Opinion of the European Economic and Social Committee on the Proposal for a Regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 COM(2005) 567 final — 2005/0227 (COD)
Date: 2006-07-05
Institutions: European Economic and Social Committee
Subjects: biotechnology, medicinal product, pharmaceutical legislation, public health, therapeutics

16.12.2006

EN

Official Journal of the European Union

C 309/15

Opinion of the European Economic and Social Committee on the Proposal for a Regulation of the
European Parliament and of the Council on advanced therapy medicinal products and amending
Directive 2001/83/EC and Regulation (EC) No 726/2004

COM(2005) 567 final — 2005/0227 (COD)

(2006/C 309/03)

On 10 January 2006 the Council decided to consult the European Economic and Social Committee, under
Article 95 of the Treaty establishing the European Community, on the abovementioned proposal.

The Section for the Single Market, Production and Consumption, which was responsible for preparing the
Committee's work on the subject, adopted its opinion on 31 May 2006. The rapporteur was Mr Bedossa.

At its 428th plenary session, held on 5 and 6 July 2006 (meeting of 5 July), the European Economic and
Social Committee adopted the following opinion by 150 votes, with one abstention.

1. Summary

The Committee welcomes this proposal for a Regulation
1.1
of the European Parliament and of the Council on advanced
therapy medicinal
amending Directive
2001/93/EC and Regulation (EC) No 726/2004.

products

and

1.2
Against a backdrop of accelerating scientific progress,
especially in the field of biotechnology, there is a real need for
clarification, rigour and expertise.

1.3
The aim of the proposal is to provide a coherent picture
of the various advanced therapies, to fill the existing regulatory
gap and to bolster specific evaluation by the European Medi-
cines Agency in these new disciplines. This will secure:

— a swift response to the demands of patients and expecta-
tions in the industry with regard to research into and the
development of regenerative medicine;

— a high level of health protection for European patients;

— overall

legal certainty, while allowing for sufficient flex-
in order to keep pace with the

level

ibility at technical
evolution of science and technology.

Given the particularities of advanced therapy products,
1.4
it is essential to provide a robust and comprehensive regulatory
framework that is applicable in all Member States.

A regulation is therefore considered as being the most
1.5
appropriate legal
instrument. This is all the more important
given that current public health issues regarding advanced
therapy medicinal products will remain unresolved in the EU
until a specific legislative system is put in place.

1.6
However, some aspects of this draft regulation may give
rise to implementing problems, in view of the definitions used,
with the draft directive on medical devices. Care must be taken
to ensure that the final text clears up outstanding questions and
possible doubts. For instance:

— What

is the point

in this new regulation given that
advanced gene and cell
therapy medicinal products are
already governed by specific directives on pharmaceutical
products?

— The definitions given in Article 2b,

in particular, appear

complicated and are rather superfluous.

— It

is also clear that national pharmaceutical
might stand in the way of European legislation.

legislation

— It would have been preferable in this case to use a more

flexible approach and begin with mutual recognition.

— The question of autologous products of non-industrial
origin in the hospital sector also raises the issues of ‘border
line’ products of other origins and of rules applying at
European level.

2. General comments

2.1
An article by article examination of the regulation raises
a number of comments, questions and recommendations. With
regard to Article 2: ‘Definitions’ (1):

The definitions concerning gene therapy and somatic
2.2
cell therapy do not generally pose any problems given that
reflection and experience have led to a consensus. These
products are classed as medicines and are already regulated as
such within the Community.

2.2.1
The definition of a tissue engineered product seems
more complex however. As currently worded, the first indent
of Article 2(1)(b) states that a tissue engineered product
‘contains or consists of engineered cells or tissues’, without
specifying ‘as an integral part’. In practice, therefore, medical
devices which contain tissue engineered products ‘with an
ancillary function’ are also included among innovative medic-
inal products. This makes the provisions of the proposed direc-
tive on medical devices meaningless.

(1) COM(2005) 567 final.

