Common Position (EC) No 40/1999 of 27 September 1999 adopted by the Council, acting in accordance with the procedure referred to in Article 251 of the Treaty establishing the European Community, with a view to adopting a Regulation of the European Parliament and of the Council on orphan medicinal products
Date: 1999-09-27
Institutions: Council of the European Union
Subjects: drugs classification, marketing, medicinal product, research and development

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COMMON POSITION (EC) No 40/1999

adopted by the Council on 27 September 1999

with a view to adopting Regulation (EC) No (cid:133)/1999 of the European Parliament and of the
Council of (cid:133) and of the Council on orphan medicinal products

(1999/C 317/04)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE
EUROPEAN UNION,

Having regard to the Treaty establishing the European
Community, and in particular Article 95 thereof,

Having regard to the proposal from the Commission (1),

Having regard to the Opinion of the Economic and Social
Committee (2),

Acting in accordance with the procedure laid down in Article
251 of the Treaty (3),

Whereas:

to diagnose, prevent or

(1) Some conditions occur so infrequently that the cost of
developing and bringing to the market a medicinal
the condition
product
would not be recovered by the expected sales of the
medicinal product. The pharmaceutical industry would be
unwilling to develop the medicinal product under normal
market conditions. These medicinal products are called
(cid:145)orphan(cid:146).

treat

therefore necessary

(2) Patients suffering from rare conditions should be entitled
It
to the same quality of treatment as other patients.
is
research,
to
development and bringing to the market of appropriate
medications by the pharmaceutical
Incentives
for the development of orphan medicinal products have
been available in the United States since 1983 and in
Japan since 1993.

stimulate

industry.

the

to stimulate
the development of orphan medicinal
products. Such action is best taken at Community level
in order to take advantage of the widest possible market
and to avoid the dispersion of limited resources. Action
at Community level
is preferable to uncoordinated
measures by the Member States which may result
in
to
competition
intra-Community trade.

distortions

barriers

and

of

(4) Orphan medicinal products eligible for incentives should
It seems most
be easily and unequivocally identified.
the
result
appropriate
establishment of an open and transparent Community
procedure for
the designation of potential medicinal
products as orphan medicinal products.

through

achieve

this

to

(5) Objective criteria for designation should be established.
Those criteria should be based on the prevalence of the
condition for which diagnosis, prevention or treatment is
sought. A prevalence of not more than five affected
persons per 10 000 is generally
the
appropriate threshold. Medicinal products intended for a
life-threatening,
serious and
chronic condition should be eligible even when the
prevalence is higher than five per 10 000.

seriously debilitating or

regarded as

States

should be

(6) A Committee composed of experts appointed by the
Member
established to examine
applications for designation. This Committee should also
include three representatives of patients’ associations,
designated
other
persons, also designated by the Commission, on a
recommendation from the European Agency for
the
Evaluation of Medicinal Products. The Agency should be
responsible for the adequate coordination between the
Committee on orphan medicinal products and the
Committee on proprietary medicinal products.

the Commission,

three

and

by

(3)

In the European Union, only limited action has been
taken so far, whether at national or at Community level,

(1) OJ C 276, 4.9.1998, p. 7, and

OJ C (cid:133) (not yet published in the Official Journal).

(2) OJ C 101, 12.4.1999, p. 37.
(3) Opinion of the European Parliament of 9 March 1999 (OJ C 175,
21.6.1999, p. 61), Council Common Position of 27 September
1999 (not yet published in the Official Journal) and Decision of the
European Parliament of (cid:133) (not yet published in the Official
Journal).

(7) Patients with such conditions deserve the same quality,
safety and efficacy in medicinal products as other
patients. Orphan medicinal products should therefore be
submitted to the normal evaluation process. Sponsors of
orphan medicinal products should have the possibility of
to
obtaining a Community authorisation.
facilitate
a
Community authorisation, fees to be paid to the Agency
should be waived at least in part. The Community budget
should compensate the Agency for the loss in revenue
thus occasioned.

