CELEX: 51985PC0263
Language: en
Date: 1985-05-29
Title: AMENDED PROPOSAL FOR A COUNCIL DIRECTIVE RELATING TO THE PROTECTION OF DIALYSIS PATIENTS BY MINIMIZING THE EXPOSURE TO ALUMINIUM

No C 150/6                               Official Journal of the European Communities                                          20.6.85
                                                                     II
                                                          (Preparatory Acts)
                                                   COMMISSION
              Amended proposal for a Council Directive relating to the protection of dialysis patients by
                                             minimizing the exposure to aluminium
                                                        COM(85) 263 final
              (Submitted by the Commission to the Council pursuant to the second paragraph of Article 149 of
                                                 the EEC Treaty on 3 June 1985)
                                                            (85/C 150/04)
                      ORIGINAL PROPOSAL                                                            AMENDED PROPOSAL
Having regard to the Treaty establishing the European                        Having regard to the Treaty establishing the European
Economic Community, and in particular Articles 100 and                       Economic Community, and in particular Article 100 (two
235 thereof,                                                                 words deleted) thereof,
                                              Last t h r e e c i t a t i o n s u n c h a n g e d
                                                               Recital 1
Whereas at the Conference held in Paris in October
1972 the Heads of State or of Government affirmed that
the first aim of economic expansion, which is not an end
in itself, should be to enable disparities in living
conditions to be reduced and that it should result in an
improvement in the quality of life as well as in standards
of living;                                                                   Deleted
                                                               Recital 2
Whereas, in view of the growth in the number of renal                       Whereas the number of persons in the Community having
dialysis patients in the Community, of their continued                       to resort to dialysis in order to preserve normal living
health problems and of the economic cost of renal                            conditions is rising considerably;
dialysis treatment, it is necessary to lay down rules aimed
at increasing the protection of the health of these
patients;
                                                               Recital 3
Whereas it is necessary that renal dialysis patients benefit
from the same health protection when travelling within
the Community;                                                               Deleted
                                                         Recital 3 (a) (new)
                                                                            Whereas the protection of persons undergoing dialysis
                                                                             requires that standards of purity be laid down, to be met
                                                                             on the one hand by dialysis concentrates and prepared
                                                                             dialysis fluids and on the other hand by the water used
                                                                             for the dilution of the concentrates to prepare dialysis
                                                                             fluids;
                                                               Recital-4
Whereas clinical observations and epidemiological
studies have shown that aluminium accumulates in the
body of dialysis patients;                                                   Deleted
 ---pagebreak--- 20. 6. 85                               Official Journal of the European Communities                                 No C 150/7
                      ORIGINAL PROPOSAL                                                   AMENDED PROPOSAL
                                                      Recital 4 (a) (new)
                                                                    Whereas these measures should relate in particular to the
                                                                    aluminium content of dialysis concentrates and fluids and
                                                                    diluting water;
                                                            Recital 5
Whereas clinical observations have shown that with
elevated body burdens of aluminium, severe health
effects and in particular encephalopathy develops in two
to three years;                                                     (Incorporated in new Recital 8 (a))
                                                      Recital 5 (a) (new)
                                                                    Whereas a disparity between the provisions applicable or
                                                                    in the process of being drawn up in the Member States,
                                                                    relating to the aluminium content of dialysis concentrates,
                                                                    prepared dialysis fluids and the diluting water, is likely on
                                                                    the one hand to constitute a barrier to the free movement
                                                                    of such concentrates and fluids within the Community
                                                                    and, on the other, to bring about differences in the
                                                                    standard of dialysis treatment which may constitute a
                                                                    barrier to the free movement of persons undergoing
                                                                    dialysis in the Community; whereas as a consequence
                                                                    such a disparity will directly affect the functioning of the
                                                                    common market and steps should be taken in this field
                                                                    for the approximation of such provisions in accordance
                                                                    with Article 100 of the Treaty;
                                                            Recital 6
Whereas the determination of aluminium in plasma or
serum provides an indication of the aluminium body
burden and the reference levels help in the management
of the dialysis patients;                                           (Incorporated in new Recitals 8 (a) and 10 (a))
                                                      Recital 6 (a) (new)
                                                                    Whereas, although Council Directives 65/65/EEC (')
                                                                    75/318/EEC( 2 ) and 75/319/EEC (3) lay down the
                                                                    general conditions governing the placing on the market
                                                                    of proprietary medicinal products, specific limit values
                                                                    should in addition be set for aluminium dialysis
                                                                    concentrates and prepared dialysis fluids, account being
                                                                    taken of the work of the European Pharmacopoeia, and
                                                                    the labels of such products should indicate their
                                                                    aluminium content;
                                                            Recital 7
Whereas it is appropriate to consider a comprehensive
approach and cover all types of renal dialysis methods
and all sources of aluminium;                                       Deleted
                                                                    0) OJ No 22, 9. 2. 1965, p. 369/65.
