No C 36/30 Official Journal of the European Communities 8. 2. 88 
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(87) 697 final 
(Submitted by the Commission to the Council on 12 January 1988) 
(88/C 36/05) 
THE COUNCIL OF THE EUROPEAN COMMUNITIES, 
Having regard to the Treaty establishing the European 
Economic Community, and in particular Article 100A 
thereof, 
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; 
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 (l), as last amended by Directive 
87/21/EEC (2), 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 
radiopharmaceuticals; 
Whereas, in accordance with Article 5 of Directive 
87/22/EEC (5) 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 
radiopharmaceuticals before 22 December 1987; 
Whereas in the case of radiopharmaceuticals authorization 
should be required for industrially prepared 
radiopharmaceuticals, generators, kits and precursor 
radiopharmaceuticals; whereas, however, a separate 
authorization should not be required for 
H OJ No 22, 9. 2. 1965, p. 369/65. 
(2) OJ No L 15, 17. 1. 1987, p. 36. 
(3) OJ No L 147, 9. 6. 1975, p. 13. 
(4) OJ No L 332, 28. 11. 1983, p. 1. 
(5) OJ No L 15, 17. 1. 1987, p. 38. radiopharmaceuticals in their finished form which are made 
up exclusively 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 
approximation 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 (6), as last amended by Directive 
87/19/EEC of 22 December 1986 (7), 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 (8); whereas account 
should also be taken of Directive 80/836/Euratom (9) 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 (9), as last amended 
by Council Directive 84/467/Euratom of 3 September 
1984 (10), the objective of which is to prevent the exposure of 
workers or patients to excessive or unnecessarily high levels 
of ionizing radiation, and in particular oi 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: 
Article 1 
1. In derogation from Article 34 of Directive 
75/319/EEC and subject to the provisions of this Directive, 
(«) OJNoL 147,9.6. 1975, p. 1. 
(7) OJ No L 15, 17. 1. 1987, p. 31. 
(8) OJ No L 265, 5. 10. 1984, p. 1. 
(") OJ No L 246, 17. 9. 1980, p. 1. 
(10) OJ No L 265, 5. 10. 1984, p. 4. 
^ ^ Official journal of the European Communities l^oC^^l 
the provisions of Ui^ective^^^^ECand^^l^^EC 
shall apply to radiopharmaceuticals for human use^ 
e^cludin^ radionuclides in the form of sealed sources. 
^. Por the purposes of this lOirective^ the following 
definitions shall apply^ 
— aeadiopharmaceuticaf shall mean any medicinal product 
which^ when ready for use^ contains one or more 
radionuclides ^radioactive isotopes^ included for a 
medicinal purposed 
— ^enerator^ shall mean any system mcorporatm^afi^ed 
parent radionuclide from which is producedadau^hter 
radionuclide which is to he removed hyelution and used 
maradiopharmaceutical^ 
— ^iC shall mean any industrial preparation to he 
reconstituted or combined with radionuclides in the 
final radiopharmaceuticals usually prior to its 
administrations 
— ^precursor radiopharmaceuticals shall mean any other 
mdustriallyproducedradionuchdefortheradiolahellin^ 
of another substance pTior to administration. 
^. ^othin^mthisUirectiveshallmany waydero^ate 
from the Community rules for the radiation protection of 
persons under^oin^medicale^ammationor treatment or 
from the Community ruleslaym^down the basic safety 
standards for the health protection of the general public and 
workers against the dangers of loni^in^ radiation. 
Idie authorisation referred to m Article ^ of directive 
D^D^PPCshall be required for generators'lots^ precursor 
radiopharmaceuticals and industrially prepared 
radiopharmaceuticals.r^owever^authori^ation shall not be 
required foraradiopharmaceutical in its ready for use form^ 
if the radiopharmaceutical is prepared by an approved 
person in an approved health care establishment exclusively 
from authorised generators' l^its or precursor 
radiopharmaceuticals in accordance with the manufacturers 
instructions. 
Ar^^^ 
In addition to the requirements set out m Article ^ of 
directive ^^^^^PPC^ an application for authorisation to 
market a generator shall also contain the following 
information and particulars^ 
— 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 preparations 
— qualitative and quantitative particulars of the eluate. Ar^^^ 
Por radiopharmaceuticals^ in addition to themformation 
referred to in Article ^a of Uirective De^DBoBPPC^ the 
summary of product characteristics referred to in pomt^of 
the second paragraph of Article^ofPoirective^^^^PPC 
shall contain the following additional pomts^and^ 
^. full details of radiation dosimetry^ 
^. additional detailed instructions for preparations 
and where appropriated maximum storage time during 
which any intermediate preparation such as an eluate or 
the ready touse pharmaceutical willconformwithits 
specificationsB 
Ar^^^ 
Idie outer carton and the tin of medicinal products 
contamm^radionuclides shall be labelled in accordance with 
the regulations forthe safe transport of radioactive materials 
laid down by the International Atomic Pner^y Agency, 
^loreover^ the labelling shall comply with the following 
provisions^ 
^ The label on the shielding shall include the particulars 
mentioned in Article t^3 of directive ^^^^PPC. In 
additionmhe labelling on the shielding shall explain in 
full thecodm^s used on thevial and shall indicated where 
necessary^ for a^iven timeanddate^ the amount of 
radioactivity per dose or per vial and thenumber of 
capsules or^forhquidsmhe number of milhlitres in the 
container. 
^ The vial shall be labelled with the following 
informations 
— the name or codeofthe medicinal product including 
the name or chemical symbol of the radionuclides 
— the batch identification and expiry date^ 
— the international symbol for radioactivity^ 
— the name of the manufacturers 
— theamountof radioactivityasspecifiedunder^ 
above. 
Ar^^^ 
1. member states shall ensure thatadetailed instruction 
leaflet is enclosed with the pac^a^m^ of 
radiopharmaceuticals^ generators' l^its or precursor 
radiopharmaceuticals. The te^t of this leaflet shall be 
established in accordance with the provisions of Article^of 
Uirective^^t^^EEC and shall contain all the information 
referred to therein. In additionmb^ leaflet shall include any 
precautions to be taleenbythe user and the patient durm^the 
preparation and administration of the product and special 
precautions for the disposal of the container and its unused 
contents. 
No C 36/32 Official Journal of the European Communities 8. 2. 88 
2. Member States shall permit the use of user information 
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 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 paragraph 1 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.