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COM (83) 367 
 
 
 
Vol. 1983/0 143 
  
 
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In accordance with Council Regulation (EEC, Euratom) No 354/83 of 1 February 1983 
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In Übereinstimmung mit der Verordnung (EWG, Euratom) Nr. 354/83 des Rates vom  1. 
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COMMISSION  OF THE EUROPEAN  COMMUNITIES 
COM(83)  367  final 
Brussels,  16 June 1983 
REPORT  FROM THE  COMMISSION  TO THE COUNCIL 
ON THE  LIST  OF ACTIVE INGREDIENTS  WHICH  MAY BE USED FOR PREPARING 
PRE-MIXES FOR MEDICATED FEEDINGSTUFFS 
COM(83)  367  final 

- 2 -
COMMISSION  REPORT  TO THE  COUNCIL 
ON THE LIST OF  ACTIVE  INGREDIENTS  WHICH MAY BE  USED  FOR  PREPARING 
PRE-MIXES  FOR  MEDICATED  FEEDINGSTUFFS 
1. In accordance  with  paragraph 3 of Article 2 of Council Directive  81/851/EEC 
the purpose of this  report  is to enable the Council to deliberate, by 
October  1983, on the list of pharmacological molecules (or active 
ingredients) which may be used for preparing pre-mixes, and on 
the procedure for drawing up such a list. 
In view of the complexity of this  matter,  which has in the past been the 
cause  of numerous misunderstandings, the Commission has conducted a 
thorough study of the subject, a copy of which is attached to this report. 
The study includes a description of the situation, a discussion of 
possible  solutions and the procedures connected  with  a Community list of 
active ingredients. The Annex contains a list of 19 "Community" active 
ingredients, together  with  a second list of other active ingredients in 
current use. 
2. There are several Directives and proposals aimed at protecting the 
European  consumer, directly or indirectly,  from  the risks associated  with 
residues  in meat, milk and eggs. Pre-mixes for medicated feedingstuffs, 
used  in industrial livestock farming for the  treatment  of infectious or 
parasitic  diseases,  are already regulated by Directives  81/851/EEC  and 
81/852/EEC  relating to veterinary medicinal products. Certain pharmaco­
logically  active ingredients are regulated by the amended Directive 
70/524/EEC concerning  additives in feedingstuffs, by Directive  81/602/EEC" 
concerning  substances having a hormonal or a thyrostatic action and by 
Directive  83/90/EEC as far as examination for residues in animals and 
meat is concerned. This group of enactments is supplemented by the proposal 
for a directive' on the manufacture,  putting  into  circulation and supply 
of medicated feedingstuffs, by the proposal for a directive relating to 
residues  of antibiotics in fresh meat, by the proposal for a directive 
on the fixing of maximum levels for pesticide residues in and on foodstuffs 
of animal origin and by two proposals for regulations concerning, on the 
one hand, the  possession,  distribution and administration to animals of 
certain substances  with  a hormonal action and, on the other, the control 
of the residues of such substances. 
1 
2 
3 
4 OJ No L 317, 6.11.1981 
OJ No L 270, 14.12.1970 
OJ No L 222,  7.8.1981 
OJ No L 59, 5.3 .1983 5 
6 
7 
8 OJ No C 41, 16.2.1982 
OJ No C 251 , 1 .10.1981 
OJ No C 56, 6.3 .1980 
C0M(80)920  and C0M(80)922,  6.1.1981 

- 3 -
3. When the directives relating to veterinary medicinal products were adopted, 
the Council undertook, at  Italy's  request, to deliberate on a list of 
active ingredients which may be used for preparing pre-mixes. Although 
a majority of the experts consulted by the Commission considered the existing 
directives adequate, the  Italian  authorities thought  that  pre-mixes should 
be governed by an even stricter set of rules. 
For reasons of cost, antibiotics and antiparasitics are administered 
collectively in industrial livestock farming, in the form of medicated 
feedingstuf fs. These medicated f eedingstuf fs are produced from a concentrate 
of medicinal products: the pre-mix. 
The Italian  authorities take the view  that  this form of collective therapy 
cannot be monitored correctly unless a strict  limit  is placed on the number 
of active ingredients authorized in the Community. This would also have the:: 
advantage of facilitating  intra-Community trade in meat, milk and eggs. 
The majority of experts consider  that  if Directives  81/851/EEC  and 
81/852/EEC  are correctly implemented by the Member States, and the 
Committee for Veterinary Medicinal Products plays its coordinating role 
effectively, there will be no need for a restrictive list.  Such  a list 
would,  in any  case,  discourage veterinary pharmaceutical research. 
This  type of positive list has existed in the Community for  12  years in 
a related field,  that  of additives to animal feedingstuff s. A similar 
system  is applied to pre-mixes for medicated feedingstuf fs in  Italy  and 
in the United States. 
As far as the Community is concerned, the foremost advantage of a restrictive 
list of active ingredients for use in pre-mixes would be tKat it would help 
to prevent disruptions in  intra-Community trade in animal products of the 
type  that  arose in relation to hormones between  1979  and  1981.  Monitoring 
of residues on livestock farms or in slaughterhouses would also become 
simpler . 

