COMMISSION OF THE EUROPEAN COMMUNITIES 
C0MC93) 220 final - SYN 310,311 
Brussels, 1 June 1993 
JEW 
Re-examined proposal for a SYN 310 
COUNCIL DIRECTIVE 
modifying Directives 65/65/EEC, 75/318/EEC and 75/319/EEC 
relating to medicinal products 
Re-examined proposal for a SYN 311 
COUNCIL DIRECTIVE 
modifying Directives 81/851/EEC and 81/852/EEC 
on the approximation of the laws of the Member States 
relating to veterinary medicinal products 
(presented by the Commission pursuant to Article 149(2)(d) 
of the EEC Treaty) 
- 2 
On 21 April 1993 the European Parliament examined three Common Positions 
reached by the Council on 17 December 1992 relating to the following proposals of 
the Commission: 
proposal for a Council Directive modifying Directives 65/65/EEC, 75/318/EEC 
and 75/319/EEC relating to medicinal products (SYN 310); 
proposal for a Council Directive modifying Directives 81/851/EEC and 
81/852/EEC on the approximation of laws of the Member States relating to 
veterinary medicinal products (SYN 311); 
proposal for a Council Directive repealing Directive 87/22/EEC on the 
approximation of national measures relating to the placing on the market of high 
technology medicinal products, particularly those derived from biotechnology 
(SYN 312). 
The parliament has, during the second reading of the co-operation procedure, adopted 
13 amendments to the first proposal, 4 amendments to the second proposal and no 
amendments to the third proposal. 
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined 
the first two proposals, having it in mind to take up some of the amendments of the 
parliament, as described hereafter. 
The Commission wishes, meanwhile, to remind the Parliament and the Council that 
the decentralised procedure for the authorisation of medicinal products for human and 
veterinary use instituted by these Directives will not be able to function in the absence 
of the European Medicines Evaluation Agency. 
Consequently, the Commission hopes that the Parliament will be prepared rapidly to 
give its opinion on the change envisaged by the Council in the legal base of the 
proposal for a Regulation laying down Community procedures for the authorisation 
and the supervision of medicines for human and veterinary use, and establishing an 
European Agency for the evaluation of medicinal products (SYN 309). As far as this 
is concerned, the Commission recalls it preference for article 100A as the legal base 
for the Regulation. 
- 3 -
REVISED PROPOSAL FOR A COUNCIL DIRECTIVE (SYN 310) 
MODIFYING DIRECTIVES 65/65/EEC, 75/318/EEC AND 75/319/EEC 
RELATING TO MEDICINAL PRODUCTS 
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined 
the above proposal, having it in mind to take up 5 of the 13 amendments of the 
Parliament, as detailed in annex 1. The amendments rejected by the Commission can 
be found in annex 2. 
i Amendments accepted by the Commission 
The CoML^esio:- if. i\.ady to accept the amendments whi.h • ! tr-d already 
'-;c?"tfd \\i the I:-" "-.di^g, but which the Council has ;'••_ ». .i"ed h: ils 
C?.'•• >m:r- r '^i*;"»n 
1 -' i • .-..,.''• 
ia»ion oi 
Two amendments relating to pharmacovigi!anc\." (Direcih:.. fô/65/FEC 
artiele 10 (Î) and 75/319/EEC article 29g) have the merit ;.-i introducing a 
greater coherence with the corresponding text of articles 46 and 47 of the 
Regulation. 
2. Amendments rejected by the Commission 
The Commission is not prepared to accept the other eight amendments for the 
following reasons: 
Concerning the amendment of article 7 (2) of Directive 65/65/EEC, the text of 
the common position is preferable because it defines in a more detailed manner 
the mechanism of co-ordination between the Member States when they receive 
simultaneously the same file, and moreover clarifies which documents should be 
exchanged, and what should be the time limits. 
- 4 
Four amendments introduce concepts and terminology into the field of 
pharmacovigilance incompatible with those practised by the Community and 
recommended by the World Health Organisation. The amendments concerned 
are those to article 10(2) of Directive 65/65/EEC, as well as those to articles 29a, 
29b and 29d of Directive 75/319/EEC. 
The amendment of article 13(1) third sub-paragraph (a) new of Directive 
75/319/EEC aims to establish a right to indemnity when national authorities 
initiate hastily the supplementary period of 90 days which is allowed for in order 
to examine conflicts in decisions between Member States. The Commission 
considers that it falls to the national courts to sanction possible abuses in line 
with national law, without having to create a new right of damages under 
Community law. 