                                                                    (2) O J N o L 147,9.6. 1975, p. 1.
                                                                    (3) OJ No L 147, 9. 6. 1975, p. 13.
 ---pagebreak--- No C 150/8                              Official Journal of the European Communities                                    20.6.85
                      ORIGINAL PROPOSAL                                                   AMENDED PROPOSAL
                                                      Recital 7 (a) (new)
                                                                    Whereas by means of Directive 80/778/EEC (') the
                                                                    Council has already laid down a series of standards
                                                                    relating to the quality of water intended for human
                                                                    consumption;
                                                            Recital 8
Whereas the aluminium accumulating in the body of
dialysis patients may arise from the dialysis fluids,
including the water used for the dilution of the
concentrates, the dialysis instrumentation, and the
aluminium salts taken orally for phosphate bindings;                (Incorporated in new Recitals 8 (a) and 10 (a))
                                                      Recital 8 (a) (new)
                                                                    Whereas, in order to limit the risks of osteomalacia due
                                                                    to aluminium and to eliminate the risks to dialysis
                                                                    patients of encephalopathy caused by the presence of
                                                                    aluminium in dialysis fluids, a maximum value should be
                                                                    set for aluminium not only in dialysis concentrates but
                                                                    also in the diluting water, and whereas this value should
                                                                    be lower than that laid down in Directive 80/778/EEC
                                                                    where this water is used for purposes of dialysis;
                                                            Recital 9
Whereas recent scientific data have shown that the
aluminium body burden increases if the aluminium level
in the renal dialysis fluids exceeds 10-20 (ig/1;                    Deleted
                                                      Recital 9 (a) (new)
                                                                    Whereas, in order to ensure that the maximum values are
                                                                    respected, provision should be made for Member States
                                                                    to take the necessary steps to ensure that appropriate
                                                                    monitoring is performed of aluminium concentration in
                                                                    dialysis fluids;
                                                            Recital 10
Whereas Council Directive 80/778/EEC of 15 July 1980
 relating to the quality of water intended for human
 consumption (*) does not consider aluminium as a toxic
 substance and sets a maximum admissible concentration
 for aluminium in water of 0,2 jxg/l and a guide level of
 0,05 H-g/1;                                                         (Incorporated in new Recital 7 (a))
                                                      Recital 10 (a) (new)
                                                                    Whereas, in order to ensure the effectiveness of harmo-
                                                                     nization, the oral intake of aluminium should be reduced
                                                                     as far as possible and provision should be made to ensure
                                                                     that the authorities responsible for dialysis treatment are
                                                                     fully informed of the risk of the toxic effects of
                                                                     aluminium for dialysis patients; whereas in addition it
                                                                     (') OJL229, 30. 8. 1980, p. 11.
 ---pagebreak--- 20. 6. 85                              Official Journal of the European Communities                               No C 150/9
                     ORIGINAL PROPOSAL                                                  AMENDED PROPOSAL
                                                                   seems advisable, with a view to evaluating the
                                                                   effectiveness of harmonization, to measure on a regular
                                                                   basis the aluminium levels in plasma, which measurements
                                                                   constitute a very useful indication of the body burdens of
                                                                   aluminium of dialysis patients;
                                                          Recital 11
Whereas recent scientific data clearly demonstrated that
if aluminium concentrations in excess of 50 jig/1 are
present in the water intended for renal haemodialysis
there is the probability of encephalopathy developing in
a significant number of patients;                                  (Incorporated in new Recital 8 (a))
                                                     Recital 11 (a) (new)
                                                                   Whereas the accuracy required in the assessment of
                                                                   aluminium levels will be more easily and harmoniously
                                                                   achieved by the Member States within the framework of
                                                                   a Community programme to enhance the quality of
                                                                   methods of analysis and establish reference methods;
                                                          Recital 12
Whereas there may be considerable variability in the
aluminium level in the mains water supply;                         Deleted
                                                     Recital 12 (a) (new)
                                                                   Whereas scientific and technical progress requires a rapid
                                                                   adaptation of the reference methods of analysis
                                                                   mentioned in this Directive; whereas, in order to facilitate
                                                                   the implementation of measures required to this end,
                                                                   provision should be made for a procedure involving close
                                                                   cooperation between the Member States and the
                                                                   Commission within a Committee on the adaptation to