4 
Lastly,  it would allow a rationalization  both  of the advance preparation 
of medicated feedingstuffs (which applies to only certain standard 
prescriptions) and of their storage. 
There  are however disadvantages. The new active ingredients could only be 
used  in pre-mixes after a rather long procedure, involving the amendment 
of the Community list of active ingredients and the issuing of a national 
marketing authorization for the pre-mix in question.  Such  restrictions 
could  affect the one-third share of the veterinary pharmaceutical market 
accounted  for by pre-mixes, and, consequently, research in this  area. 
It should, however, be pointed out  that  the remaining two-thirds, 
proprietary medicinal products and veterinary medicinal products, 
administered on an animal-by-animal  basis,  are not affected by this 
rest ri cti on . 
5. The procedures for drawing up and amending a Community list of 
active ingredients for use in pre-mixes, are described in detail in the 
study accompanying this report. Amendments to the list would be adopted 
according  to the procedure employed by the Standing Veterinary Committee, 
since  the  latter  is already concerned  with  Community authorizations for 
the standard prescriptions referred to in the proposal for a directive 
concerning  medicated feedingstuffs. This should make it possible to 
establish  a genuine Community policy regarding medicated feedingstuffs . 
Marketing of the pre-mixes containing active ingredients included in the 
Community list is authorized by each of the Member  States,  in accordance 
with  Directives  81/851/EEC  and  81/852/EEC.  When a manufacturer wishes to 
obtain an authorization for a pre-mix containing an active ingredient 
which is not included in the Community list, the procedure employed by 
the Committee for Veterinary Medicinal Products should be followed,  with 
certain changes in the procedure. The application would be examined by 
the Committee  itself,  which would then deliver an opinion on the quality, 
safety and efficacy of the pre-mix in question and on the advisability 
of amending, in consequence, the Community list of active ingredients. 

- 5 -
6. The  first  version of the  initial  Community List of 19 active ingredients 
currently used in four or more Member States is given in Annex I to the 
attached study. This  initial  list could be extended by the addition of 
between 15 and 20 active ingredients selected  from  the 89 substances used 
in fewer than four Member States, which are listed in Annex II to the 
study. 
The general criteria of Directive  81/852/EEC  have been adapted to the 
particular  case  of pre-mixes. Six groups of specific criteria are 
described  and apply during the examination of the pre-mix by the 
Committee for Veterinary Medicinal Products, and in relation to any 
amendment of the list following the procedure of the Committee for 
Veterinary Medicinal Products. 
Pre-mixes  placed on the market pursuant to provisions laid down prior 
to the adoption of Directive  81/851/EEC  will  have to be reviewed by the 
Member  States in accordance  with  Community criteria, between now and 
1991. 

- 6 -
ACTIVE INGREDIENTS  WHICH  MAY BE USED FOR PREPARING 
PRE-MIXES FOR MEDICATED FEEDINGSTUFFS 

ACTIVE  INGREDIENTS  WHICH MAY  BE.USED.  FOR  PREPARING 
PRE-MIXES  FOR  MEDICATED  FEEDINGSTUFFS 
1. When it adopted on 28 September 1981 Directives  81/851/EEC and 
81/852/EEC relating to veterinary medicinal products, the Council 
provided for a  difficult  point,which had delayed the adoption of these 
texts for almost three years,to be deliberated upon before October 1983, 
when these Directives are due to enter  into  force. 
The majority  of the Member States regarded the rules established by 
these two Directives as necessary and constituting an adequate means of 
safeguarding public health and protecting consumers, whilst at the same 
time  facilitating the free movement of veterinary medicinal products. 
One Member State wanted an even more stringent set of rules for application 
to pre-mixes for medicated feedingstuffs . 
2. A pre-mix can be described as a medicinal product in concentrated form, 
consisting of the active ingredient(s) and an excipient. This concentrate 
is mixed  with  a feedingstuff to  form  a medicated feedingstuff which is 
generally the most convenient means of administering a medicinal product 
to a large group of animals. 
Proprietary and ready-made medicinal products, on the other hand, are 
marketed in a  form  that  can be administered to each animal directly 
without  further  transformation,  that  of an injectable aqueous solution, 
for example. 
1, Council  Directive  81/851/EEC  of 28 September 1981 on the approximation of 
the laws of the Member States relating to veterinary medicinal products -
OJ L 317 of 6 November 1981. 
2 Council  Directive  81/852/EEC  of 28 September 1981 on the approximation of 
the laws of the Member States relating to analytical, pharmaco-toxicologica I 
and clinical standards and protocols in respect of the testing of veterinary 
medicinal products - OJ L 317 of 6 November 1981. - 7 -

- 8 -
3. The matter was  fully  discussed at Council level by pharmaceutical and 
veterinary experts. Eventually a compromise was reached whereby the 
aforementioned Directives could be adopted. 
A report  was requested to help the Council in its deliberations, in 
accordance  with  the terms of reference given to the Commission in  point  3, 
Article 2 of Directive  81/851/EEC  which states: 
"However,  medicated feedingstuffs may be prepared only  from  pre-mixes 
which have been authorized under this Directive. Within two years of 
the notification of this Directive, the Council  shall,  on the basis of 
a Commission  report  accompanied if necessary by appropriate proposals, 
deliberate on a list of pharmacological molecules which may be used for 
preparing pre-mixes and on the procedure for drawing up this list." 
"Pharmacological  molecule" must in this  case  be taken to mean any 
substance  used for the purpose of producing the required therapeutic 
effect and which is more usually described as an "active ingredient" in 
the Directives in question. 
4. In 1982 the Commission consulted a large number of bodies and individuals 
with  a view to taking stock of the current situation as regards use of 
pre-mixes  for medicated feedingstuffs, giving the competent national 
authorities the opportunity of stating their positions in this respect. 
In July and October 1982, the Commission held meetings of experts in the 
field of pre-mixes for medicated feedingstuffs, appointed by their 
respective  governments. 
The pharmaceutical industry publicly stated its own position on this 
matter at a symposium held in Rome in October 1982. 

