 0800 DocMorris NV, Jacques Waterval).

[29] See Annex 6 for further details on
differences in retail and wholesale prices between Member States.

[30] Blood, blood products – such as plasma and platelets - and stem
cell products are already routinely used in veterinary medicine.  Novel
therapies, such as gene therapy - where a viral vector is used to deliver a
therapeutic gene to treat a diseased tissue in the animal, as in the case of
progressive retinal atrophy for example - are already experimentally attempted
in veterinary medicine. Viral vectors for targeting the canine retina: a
review. Petersen-Jones, SM. Veterinary Ophthalmology, 2012, 15: 29-34.

[31] Regulators indicated that the harmonisation in this area would
remove a barrier to the free movement of goods.  EPEC Report, Assessment of the
impact of the revision of veterinary pharmaceutical legislation, 2011, p. 230

[32] Food and Veterinary Office's audit reports: Malta(http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2887)

Sweden(http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2549);

Poland (http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2504).

[33] The enforcement of the legislative framework for veterinary
medicinal products is the responsibility of the national competent authorities,
and there is presently little in the way of harmonisation between countries, or
coordinated oversight of national in-market control systems (beyond the control
of residues of veterinary medicines). Improved coordination of control systems
is particularly important to improve trust between Member States.

[34] ECDC/EMA Joint technical report The bacterial challenge, time to
react, 2009, p 15.

[35] Scientific opinion on the public health risks of bacterial strains
producing extended-spectrum beta lactmases and/or AmpC betalactamases in food
and food producing animals. EFSA Journal, 2011, 9(8):2322.

[36] European Commission Communication of 15 November 2011 to the
European Parliament and the Council - Action plan against the rising threats
from antimicrobial resistance http://ec.europa.eu/dgs/health\_consumer/docs/communication\_amr\_2011\_748\_en.pdf

[37] Joint opinion
on antimicrobial resistance focused on zoonotic infections (ECDC, EFSA, EMA,
SCENIHR), p. 34.

[38] European Commission Communication of 15 November 2011 to the
European Parliament and the Council - Action plan against the rising threats
from antimicrobial resistance http://ec.europa.eu/dgs/health\_consumer/docs/communication\_amr\_2011\_748\_en.pdf

[39] In a joint survey of HMA-V and FVE in
January 2012 veterinarians responded that they prescribe antimicrobials according to the to the
Summary of Product Characteristics ‘very regularly’ (10%), ‘regularly’ (34%),
‘occasionally’ (43%) and ‘seldom’ (13%).

[40] Twelve referrals were submitted to the CVMP
in 2011. EMA Annual report  2011, p. 51. An example of a referral due to
divergent decisions of Member States re the authorisation of an antimicrobial
may be seen here:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/veterinary/referrals/Baytril\_10/vet\_referral\_000065.jsp&mid=WC0b01ac05805c5170

[41] There is evidence in the US and Australia that direct-to-consumer
advertising of human prescription drugs leads to overprescribing and the
prescribing of new medicines over older, effective ones. No similar data exist
in the EU for veterinary medicines, however, it can be assumed that the same
mechanisms take place in the interaction between veterinarians and farmers and
in the relationship between patients and doctor.

[42] COM (2007) 23 final

[43] COM (2005) 535 final

[44] COM (2010) 608 final

[45]Animal and Plant Health Package: 
http://ec.europa.eu/dgs/health\_consumer/pressroom/animal-plant-health\_en.htm.

[46] See Annex 2 for an explanation on the use
of the Cascade.

[47] For example, there is no specific legislation for novel treatments
in Sweden, and the use of stem cells and blood within the veterinary field is
considered as clinical practice. The Italian authorities are preparing
guidelines on these therapies, whilst the UK authorities regulate blood banks
for dogs and equine stem cell centres. These different approaches mean that
animal care varies across the EU, interfering with trade between Member States
and potentially with animal health across the Union.

[48] For example, internet retailing is not allowed or not regulated in
some Member States (eg Austria and Belgium) but it is regulated or allowed in others
(UK, Ireland, Germany).