                                                                   scientific and technical progress;
                                                          Recital 13
Whereas the interconnection of water grid systems may
render this variation unpredictable and there is therefore
the need for close cooperation between the responsible
authorities for water distribution and the renal dialysis
units;                                                             Deleted
                                                     Recital 13 (a) (new)
                                                                   Whereas the cost of applying the standards laid down in
                                                                   this Directive is significantly lower than the additional
                                                                   costs presently involved in the treatment of dialysis
                                                                   patients suffering from encephalopathy and osteomalacia
                                                                   caused by the excessive intake of aluminium; whereas the
                                                                   result will be a significant reduction in the costs of
                                                                   dialysis;
                                                          Recital 14
Whereas the efficiency of various water treatment
methods for the removal of aluminium depends on the
concentration and chemical form of the aluminium
present in water;                                                  Deleted
 ---pagebreak--- No C 150/10                             Official Journal of the European Communities                                 20. 6. 85
                      ORIGINAL PROPOSAL                                                    AMENDED PROPOSAL
                                                           Recital 15
Whereas at present demineralization and reverse osmosis
appear to be the water treatment techniques most appro-
priate;                                                              Deleted
                                                           Recital 16
Whereas it is necessary to minimize the aluminium
concentration in the dialysis concentrates, haemo-
filtration and peritoneal dialysis solutions; whereas it is
however recognized that due to technical difficulties a
stepwise approach is necessary; whereas Member States
should be encouraged to achieve these low levels as soon
as possible;                                                         (Incorporated in new Recital 8 (a))
                                                           Recital 17
Whereas these provisions supplement the general
requirements laid down for medicinal preparations in
Council Directives 65/65/EEC (*), 75/318/EEC (2) and
75/319/EEC (3).                                                      (Incorporated in new Recital 6 (a))
                                                           Recital 18
Whereas it is desirable to minimize the oral intake of
aluminium and develop substitute treatment methods;                  (Incorporated in new Recital 10 (a))
                                                           Recital 19
Whereas it is recognized that at present the analytical
methodology is deficient for the analysis of aluminium in
water, dialysis fluids and body fluids at the concentration
required for the protection of dialysis patients as set out
in this Directive, and that the setting up of quality
assurance procedures and the development of reference
materials is urgently required, and that the Commission
should be entrusted with the implementation of these
measures,                                                            (Incorporated in new Recital 11 (a))
                                                             Article 1
This Directive concerns the protection of renal dialysis             1.    The purpose of this Directive is to establish
patients from the toxic effects of aluminium absorption              common rules for the maximum permissible aluminium
from all sources, by monitoring the aluminium levels in              content of dialysis fluids, in order:
plasma and dialysis fluids and minimizing the absorption.
                                                                     (a) to remove obstacles to trade in dialysis concentrates
                                                                         and prepared dialysis fluids;
                                                                     (b) to remove obstacles to the free movement in the
                                                                         Community of persons undergoing dialysis for renal
                                                                         insufficiency;
                                                                         while at the same time ensuring the protection of
                                                                         such persons.
0) OJ No 22, 9. 2. 1965, p. 369/65.
(2) OJ No No L 147, 9. 6. 1975, p. 1.
C) OJ No L 147, 9. 6. 1975, p. 43.
 ---pagebreak--- 20.6.85                                 Official Journal of the European Communities                                No C 150/11
                      ORIGINAL PROPOSAL                                                    AMENDED PROPOSAL
                                                                            In this Directive:
                                                                         dialysis concentrate means any solution which can be
                                                                         diluted with water for the purpose of making up a
                                                                         dialysis fluid;
                                                                         dialysis fluid means any solution, whether a prepared
                                                                         dialysis fluid or a fluid made up from dialysis
                                                                         concentrate diluted with water, used for the purpose
                                                                         of human dialysis;
                                                                         diluting water means any water which is added to a
                                                                         dialysis concentrate in order to prepare a dialysis
                                                                         fluid;
                                                                         haemofiltration solution means any solution used as a
                                                                         replacement fluid in haemofiltration;
                                                                        peritoneal dialysis solution means any solution used
                                                                         for the purpose of peritoneal dialysis, including the
                                                                         solutions known as IPD, CAPD and C C P D ;
                                                                        prepared dialysis fluid means any fluid supplied in
                                                                         such a form as to be ready for use without the
                                                                         addition of diluting water.