- 9 -
5. First of all, the terms of the debate must be clarified and the pre-mix 
described  from  the  point  of view of its prominence in veterinary therapy, 
i.e. in legal and economic terms. 
Subsequently,  an analysis must be made of the possible solutions offered 
to the CounciI. 
Lastly,  the Commission has studied the feasibility of having an approved 
list meeting the Council's requirements; the procedures involved and the 
method of drawing up the list are described in detail. 
The embryo of the  initial  Community list of active ingredients 
for use in the preparation of pre-mixes for medicated feedingstuffs is 
contained in Annex I. A list of the other active ingredients currently 
used  in certain Member States is given in Annex II by way of information. 

- 10 -
I. IMPORTANCE  OF THE  PRE-MIX  IN VETERINARY  THERAPY 
6. Before examining in detail the problem of pre-mixes, it is necessary to 
consider  the interests at stake, economic aspects of the problem and the 
other Community regulations either in force or being drawn up. Any 
discussion  of pre-mixes cannot fail to take account of the other 
veterinary matters submitted to the  Council. 
7. Interests involved in the Community 
Pre-mixes  are intended, above all, for use in the collective anti-infective 
and anti-parasitic therapy practised on farms which generally have large 
numbers of animals. 
Any type of regulation in this field must take account of certain 
priorities. 
Firstly,  it is vital  that  the meat, milk and eggs produced by these farms 
be free  from  any harmful residue when they are circulated  within  the 
Community.  Each  Member State is responsible for protecting not only its 
own consumers, but European consumers in general. The level of consumer 
protection established by Community regulations must be regarded as 
adequate by all Member States,  without  exception. More than anything  else, 
it is a question of avoiding trade disruptions of the type  that  occurred 
in 1980  with  regard to hormonal substances, when it was necessary to 
adopt an ad hoc directive. It is  important  to avoid obstacles to the 
movement of livestock products. 
Community farmers must have  access,  at 
reasonable  prices, to the most appropriate, effective and reliable forms 
of therapy. Furthermore, human health must be protected not only  from 
residues,  but also  from  any environmental hazards and unfavourable 
repercussions  such as the appearance of resistance to antibiotics. 

- 11 -
Lastly,  these measures must not constitute barriers to trade in pre-mixes 
or in medicated feedingstuffs in the Community. 
8. Economic aspects of veterinary therapy 
The key factors in veterinary medicine are economic ones. If treatment 
becomes  too expensive, a sick animal will be slaughtered rather than 
treated. 
There  are few official statistics on veterinary medicinal products 
(production or trade) since the usual sources make no distinction between 
medicinal  products intended for human consumption and veterinary medicinal 
products, the latter accounting for no more than about one-twentieth of 
the pharmaceutical industry's overall turnover. 
At the  EFPIA symposium  in Rome,  various estimates were advanced by the 
representatives of the pharmaceutical industry, farmers, and the 
producers  of compound feedingstuffs. This information was compared  with 
information from other sources, in particular the Community's agricultural 
accounts.  Unfortunately the latter contain few, if any, details of 
veterinary medicinal products. 
The cost of veterinary medicinal products is estimated on average at 
between 1% and 1.5% of the value of the marketed livestock.  Losses 
resulting from  sickness,  on the other hand, amount to 15% or 20% of the 
same  value. Consequently, consistent improvements in veterinary therapy 
are likely to result in considerable savings. 
In France,  for example, the consumption of veterinary medicinal products 
can be broken down by type of farming, as follows: 
- cattle: 68.6% 
- poultry: 9.5% 
- pigs: 9.1% 
- sheep: 7.3% 
- other: 5.5% 
EFPIA:  European Federation of Pharmaceutical Industries' Associations. 

- 12 -
It can also be broken down  into  three main therapy groups: 
- serums and vaccines: 25-30% 
- anti-infectives: 20-25% 
- anti-parasitic agents: 20-25% 
In 1981 Community  sales  of veterinary medicinal products by the pharma­
ceuticals  industry amounted to almost 1 000 million ECU. 
In the same year,  sales  of medicated feedingstuffs in the Community were 
estimated at 800 million ECU. The pre-mix accounted for between 15% and 
30% of the  total  cost of the medicated feedingstuff. 
9. Links  with  other Community legislation 
There  are already several directives and proposals for directives serving 
to protect the European consumer of animal products  from  risks relating 
to residues of substances  with  a pharmacological action.  Such  residues 
may be the active ingredients or their metabolites, following processing 
within  the animal organism. 
It seems advisable therefore to discuss pre-mixes in a more general 
context,  with  reference to the various rules governing, directly or 
indirectly, the use of these active ingredients in livestock farming. 
(a) Placing on the market of veterinary medicinal products 
As from  October 1983, veterinary medicinal products, including 
pre-mixes  for medicated feedingstuffs,  will  have to meet the 
quality, safety and efficacy criteria of Directives  81/851/EEC 
and 81/852/EEC  before receiving marketing authorization  from  each 
Member  State. Medicinal products which have already been marketed 
will  gradually be revised according to the same criteria between 
now and 1991. 