[49] The enforcement of the legislation on  veterinary medicines is the
responsibility of the national competent authorities. Currently the European
Commission has the competence to carry out inspections to audit control systems
in Member States for residues of veterinary medicines, like other activities
affecting food safety. Some Member States have not fully implemented or
correctly transposed the requirements of the veterinary medicines legislation
(eg: Malta, Sweden, Poland). Food and Veterinary Office's audit reports:

Malta ( http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2887);

Sweden (http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2549);

Poland (http://ec.europa.eu/food/fvo/rep\_details\_en.cfm?rep\_id=2504).

[50] Effectiveness: the extent to which options achieve the objectives
of the proposal; Efficiency: the extent to which objectives can be achieved for
a given level of resources/at least cost; Coherence: the extent to which
options are coherent with the overarching objectives of EU policy, and the
extent to which they are likely to limit trade-offs across the economic,
social, and environmental domain. Impact assessment guidelines.

[51] The calculations on the administrative burdens took into account
the cost of the centralised procedure as a baseline, and the replacing of the
decentralised and mutual recognition procedures by what is in effect the
national procedure (the application only needs to be submitted to one national
authority). The estimate of the administrative burdens required a
"shifting" of all applications currently going through the
decentralised and the mutual recognition procedures to the national procedure
(in one year). EPEC Assessment of the impact of the revision of veterinary
pharmaceutical industry legislation report, 2011, p. 170-173.

[52] The administrative burdens are estimated to
be the same those in the option 7 (concerning costs related to the preparation
of one dossier to be assessed only once), the only difference between the two
options is that in option 7 a Member State is responsible for the assessment of
the dossier and in option 8 the assessment is carried out by an EU body. EPEC
Report on the assessment of the impact of the revision of pharmaceutical
legislation, 2011, p. 170-174.

[53] More than 75% of the respondents consider it necessary that the
number of authorisation procedures should be simplified by reducing it to only
one. See Annex 9 for public consultation results.

[54] The impact of this option on the
administrative burdens was calculated taking on board the number of
applications for new marketing authorisations, variations to existing
authorisations and renewals that would switch from the mutual recognition,
decentralised and national procedures to the centralised procedure. The
industry was consulted and suggested that the best proxy indicator of demand
for this switch would be the number of applications submitted through the
mutual recognition and the decentralised procedures that involved at least ten
countries. EPEC Report on the assessment of the impact of the revision of
pharmaceutical legislation, 2011, p. 167-170.

[55] The impact on administrative burdens was roughly estimated by
replacing the annual cost of an application for a new marketing authorisation
submitted through mutual recognition with the cost of an administrative
assessment (based on the cost of a simple variation). EPEC Report on the
assessment of the impact of the revision of pharmaceutical legislation, 2011,
p. 189-191.

[56] See Notice to applicants volume 6C Guidance on the assessment of
environmental risks of veterinary medicinal products June 2009, p. 5. According
to IFAH-Europe all originator products have gone through an environmental risk
assessment (ERA) in at least one Member State either at a renewal or at first
registration. ERAs have requested for renewals of existing products in several
Member States. The level of assessment may have been different over time as
guidelines and standards have changed.

[57] The calculation of the savings to the industry was based on the
fact that this option would involve the abolition of the requirement for a
marketing authorisation holder to submit periodic safety updates. EPEC Report
on the assessment of the impact of the revision of pharmaceutical legislation,
2011, p. 195-197.

[58] The calculation on the savings to the industry were based on
abolishing the requirements to submit Type IA variations, which no longer would
be assessed by national authorities - the changes to the marketing
authorisation would be implemented by the pharmaceutical company and simply
notified to the national authorities.  However, a more accurate estimate is not
possible as this would depend on the types of variations that could be included
within the simplification exercise.  EPEC Report on the assessment of the
impact of the revision of pharmaceutical legislation, 2011, p. 208-209.

[59] Accurate figures for the savings resulting from the adoption of
this policy option could not be calculated, as the proportion of the products
that might require renewal is unknown. However, representatives of the industry
considered that around 95% of the currently authorised products can be
considered low risk and so it is possible that only 5 % would need to be
renewed.  EPEC Report on the assessment of the impact of the revision of
pharmaceutical legislation, 2011, p. 199-200.

