MEMO/01/267
Brussels, 18 July 2001
Reform of EU Pharmaceutical Legislation
1. Background: Current Regulatory Context
In order to remove obstacles to the internal market in pharmaceuticals while at the
same time ensuring a high level of public health protection, the Community has,
since 1965, gradually developed a harmonised legislative framework for medicinal
products. The current system is based on two separate procedures for the granting
of marketing authorisation for a medicinal product:

The centralised procedure leads to a single marketing authorisation valid
throughout the whole Community, which is granted in the form of a Commission
decision and is based on a scientific evaluation by the committees created within
the European Agency for the Evaluation of Medicinal Products (EMEA) in
London. This procedure is mandatory for certain medicinal products developed
by means of biotechnological processes, and is optional for certain other
categories of medicinal products, such as those which contain new active
substances, and those presented for an entirely new indication constituting a
significant innovation.

For those medicinal products not eligible for the centralised procedure, or where
the applicant chooses not to follow the centralised procedure, the system
provides for a mutual recognition procedure. This procedure has to be used by
the applicant whenever an application for marketing authorisation for a medicinal
product concerns two or more Member States.
Regulation 2309/93 – introducing the centralised procedure, which entered into force
in 1995 - established for the Commission the obligation to report on the experience
acquired as a result of the operation of the two authorisation procedures within six
years after the entry into force of the Regulation. In order to execute this obligation a
study was conducted by an external consultant on behalf of the Commission1, on the
basis of which the Commission has prepared and report and the proposals for the
revision are presented.
Apart from the authorisation procedures, reflections on necessary legislative
amendments have been extended to other aspects of the pharmaceutical legislation,
in order to take into consideration the development of science and technology,
certain positions taken by the European Parliament (reports) and/or by the Council
(conclusions or resolutions), and more generally in the evolution of the European
society. The review of the pharmaceutical legislation pursues a set of four major
objectives:
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“Evaluation of the operation of Community procedures for the authorisation of medicinal
products”, Evaluation carried out on behalf of the European Commission, Cameron
McKenna – Andersen Consulting, available on http://pharmacos.eudra.org

To ensure a high level of public health protection for the European citizen, in
particular by allowing rapid access to innovative and safe products and by tight
market surveillance, based on reinforced procedures of control and pharmacovigilance. With regard to veterinary medicinal products, the level of protection of
animal health should be improved in particular by increasing the number of
medicinal products available.

To further complete the internal market in pharmaceuticals and to establish a
regulatory framework favourable to the competitiveness of European
pharmaceutical industry, while taking into consideration the aspects of
globalisation.

To meet the challenges of an enlargement of the European Union.

To rationalise and to simplify, as far as possible, the system and to improve its
global coherence, its visibility and the transparency of the procedures.
These intrinsically linked goals can be realised optimally only if the review achieves a
sound overall equilibrium between all of them. This requires a balance between the
centralised and decentralised systems, since the same fundamental objectives,
namely to ensure a high level of public health protection and to contribute to the
completion of the internal market in medicinal products, apply to both procedures. In
general, the evaluation of the existing authorisation procedures has proven that the
system in place since 1995 works well and has contributed to achieving a high level
of public health protection as well as progressing the internal market in
pharmaceuticals in Europe. As a consequence, there is no need to fundamentally
change the current system with its dual structure. The objective of the review is
therefore limited to optimisation and amendment of the present procedures, while
keeping their general structure.
2. Assessment of the existing system and proposals in the review
Centralised procedure
Authorisation procedure
There is a general opinion within all interested parties that the centralised system
works with a high level of satisfaction. The procedure has proven its effectiveness for
biotechnology and innovative medicinal products. There is also general recognition
of the very considerable contribution made by the EMEA. Nevertheless, the
Commission considered that, in order to boost competitiveness by helping innovative
companies and to cope with foreseeable future evolution in terms of innovation and
technical progress, the scientific profile of the EMEA should be reinforced by
providing additional scientific support and by better specifying and expanding some
of its tasks. In order to achieve this, an increased and flexible scientific expertise (inhouse or by establishing communication channels outside the Agency) is needed.
A significant number of companies and Member State authorities are in favour of the
centralised system being opened up to a broader range of products, in order to
correspond to the needs of the market as they developed in the last years and the
need for a unique scientific assessment, especially as new active substances are
concerned. The Commission agrees that the assessment procedure and the final
decision process are, in some cases, not rapid and not flexible enough. In case of
innovative products, slow development in the procedure might neutralise the
beneficial effects that the placing of the market of innovative products might have on
society.
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The development of new technologies also justifies a review of the assessment
procedures. Solutions were also needed in two situations, which are not covered by
the existing legislation: On the one hand, the cases where the availability of a given
product is indispensable for reasons of public health, and on the other hand, the fact
that very often certain patients could obtain and have at their disposal certain
medicines, which are not covered by an authorisation (compassionate use).
Improvements are also needed in terms of transparency, in both respects, regarding
information on the product characteristics and the assessment reports on the
medicinal products, as well as the reasons and the documentation on which a
decision on granting or refusing an authorisation is based, including dissemination by
the Agency of the documents on which the authorisation decision is based. A
general transparency requirement has also been judged necessary to allow to any
interested person to have access to a number of documents which are not of
confidential nature.
Finally, the Commission recognised that there is a need to strengthen pharmacovigilance and supervision requirements, by reinforcing the duties of the marketing
authorisation holders.
Main changes proposed

The list of products for which the centralised procedure is mandatory is
expanded to all new active substances, i.e. any substance, which has not been
part of an authorised medicinal product in any of the Member States.

