No C 308/26 Official Journal of the European Communities 3. 12. 88 
Amended proposal for a Council Directive extending the scope of Directives 65/65/EEC and 
75/319/EEC on the approximation of provisions laid down by law, regulation or administrative 
action relating to proprietary medicinal products and laying down additional provisions for 
radiopharmaceuticals (') 
COM(88) 663 final — SYN 114 
(Submitted by the Commission to the Council pursuant to the third paragraph of Article 149 of the 
Treaty on 11 November 1988) 
(88/C 308/10) 
(') OJ No C 36, 8. 2. 1988, p. 30. 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
Title unchanged 
THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Having regard to the Treaty establishing the European 
Economic Community, and in particular Article 100A 
thereof, THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Visas unchanged 
Having regard to the proposal from the Commission, 
In cooperation with the European Parliament, 
Having regard to the opinion of the Economic and 
Social Committee, 
Whereas disparities in the provisions currently laid down 
by law, regulation or administrative action by Member 
States may hinder trade in radiopharmaceuticals within 
the Community; First to fourth recitals unchanged 
Whereas the essential aim of any rules governing the 
production, distribution or use of medicinal products 
must be to ensure a high level of protection of public 
health; 
Whereas the provisions laid down by Directive 
65/65/EEC O, as last amended by Directive 
87/21/EECO, and Second Directive 75/319/EEC (3), 
as last amended by Directive 83/570/EEC (4), on the 
approximation of provisions laid down by law, regulation 
or administrative action relating to proprietary medicinal 
products, although appropriate are inadequate for radio­
pharmaceuticals; 
(') OJ No 21, 9. 2. 1965, p. 369/65. 
(2) OJ No L 15, 17. 1. 1987, p. 36. 
O OJ No L 147, 9. 6. 1975, p. 13. 
(4) OJ No L 332, 28. 11. 1983, p. 1. 
3. 12. 88 Official Journal of the European Communities No C 308/27 
ORIGINAL PROPOSAL 
Whereas in accordance with Article 5 of Directive 
87/22/EEC (') on the approximation of national 
provisions relating to the placing on the market of high 
technology medicinal products, particularly those derived 
from biotechnology, the Commission is required to 
submit proposals to harmonize, along the lines of 
Directive 75/319/EEC, the conditions for authorizing 
the manufacture and placing on the market of radiophar­
maceuticals before 22 December 1987; 
Whereas in the case of radiopharmaceuticals authori­
zation should be required for industrially prepared 
radiopharmaceuticals, generators, kits and precursor 
radiopharmaceuticals; whereas, however, a separate 
authorization should not be required for radiopharma­
ceuticals in their finished form which are made up exclu­
sively from authorized kits, generators or precursor 
radiopharmaceuticals in health care establishments; 
Whereas the Commission should be empowered to adopt 
any necessary changes in the requirements for the testing 
of proprietary medicinal products set out in the Annex to 
Directive 75/318/EEC of 20 May 1975 on the approxi­
mation of the laws of the Member States relating to 
analytical, pharmaco-toxicological and clinical standards 
and protocols in respect of the testing of proprietary 
medicinal products (2), as last amended by Directive 
87/19/EEC of 22 December 1987 (3), to take account of 
the special nature of radiopharmaceuticals in close 
cooperation with the Committee for the Adaptation to 
Technical Progress of the Directives on the Removal of 
Technical Barriers to Trade in the Proprietary Medicinal 
Products Sector; 
Whereas any rules governing radiopharmaceuticals must 
take into account the provisions of Directive 
84/466/Euratom of 3 September 1984 laying down basic 
measures for the radiation protection of persons 
undergoing medical examination or treatment (4); 
whereas account should also be taken of Directive 
80/836/Euratom ($) which amends the Directives laying 
down the basic safety standards for the health protection 
of the general public and workers against the dangers of 
ionizing radiation as last amended by Council Directive 
84/467/Euratom 1984 (6), the objective of which is to 
(') JO No L 15, 17. 1. 1987, p. 38. 
(2) JO No L 147, 9. 6. 1975, p. 1. 
(') JO No L 15, 17. 1. 1987, p. 31. 
(4) JO No L 265, 5. 10. 1984, p. 1. 
(5) JO No L 246, 17. 9. 1980, p. 1. 