- 13 -
(b) Hormones 
Although hormones  are not  normally admimstered  in the  form  of 
medicated feedingstuffs, being mainly implanted,  and  although their 
use in animal  nutrition  is not  admitted,  it is  worth  pointing  out 
that  Council Directive  81/602/EEC prohibits  the  placing  on the 
market  of  stilbenes  and  thyrostatic substances.  Two  proposals for 
Council  regulations concern  the  control  on  substances having  a 
hormonal effect,  in the one  case  from  the  point  of  view  of their 
possession,  distribution  and use, and in the  other from  that  of  their 
residues  in  animals  and  meat. 
The use of  oestradiol, testosterone, progesterone, trenbolone  and 
zeranol  for  fattening purposes  has  been studied  by the  Commission  in 
contact  with  the  various advisory committees concerned.  A proposal 
on this subject will  be  forwarded  to the  Council. 
(c) Additives  in  feedingstuffs 
The amended list  of  additives annexed  to Council Directive  70/524/EEC 
includes  a number  of substances used  in collective prophylaxis, 
namely coccidiostats  and  histomonostats.  The  proposal  for a  third 
directive amending Directive  70/524/EEC aims  at subjecting preparations 
containing authorized additives  to  Community registration  and at 
reserving  the  right  to  supply substances having  a prophylactic effect 
solely  to  manufacturers recognized  in accordance  with  Community 
criteria. 
Under  the  present circumstances,  it does  not  seem appropriate  to 
amend  the  system applicable  to  additives  with a  medicinal action. 
Such  an  amendment  would,  in fact, result  in a  setback  f-om the 
Community point  of  view,  since harmonization  in the  Yield  of additives 
is more extensive than  that  hitherto  achieved  in the  field  of 
veterinary medicines.  For the  moment, these additives  will not be 
regarded  as  pre-mixes  for  medicated feedingstuffs unless they  are 
used  in larger doses  or under conditions other than those provided 
for in  Directive  70/524/EEC. 
1 
2 
3 
4 OJ L 222,  7.8.1981,  p. 32 
C0M(80)920  and  C0M(80)922, 6.1.1981 
OJ L 270,  14.12.1970,  p. 1 
OJ C 197,  13.8.1977,  p. 9 

- 14 -
Point  5 of Article 1 of Directive  81/851/EEC  relating to veterinary 
medicinal  products states  that  Member States "shall take any necessary 
steps  to ensure  that  antibiotics and hormone substances which may be 
used  for the preparation of veterinary medicinal products are made 
available  to only natural or legal persons duly authorized to be in 
possession  of them under national laws." 
The purpose of this provision is to prevent certain stockfarmers  from 
acquiring directly supplies of chemical substances in order to make 
their own medicated feedingstuffs or other unauthorized veterinary 
medicinal  products. (d) Trade in_ant;[biotics and substances having a hormonal action 
(e) Medicated feedingstuffs 
On 20 January 1982, the Commission transmitted to the Council a 
proposaI on the manufacture,  putting  into  circulation and supply 
of medicated feedingstuffs in the Community. 
These  medicated feedingstuffs must be based on pre-mixes authorized 
in accordance  with  Directive  81/851/EEC  relating to veterinary 
medicinal  products. 
The only medicated feedingstuffs authorized to be put  into  circulation 
are those produced in accordance  with  this proposal and presented 
with  appropriate packaging and labelling. 
Medicated  feedingstuffs may be supplied to stockfarmers only on 
presentation of a prescription  from  a registered veterinarian. 
Certain  commonly used formulae or standard prescriptions of medicated 
feedingstuffs could be covered by a Community authorization in 
accordance  with  the procedure of the Standard Veterinary Committee 
laid down in the proposal. 
1 OJ C 41, 16.2.1982 

- 15 -
(f) Residues  in fresh meat 
Council  Directive  83/90/EEC amending Directive  64/433/EEC  on health 
problems affecting intra-Community trade in fresh meat provides for 
the examination of any residues in animals and meat. The Commission 
has placed before the Council a proposal for a directive relating to 
residues  of antibiotics in fresh meat of Community origin and a 
proposal  for a directive on the fixing of maximum levels for pesticide 
residues  in and on foodstuffs of animal origin. 
10. The problem of pre-mixes for medicated feedingstuffs: details 
The use of medicated feedingstuffs raises a number of health-related and 
zootechnical  problems, specific to this  form  of administration. 
Intensive farming involves greater prophylactic or therapeutic needs, the 
three main reasons being  that: 
- high stock-density and, perhaps, the  different  origins of animals are 
liable to accelerate the spread of  diseases; 
- certain stock-farming conditions may prove to be stress-inducing and 
may therefore give rise to particular  diseases; 
- animals sometimes show certain anatomical or physiological weaknesses 
that  increase their vulnerability to infectious or parasitic  diseases. 
There  is therefore a distinct pathology specific to industrial-scale 
intensive farming. For obvious reasons of cost, and in view of the large 
numbers of animals involved, antibiotics or anti-parasitics must be given 
collectively in their feed. 
Collective  dosing in drinking water is not common practice since the 
active ingredients are frequently insoluble or unstable and water cannot 
be replaced at a sufficient rate. 
1 
2 
3 OJ L 59, 5.3.1983 
OJ C 251,  1.10.1981 
OJ C 56, 6.3.1980 

- 16 -
When  treatment  is administered collectively through the medium of a 
medicated feedingstuff , the dose of medicinal product actually received 
by each animal will, however, vary because the sickest animals eat very 
little. 
Furthermore, the dose received and, consequently, the effectiveness of 
treatment  will  depend on the pharmaceutical quality of the pre-mix, its 
compatibility  with  the feedingstuff in question and, lastly, on how well 
the preparation is mixed. 
The special problems involved in pre-mixes for medicated feedingstuffs 
have been at the centre of the experts' discussions and various opinions 
have been put forward in an  effort  to find  a suitable solution. 