The centralised procedure is open, on an optional basis, to
- any other product for which the applicant shows that the product constitutes a
significant innovation or that there is a Community interest, for patients and
for animals
- to immunological veterinary products subject to Community prophylactic
measures or
- to generic medicinal products of centrally authorised medicinal products
 The different steps for the authorisation procedure remain basically the same for
both human and veterinary medicinal products.

The authorisation procedure is accelerated by shortening some deadlines in the
different steps of the procedure.

Accelerated assessment procedures (fast track procedures) are foreseen for
medicinal products of major interest from the point of view of public health and
therapeutic innovation.

The possibility is introduced to obtain conditional authorisations; the possibility of
an authorisation under exceptional circumstances will be maintained and
reinforced.

Regarding compassionate use of medicinal products for human use, the EMEA
shall be able to adopt recommendations, establishing the conditions for this
compassionate use to be put into practice, to be applied by Member States.

The limits regarding the validity of the authorisation are abolished; authorisations
are valid for unlimited duration.
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
The marketing authorisation holder will have to actually market the authorised
medicinal product, within a certain period, otherwise the authorisation ceases to
be valid. There is also an obligation to inform the Agency on the dates of actual
marketing of the medicinal product in the Member states or if the product ceases
to be marketed.

Periodic safety reports, in the context of pharmaco-vigilance, will have to be
prepared and reviewed more frequently than in the current system.
3. EMEA
The form and composition of the scientific committees and the Management Board
of the EMEA needed to be reviewed in order to take into account the future
enlargement of the European Union, to be in line with the last proposals adopted by
the Commission for the creation of the European Food Authority and the two
Agencies on Maritime and Air Safety and to provide sufficient guarantees that the
interests of the civil society and industry are represented. It also seemed appropriate
to create an Advisory Board, with an advisory role for the Member States, the EMEA
and the Commission.
The scope of activities of the EMEA should go beyond the evaluation of medicinal
products in the context of the marketing authorisation, by strengthening its role as a
scientific adviser. The EMEA should also be competent to give scientific advice to
companies, in particular to small and medium companies developing
biotechnological or innovative products. Co-operation with the World Heath
Organisation has also been considered indispensable for the assessment of certain
medicinal products intended exclusively for the markets of third countries.
On the basis of the Commission’s experience in the field of parallel distribution,
action needed to be taken in order to ensure coherence in the application of
Community legislation.
Finally, the supervisory function of the EMEA needed to be reinforced by giving it the
possibility to impose directly financial sanctions on the holders of market
authorisation if they fail to observe certain obligations laid down in connection with
the authorisations.
Main changes proposed

The structure of the EMEA is being completed in order to include certain
Committees already in place (Committee Orphan Medicinal Products) or to be
created by new legislative instruments (Committee of Herbal Medicinal
Products).

An Advisory Board is created, composed of representatives of the national
authorities, which will have a consultative function with respect to authorisation
procedures.

Increased flexibility is being introduced as regards creation of the different
expert-specialised groups, working parties, scientific committees and possibility
of delegation to those of different tasks. There is also a possibility of using
experts from outside the EU provided that certain guarantees are respected.
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
The structure of the Management Board is being reviewed to take into
consideration the future enlargement of the EU, the need for an adequate
representation of the civil society (patients, industry) and the proposed structure
for the new Agencies (Food Authority, Maritime Safety Agency and Air Safety
Agency).

The EMEA will contribute more actively in the framework of dialogues on
international harmonisation.

The EMEA is being attributed the task of ensuring that the conditions laid down
in Community legislation on medicinal products and in the marketing
authorisation are observed in the case of parallel distribution authorised under
the centralised procedure.

The committees forming part of the EMEA assist the Executive Director of the
EMEA and the Commission in drawing up, at their request, any opinions on
scientific matters concerning medicinal products.