[60] The industry (IFAH-Europe) reported that a break-even point for the
initial major product is ten years and the break-even for a major product with
an additional minor product is about 15 years.

[61] Data of IFAH-Europe based on estimations of ten companies involving
in total of 172 products.

[62] MedicAnimal report on online sales of veterinary medicines, 2011.

[63] See Annex 6 for further details.

[64] As an example of the current costs to the industry of placing on
the market novel treatments, the fees for operation of blood banks in the UK
are £2,830 for a first inspection and £ 2,970 for a second inspection. The fees for the operation of a stem cell centre are £3,270. The fees for a variation are £ 305. There are three
stem cell centres operating in the UK and one
blood bank. Data from 2012.

[65] The latest ESVAC report compiled sales of
antimicrobials in 19 countries. Sales of veterinary antimicrobial agents in nineteen
EU/EEA countries in 2010 (EMA/88728/2012).

http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2012/10/WC500133532.pdf.

[66] The sales of
medicines generates 25% of the profits of veterinary surgeons in Denmark and
generates between 30 and 75% of the turnover of veterinary practices in the
Netherlands. Berenchot report,
What would be the effects of decoupling the prescription and sale of veterinary
medicines by veterinarians? 2010. http://www.fve.org/uploads/publications/docs/berenschot%20report\_02\_2010.pdf.

[67] Encadrement des pratiques commerciales pouvant influencer la
prescription des antibiotiques vétérinaires. Rapport de Inspection générales
des finances, Inspection générale des affaires sociales et Conseil général de
l’agriculture, de l’alimentation et des espaces ruraux, Mai 2013.

[68] Sales of veterinary antimicrobial agents in
19 EU/EEA countries in 2010 (EMA/88728/2012). http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2012/10/WC500133532.pdf.

[69] UK figures = 0.7 million pounds (February
2013). Source: Questionnaire from the European Commission to the CMDv on policy
proposals for the revision of the veterinary medicines legislation.

[70] Effectiveness is the extent to which the options achieve the
proposed objectives; efficacy is the extent to which the objectives can be
achieved at the lowest cost; coherence is the extent the policy options are
coherent with the objectives of the EU policies and the extent to which they
are likely to limit trade-offs across the economic, social and environmental
domains. Impact assessment guidelines.

[71]The OIE developed a list of critically important antimicrobials for
veterinary medicine: http://web.oie.int/downld/Antimicrobials/OIE\_list\_antimicrobials.pdf.

[72] See Annex 6 for detailed information on the problem of
antimicrobial resistance.

[73] Action point 7 in the Commission's action plan against the rising
threat from antimicrobial resistance refers to the promotion of efforts to
analyse the need for new antibiotics into veterinary medicine. To this effect,
it recommends the evaluation of the need and possible introduction of
incentives that trigger development in veterinary medicines to increase the
likelihood that innovations reach the market within the review of the rules on
veterinary medicines foreseen in 2013.

[74] http://ec.europa.eu/health/files/pharmacos/news/emea\_final\_report\_vfrev2.pdf

[75] http://ec.europa.eu/food/animal/diseases/strategy/animal\_health\_advisory\_committee\_en.htm

[76] Vetoquinol Annual Financial report 2010

[77] Benchmarking the Competitiveness of the
Global Animal Health Industry report, 2011, p. 31.

[78] Source: EPEC Report, Assessment of the impact of the revision of
veterinary pharmaceutical legislation, 2011.

[79] The scope of line extensions covers changes to active ingredients,
pharmaceutical form or route of administration, and also addition of a new
food-producing species to the market authorisation.

[80] Brand’ is used to identify an individual
product name.  For example, in the UK there are 8 distinct authorisations for
the product ‘Advantage’, differentiated by the species (cats or dogs), the
animal size (small or large), and the dosage.  For the purposes of analysis of
product brands, these 8 authorisations are reduced to a single record for the
brand ‘Advantage’. In addition, the impact of the differences in national
recording protocols on product authorisation data is significant.  For example,
in Finland the product ‘Advocate’ is recorded as 2 authorisations
(differentiated by species), whereas in Belgium the same product is recorded as
30 authorisations (differentiated by species, animal size, dosage etc).