- 17 -
II. POSSIBLE  SOLUTIONS  FOR  REGULATING  PRE-MIXES 
11. From the consultations conducted by the  Commission,  it emerges  that  the 
particular conditions in which medicated feedingstuffs are used for 
collective  treatment  in intensive farming appear to constitute grounds 
for a number of restrictions as regards the placing on the market of 
pre-mixes  for medicated feedingstuffs . 
Expert  opinions  differ  considerably, however, when it comes to the question 
of how the use of those active ingredients involved in the preparation of 
pre-mixes  should be regulated. The need for an additional Community 
measure  has been questioned. 
In the  light  of discussions  within  the  Council,  a normal interpretation 
of point  3 of Article 2 of Directive  81/851/EEC  indicates  that  the  Council 
intended to deliberate on a restrictive list of active ingredients for 
use in the preparation of pre-mixes. 
Given  the opinions expressed by various experts, it would seem valuable 
to set out the other options before examining the pros and cons of a 
restrictive list of active ingredients. 
12. Value of such a list 
A number of the experts consulted regard the system of marketing 
authorization  instituted  by Directive  81/851/EEC  as an adequate means of 
guaranteeing the safe use of medicated feedingstuffs. The national 
authorities may authorize a pre-mix, restricting the conditions of use 
and making it compulsory for labels to contain all informs Lion relevant 
to safety and health protection. 
The pharmaceutical industry, represented by the  EFPIA,  considers  that  the 
criteria for refusing authorization, referred to in Article 11 of 
Directive  81/851/EEC,  must be judged on the merits of the pre-mix  itself. 
In particular, proof should not be required of the advisability or 
necessity  of authorizing a pre-mix, especially in relation to the other 
pre-mixes  available on the market. 

- 18 -
In contrast, other experts take the view  that  it is essential to impose 
a basic  limitation  on active ingredients at the marketing authorization 
stage,  in order to allow effective inspection of farms or slaughter­
houses.  Too many active ingredients would make this inspection particularly 
di ffi cult. 
To forestall the formal objection to the principle of such a list, 
point  3 of Article 11 provides for refusal of autorization on additional 
grounds,  pursuant to other Community provisions. 
13. The prohibited list option 
A list of substances prohibited  from  use in pre-mixes has  also  been 
recommended,  although it is not consistent  with  point  3 of Article 2 of 
Directive  81/851/EEC. 
The ban on stilbenes and thyrostatic hormones has been cited by way of 
example.  Few hormones are likely to be  used,  however. On the contrary, 
a great many active ingredients  with  an anti-infective or anti-parasitic 
action are likely to be placed on the market in the  form  of pre-mixes. 
A prohibited list of anti-infective or anti-parasitic agents would, 
therefore, have only a limited effect. 
As the texts stand, the Committee for Veterinary Medicinal Products can 
transmit to the Member States its opinion as to the advisability of 
suspending  or withdrawing marketing authorizations for medicinal products 
apparently harmful under normal conditions of use (Article 20 of Direc­
tive  81/851/EEC).  This opinion  could,  in particular, refer to active 
ingredients which should no longer be used in veterinary medicine. 

- 19 -
14. The DTOS and cons of an approved List 
Pursuant  to Directives  81/851/EEC  and  81/852/EEC  the Member States have 
the power to authorize or refuse the placing on the market of pre-mixes. 
It would be possible to compile a "retrospective" list of the active 
ingredients authorized by each of the Member States. This would amount to 
an administrative task which could be performed by the Committee for 
Veterinary Medicinal Products on the basis of the notifications provided 
for in Article 42 of Directive  81/851/EEC. 
The Council must therefore deliberate on the question of an "a priori" 
restrictive list, taking account of the probable pros and cons of such a 
system. 
(a) The drawbacks of a restrictive list 
The main drawback of an approved list of, say, 30-40 active ingredients 
is that  it would impose a fundamental  limit  on the number of thera­
peutic options and, to some extent, discourage research in the field 
of veterinary pharmacology. The selection would principally be 
intended to meet all the requirements as regards therapy based on 
medicated feedingstuffs. It is likely  that  only active ingredients 
presenting considerable advantages over those listed would be added 
or would replace the  latter. 
It should however be pointed out  that  such restrictions do not apply 
to any  form  of veterinary medicinal product other than medicated 
feedingstuffs. Proprietary or ready-made medicinal products, which 
account  for  two-thirds  of the  sales  of the pharmaceutical industry, 
still present a challenge at research  level. 

- 20 -
It may seem preferable for new active ingredients to be placed on the 
market initially in a pharmaceutical  form  intended for  treatment  of 
individual animals, such as a proprietary or ready-made medicinal 
product. The experience thus acquired would at a later stage make it 
possible  to judge more effectively the benefits or risks involved in 
using  the new active ingredient for collective therapy, administered 
in the  form  of medicated feedingstuffs. 
A list of active ingredients has frequently been opposed on technical 
grounds.  Experts have pointed out  that  the quality, efficacy and 
safety of a medicinal product cannot be  assessed  satisfactorily on 
the basis  of a single active ingredient. In fact, the bioavailability 
of the active ingredient, its metabolism and its elimination depend 
to a large extent on the method of administration, dosage and galenical 
properties of the preparation actually administered. 
The approved list thus serves only as a  form  of pre-selection, whereas 
any definitive judgment  will  have to be concerned  with  the pre-mix 
itself. 
(b) The advantages of a restrictive list 
Directive  70/524/EEC  concerning additives in feedingstuffs provides 
an example of a restrictive list, which has been extended to include 
medicated feedingstuffs in the legislation of the United States and 
Italy,  for example. 
At Community  level,  an"*fepproved list of active ingredients is 
advantageous  in that  it amounts to a formal agreement between live­
stock-breeding countries and those countries consuming animal products, 
on medicinal products authorized for collective administration. 
The concertation procedures  within  the Committee for Veterinary 
Medicinal  Products result only in non-binding opinions, pursuant to 
Directive  81/851/EEC,  as it stands.  Such  an agreement would make it 
possible  to avoid disruptions of intra-Community trade in animal 
products. 