                                                     Article 2, paragraph 1
Member States shall inform all persons in charge of the
management of renal dialysis patients that the regular
monitoring of aluminium in the plasma or serum of these
patients is desirable for attempting to protect them
against the toxic effects of aluminium, and shall provided
recommended reference levels for aluminium in serum or
plasma.                                                             (Modified and moved to new Article 6 (a), paragraph 1)
                                                    Article 2, paragraph 2
Recommended reference levels of aluminium in plasma
or serum, monitoring frequency and analytical methods
are given in Annex 1.                                               (Unchanged and moved to new Article 6 (a), paragraph 2)
                                                      Article 2 (a) (new)
                                                                    1.     When the competent authorities in the Member
                                                                    States authorize the marketing of prepared dialysis
                                                                    solutions and dialysis concentrates in accordance with the
                                                                    provisions of Directives 65/65/EEC, 75/318/EEC and
                                                                    75/319/EEC, they must ensure that:
                                                                    — the total amount of aluminium present in the dialysis
                                                                        concentrates shall not contribute more than 10 |ig/l
                                                                        to the aluminium concentration of the dialysis fluid
                                                                        when made up;
                                                                    — the aluminium concentration in the prepared dialysis
                                                                        fluid supplied for peritoneal dialysis solution does not
                                                                        exceed 15 ug/1 as from 1 January 1986 and 10 jig/1 as
                                                                        from 1 January 1988;
 ---pagebreak--- No C 150/12                             Official Journal of the European Communities                                   20.6.85
                      ORIGINAL PROPOSAL                                                    AMENDED PROPOSAL
                                                                     — the aluminium concentration in the prepared heamo-
                                                                         filtration and peritoneal dialysis solutions and
                                                                         concentrated saline solutions for heamodialysis does
                                                                         not exceed 10 (ig/1.
                                                                     2.     In addition they must ensure that all dialysis
                                                                     solutions and concentrates put on the market shall bear a
                                                                     label showing the maximum concentration of aluminium
                                                                     they are likely to contain (after dilution in the case of
                                                                     dialysis concentrates).
                                                     Article 3, paragraph 1
From 1 January 1986 Member States shall ensure that                  From 1 January 1986 Member States shall ensure that
the aluminium level in the dialysis fluids does not exceed           the aluminium level in the dialysis fluids does not exceed
30 |ig/l; it is recommended however that these levels do             30 u.g/1; however, this aluminium level must be restricted
not exceed 10 Hg/1.                                                  to a maximum of 10 ug/1 as from 1 January 1988.
                                                     Article 3, paragraph 2
For the purpose of this Directive dialysis fluids shall
mean all the solutions used for the purpose of haemo-
dialysis.                                                             Deleted
                                                  Article 3, paragraph 2 (new)
                                                                      Member States shall take all necessary measures to
                                                                     ensure regular monitoring of the aluminium concen-
                                                                     tration in the dialysis fluid.
                                                                      Guidance regarding the sampling methods, the frequency
                                                                      of monitoring and the analytical methods is given in
                                                                     Annex 1.
                                                      Article 3, paragraph 3
 Member States shall take all necessary measures to
 ensure regular monitoring of the aluminium concen-
 tration in the dialysis fluid.                                       (Moved to Article 3, paragraph 2)
                                                      Article 3, paragraph 4
 When the results of analysis show that the level of
 30 u.g/1 is exceeded, Member States shall ensure that
 appropriate remedial action is taken.                                Deleted
                                                      Article 3, paragraph 5
 Guidance regarding the sampling methods, the frequency
 of monitoring and the analytical methods is given in
 Annex 1.                                                             (Moved to Article 3, paragraph 2)
                                                      Article 3, paragraph 6
 The level of 30 u,g/l shall be regularly reviewed by the
 Commission, and proposals made in order to achieve the
 recommended level of 10 |Xg/l as soon as possible.                   Deleted
 ---pagebreak--- 20.6.85                                 Official Journal of the European Communities                                        No C 150/13
                      ORIGINAL PROPOSAL                                                           AMENDED PROPOSAL
                                          Article 4, paragraph 1 unchanged
                                                         Article 4, paragraph 2
For the purpose of this Directive diluting water shall
mean that water which is added to dialysis concentrate
to prepare dialysis fluid.                                                   Deleted
                                                     Article 4, paragraph 2 (new)
                                                                            Member States shall ensure that diluting water is appro-
                                                                            priately treated for the removal of aluminium if the
                                                                            aluminium level exceeds 30 jig/1 as from 1 January 1986
                                                                            and 10 jig/1 as from 1 January 1988.