[81] The authorised
product databases provided by competent authorities did not indicate which
products are actually marketed.  Instead, the availability of authorised products
was investigated by collecting data from a sample of marketing authorisation holders
for 5 of the 6 case study countries[81].

[82] It should be noted that the data collected is not
complete, due to the lack of a centralised EU wide source of information on
product authorisations and errors and omission in the Member States' databases.
EPEC Report Assessment of the impact of the revision of veterinary
pharmaceutical legislation, 2011, p. 90.

[83] The data refer more correctly to the number
of authorised "brands" (the individual product name) rather than the
number of marketing authorisations as the methodology to record products in
databases may vary in the Member States. For example, as indicated previously in
Finland the product Advocate is recorded as 2 authorisations (differentiated by
species) but the same product is recorded as 30 authorisations in Belgium
(differentiated by species, animal size, dosage etc).  For the purpose of the
study the various authorisations were recorded as one brand. EPEC Report
Assessment of the impact of the revision of veterinary pharmaceutical
legislation, 2011, p. 20, 23.

[84] There is presently no EU definition of a
minor species, though a paper produced by the EMA has defined ‘major species’
as cattle, sheep (for meat), pigs, chickens, salmon, dogs and cats. EMA (2009)
Guidane for companies requesting classification as MUMS/limited markets.

[85] Consisting of the two types of companion
animal (dogs and cats) together with the principal food-producing species, as
well as bees and fish species.  All other animals were grouped together into an
‘other category’ (e.g. rabbits, ducks, geese and other companion animals).

[86] WHO Collaborating Centre for Drug Statistics Methodology (2010)
Guidelines for ATCvet classification 2010

[87] EMA Annual report 2011, p. 47.

[88] http://www.etpgah.eu/action-plan.html

[89] Report of the Task Force on Availability of Veterinary Medicines,
2007

[90]  The pharmaceutical industry reported that
in the EU major new veterinary medicines take around 8 to 12 years to be
developed and authorised, at a cost of around 80-300 million dollars. These
figures take into account project failures, capital costs and the time needed
to complete the development cycle. Figures are given in US dollars, the
functional currency of the global animal health industry. It is estimated that
around 10-15 years of sales are required for a company to recover this
investment. IFAH-Europa Impact Assessment Data Package report, 2010, p. 21; .
Benchmarking the competitiveness of the global animal health strategy report
2011, p. 12.

[91] EPEC Report assessment of the impact of the
revision of the veterinary medicines legislation, 2011, p. 140.

[92] In most cases, staff costs comprise the
majority of the administrative burden incurred by businesses.  Equipment costs
are typically low, except in the case of packaging and labelling costs. 
Outsourced costs are relatively large where external expertise is used
significantly (e.g. as part of the compilation of a dossier for an application
for a new MA). EPEC Report assessment of the impact of the revision of the
veterinary medicines legislation, 2011, p 27.

[93] Period Safety Update Reports (PSURs)

[94] IFAH-Europe Impact Assessment Data Package
Report, 2010, p. 77-78.

[95] EPEC report, Assessment of the impact of
the revision of veterinary pharmaceutical legislation, 2011, p. 20.

[96] IFAH-Europe Impact Assessment Data Package
Report, 2010, p. 45.

[97] Type IA variations are minor changes to the marketing
authorisation that have only a minimal impact  or no impact on the quality,
safety or efficacy of the product).

[98] Approaches towards variations submitted
through the CP, MRP and DCP were harmonised in 2008 with Commission Regulation
(EC) No.1234/2008, and in 2009 variations submitted through the National
Procedure were included within this framework through Directive 2009/53/EC, the
deadline for the transposition of which was 20 January 2011.

[99] Benchmarking the Competitiveness of the Global Animal Health Industry
Report, 2012, p. 61.

[100] Companies in Canada spend overall 26 % of
their local budget on defensive research and only around 14-16 % in Australia,
Japan and USA.  But the reasons for maintaining or increasing expenditure in
defensive research are the same worldwide: deterioration in the regulatory
environment (for 79% of companies in Europe), acquisition of companies with
products on the market and regulator product reviews. Benchmarking the
Competitiveness of the Global Animal Health Industry Report, 2012, p. 14.