- 21 -
Monitoring of residues on Livestock farms and in slaughterhouses in 
the Member States could be rationalized if the number of authorized 
active ingredients were reduced. It would mean simpler testing 
techniques. 
Manufacturers of compound feedingstuffs are not opposed to a reduction 
in the number of active ingredients since this would enable them to 
rationalize production and storage of medicated feedingstuffs. 
Although the  latter  actually account for  less  than 2% of animal 
feedingstuffs, they are produced in a considerable range. 
The proposal for a directive on medicated feedingstuffs transmitted 
by the Commission on 20 January 1982 is equally concerned  with 
rationalization. Pursuant to this proposal the only medicated feeding-
stuffs which can be prepared in advance are those corresponding to a 
standard prescription for which a Community or national authorization 
has been granted. A Community list of active ingredients would thus 
be particularly useful for the purposes of defining standard 
prescriptions and for the free movement of Community standard 
prescriptions. 
Lastly,  the free movement of pre-mixes containing active ingredients 
included in the Community list is facilitated. In principle, the 
application for marketing authorization in respect of the pre-mix, 
submitted by the manufacturer to each Member State,  will  benefit  from 
the exemptions provided for in  point  10(a) and (b) of Article 5 of 
Directive  81/851/EEC.  Most of the toxicologicaI and clinical tests 
will  not have to be repeated for a pre-mix wj^sn the ingredient is 
recognized  as effective and relatively  safe. 

- 22 -
15. The Commission is considering the suitability of  putting  forward its 
proposals  according to the guidelines outlined below. 
The content of the list and the criteria and procedure for amendments 
envisaged  are based largely on the outcome of two meetings of government 
experts organized by the Commission in 1982. 
As from the date of entry  into  force, the Member States would grant 
marketing authorizations only in respect of those pre-mixes containing 
one or more active ingredients included in the Community list. It should 
be pointed out  that  pre-mixes placed on the market pursuant to provisions 
pre-dating Directive  81/851/EEC  will have to be reviewed by the Member 
States  between now and 1991. The Community list of active ingredients 
would thus take  full  effect as from  that  deadline, October 1991. 
16. The initial list 
The Commission has asked the Member States to present a list of the 
active ingredients they would wish to include on the list of substances 
for use in the preparation of pre-mixes. 
Several  dozen active ingredients appear on each of the lists submitted 
by the Member States, a  total  of over 100 different active ingredients. 
Only  19 active ingredients were proposed by 4 or more Member States. 
These  19 active ingredients, which could form the basis of the Community 
list, are listed in Annex I to this report. III. PROCEDURE  FOR  DRAWING  UP THE LIST 

- 23 -
The Community List could be completed by the addition of between 15 and 
20 of the most important substances, selected from the other active 
ingredients proposed by fewer than 4 Member States (Annex II). 
The Community List initially adopted by the Council would refer to fewer 
than  forty  active ingredients and would subsequently be amended by the 
addition, deletion or substitution of other substances according to the 
procedures  described below. 
17. Criteria for amendment of the list 
The initial list must take account of the present situation and will thus 
be adopted more or  less  pragmatically. 
The general criteria laid down in Council Directive  81/852/EEC  will be 
applicable  in the  case  of any amendment of the list of active ingredients 
for use in the preparation of pre-mixes for medicated feedingstuffs. 
It is  difficult  to evaluate an active ingredient  without  reference to the 
pre-mix in which it is contained. The procedures described later in this 
document are intended to resolve this difficulty by linking the addition 
of a new active ingredient to a prpcedure for marketing authorization. 
It is possible, however, to lay down a number of specific criteria to be 
taken  into  consideration in respect of the inclusion of a new active 
ingredient in the Community list. This amounts basicalLy to adapting the 
general  criteria of Directive  81/852/EEC  to the special crease of 
pre-mixes. 
These  specific criteria can be expressed as follows: 

- 24 -
(a) Either alone or in association, the active ingredient shall be used 
for the  treatment  of frequent or recurring morbid syndromes, 
occasioned  by the conditions of industrial-scale intensive stock-
farming, always provided  that  it can be administered correctly, safely 
and effectively to sick animals or to those exposed to infection. 
(b) The active ingredient shall preferably exert a local action on the 
target  organ, in particular at gastro-intestinal  level. 
(c) The active ingredient shall be absorbed only to a very limited extent 
or, if absorbed, give rise to residues rapidly metabolized in the 
organs  and tissues.  Residues  and their metabolites are rapidly 
eliminated. 
(d) The active ingredient and any metabolites shall be: 
- sensibilizing or allergizing to only a very limited extent, 
- toxic to only a very limited extent (i.e. in terms of acute, 
chronic  or recurring toxicity), 
- non-carcinogenic, 
- non-mutagenic. 
(e) The active ingredient shall preferably be of  little  importance in 
human therapy and shall not encourage the appearance of germs or 
parasites  resistant to anti-infective treatments. 
(f) The active ingredient, its residues or its metabolites shall be 
easily  identifiable on stockfarms or in slaughterhouses. 