The amendment of article 14 (4) of directive 75/319/EEC calls into doubt again 
the unity of the market and of the Community examination criteria, since it 
permits a medicinal product, considered through a Community arbitration 
procedure not to be efficacious, to remain authorised in the country of origin. It 
should be remembered that a traditional medicinal product, of which the efficacy 
recognised only by a single Member State, is not affected by the Community 
arbitration procedure, unless the firm which markets it itself decides to have it 
recognised by other countries, thus taking the risk of seeing it rejected. 
The amendment to article 29f first paragraph (a) new of Directive 75/319/EEC 
risks creating a system of press censorship. The Commission does not think it 
appropriate that national or community authorities should institute a system of 
prior authorisation for any information, which concerns medicinal products, even 
if it is alarmist. 
- 5 
ANNEX 1 AMENDMENTS ACCEPTED BY THE COMMISSION 
Common position of the Council Amendments 
Third recital 
Whereas in the interests of public 
health it is necessary that decisions 
on the authorization to place 
medicinal products on the market be 
exclusively based on the criteria of 
quality, safety and efficacy; whereas 
these criteria have been extensively 
harmonized by Council Directive 
65/65/EEC of 26 January 1965 on the 
approximation of provisions laid down 
by law, regulation or administrative 
action relating to medicinal 
products, by Council Directive 
75/319/EEC, and by Council Directive 
75/318/EEC of 20 May 1975 on the 
approximation of the laws of the 
Member States relating to analytical, 
pharmacotoxicological and clinical 
standards and protocols in respect of 
the testing of medicinal products; 
whereas, however, Member States 
should exceptionally be able to 
prohibit the use on their territory 
of medicinal products which infringe 
objectively defined concepts of 
public order or public morality; Whereas in the interests of public 
health and consumers of medicinal 
products it is necessary that 
decisions on the authorization to 
place medicinal products on the 
market be exclusively based on the 
criteria of quality, safety and 
efficacy; whereas these criteria have 
been extensively harmonized by 
Directive 65/65/EEC of 26 January 
1965 on the approximation of 
provisions laid down by law, 
regulation or administrative action 
relating to medicinal products, by 
Directive 75/319/EEC, and by Council 
Directive 75/318/EEC of 20 May 1975 
on the approximation of the laws of 
the Member States relating to 
analytical, pharmaco-toxicological 
and clinical standards and protocols 
in respect of the testing of 
medicinal products; whereas, however, 
Member States should exceptionally be 
able to prohibit the use on their 
territory of medicinal products which 
infringe objectively defined concepts 
of public order or public morality; 
- 6 -
Common position of the Council Amendments 
ARTICLE 1(4) 
Article 4b, second paragraph a (new) (Directive 65/65/EEC) 
Before a medicinal product is placed 
on the market the competent 
authorities shall forward to the 
European Aaencv for the Evaluation of 
Medicinal Products a copy of the 
decision together with the summary of 
the product characteristics referred 
Ço in this Article. The Aaencv shall 
give the authorized medicinal product 
a European Register number which 
shall be marked on the packaging; the 
register number shall be preceded bv 
the initials of the Member States in 
which the product has been 
authorized. 
ARTICLE 1(6) 
Article 7(1) (Directive 65/65/EEC) 
1. Member States shall take all 
appropriate measures to ensure that 
the procedure for granting an 
authorization to place a medicinal 
product on the market is completed 
within 2JL9_ days of the submission of 
a valid application. 1. Member States shall take all 
appropriate measures to ensure that 
the procedure for granting an 
authorization to place a medicinal 
product on the market is completed 
within V40 days of the date the 
application is submitted. 
ARTICLE 1(9) 
Article 10(1) (Directive 65/65/EEC) 
1. Authorization shall be valid for 
five years and shall be renewable for 
five-year periods, on application by 
the holder at least three months 
before the expiry date and after 
consideration of a dossier updating 
the information previously submitted. 1. Authorization shall be valid for 
five years and shall be renewable for 
five-year periods, on application by 
the holder at least three months 
before the expiry date and after the 
competent authority has considered a 
dossier containing up-to-date 
pharmacovigilance data and the other 
information relevant to the 
supervision of the medicinal product. 
- 7 -
Common position of the Council Amendments 
ARTICLE 3(3) 
Article 29g (Directive 75/319/EEC) 
In order to facilitate the exchange 
of information about 
pharmacovigilance within the 
Community, the Commission, in 
consultation with the Agency, Member 
States and interested parties, shall 
draw up guidance on the collection, 
verification and presentation of 
adverse reaction reports. In order to facilitate the exchange 
of information ab ou t 
pharmacovigilance within the 
Community, the Commission, in 
consultation with the Agency, Member 
States and interested circles, shall 
draw up guidance on the collection, 
verification and presentation of 
adverse reaction reports. 