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2.2.2
The wording of the second indent of Article 2(1)(b)
could also give rise to implementing difficulties and, in particu-
lar, overlap with the medical device directive. As tissue engi-
neered products are covered by legislation on medicinal
products,
it would be desirable to mention their primary
activity of disease treatment or prevention, or of altering
physiological functions through pharmacological,
immunolo-
gical or metabolic action, rather than just referring to their
properties for ‘regenerating, repairing or replacing a human
tissue’, as these properties are also shared by some types of
medical device.

2.3
An effort has been made to narrow down the exact defi-
nition of a ‘tissue engineered product’ as much as possible.
Nevertheless, the difference from cell therapy (bone marrow
transplants, stem cell transplants, umbilical cord blood trans-
plants, adult or embryonic stem cells, etc.) is not entirely clear.

2.4
The Committee proposes that examples of products
currently considered to have been generated by tissue engi-
neering be used as a starting point for attempts to clarify the
definition. This would assist understanding, particularly since it
is no secret that the subject is the focus of debate and contro-
versy, particularly regarding embryonic stem cells.

At this point, there are no ethical problems apart from

2.5
those surrounding human embryonic stem cells (HESC).

2.6
The controversy centres on the means of producing
stem cells. More specifically, the production of these cells by
nuclear transfer (in other words cloning) raises major ethical
questions, and no real consensus has been found within the
European Union to this day. Current concerns focus on the
risks of reproductive cloning, egg trafficking and the commer-
cialisation of human body parts.

2.7
Such practices are explicitly condemned by the Euro-
pean Convention on Bioethics (Oviedo Convention, 1998) and
by the International Bioethics Committee (UNESCO, 1997).

In the absence of a consensus between EU Member

2.8
States, HESC use falls within national responsibility.

The detail given in the recitals (2) is therefore essential,
2.9
as it gives clear consideration to the reality of the debate and
this text regulating advanced therapy medicinal
states that
products at Community level is not designed to ‘interfere with
decisions made by Member States on whether to allow the use
of any specific type of human cells, such as embryonic stem
cells, or animal cells’.

Neither is it designed to ‘affect

2.10
the application of
national legislation prohibiting or restricting the sale, supply or
use of medicinal products containing, consisting of or derived
from these cells’.

(2) COM(2005) 567 final, 6th recital.

3. Specific comments

3.1
The harmonisation of the principles governing other
modern biotechnological medicines currently covered by Com-
munity-level regulations involves a centralised authorisation
procedure, i.e. a single scientific evaluation of the quality, safety
and effectiveness of advanced therapy medicinal products.

However, unlike traditional medical

3.2
these
therapies by their very nature require specific pre-clinical and
clinical procedures, with particular emphasis on expertise, risk
management and post-marketing authorisation (MA) pharma-
covigilance.

treatments,

3.3
The present draft regulation is right to stress the need to
develop specific expertise in the evaluation of these products
within the European Medicines Agency's Committee for Medic-
inal Products for Human Use (CHMP (3)), also involving patient
associations in the evaluation groups.

The proposal

3.4
to set up a Committee for Advanced
Therapies (CAT (4)) which the CHMP would consult on every-
thing concerning the evaluation of data regarding advanced
therapy medicinal products before issuing its final scientific
opinion, is key.

3.5
This committee will bring together the few top experts
currently working in the Community in the area of advanced
therapy medicinal products and selected representatives of the
parties concerned.

It

3.6
is wholly justified as it will provide a means of
defining not only scientific procedures but also standards for
follow
good clinical and manufacturing practice and will
evaluation through to marketing authorisation (MA) and
beyond to post-marketing authorisation.

3.7
The mention of the principle whereby ‘human cells or
tissues contained in advanced therapy medicinal products
should be procured from voluntary and unpaid donation’
is
important. It responds to the constant concern to raise safety
standards for tissue and cells, remove the risk of commercia-
lising human body parts, and protect human health.

The proposal confirms the advisory role of the European
3.8
Medicines Agency. This role will be critical on all kinds of issue
that may arise as science evolves, be it
the production of
advanced therapy medicines, good manufacturing practice or
rules relating to the summary of product characteristics, label-
ling or the package leaflet stating technical specificities, or
when it is necessary to define the dividing line with other fields
(such as cosmetics or certain medical devices).