[101] Report Outcome of SME office survey on the
implementation of the SME Regulation Commission Regulation (EC) 2049/2005.

[102] IFAH-Europe Impact Assessment Data Package
Report, 2010, p 40-43.

[103] IFAH-Europe Impact Assessment Data Package
Report, 2010, p. 40-43.

[104] Please refer to Glossary for a brief
description of the current legal requirements for placing a homeopathic product
on the market.

[105] For example, there are 69 businesses selling veterinary medicines in the
UK (turnover between £130.000 and £230 million). Germany has over 100 human
online pharmacies that also sell veterinary medicines. White paper Medicanimal,
State of Play of the online sales of veterinary medicines, December 2011.

[106] White paper Medicanimal, State of Play of
the online sales of veterinary medicines, December 2011.

[107] White paper Medicanimal, State of Play of
the online sales of veterinary medicines, December 2011.

[108]
http://www.who.int/patientsafety/implementation/amr/en/index.html

[109] www.fvm.dk/.../DWSDownload.aspx?...resistance%2FAMR...Margar.

[110] A subset of drug-resistant bacteria is
responsible for about 25,000 human deaths annually in 29 countries in the EU
and 12,000 deaths in the US. In the EU, Iceland and Norway, the costs of these
infections reach at least 1.5 billion euros every year. Approximately 4 million
patients are estimated to acquire a health-care associated infection in the EU
every year. In the veterinary sector, common bacteria causing diarrhoea or
respiratory infections in several species have become more resistant to
commonly used veterinary antimicrobials, causing increased suffering and
mortality in animals, and consequently production losses and extra costs as
well as occupational hazards to animal keepers. Communication from the
Commission to the European Parliament and Council – Action plan against the
rising threats from antimicrobials resistance. 2011, p. 2. Transatlantic
taskforce on antimicrobial resistance, 2011, p. 3.

[111] ECDC/EMA Joint technical report The
bacterial challenge, time to react, 2009. p 15.

[112] Scientific opinion on the public health
risks of bacterial strains producing extended-spectrum beta lactmases and/or
AmpC betalactamases in food and food producing animals. EFSA Journal, 2011, 9(8):2322.

[113] http://www.fao.org/ag/againfo/programmes/en/empres/news\_270412.html.

[114] The problem of zoonotic
bacteria transmitting antimicrobial resistance is complex, as besides the use
of antimicrobials there are also other factors linked to bacterial populations,
such as the characteristics of the bacteria under consideration, including
their virulence and their capacity to spread. Joint opinion on antimicrobial
resistance focused on zoonotic infections (ECDC, EFSA, EMA, SCENIHR), p. 34.

[115] ESVAC 2012 report,
http://www.ema.europa.eu/docs/en\_GB/document\_library/Report/2012/10/WC500133532.pdf

[116] The average cost of veterinary medicines is 1.8-4.4% of the total
operating costs, Berenschot Report 2010, What would be the effects of
decoupling the prescription and sale of veterinary medicines by veterinarians?;
http://www.cbg-meb.nl/CBG/en/veterinary-medicines/actueel/20100309-Berenschot-report-on-antibiotics-use/default.htm

[117] U.S. Jensen et al.,
2010. Journal of Antimicrobial Chemotherapy, April 2010.

[118]Influence of patients’ requests for
direct-to-consumer advertised antidepressants a randomized controlled trial. Kravitz L.R. et al, JAMA. 2005;293(16):1995-2002;
Influence of direct to consumer
pharmaceutical advertising and patients' requests on prescribing decisions: two
site cross sectional survey. Mintzes, B. et al. BMJ 2002; 324: 278

[119] In a joint survey of HMA-V and FVE in
January 2012  veterinarians responded  that they prescribe antimicrobials according to the to the Summary
of Product Characteristics ‘very regularly’ (10%), ‘regularly’ (34%),
‘occasionally’ (43%) and ‘seldom’ (13%).

[120] The production of medicated feed is
regulated by Council Directive 90/167/EEC of 26 March 1990 laying down the
conditions governing the preparation, placing on the market and use of
medicated feedingstuffs in the Community. The revision of the medicated feed
legislation is included in the Commission Working Programme 2013.