                                                        Article 4, paragraph 3
Member States shall ensure that diluting water is appro-
priately treated for the removal of aluminium if the
aluminium level exceeds 30 u,g/l.
Even if the levels of aluminium in the diluting water are
below 30 ji.g/1 treatment of the water may be desirable in
view of possible contributions of dialysis concentrates
and of the instrumentation and in order to achieve the
recommended levels set in Article 3 (1).                                    (Modified and moved to Article 4, paragraph 2 (new))
                                                     Article 4, paragraph 3 (new)
                                                                            Guidance regarding the water treatment methods com-
                                                                            patible with its use in haemodialysis is given in Annex 3.
                                                        Article 4, paragraph 4
Guidance regarding the water treatment methods is                           (Modified and moved to Article 4, paragraph 3 (new)
given in Annex 3.
                                                        Article 5, paragraph 1
Member States shall ensure that the authorities                             Member States shall ensure that the authorities
responsible for water distribution are informed of all the                  responsible for water distribution are informed of all the
renal dialysis units and haemodialysis patients using the                   dialysis centres using the water distributed by these auth-
water distributed by these authorities.                                     orities.
                                                        Article 5, paragraph 2
The authorities responsible for water distribution shall                    The authorities responsible for water distribution shall
inform, if possible in advance, all renal dialysis units of                 inform, if possible in advance, all renal dialysis centres of
any important change in the water treatment procedures                      any important changes in the water treatment procedures
which may increase the aluminium concentration in the                       which may increase the aluminium concentration in the
water.                                                                      water and shall urge the renal dialysis centres to inform
                                                                            the patients in their care accordingly.
                                          A r t i c l e 5, p a r a g r a p h 3 u n c h a n g e d
 ---pagebreak--- No C 150/14                             Official Journal of the European Communities                                  20.6. 85
                     ORIGINAL PROPOSAL                                                   AMENDED PROPOSAL
                                                     Article 6, paragraph 1
For the purposes of this Directive:
—    Dialysis concentrate shall mean all the solutions used
    in the Community for the purpose of preparing
    dialysis fluids;
—    Peritoneal dialysis solution shall mean all solutions
    used in the Community for the purpose of peritoneal
    dialysis (i.e. IPD, CAPD, CCPD);
—    Haemofiltration solution shall mean all solutions used
    in the Community for the purpose of replacement
    fluids in heamofiltration.                                      (Unchanged and moved to Article 1, paragraph 2)
                                                     Article 6, paragraph 2
Member States shall take the appropriate measures to
ensure that:
— the total amount of aluminium present in the dialysis
   concentrate supplied for the purpose of preparing
   dialysis fluids shall not contribute more than 10 u.g/1
   to the aluminium concentration of the dialysis
   solution. Attempts should however be made to
   further reduce the aluminium concentration to as low
   a level as possible;
— the aluminium concentration in the dialysis fluid
   supplied for peritoneal dialysis solution does not
   exceed 15 jxg/1. Attempts should be made to further
   reduce the aluminium concentration to as low a level
   as possible;
— the aluminium concentration in the haemofiltration
   solutions does not exceed 10 jxg/1.                              (Modified and moved to Article 2 (a) (new))
                                                      Article 6 (a) (new)
                                                                    1.    In order to protect all individuals suffering from
                                                                    renal insufficiency and undergoing dialysis from the toxic
                                                                    effects of aluminium, Member States shall provide to all
                                                                    persons in charge of dialysis centres, information
                                                                    regarding the toxicity of aluminium and shall indicate the
                                                                    desirability of monitoring regularly the aluminium level in
                                                                    the plasma of these individuals.
                                                                    2.    Recommended reference levels of aluminium in
                                                                    plasma or serum, monitoring frequency and analytical
                                                                    methods are given in Annexes 1 and 2.
 ---pagebreak--- 20.6. 85                                   Official Journal of the European Communities                                          No C 150/15
                       ORIGINAL PROPOSAL                                                             AMENDED PROPOSAL
                                         A r t i c l e s 7, 8, 9, 10, 11 a n d 12 u n c h a n g e d
                                                            Annex 1 unchanged
                                                 A n n e x 2, p a r a g r a p h 1 u n c h a n g e d
                                          A n n e x 2, p a r a g r a p h s 2 a n d 3 — Deleted
                                                                     Annex 3
In general at present both demineralization techniques and                     With the exception of water softening techniques, both deminer-
reversed osmosis may be used for this treatment. The choice will               alization techniques and reversed osmosis may be used for this
depend on the local circumstances.                                             treatment. The choice will depend on the local circumstances.