- 25 -
18. Authorization of  pre-mixes 
Pre-mixes  containing one or  more active ingredients included in the 
Community  list will be authorized by  each of the Member  States  concerned 
according to the usual national  marketing  authorization (MA)  procedure. 
It will  be possible to  implement  the procedure  whereby  an application can 
be made via the  Committee  for Veterinary Medicinal  Products  to extend  a 
national  MA to  five or more Member  States  (Chapter  IV of Directive 
81/851/EEC). 
Existing  procedures  will have to be adapted  in respect of MA applications 
concerning  pre-mixes  containing an active ingredient not included in the 
Community  list. It would be advisable to  combine  the national MA  procedure 
with the  procedure  for amending  the Community  list. Taking  as a model the 
amendment  to the  annexes  of Directive  70/524/EEC  concerning additives in 
feedingstuffs,  it seems appropriate to provide for  scientific  consultation 
at the level of the  Committee  for Veterinary Medicinal  Products  before the 
decision-making  stage  involving the Standing Veterinary  Committee,  which 
already has  responsibility  for medicated  feedingstuffs. 
(a) Consultation with the  Committee  for Veterinary Medicinal  Products 
If a manufacturer  wishes  to obtain an MA for a  pre-mix  containing an 
active ingredient not included in the  Community  list, he shall forward 
his application, together with the information and  documents  referred 
to in Article  5 of the  aforementioned  Directive  81/851/EEC,  to six 
Member States,  sending  a copy to the  Committee  for Veterinary Medicinal 
Products. It should be pointed out that the present  procedure  of the 
Committee  for Veterinary Medicinal  Products  already involves at least 
six Member  States: the  Member  State of  origin  and the  five or more 
Member States referred to in the application. 
Unlike the present  procedure,  this new procedure  involves a  joint 
examination  of the dossier. For  this purpose  the Committee  appoints 
from amongst  its members  or from amongst  the experts authorized by 
the latter,  rapporteurs responsible for  examining  the analytical, 
pharmacological and toxicologicaI and  clinical  aspects of the 
appli cation. 

- 26 -
Within 180 days of receiving  the application,  the Committee  shall 
express an opinion concerning,  firstly,  the quality, safety  and 
efficacy  of the  pre-mix,  taking  account  of the  proposed  conditions 
of use, and,  secondly,  the advisability  of amending  the Community 
list of active ingredients. This timelimit  is aligned  on that of the 
present Committee  procedure:  120 days for objections plus  60 days for 
the opinion. This timelimit  can be  suspended  if necessary, allowing 
the applicant  time to supply further  documentation  or to  provide 
oral or written explanations. 
The Committee  shall forthwith  communicate  its opinion  to the Member 
States and the  Commission  or, should there  be any  disagreement,  shall 
communicate  the opinions  of its members. 
The Member  States  concerned  shall not authorize  the pre-mix  unless the 
active ingredient  in question  is included  in the  Community  list 
following  the second phase of the  procedure  described  above. 
(b) Amendment_of_the_I2st 
Any amendment of the  list of active ingredients  for use in the 
preparation  of pre-mixes  for medicated  feedingstuffs  shall be subject 
to the conventional  procedure  known as "the  committee  on rules". 
The Standing Veterinary  Committee,  established  by Council Decision 
68/361/EEC  shall be requested  to deliberate  by its Chairman,  either 
on his own  initiative  or at the  request  of the Member  State,  on the 
basis of the  opinion  of the  Committee  for Veterinary Medicinal Products. 
The opinion  of the  Committee  for Veterinary Medicinal  Products  may 
favour the inclusion  of a new  active ingredient following  examination 
of the application submitted  by the  manufacturer  as described  under 
(a) above.  This opinion  may also concern  the removal  from the 
Community  list of an  active ingredient  when Article  20 of  Directive 
81/851/EEC  is brought  into play, i.e.  when the  pre-mix  in question 
is rejected  or withdrawn  from the market in one or more Member  States. 
1 0J L 255,  18.10.1968 

- 27 -
The procedure  adopted  by the  Standing Veterinary  Committee  is based 
on that already  used for additives  to feedingstuffs,  or that which is 
proposed  for standard prescriptions  for medicated  feedingstuffs. This 
will enable  the decisions  taken in these closely  interlinked  sectors 
to be fully consistent. 
The Commission  representative  shall submit  a draft amendment to the 
list. The Standing Veterinary  Committee  shall deliver its opinion  on 
this amendment  within  a deadline  determined  by the  Chairman  and 
depending  on the  urgency  of the  matter.  A majority  of 45  votes shall 
be required. 
Within the Standing Veterinary  Committee,  the votes of the Member 
States shall be weighted  in accordance  with paragraph  2 of Article  148 
of the Treaty.  The Chairman  shall not participate  in the  vote. 
The Commission  shall adopt the amendment to the  list if it  agrees 
with the Committee's  opinion.  Should  it fail to agree with the 
Committee's  opinion  or should no opinion  be delivered,  the Commission 
shall submit  to the  Council  as soon as possible  a proposal  for an 
amendment to the  list. 
The Council  shall adopt  this amendment by a  qualified  majority. 
If the Council  has not  acted by the end of the  three-month  period 
following  referral  of the  matter,  the Commission  shall adopt the 
proposed  amendment and  provide  for its immediate  implementation. 
(c) Issuing of the  authorization 
After the two  stages in the  procedure  (firstly,  the Committee  for 
Veterinary Medicinal  Products  and, secondly,  the Standing Veterinary 
Committee)  and following inclusion  of the  active ingredient  in 
question  in the  Community  list, the six or more Member  States 
concerned  shall express  an opinion  on the  application  for marketing 
authorization. 