Such guidance shall take into account 
the work carried out bv the WHO on 
the harmonization of terminology and 
classification in the field of 
pharmacovigilance, It shall also 
establish the arrangements for use of 
the data-processing network between 
the competent authorities in the 
event of an alert concerning a 
manufacturing fault or serious 
undesirable reactions, and other 
pharmacovigilance information on 
medicinal products marketed in the 
Community. 
- 8 -
ANNEX 2 AMENDMENTS REJECTED BY THE COMMISSION 
Common position of the Council Amendments 
ARTICLE 1(6) 
Article 7(2) (Directive 65/65/EEC) 
2. Where a Member State notes that an 
application for authorization 
submitted after 1 January 1995 is 
already under active examination in 
another Member State in respect of 
that medicinal product, the Member 
State concerned mav decide to suspend 
the detailed examination of the 
application in order to await the 
assessment report prepared by the 
other Member State in accordance with 
Article 4b. 2. In assessing applications for 
authorization. the competent 
marketing authorities 
each Qtfrer anâ ffiây_ shall assist 
entrust one 
another with assessments of all or 
part of the dossier. 
The competent authorities of the 
Member States shall notify the Agency 
and the other Member States of any 
applications for marketing 
authorization thev receive. 
The" Member State concerned shall 
inform the other Member State and the 
applicant of its decision to suspend 
derailed - examination of the 
application in question. As soon as 
it has completed the examination of 
the' application and reached a 
decision, the other Member State 
shall forward a copy of its 
assessment report to the Member State 
concerned. 
Within 90 davs of the receipt of the 
assessment report, the Member State 
concerned shall either recognize the 
decision of the other Member State 
and the summary of the product 
characteristics as approved bv it. 
or. if it considers that there are 
grounds for supposing that the 
authorization of the medicinal 
product concerned mav present a risk 
to public health, it shall apply the 
procedures set out in Articles 10 to 
14 of Directive 75/319/EEC. A Member State that receives 
notification shall. if the same 
application for authorization has 
been submitted in another Member 
State, contact the latter with a view 
to coordinating their action and 
issuing the assessment report 
jointly. 
If the Member States with an interest 
in the application do not reach 
agreement, they mav. once all other 
possibilities have been exhausted, 
have recourse to the procedure laid 
down in Chapter III of Directive 
75/319/EEC. 
- 9 
Common position of the Council Amendments 
ARTICLE 1(9) 
Article 10(2), first subparagraph (Directive 65/65/EEC) 
2. In exceptional circumstances, and 
following consultation with the 
applicant, an authorization may be 
granted subject to certain specific 
obligations, including: 2. In exceptional and duly 
substantiated circumstances, and 
following consultation with the 
applicant, an authorization may be 
granted subject to certain specific 
obligations, defined and reviewed 
annually bv the Agency, to: 
the carrying out of further 
studies following the granting of 
authorization; conduct further studies following 
the granting of authorization; 
- the notification of adverse 
reactions to the medicinal 
product. - report side-effects of 
medicinal product. the 
Common position of the Council Amendments 
ARTICLE 3d) 
Article 13(1), third subparagraph a (new) 
(Directive 75/319/EEC) 
Anv delays arising in the marketing 
of a medicinal product because this 
procedure has been initiated hastily 
or with the sole intention of causing 
a delay mav entitle the applicant to 
demand compensation in accordance 
with the legislation applicable in 
the Member State in question. 
*«V Article 3(1) 
Article 14(4) (Directive 75/319/EEC) 
A decision adopted in accordance with 
this Article shall be addressed to 
the Member States concerned by the 
matter and to the person responsible 
for marketing. The Member States 
shall either grant or withdraw 
marketing authorization, or make any 
adjustment to the terms of a 
marketing authorization which may be 
necessary to comply with the decision 
within 30 days of its notification. 
They shall inform the Commission and 
the Committee thereof. A decision adopted in accordance with 
this Article shall be addressed to 
the Member States concerned by the 
matter and to the person responsible 
for marketing. The Member States 
shall either grant or withdraw 
marketing authorization, or make any 
adjustment to the terms of a 
marketing authorization which may be 
necessary to comply with the decision 
within 30 days of its notification. 