In order
the maintenance of

granting or

the

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for

the

incentive

industry
of

investment might be

for
and marketing

(8) Experience in the United States and Japan shows that the
in the
to invest
strongest
development
orphan medicinal
products is where there is a prospect of obtaining market
exclusivity for a certain number of years during which
recovered. Data
part of
protection under Article 4(8)(a)(iii) of Council Directive
65/65/EEC of 26 January 1965 on the approximation of
provisions laid down by law, regulation or administrative
action relating to medicinal products (1) is not a sufficient
acting
that purpose. Member
incentive
independently cannot introduce such a measure without
a Community dimension as such a provision would be
contradictory to Directive 65/65/EEC. If such measures
were adopted in an uncoordinated manner by the
to
States,
Member
intra-Community
of
competition and running counter to the single market.
Market exclusivity should however be limited to the
indication for which orphan medicinal
therapeutic
product designation has been obtained, without prejudice
to existing intellectual property rights. In the interest of
patients,
the market exclusivity granted to an orphan
medicinal product should not prevent the marketing of a
similar medicinal product which could be of significant
benefit to those affected by the condition.

this would
trade,

obstacles
distortions

create
to

leading

States

(9) Sponsors of orphan medicinal products designated under
this regulation should be entitled to the full benefit of
any incentives granted by the Community or by the
Member States to support the research and development
of medicinal products for the diagnosis, prevention or
treatment of such conditions, including rare diseases.

(10) The

the

specific programme Biomed 2, of

fourth
Framework Programme for research and technological
development (1994 to 1998), supported research on the
treatment of rare diseases,
including methodologies for
rapid schemes for the development of orphan medicinal
products and inventories of available orphan medicinal
products
in Europe. Those grants were intended to
promote the establishment of cross national cooperation
in order to implement basic and clinical research on rare
diseases. Research on rare diseases continues to be a
priority for the Community, as it has been included in
research and
the
technological
2002). This
Regulation establishes a legal framework which will allow
the swift and effective implementation of the outcome of
this research.

fifth Framework Programme
(1998
development

for
to

(11) Rare diseases have been identified as a priority area for
Community action within the Framework for Action in
the field of public health. The Commission,
in its
communication concerning a programme of Community
action on rare diseases within the Framework for Action
in the field of public health has decided to give rare
diseases priority within the public health framework. The
European Parliament and the Council have adopted

Decision No 1295/1999/EC of 29 April 1999 adopting a
programme of Community action on rare diseases within
the framework for action in the field of public health
(1999 to 2003) (2),
to provide
including
information, to deal with clusters of rare diseases in a
population and to support relevant patient organisations.
This regulation implements one of
the priorities laid
down in this programme of action,

actions

HAVE ADOPTED THIS REGULATION:

Article 1

Purpose

The purpose of this Regulation is to lay down a Community
procedure for the designation of medicinal products as orphan
medicinal products and to provide incentives for the research,
development and placing on the market of designated orphan
medicinal products.

Article 2

Definitions

For the purposes of this Regulation:

(a)

(cid:145)medicinal product(cid:146) means a medicinal product for human
use, as defined in Article 2 of Directive 65/65/EEC;

(b)

(cid:145)orphan medicinal product(cid:146) means a medicinal product
designated as such under the terms and conditions of this
Regulation;

(c)

(cid:145)sponsor(cid:146) means any legal or natural person, established in
the Community, seeking to obtain or having obtained the
designation of a medicinal product as an orphan medicinal
product;

(d)

(cid:145)Agency(cid:146) means the European Agency for the Evaluation of
Medicinal Products.

(1) OJ L 22, 9.2.1965, p. 369/65. Directive as last amended by

Council Directive 93/39/EEC (OJ L 214, 24.8.1993, p. 22).

(2) OJ L 155, 22.6.1999, p. 1.