- 28 -
In return  for a  considerable extension  of the  time-limits  (nine 
to twelve  months  in all) the applicant  will be able to look 
forward to Community-wide  recognition  of his  pre-mix.  The Member 
States  will have had to  agree upon a common  authorization 
policy in respect  of pre-mixes. 
18. CONCLUSION 
This report  is intended  to enable the Council  to deliberate, with 
full knowledge  of the  facts, on the  list of active ingredients  which 
may be used for preparing  pre-mixes  and on the  procedure  for drawing 
up t he Ii st. 
The majority  of government  experts consulted  by the  Commission  are 
not convinced  of the  need for such a list, whereas  the Italian 
authorities  have insisted  that it is  important  for intra-Community 
trade in animal products. 
This report should therefore enable  the Council,  after due deliberation 
in accordance  with Article  2, paragraph  3 of Directive  81/851/EEC,  to 
affirm the need for such a list and to  express  an opinion  on the 
procedures  for drawing  up and  amending  the list. The Commission  is 
considering  the suitability  of transmitting  a formal proposal  on 
the matter. 
Subject to this proposal, that  may be  added,  and given the adoption 
by the Council  of the  proposal  relating  to the  marketing  of medicated 
feedingstuffs,  the various aspects  of marketing authorization  for 
veterinary  medicinal products  will be dealth with  by Community  law. 
It should nevertheless  be pointed  out that, in the  light of experience 
and by 1987 at the  latest,  the Commission  will submit  to the  Council, 
in accordance  with Article  23 of  Directive  81/851/EEC,  "a proposal 
containing  all appropriate  measures  for the  abolition  of any 
remaining  barriers  to the  free movement of  veterinary medicinal 
products." 

- 29 -
ANNEX I 
COMMUNITY  APPROVED  LIST OF ACTIVE INGREDIENTS FOR USE IN THE PREPARATION 
OF PRE-MIXES FOR MEDICATED FEEDINGSTUFFS 
AMPROLIUM 
APRAMYCINE 
CHLOROTETRACYCLINE 
DIMITRIDAZOLE 
FURAZOLIDONE 
LINCOMYCIN 
NEOMYCIN 
OXYTETRACYCLINE 
PENICILLIN  G PROCAINE 
RONIDAZOL 
SPECTINOMYCIN 
SPIRAMYCIN 
SULFADIMETHOXYNE 
SULFADIMIDINE 
SULFAQUINOXALINE 
TETRACYCLINE 
TIAMULINE 
TRIMETHOPRIM 
TYLOSIN 

- 30 -
ANNEX II 
OTHER ACTIVE  INGREDIENTS CURRENTLY USED IN THE PREPARATION OF PRE-MIXES FOR  
MEDICATED  FEEDINGSTUFFS 
AMINITROZOLE 
AMINONITROTHIAZOLE 
AMMONIUM  CHLORIDE 
AMOXICYLLIN 
AMPICILLIN 
ARSANILIC  (ACID) 
AVOPARCINE 
BACITRACIN 
BAMBERMYCINS 
BUQUINOLATE 
CAMBENDAZOLE 
CARBADOX 
CHOLINE (CHLORIDE) 
CLOXACILLIN 
COLECALCIFEROL 
COLISTIN 
CYANOCOBALAMIN 
DECOQUINATE 
DIAVERIDINE 
DIIODOHYDROXYQUINOLINE 
DIHYDROSTREPTOMYCIN 
DINITOLMIDE  (D.O.T.) 
ERYTHROMYCIN 
ETHOPABATE 

- 31 -
FEBANTEL 
FENBENDAZOLE 
FLUBENDAZOLE 
FLUMEQUINE 
FOLIC (ACID) 
FORMYLSULFATHIAZOLE 
FRAMYCETIN  SULPHATE 
FURALTADONE 
GENTAMYCIN 
GRISEOFULVIN 
HALOFUGINONE 
HALOXON 
HALQUINOL 
IPRONIDAZOLE 
KANAMYCIN 
LEVAMISOLE 
LYSINE 
MEBENDAZOLE 
MENADIONE 
DL-METHIONINE 
METHYL-(4 ACETAMID0-2-ETH0XYBENZ0ATE) 
METYRIDINE 
MONENSIN  SODIUM 
MORANTEL 
MYO-INOSITOL 

- 32 -
NARASINE 
NICARBAZIN 
NICLOSAMIDE 
NICOTINIC  (ACID) 
NIFURPRAZINE 
NIFURSOL 
NIHYDRAZONE 
NIRIDAZOLE 
NITROFURAL 
NYSTATIN 
OLAQUINDOX 
OLEANDOMYCIN 
OXFENDAZOLE 
OXIBENDAZOLE 
OXYCLOZANIDE 
PARBENDAZOLE 
PARCONAZOLE 
PAROMOMYCIN 
PHENOXYTHIAZINE 
PHTHALYLSULFATHIAZOLE 
PIPERAZINE 
POLYOXYALKELENE 
PYRANTEL 
PYRIMETHAMINE 
RAFOXANIDE 
RESERPINE 
ROBENIDINE 
ROXARSONE 

- 35 -
SULFACHLOROPYRAZINE 
SULFACHLOROPYRIDAZINE 
SULFADIAZINE 
SULFAGUANIDINE 
SULFAMERAZINE 
SULFAMETHOXYDIAZINE 
SULFAMETHOXYPYRI DAZINE 
SULFAPYRAZOLE 
TETRAMISOLE 
THIOPHANATE 
TIABENDAZOLE 
VIRGINIAMYCIN