(3) CAT: Committee for Advanced Therapies
(4) It should be noted, when it comes to the membership of the CAT,
that some language versions of COM(2005)567 final — 2005/0227
(COD) use the term ‘surgeons’, whereas others refer to ‘doctors’.
This opinion refers to doctors not surgeons.

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that

Some have pointed out

3.8.1
the procedures used
might be expensive, whereas national authorisation procedures
are by nature more economical. There is also the problem of
transition periods being longer than EU transition
national
periods (five years as opposed to two). The political risk posed
by decentralised national procedures may hinder access to
advanced therapy medicinal products, as some Member States
have access and others do not.

Lastly, the proposal takes a useful look at the economic
3.9
dimension (5).
In the context of global competition in the
health industry, the European Union must claim its rightful
place on both the internal and global markets.

3.10
The economic risks linked with uncertainty or rapid
changes in science, and the considerable cost of studies, hold
back major and lasting investment in the field of medicine and
advanced therapy medicinal products in particular.

ments in scientific data (e.g. duration of data validity, data
storage conditions),
to provide permanent protection for
patient health and, more generally, to abide by ethical stan-
dards.

3.15
The planned report on the ‘implementation of this
Regulation after experience has been gained’ should provide an
opportunity for debate within the bodies concerned (in particu-
lar the Committee for Advanced Therapies (CAT) and the
Committee for Medicinal Products for Human Use (CHMP)).

3.15.1
However, the subordination of the CAT to the CHMP
(the original mechanism for providing expertise) will weigh
procedures down considerably and may give rise to unneces-
sary contradictions.

Furthermore, it is frequently small and medium-sized
3.11
companies that carry out the studies necessary to demonstrate
the quality and non-clinical safety of advanced therapy medic-
inal products, and these do not always originate from previous
experience in the pharmaceutical
field (typically taking the
form of spin-offs from biotech laboratories or manufacturers of
medical devices).

3.16 More generally, the planned publication of the report
(Chapter 8, Article 25) could include not only ‘comprehensive
information on the different types of advanced therapy medic-
inal products authorised pursuant to this Regulation’ but also
information and results concerning the incentive measures
‘Scientific
provided for in Chapter 6 (Articles 17-18 and 19):
Advice’, ‘Scientific recommendation on advanced therapy classi-
fication’ and ‘Certification of quality and non-clinical data’.

3.12
The Commission proposes a ‘system of early evaluation
and certification of quality and non-clinical safety data by the
Agency, independently of any marketing authorisation applica-
tion’
in order to support and encourage SMEs carrying out
studies. This seems appropriate.

4. Conclusions

3.12.1 Meanwhile, in tissue engineering, products are often
developed by SMEs, with the generation of start-ups and spin-
offs, rather than by major pharmaceutical companies. This
gives rise to a number of comments:

— What must this regulation cover in order for it to become
surely engender a heated debate,

operational?
although the technologies used are full of promise.

It will

On the whole,

4.1
this draft regulation is relevant and
useful. It provides a means of keeping up with scientific devel-
opments and deciding on definitions and the conditions for
serving
using advanced therapy medicinal products,
patients' interests.

thus

— The membership of the CAT also poses a problem owing
to its dependence on the CHMP (which is made up of one
representative per Member State).

— The legislative framework used is inadequate, as these are
unconventional pharmaceutical products that will require
changes to other texts.

— The precautions taken regarding the use of stem cells may
provoke a veto in the countries concerned, as the wording
must be acceptable to avoid problems with the small print.

The aim of facilitating the evaluation of any subse-
3.13
quent request for marketing authorisation using the same data,
should be supported and encouraged.

However, care should be taken and the provision
3.14
altered if necessary in order to take account of rapid develop-

(5) See COM(2005) 567 final, 23rd recital.