(6) Jo No L 265, 5. 10. 1984, p. 4. AMENDED PROPOSAL 
Whereas in the case of radiopharmaceuticals, generators, 
kits and precursors authorization should be required; 
whereas, however, a specific authorization should not be 
required for radiopharmaceuticals in their finished form 
which are made up exclusively from authorized kits, 
generators or radiopharmaceuticals in health care estab­
lishments; 
Whereas the Commission should be empowered to adopt 
any necessary changes in the requirements for the testing 
of proprietary medicinal products set out in the Annex to 
Directive 75/318/EEC of 20 May 1975 on the approxi­
mation of the laws of the Member States relating to 
analytical, pharmaco-toxicological and clinical standards 
and protocols in respect of the testing of proprietary 
medicinal products, as last amended by Directive 
87/19/EEC to take account of the special nature of 
radiopharmaceuticals in close cooperation with the 
Committee for the Adaptation to Technical Progress of 
the Directives on the Removal of Technical Barriers to 
Trade in the Proprietary Medicinal Products Sector, thus 
ensuring the greater quality, safety and efficacy of the 
medicinal products; 
Unchanged 
No C 308/28 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
prevent the exposure of workers or patients to excessive 
or unnecessarily high levels of ionizing radiation, and in 
particular of Article 5c thereof, which requires prior 
authorization for the addition of radioactive substances 
to medicinal products as well as for the importation of 
such medicinal products, 
HAS ADOPTED THIS DIRECTIVE: HAS ADOPTED THIS DIRECTIVE: 
Article 1 
1. In derogation from Article 34 of Directive 
75/319/EEC and subject to the provisions of this 
Directive, the provisions of Directives 65/65/EEC and 
75/319/EEC shall apply to radiopharmaceuticals for 
human use, excluding radionuclides in the form of sealed 
sources. Article 1 
1. Unchanged 
2. For the purposes of this Directive, the following 
definitions shall apply: 2. For the purposes of this Directive, the following 
definitions shall apply: 
'radiopharmaceutical' shall mean any medicinal 
product which, when ready for use, contains one or 
more radionuclides (radioactive isotopes) included 
for a medicinal purpose, 'radiopharmaceutical' shall mean any medicinal 
product which, when ready for use, contains one or 
more radionuclides (radioactive isotopes) included 
for a medicinal purpose, 
'generator' shall mean any system incorporating a 
fixed parent radionuclide from which is produced a 
daughter radionuclide which is to be removed by 
elution and used in a radiopharmaceutical, 'generator' shall mean any system incorporating a 
fixed parent radionuclide from which is produced a 
daughter radionuclide which is to be removed by 
elution or by any other method and used in a radio­
pharmaceutical, 
'kit' shall mean any industrial preparation to be 
reconstituted or combined with radionuclides in the 
final radiopharmaceutical, usually prior to its admin­
istration, — 'kit' shall mean any preparation to the reconstituted 
or combined with radionuclides in the final radio­
pharmaceutical, usually prior to its administration, 
'precursor radiopharmaceutical' shall mean any other 
industrially produced radionuclide for the radio-
labelling of another substance prior to administration. — 'precursor' shall mean any other radionuclide 
produced for the radio-labelling of another substance 
prior to administration. 
3. Nothing in this Directive shall in any way derogate 
from the Community rules for the radiation protection 
of persons undergoing medical examination or treatment 
or from the Community rules laying down the basic 
safety standards for the health protection of the general 
public and workers against the dangers of ionizing 
radiation. 3. Unchanged 
3. 12. 88 Official Journal of the European Communities No C 308/29 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
Article 2 
The authorization referred to in Article 3 of Directive 
65/65/EEC shall be required for generators, kits, 
precursor radiopharmaceuticals and industrially prepared 
radiopharmaceuticals. However, authorization shall not 
be required for a radiopharmaceutical in its ready for use 
form, if the radiopharmaceutical is prepared by an 
approved person in an approved health care estab­
lishment exclusively from authorized generators, kits or 
precursor radiopharmaceuticals in accordance with the 
manufacturer's instructions. Article 2 
The authorization referred to in Article 3 of Directive 
65/65/EEC shall be required for generators, kits, 
precursor radiopharmaceuticals and industrially prepared 
radiopharmaceuticals. However, authorization shall not 
be required for a radiopharmaceutical prepared at the 
time of use by a person or by an establishment auth­
orized, according to national legislation, to use such 
medicinal products in an approved health care estab­
lishment exclusively from authorized generators, kits or 
precursor radiopharmaceuticals in accordance with the 
manufacturer's instructions. 
Article 3 
In addition to the requirements set out in Article 4 of 
Directive 65/65/EEC, an application for authorization 
to market a generator shall also contain the following 
information and particulars: Article 3 
Unchanged 
a general description of the system together with a 
detailed description of the components of the system 
which may effect the composition or quality of the 
daughter nucleid preparation, 
qualitative and quantitative particulars of the eluate. 