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Article 3

Criteria for designation

1. A medicinal product shall be designated as an orphan
medicinal product if its sponsor can establish:

(a)

it

is

intended for

that
the diagnosis, prevention or
treatment of a life-threatening or chronically debilitating
condition affecting not more than five in 10 000 persons
in the Community when the application is made, or

it

is

intended for

that
the diagnosis, prevention or
treatment of a life-threatening, seriously debilitating or
serious and chronic condition in the Community and that
without incentives it is unlikely that the marketing of the
medicinal product
in the Community would generate
sufficient return to justify the necessary investment;

and

(b) that

there exists no satisfactory method of diagnosis,
prevention or treatment of the condition in question that
has been authorised in the Community or, if such method
exists, that the medicinal product will be of significant
benefit to those affected by that condition.

2. The Commission shall adopt the necessary provisions for
implementing this Article in the form of an implementing
Regulation in accordance with the procedure laid down in
Article 72 of Council Regulation (EEC) No 2309/93 (1).

(b) to advise the Commission on the establishment and
development of a policy on orphan medicinal products for
the European Union

(c)

the Commission in liaising internationally on
to assist
matters relating to orphan medicinal products, and in
liaising with patient support groups

(d) to assist the Commission in drawing up detailed guidelines.

3. The Committee shall consist of one member nominated by
three members nominated by the
each Member State,
Commission to represent patients’ organisations and three
members nominated by the Commission on the basis of a
recommendation from the Agency. The members of
the
Committee shall be appointed for a term of three years, which
shall be renewable. They may be accompanied by experts.

4. The Committee shall elect its Chairman for a term of three
years, renewable once.

5. The representatives of the Commission and the Executive
Director of the Agency or his representative may attend all
meetings of the Committee.

6. The Agency
Committee.

shall provide

the

Secretariat of

the

7. Members of the Committee shall be required, even after
their duties have ceased, not to disclose any information of the
kind covered by the obligation of professional secrecy.

Article 5

Article 4

Procedure for designation and removal from the register

Committee for Orphan Medicinal Products

1. A Committee for Orphan Medicinal Products, hereinafter
referred to as (cid:145)the Committee(cid:146),
is hereby set up within the
Agency.

2. The task of the Committee shall be:

(a)

to examine any application for
the designation of a
medicinal product as an orphan medicinal product which
is submitted to it in accordance with this regulation

1.
In order to obtain the designation of a medicinal product
as an orphan medicinal product, the sponsor shall submit an
application to the Agency at any stage of the development of
the medicinal product before the application for marketing
authorisation is made.

2. The application shall be accompanied by the following
particulars and documents:

(a) name or corporate name and permanent address of the

sponsor,

(b) active ingredients of the medicinal products,

(1) OJ L 214, 24.8.1993, p. 1. Regulation as amended by Commission

Regulation (EC) No 649/98 (OJ L 88, 24.3.1998, p. 7).

(c) proposed therapeutic indication,

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(d)

justification that the criteria laid down in Article 3(1) are
the stage of development,
met and a description of
including the indications expected.

which applications for transfer shall be made and the content
of such applications and all the particulars of the new sponsor.

3. The Commission shall, in consultation with the Member
States,
the Agency and interested parties, draw up detailed
guidelines on the required format and content of applications
for designation.

12. A designated orphan medicinal product shall be removed
from the Community Register of Orphan Medicinal Products:

(a) at the request of the sponsor,

4. The Agency shall verify the validity of the application and
summary
prepare
to the Committee. Where
a
appropriate,
it may request the sponsor to supplement the
particulars and documents accompanying the application.

report

(b)

it

if
is established before the market authorisation is
granted that the criteria laid down in Article 3 are no
longer met in respect of the medicinal product concerned,

5. The Agency shall ensure that an opinion is given by the
Committee within 90 days of the receipt of a valid application.

(c) at the end of the period of market exclusivity as laid down

in Article 8.

6. When preparing its opinion, the Committee shall use its
If such a consensus
best endeavours to reach a consensus.
cannot be reached, the opinion shall be adopted by a majority
of two-thirds of the members of the Committee. The opinion
may be obtained by written procedure.