In adopting its decision, the Member 
State in which the authorization was 
originally granted shall take into 
account experience with the medicinal 
product in question. An existing 
national authorization may be upheld, 
even in the event of a prior negative 
Decision in accordance with this 
Article, if the medicinal product is 
harmless and of high gualitv. They 
shall inform the Commission and the 
Committee thereof. 
11 -
Common position of the Council Amendments 
ARTICLE 3(3) 
Article 29a (Directive 75/319/EEC) 
In order to ensure the adoption of 
appropriate regulatory decisions 
concerning the medicinal products 
authorized within the Community, 
having regard to information obtained 
about adverse reactions to medicinal 
products under normal conditions of 
use, the Member States shall 
establish a pharmacovigilance system. 
This system shall be used to collect 
information useful in the 
surveillance of medicinal products, 
with particular reference to adverse 
reactions in human beings, and to 
evaluate such information 
scientifically. In order to ensure the adoption of 
appropriate regulatory decisions 
concerning the continued 
authorization of medicinal products 
within the Community, having regard 
to information obtained about the 
side-effects of medicinal products 
under normal conditions of use, 
Member States shall establish a 
pharmacovigilance system for 
collecting information about the 
side-effects of medicinal products in 
human beings and for the scientific 
evaluation of such information, such 
that the information about side-
effects is systematically related to 
the information on the consumption of 
medicinal products. 
ARTICLE 3(3; 
Article 29b, indents (Directive 75/319/EEC) 
"adverse reaction" means a 
reaction which is harmful and 
unintended and which occurs at 
doses normally used in man for the 
prophylaxis, diagnosis or 
treatment of disease or the 
modification of physiological 
function; "side-effects" means a reaction 
which is harmful and unintended 
and which occurs at doses normally 
used in man for the prophylaxis, 
diagnosis or treatment of disease 
or the modification of 
physiological function; 
"serious adverse reaction" means 
an adverse reaction which is 
fatal, 1ife-threatening, 
disabling, incapacitating, or 
which results in or prolongs 
hospitalization; 
"unexpected adverse reaction" 
means an adverse reaction which is 
not mentioned in the summary of 
product characteristics; 
serious unexpected adverse 
reaction" means an adverse 
reaction which is both serious and 
unexpected. "serious side-effects" means an 
unfavourable reaction which is 
fatal, 1ife-threatening, 
disabling, incapacitating, or 
which results in hospitalization 
or prolonged hospitalization; 
"unexpected side-effects" means an 
unfavourable reaction which is not 
mentioned in the summary of 
product characteristics; 
"serious unexpected side-effects" 
means an unfavourable reaction 
which is both serious and 
unexpected. 
Common position of the Council Amendments 
ARTICLE 3(3) 
Article 29d(1)(Directive 75/319/EEC) 
1. The person responsible for placing 
the medicinal product on the market 
shall be required to record and to 
report all suspected serious adverse 
reactions which are brought to his 
attention by a health care 
professional to the competent 
authorities immediately, and in any 
case within 15 days of their receipt 
at the latest-1. The person responsible for 
placing the medicinal product on the 
market shall be required to record 
and to report all suspected serious 
unexpected side-effects which are 
brought to his attention by a 
qualified health care professional to 
the competent authorities 
immediately, and in any case within 
15 days of their receipt. 
ARTICLE 3(3) 
Article 29f, first paragraph a (new) (Directive 75/319/EEC) 
The Member States shall take steps to 
ensure that pharmacovigilance data 
which is not officially confirmed and 
which mav give rise to unnecessary 
alarm is not disseminated. The 
dissemination of data which has not 
been officially confirmed, if it 
proves to be inaccurate, mav be the 
subject of compensation in accordance 
with the legislation of each Member 
- 13 -
REVISED PROPOSAL FOR A COUNCIL DIRECTIVE SYN 311 
MODIFYING DIRECTIVES 81/851/EEC AND 81/852/EEC ON THE 
APPROXIMATION OF LAWS OF THE MEMBER STATES RELATING TO 
VETERINARY MEDICINAL PRODUCTS 
In accordance with Article 149(2)(d) of the Treaty, the Commission has re-examined 
the above proposal, in order to assimilate three of the four amendments from the 
parliament, as detailed in annex 1. The amendment rejected can be found in annex 2. 
1. Amendments accepted by the Commission 
The Commission is prepared to accept the amendments which it had already 
accepted during the first reading, but which the Council did not retain in its 
common position. 