Article 4 
For radiopharmaceuticals, in addition to the information 
referred to in Article 4a of Directive 65/65/EEC, the 
summary of product characteristics referred to in point 9 
of the second paragraph of Article 4 of Directive 
65/65/EEC shall contain the following additional points 
7 and 8: Article 4 
Unchanged 
'7. full details of radiation dosimetry; 
8. additional detailed instructions for preparation, and 
where appropriate, maximum storage time during 
which any intermediate preparation such as an eluate 
or the ready to use pharmaceutical will conform with 
its specifications.' 
Article 5 
The outer carton and the tin of medicinal products 
containing radionuclides shall be labelled in accordance 
with the regulations for the safe transport of radioactive 
materials laid down by the International Atomic Energy 
Agency. Moreover, the labelling shall comply with the 
following provisions: Article 5 
Unchanged 
No C 308/30 Official Journal of the European Communities 3. 12. 88 
ORIGINAL PROPOSAL AMENDED PROPOSAL 
(a) The label on the shielding shall include the 
particulars mentioned in Article 13 of Directive 
65/65/EEC. In addition, the labelling on the 
shielding shall explain in full the codings used on the 
vial and shall indicate, where necessary, for a given 
time and date, the amount of radioactivity per dose 
or per vial and the number of capsules or, for 
liquids, the number of millilitres in the container; 
(b) The vial shall be labelled with the following infor­
mation : 
— the name or code of the medicinal product 
including the name or chemical symbol of the 
radionuclide, 
— the batch identification and expiry date, 
— the international symbol for radioactivity, 
— the name of the manufacturer, 
— the amount of radioactivity as specified under (a) 
above. 
Article 6 
1. Member States shall ensure that a detailed 
instruction leaflet is enclosed with the packaging of 
radiopharmaceuticals, generators, kits or precursor 
radiopharmaceuticals. The text of this leaflet shall be 
established in accordance with the provisions of Article 6 
of Directive 75/319/EEC and shall contain all the infor­
mation referred to therein. In addition, the leaflet shall 
include any precautions to be taken by the user and the 
patient during the preparation and administration of the 
product and special precautions for the disposal of the 
container and its unused contents. Article 6 
Unchanged 
2. Member States shall permit the use of user infor­
mation leaflets which have been established in more than 
one of the languages of the Community provided that 
the information contained in all the language versions of 
the leaflet is identical. 
Article 7 
Any amendments which are necessary in the testing 
requirements for medicinal products set out in the Annex 
to Directive 75/318/EEC to take account of the 
extension of the scope of Directives 65/65/EEC and 
75/319/EEC to cover radiopharmaceuticals shall be 
adopted in accordance with the procedure laid down in 
Article 2c of Directive 75/318/EEC. Any such 
amendments shall come into effect on the same date as 
this Directive. Article 7 
Any amendments which are necessary in the testing 
requirements for medicinal products set out in the Annex 
to Directive 75/318/EEC to take account of the 
extension of the scope of Directives 65/65/EEC and 
75/319/EEC to cover radiopharmaceuticals shall be 
adopted in accordance with the procedure laid down in 
Article 2c of Directive 75/318/EEC. 
Second sentence deleted. 
3. 12. 88 Official Journal of the European Communities No C 308/31 
ORIGINAL PROPOSAL 
Article 8 
1. Member States shall take the necessary measures to 
comply with this Directive not later than 1 January 1991. 
They shall forthwith inform the Commission thereof. 
2. Requests for marketing authorization for products 
covered by this Directive lodged after the time limit 
referred to in the first paragraph must comply with the 
provisions of this Directive. 
3. This Directive shall be progressively extended to 
existing medicinal products covered by this Directive 
before 31 December 1992. 
Article 9 
This Directive is addressed to the Member States. AMENDED PROPOSAL 
Article 8 
1. Save In the case provided for in paragraph 2, 
Member States shall take the necessary measures to 
comply with this Directive not later than 1 January 1991. 
They shall forthwith inform the Commission thereof. 
2. In the event of the amendments to Directive 
75/318/EEC referred to in Article 7 not being adopted 
by the date referred to in paragraph 1, this date shall be 
replaced by the date of adoption. 
3. Requests for marketing authorization for products 
covered by this Directive lodged after the date of 
implementation comply with the provisions of this 
Directive. 
4. This Directive shall be progressively extended to 
existing radiopharmaceutical medicinal products covered 
by this Directive before 31 December 1992. 
Article 9 
Unchanged