CELEX: 51988PC0663(04)
Language: en
Date: 1988-11-10
Title: 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

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,                               THE COUNCIL OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European                  Visas unchanged
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              First to fourth recitals unchanged
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 O ,            as last     amended      by    Directive
8 7 / 2 1 / E E C O , 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.
 ---pagebreak---  3. 12. 88                             Official Journal of the European Communities                           No C 308/27
                      ORIGINAL PROPOSAL                                              AMENDED 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-             Whereas in the case of radiopharmaceuticals, generators,
zation should be required for industrially prepared              kits and precursors authorization should be required;
radiopharmaceuticals, generators, kits and precursor             whereas, however, a specific authorization should not be
radiopharmaceuticals; whereas, however, a separate               required for radiopharmaceuticals in their finished form
authorization should not be required for radiopharma-            which are made up exclusively from authorized kits,
ceuticals in their finished form which are made up exclu-        generators or radiopharmaceuticals in health care estab-
sively from authorized kits, generators or precursor             lishments;
radiopharmaceuticals in health care establishments;
Whereas the Commission should be empowered to adopt              Whereas the Commission should be empowered to adopt
any necessary changes in the requirements for the testing        any necessary changes in the requirements for the testing
of proprietary medicinal products set out in the Annex to        of proprietary medicinal products set out in the Annex to
Directive 75/318/EEC of 20 May 1975 on the approxi-              Directive 75/318/EEC of 20 May 1975 on the approxi-
mation of the laws of the Member States relating to              mation of the laws of the Member States relating to
analytical, pharmaco-toxicological and clinical standards        analytical, pharmaco-toxicological and clinical standards
and protocols in respect of the testing of proprietary           and protocols in respect of the testing of proprietary
medicinal products (2), as last amended by Directive             medicinal products, as last amended by Directive
87/19/EEC of 22 December 1987 (3), to take account of            87/19/EEC to take account of the special nature of
the special nature of radiopharmaceuticals in close              radiopharmaceuticals in close cooperation with the
cooperation with the Committee for the Adaptation to             Committee for the Adaptation to Technical Progress of
Technical Progress of the Directives on the Removal of           the Directives on the Removal of Technical Barriers to
Technical Barriers to Trade in the Proprietary Medicinal         Trade in the Proprietary Medicinal Products Sector, thus
Products Sector;                                                 ensuring the greater quality, safety and efficacy of the
                                                                 medicinal products;
Whereas any rules governing radiopharmaceuticals must            Unchanged
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.
 ---pagebreak---  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                                                        Article 1
 1.    In derogation from Article 34 of Directive                 1.    Unchanged
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.
2.     For the purposes of this Directive, the following         2.    For the purposes of this Directive, the following
definitions shall apply:                                         definitions shall apply:
    'radiopharmaceutical' shall mean any medicinal                   'radiopharmaceutical' shall mean any medicinal
    product which, when ready for use, contains one or               product which, when ready for use, contains one or
    more radionuclides (radioactive isotopes) included               more radionuclides (radioactive isotopes) included
    for a medicinal purpose,                                         for a medicinal purpose,
    'generator' shall mean any system incorporating a                'generator' shall mean any system incorporating a
    fixed parent radionuclide from which is produced a               fixed parent radionuclide from which is produced a
    daughter radionuclide which is to be removed by                  daughter radionuclide which is to be removed by
    elution and used in a radiopharmaceutical,                       elution or by any other method and used in a radio-
                                                                     pharmaceutical,
    'kit' shall mean any industrial preparation to be            — 'kit' shall mean any preparation to the reconstituted
    reconstituted or combined with radionuclides in the              or combined with radionuclides in the final radio-
    final radiopharmaceutical, usually prior to its admin-           pharmaceutical, usually prior to its administration,
    istration,
    'precursor radiopharmaceutical' shall mean any other         — 'precursor' shall mean any other radionuclide
    industrially produced radionuclide for the radio-                produced for the radio-labelling of another substance
    labelling of another substance prior to administration.          prior to administration.
3.    Nothing in this Directive shall in any way derogate        3.    Unchanged
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.
 ---pagebreak--- 3. 12. 88                               Official Journal of the European Communities                          No C 308/29
                       ORIGINAL PROPOSAL                                               AMENDED PROPOSAL
                            Article 2                                                      Article 2
The authorization referred to in Article 3 of Directive           The authorization referred to in Article 3 of Directive
65/65/EEC shall be required for generators, kits,                  65/65/EEC shall be required for generators, kits,
precursor radiopharmaceuticals and industrially prepared           precursor radiopharmaceuticals and industrially prepared
radiopharmaceuticals. However, authorization shall not             radiopharmaceuticals. However, authorization shall not
be required for a radiopharmaceutical in its ready for use         be required for a radiopharmaceutical prepared at the
form, if the radiopharmaceutical is prepared by an                 time of use by a person or by an establishment auth-
approved person in an approved health care estab-                 orized, according to national legislation, to use such
lishment exclusively from authorized generators, kits or          medicinal products in an approved health care estab-
precursor radiopharmaceuticals in accordance with the              lishment exclusively from authorized generators, kits or
manufacturer's instructions.                                      precursor radiopharmaceuticals in accordance with the
                                                                   manufacturer's instructions.
                           Article 3                                                       Article 3
In addition to the requirements set out in Article 4 of           Unchanged
Directive 65/65/EEC, an application for authorization
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 preparation,
     qualitative and quantitative particulars of the eluate.
                           Article 4                                                       Article 4
For radiopharmaceuticals, in addition to the information          Unchanged
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:
'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                                                      Article 5
The outer carton and the tin of medicinal products                Unchanged
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:
 ---pagebreak---  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                                                        Article 6
1.     Member States shall ensure that a detailed                  Unchanged
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.
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                                                        Article 7
Any amendments which are necessary in the testing                  Any amendments which are necessary in the testing
requirements for medicinal products set out in the Annex           requirements for medicinal products set out in the Annex
to Directive 75/318/EEC to take account of the                     to Directive 75/318/EEC to take account of the
extension of the scope of Directives 65/65/EEC and                 extension of the scope of Directives 65/65/EEC and
75/319/EEC to cover radiopharmaceuticals shall be                  75/319/EEC to cover radiopharmaceuticals shall be
adopted in accordance with the procedure laid down in              adopted in accordance with the procedure laid down in
Article 2c of Directive 75/318/EEC. Any such                       Article 2c of Directive 75/318/EEC.
amendments shall come into effect on the same date as
this Directive.
                                                                   Second sentence deleted.
 ---pagebreak--- 3. 12. 88                             Official Journal of the European Communities                            No C 308/31
                    ORIGINAL PROPOSAL                                               AMENDED PROPOSAL
                         Article 8                                                       Article 8
1.    Member States shall take the necessary measures to         1.   Save In the case provided for in paragraph 2,
comply with this Directive not later than 1 January 1991.        Member States shall take the necessary measures to
They shall forthwith inform the Commission thereof.              comply with this Directive not later than 1 January 1991.
                                                                They shall forthwith inform the Commission thereof.
2.    Requests for marketing authorization for products          2.   In the event of the amendments to Directive
covered by this Directive lodged after the time limit            75/318/EEC referred to in Article 7 not being adopted
referred to in the first paragraph must comply with the         by the date referred to in paragraph 1, this date shall be
provisions of this Directive.                                   replaced by the date of adoption.
3.    This Directive shall be progressively extended to          3.   Requests for marketing authorization for products
existing medicinal products covered by this Directive           covered by this Directive lodged after the date of
before 31 December 1992.                                        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                                                       Article 9
This Directive is addressed to the Member States.               Unchanged