[121] Antibiotics used at low doses in animal feeds are considered to improve
animals' growth performance.

[122] http Regulation (EC) No 1831/2003 of the 
European Parliament and of the Council on 22 September 2003 on additives for
use in animal nutrition. ://irmm.jrc.ec.europa.eu/SiteCollectionDocuments/EC-1831-2003.pdf

[123] http://www.gao.gov/Products/GAO-11-801

[124] In the USA a US federal court ruled that the
FDA should start proceedings to withdraw the approval of certain uses of
antibiotics used in food production. The FDA is introducing a voluntary
initiative to change how medically important antimicrobials are labeled and
used in food-producing animals, and is stopping the use of certain antibiotics
to enhance growth or improve feed conversion efficiency in animals. http://www.fda.gov/downloads/animalveterinary/guidancecomplianceenforcement/guidanceforindustry/ucm216936.pdf.

[125] The current legislation does not provide a
legal tool to restrict the use of the cascade, the current legislation is based
on an assessment of each application of a veterinary medicinal product and does
not specify that for the assessment of risk of antimicrobial resistance the similarities
with other products have to be considered (a new product may lead to a decrease
or increase of  the overall risk of use of a class of veterinary
antimicrobials) and the risks from contact with treated animals should be
included.

[126] Since 2000, 66
referrals took place of which 42 concerned antimicrobials.

[127]
http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/Home\_Page.jsp&mid=

[128]
http://www.ecdc.europa.eu/en/Pages/home.aspx

[129] http://www.efsa.europa.eu/

[130] Joint opinion on antimicrobial resistance
focused on zoonotic infections, EFSA Journal 2009, 7 (11):1372, p. 7.

[131] Joint opinion on antimicrobial resistance
focused on zoonotic infections, EFSA Journal 2009, 7 (11):1372, p. 7.

[132]
http://www.consilium.europa.eu/uedocs/cms\_data/docs/pressdata/en/lsa/131126.pdf.

[133]http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+REPORT+A7-2012-0373+0+DOC+XML+V0//EN.

[134] Joint opinion on antimicrobial resistance
focused on zoonotic infections (The joint opinion on antimicrobial resistance
(AMR) focused on zoonotic infections (ECDC/EFSA/EMA/SCENIHR (2009)) http://www.ema.europa.eu/docs/en\_GB/document\_library/Other/2009/11/WC500015452.pdf).

[135] List of
products for bees authorised in the Member States as per October 2011: 
http://www.hma.eu/uploads/media/136\_Questionnaire\_-\_Bee\_products\_in\_EU\_24.10.11\_EMA-CMDv-36668-2009.pdf.

[136] Discontools is a joint initiative of the
industry and stakeholders such as the research community, regulators and users,
and encouraged by the European Commission , aiming to provide a mechanism for
focusing and prioritising research to deliver new and improved vaccines,
pharmaceuticals and diagnostic tests. http://www.discontools.eu/Diseases/Detail/87.

[137] COM (2010) 714, final;

[138]European Parliament resolution of 15
November 2011 on honeybee health and the  challenges of the beekeeping sector

[139] Council conclusions on the Communication
from the Commission to the European Parliament

and the Council on Honeybee
Health http://www.consilium.europa.eu/uedocs/cms\_data/docs/pressdata/en/agricult/122023.pdf

[140]Based on the industry estimation, it was
calculated that only 5% of the current veterinary medicines would require a
full scientific assessment per year. The administrative burdens associated with
the registration exercise was assumed to cost the equivalent of applying for a
type 1A variation (simple administrative procedure), which would also be
applicable to subsequent product maintenance requirements. EPEC Report on the
assessment of the impact of the revision of pharmaceutical legislation, 2011,
p. 178-182.

[141] Minimising regulatory burdens for SMEs –
adapting EU regulation to the needs of micro-enterprises.

[142] Effectiveness is the extent to which the options achieve the
proposed objectives; efficacy is the extent to which the objectives can be
achieved at the lowest cost; coherence is the extent the policy options are
coherent with the objectives of the EU policies and the extent to which they
are likely to limit trade-offs across the economic, social  and environmental
domain. Impact assessment guidelines

[Top](#document1)