The role given to the European Agency (Directive 81/851/EEC, article 5b, third 
paragraph new) in attributing European number to each medicinal product which 
is authorised in the Community in the future will contribute to a greater 
transparency of the market. The present wording of this amendment envisages 
that the countries which have authorised the medicine should be mentioned, 
which will avoid any risk of confusion with the numbers attributed to community 
authorisations. 
The reduction of the duration of the national examination procedure from 210 
days to 140 (Directive X1/85 l/EEC, article 8( I )) takes account of the fact that, as 
a general rule, the national procedure concerns conventional medicines, and not 
high-technology medicines dealt with under the centralised procedure, the 
examination of which requires a longer time-limit, of the order of 210 days. 
The amendment relating to pharmacovigilance (Directive 81/851/EEC article 
42g) has the merit of introducing a greater coherence with the corresponding text 
of articles 46 and 47 of the Regulation. 
2. Amendments rejected by the Commission 
The Commission is not prepared to accept the amendment of article 15(1) of 
Directive 81/851/EEC, because it introduces into the five yearly re-examination 
of the authorization of a veterinary medicinal product concepts which are not 
clear and which appear to move away from the customary criteria of 
authorization (quality, security and efficacy). 
- 14 -
AjsiNRy t AMENDMENTS ACCEEEEDBYJTHE_COMMISSION 
Common position of the Council Amendments 
ARTICLE 1(5) 
Article 5b, third paragraph (new) 
(Directive 81/851/EEC) 
Before a medicinal product is placed 
on the market the competent 
authorities shall forward to the 
European Agency for the Evaluation of 
Medicinal Products a copy of the 
decision together with the summary of 
the product characteristics referred 
to in this Article. The Agency shall 
give the authorized veterinary 
medicinal product a European Register 
number which shall be marked on the 
packaging; the registration number 
shall be preceded by the initials of 
the Member State in which the 
product's use has been authorized. 
ARTICLE 1(6) 
Article 8(1) 
(Directive 81/851/EEC) 
1. Member States shall take all 
appropriate measures to ensure that 
the procedure for granting an 
authorization to place a veterinary 
medicinal product on the market is 
completed within 210 days of the 
submission of a valid application. 1. Member States shall take all 
appropriate measures to ensure that 
the procedure for granting an 
authorization to place a medicinal 
product on the market is completed 
within 140 days of the date the 
application is submitted. 
ARTICLE 1(12) 
Article 42g 
(Directive 81/851/EEC) 
In order to facilitate the exchange 
of information about 
pharmacovigilance within the 
Community, the Commission, in 
consultation with the Agency, Member 
States and interested parties, shall 
draw up guidance on the collection, 
verification and presentation of 
adverse reaction reports. In order to facilitate the exchange 
of information about 
pharmacovigilance within the 
Community, the Commission, in 
consultation with the Agency, Member 
States and interested circles, shall 
draw up detailed guidance on the 
collection, verification and 
presentation of adverse reaction 
reports. Such guidance shall take 
into account the work carried out bv 
the WHO on the harmonization of 
terminology and classification in the 
field of pharmacovigilance, where 
this can be used in connection with 
veterinary medicinal products. The 
guidance shall also establish the 
arrangements for the use of the 
information network among the 
competent„au_thori tips in the__event_pf 
JLQ-JLU\lJL^QI?gf-LU3Jnq a nianuf acturinq 
fault or serious adverse reactions, 
as well as other pharmacovigilance 
information on veterinary medicinal 
products marketed in the Community. 
- 15 -
ANNfiX 2 AMENDMENTS REJECT*vn KV Jim COMMISSION 
Common position of the Council Amendments 
ARTICLE 1(9) 
Article 15(1) 
(Directive 81/851/EEC) 
1. Authorization shall be valid for 
five years and shall be renewable for 
five-year periods, on application by 
the holder at least three months 
before the expiry date and after 
consideration of a dossier updating 
the information previously submitted. 1. Authorization shall be valid for 
five years and shall be renewable for 
five-year periods, on application by 
the holder at least three months 
before the expiry date and after the 
competent body has considered a 
dossier containing _ updated 
pharmacovigilance data and the other 
information relevant to the 
monitoring of the product. 
When delivering its ' opinion the 
responsible body shall take account 
off any new information available on 
side-effects of. ,. ^3 medicinal 
product, its efficacy and its olacs 
in its therapeutic class. 

M 
ISSN 0254-1475 
COM(93) 220 final 
DOCUMENTS 
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Catalogue number : CB-CO-93-247-EN-C 
ISBN 92-77-55872-.' 
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