Article 6

Protocol assistance

the Committee

the opinion of

7. Where
the
application does not satisfy the criteria set out in Article 3(1),
the Agency shall
forthwith inform the sponsor. Within 90
the sponsor may submit
days of receipt of
detailed grounds for appeal, which the Agency shall refer to
the Committee. The Committee shall consider whether its
opinion should be revised at the following meeting.

the opinion,

that

is

of

the

submission

1. The sponsor of an orphan medicinal product may, prior
to
for marketing
authorisation, request advice from the Agency on the conduct
of the various tests and trials necessary to demonstrate the
quality,
in
accordance with Article 51(j) of Regulation (EEC) No 2309/93.

the medicinal product,

safety and efficacy of

application

an

circumstances,

8. The Agency shall forthwith forward the final opinion of
the Committee to the Commission, which shall adopt a
decision within 30 days of receipt of the opinion. Where, in
in
exceptional
accordance with the opinion of the Committee, the decision
shall be adopted in accordance with the procedure laid down
in Article 73 of Regulation (EEC) No 2309/93. The decision
shall be notified to the sponsor and communicated to the
Agency and to the competent authorities of
the Member
States.

the draft decision is not

shall draw up a procedure on the
2. The Agency
development
covering
orphan medicinal
of
regulatory assistance for the definition of the content of the
application for authorisation within the meaning of Article 6
of Regulation (EEC) No 2309/93.

products,

Article 7

Community marketing authorisation

9. The designated medicinal product shall be entered in the
Community Register of Orphan Medicinal Products.

Each year the sponsor shall submit

to the Agency a
10.
report on the state of development of the designated medicinal
product.

1. The person responsible for placing on the market an
orphan medicinal product may request that authorisation to
place the medicinal product on the market be granted by the
Community in accordance with the provisions of Regulation
(EEC) No 2309/93 without having to justify that the medicinal
product qualifies under Part B of the Annex to that regulation.

11. To have the designation of an orphan medicinal product
transferred to another sponsor, the holder of the designation
shall make specific application to the Agency. In consultation
with the Member States, the Agency and interested parties, the
Commission shall draw up detailed guidelines on the form in

2. A special contribution from the Community, distinct from
that provided for
in Article 57 of Regulation (EEC) No
2309/93, shall be allocated every year to the Agency. The
contribution shall be used exclusively by the Agency to waive,
in part or in total, all the fees payable under Community rules

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adopted pursuant to Regulation (EEC) No 2309/93. A detailed
report of the use made of this special contribution shall be
presented by the executive director of the Agency at the end of
each year. Any surplus occurring in a given year shall be
carried forward and deducted from the special contribution for
the following year.

shall

product

3. The marketing authorisation granted for an orphan
therapeutic
cover
medicinal
indications which fulfil the criteria set out in Article 3. This is
without prejudice to the possibility of applying for a separate
marketing authorisation for other indications outside the scope
of this Regulation.

those

only

Article 8

Market exclusivity

1. Where a marketing authorisation in respect of an orphan
medicinal product is granted pursuant to Regulation (EEC) No
2309/93 or where all
the Member States have granted
marketing authorisations in accordance with the procedures
for mutual recognition laid down in Articles 7 and 7(a) of
Directive 65/65/EEC or Article 9(4) of Council Directive
75/319/EEC of 20 May 1975 on the approximation of
provisions laid down by law, regulation or administrative
action relating to medicinal products (1), and without prejudice
to intellectual property law or any other provision of
Community law, the Community and the Member States shall
not, for a period of 10 years, accept another application for a
marketing authorisation, or grant a marketing authorisation or
accept
an application to extend an existing marketing
authorisation, for the same therapeutic indication, in respect of
a similar medicinal product.