These new technologies offer patients great hopes in
4.1.1
terms of overcoming human suffering. However, if they are to
respond to legitimate expectations, especially in the field of
regenerative medicine, research must be supervised using essen-
tial tests, and the protocols for these must offer an absolute
guarantee of patient safety. With this aim in view, the main
objectives set out
the Commission's
in the Justification of
proposal for a Regulation (point 2.1) should be to guarantee
not just a high level of health protection but also to give a
guarantee of medicinal quality assurance. The issue of non-used
waste — a rarely-discussed environmental aspect — must also
not be overlooked.

4.2
The regulation is important, especially in the realms of
gene therapy and somatic cell therapy. The caution exercised
with regard to both definitions and the use of the products of
tissue engineering clearly shows that the draft regulation is not
intended to settle the debate once and for all or to pre-empt
the deliberations of each Member State, since the ethical debate
is not yet resolved and since it depends on varying interpreta-
tions of humanist values.

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4.2.1
This draft regulation creates the preconditions for
closing the regulatory gap that exists between its subject matter
and the draft directive on medical devices. The general principle
of risk evaluation applies to both advanced therapy medicinal
products and medical devices. Complications may arise with
combination products (i.e. medical devices containing tissue
engineered elements). In such cases, both quality and safety
must be guaranteed, and the evaluation must also cover the

efficacy in use of an innovative medicinal product in a specific
medical device.

4.3
In conclusion, the Committee endorses the proposed
regulation while also stressing certain areas of concern for
which clear solutions will be needed in order for the directive
to be implemented successfully.

Brussels, 5 July 2006.

The President

of the European Economic and Social Committee

Anne-Marie SIGMUND

Opinion of the European Economic and Social Committee on the Communication from the
Commission to the European Parliament,
the European Economic and Social
the Regions — Implementing the Community Lisbon
Committee and the Committee of

the Council,

programme: A strategy for the simplification of the regulatory environment

COM(2005) 535 final

(2006/C 309/04)

On 9 December 2005 the European Commission decided to consult the European Economic and Social
Committee, under Article 262 of the Treaty establishing the European Community, on the abovementioned
proposal.

The Section for the Single Market, Production and Consumption, which was responsible for preparing the
Committee's work on the subject, adopted its opinion on 31 May 2006. The rapporteur was Mr Cassidy.

At its 428th plenary session, held on 5 and 6 July 2006 (meeting of 5 July 2006), the European Economic
and Social Committee adopted the following opinion by 146 votes in favour and six abstentions.

1. EESC conclusions and recommendations

This opinion is a referral from the Commission and is a
1.1
follow-up of its Communication of March 2005 Better Regu-
lation for Growth and Jobs in the European Union (1).

Simplification should result in a high quality regulatory

1.2
framework, easier to understand and more ‘user friendly’.

Simplification should increase respect for EU legislation

1.3
and, in the process, reinforce its legitimacy.

The Committee believes that Member States have a
1.4
heavy responsibility to ensure that EU measures are properly
transposed into their national
law and enforced. The
Committee recognises that the Interinstitutional Agreement on
Better Lawmaking (2) provides a ‘code of conduct’ for Member
States in better transposition and application of EC directives.

(1) COM(2005) 97 of 16.3.2005.
(2) OJ C 321, 31.12.2003.

What is important is that the resulting regulatory framework at
national level is both as balanced in terms of content and as
simple as possible for business, employees, consumers and all
civil society players.

1.5
The Committee wishes socio-professional actors to be
associated with the ‘comitology’ procedures of simplification of
regulation, on a model similar to the SLIM committees, but in
a more systematic way and upstream of this regulation, rather
than a posteriori as it was the case of the SLIM experiments.

The Committee would like to see more consultation
1.6
between the Commission and stakeholders similar to that
which has lead to the Communication under discussion.
It
believes that this would be a material assistance to the ‘co-regu-
lation’ (3) referred to in the Communication's paragraph 3d. It
regrets, however, the absence of any reference to ‘self-regu-
lation’ (4), something for which the EESC has been calling for
some time (5).

(3) OJ C 321, 31.12.2003.
(4) OJ C 321, 31.12.2003.
(5) Information report on ‘The State of co-regulation and self-regulation in
the Single Market’, CESE 1182/2004 fin, 11.1.2005, rapporteur: Mr
Vever.