The EMEA is being attributed the competence to impose financial sanctions.
4. Mutual recognition procedure
The mutual recognition procedure with its possibility to include only a limited number
of Member States in the procedure, offers an important flexibility for those medicinal
products intended only for a restricted part of the European market, especially in the
veterinary sector.
Concerns have been expressed regarding the duration of the authorisation
procedure, which seems too long and that in practice the Member States too often
do not recognise the marketing authorisation and the scientific evaluation carried out
by another Member State. Once objections of public health have been raised, it often
proves to be quite difficult to reach an agreement between the dissenting Member
States. Problems have also been reported with respect to the arbitration procedure.
The informal groups on mutual recognition (MRFG and VMRFG)2 that have been
established to improve the operation of the mutual recognition procedure have
worked with remarkable success. However, being an informal group with no legal
basis, there has been some concern about the legal effect of the group’s work.
The Commission also considered that the legislative framework for the follow-up of
pharmaco-vigilance measures needs improvement. The current provisions allow
Member States to suspend a marketing authorisation in case of urgency in their
territories, without ensuring the necessary follow-up at Community level. Moreover,
the existing pharmaceutical legislation does not contain provisions covering the
active substances used as starting materials for medicinal products.
The Commission has also established a clear need for a regulatory framework to
cover certain new or future forms of medical treatment, in particular those related to
gene therapy and cell therapy and to provide for an optimal balance between
innovative medicinal products and generic medicines.
2
MRFG: Mutual Recognition Facilitation Group.VMRFG: Veterinary Mutual Recognition
Facilitation Group.
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To avoid that scientific tests required to prepare an application are carried out
outside the Community for purely legal reasons, the Commission considered
appropriate to allow such kind of activity during the validity of the supplementary
protection certificate3 applied to the original product. The Commission is also in
favour of harmonisation of the time periods, and the linkage between data protection
for nationally authorised medicines and corresponding patent protection. Incentives
should be provided to further improve existing medicinal products, in particular to
develop new and important therapeutic indications. Such an incentive could be an
additional data protection period.
Moving with the times – better access to information for patients
The current ban on public advertising of prescription medicines in Europe will be
complemented by a pilot system aimed to ensure the availability of better, clear and
reliable information on authorised pharmaceuticals. This pilot system will apply to
three specific disease groups: diabetes, AIDS and asthma. These diseases are
long-term and chronic, there is a strong patient demand for information and the
results of the 5-year pilot should be relatively easy to monitor among these patient
populations. This will be coupled with strict control measures.
Homeopathic medicines
Regarding homeopathic medicinal products, it appeared necessary to further
improve the availability of these medicinal products. In the area of veterinary
medicine, also homeopathic medicinal products intended for food producing animals
should be eligible for the simplified registration procedure, in particular due to their
increasing use as organic farming.
Medicines for food producing animals
The reduction of the available veterinary medicinal products for food producing
animals is an increasing problem; the Commission considered that the review should
also address this problem. In addition, the use of existing medicinal products (i.e.
available elsewhere in the Community) by practitioners should be facilitated, in the
absence of an authorised medicinal product for a specie and/or indication concerned
on the territory of a Member State. Special provisions should be envisaged for
horses.
Main changes proposed

Concerning the duration of the national authorisation procedure, the current
deadline of 210 days is being reduced to 150 days.

The mutual recognition procedure is being facilitated by :
- introducing different modalities depending whether or not the medicinal
product is already authorised in a Member State,
- defining more precisely the concept of risk for public health,
- giving a formal and legal status to the existing MRFG/VMRFG,
- improving the arbitration phase by ensuring that the objections related to the
serious risk for public health are evaluated properly and that necessary
follow-up measures are taken; also by shortening the time limits of the
evaluation procedure.
3
Council Regulation (EEC) n° 1768/92 of 18 June 1992, concerning the creation of a
supplementary protection certificate for medicinal products, OJ L 182, 02/07/1992, p. 1.
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
Urgent action taken by one Member State will be thoroughly evaluated on a
European level; where necessary, appropriate measures are taken by all
Member States.

The Commission is empowered to lay down detailed guidelines on the
manufacturing and the use of active substances used as starting materials for
medicinal products.

The system of inspections also covers the control, under specific conditions, of
active substances used as starting materials.

The definition of medicinal product is being modified to include new therapies.

Data protection period is being harmonised with the period provided for the
centralised authorised products. An extension of one year of data protection
period can be allowed if a medicinal product, covered by the normal data
protection period, has developed a new therapeutic indication with an important
benefit for the patients.

The term of generic medicinal product is introduced and defined in the legislation.

The possibility to prepare and to file a generic application during the validity of
the supplementary protection certificate applied to the reference medicinal
product is being introduced.

Specific information on request of patients or groups of patients is being
authorised for medicinal products subject to medical prescription. As a first stage,
and in order to evaluate the effects of such a measure, this information is allowed
only for the treatment of three long-term/chronic diseases. Industry needs to
adopt principles of good conduct as well as self-regulatory control procedures,
which will be agreed with the competent authorities. After a certain period, the
implementation of these provisions should be evaluated and eventually adapted.

The option for establishing a simplified registration procedure for certain
homeopathic medicinal products is being changed into an obligation and the
provisions have been extended to food-producing animals.

As far as possible, simplified registrations granted by one Member State should
be recognised throughout the Community.

Specific provisions for veterinary medicinal products on the data protection
period are being set up; the 10 years data protection period can be extended
depending on the number of animal species for which a firm would get a
marketing authorisation.

The provisions defining the conditions for using medicinal products for foodproducing species (“cascade” provision), which are not authorised in a certain
Member State, are being revised; there is a special provision for horses.
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