it

in respect of

is established,

the fifth year,

2. This period may however be reduced to six years if, at the
the
end of
medicinal product concerned, that the criteria laid down in
Article 3 are no longer met, inter alia, where it is shown on the
basis of available evidence that
is sufficiently
profitable not to justify maintenance of market exclusivity. To
that end, a Member State shall
inform the Agency that the
criterion on the basis of which market exclusivity was granted
may not be met and the agency shall
then initiate the
procedure laid down in Article 5. The sponsor shall provide
the Agency with the information necessary for that purpose.

the product

3. By way of derogation from paragraph 1, and without
prejudice to intellectual property law or any other provision of
Community law, a marketing authorisation may be granted,

for the same therapeutic indication,
product if:

to a similar medicinal

(a)

the holder of the marketing authorisation for the original
orphan medicinal product has given his consent to the
second applicant, or

(b) the holder of the marketing authorisation for the original
orphan medicinal product is unable to supply sufficient
quantities of the medicinal product, or

(c)

the second applicant can establish in the application that
the second medicinal product, although similar to the
orphan medicinal product already authorised,
safer,
more effective or otherwise clinically superior.

is

4. The Commission shall
(cid:145)similar
medicinal product(cid:146) and (cid:145)clinical superiority(cid:146) in the form of an
implementing regulation in accordance with the procedure laid
down in Article 72 of Regulation (EEC) No 2309/93.

adopt definitions of

5. The Commission shall draw up detailed guidelines for the
application of this Article in consultation with the Member
States, the Agency and interested parties.

Article 9

Other incentives

1. Medicinal products designated as orphan medicinal
products under the provisions of
this regulation shall be
eligible for incentives made available by the Community and
by the Member States to support research into, and the
development and availability of, orphan medicinal products
and in particular aid for research for small and medium-sized
for
undertakings provided for
research and technological development.

in framework programmes

2. Before (cid:133) (*) the Member States shall communicate to the
Commission detailed information concerning any measure they
have enacted to support research into, and the development
and availability of, orphan medicinal products or medicinal
products that may be designated as such. That information
shall be updated regularly.

3. Before (cid:133) (**)
the Commission shall publish a detailed
inventory of all incentives made available by the Community
and the Member States to support research into, and the

(*) Six months
regulation.

from the date of

the entry into force of

this

(1) OJ L 147, 9.6.1975, p. 13. Directive as last amended by Directive

(**) Twelve months from the date of the entry into force of this

93/39/EEC (OJ L 214, 24.8.1993, p. 22).

regulation.

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development and availability of, orphan medicinal products.
That inventory shall be updated regularly.

Article 11

Entry into force

Article 10

General report

This Regulation shall enter into force on the day of
publication in the Official Journal of the European Communities.

its

Before (cid:133) (*) the Commission shall publish a general report on
the experience acquired as a result of the application of this
regulation,
the public health
benefits which have been obtained.

together with an account of

shall

apply as

the
from the date of
It
implementing regulations provided for in Article 3(2) and
Article 8(4).

adoption of

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at (cid:133)

For the European Parliament

The President

For the Council

The President

(*)

Six years after the date of the entry into force of this regulation.

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STATEMENT OF THE COUNCIL’S REASONS

I.

INTRODUCTION

1. On 28 July 1998 the Commission submitted to the Council a proposal for a regulation on

orphan medicinal products, based on Article 95 of the Treaty (1).

2. The Economic and Social Committee delivered its opinion on 27 January 1999 (2).

3. The European Parliament delivered its opinion at its first reading on 9 March 1999 (3). In the
light of the European Parliament’s opinion the Commission submitted an amended proposal to
the Council under cover of a letter dated 17 June 1999.

4. On 27 September 1999, the Council adopted its common position in accordance with Article

251 of the Treaty.

II. PURPOSE

5. The purpose of the proposal

is to establish a Community procedure for the designation of
medicinal products as orphan medicinal products, and to provide incentives for the research,
development and bringing to the market of orphan medicinal products, in particular by granting
market exclusivity for 10 years without prejudice to other incentives which may be introduced at
national level.

It carries out the Council’s intention, as expressed in its resolution of 20 December 1995 on
orphan medicinal products, to have (cid:145)a common European approach to rare diseases and orphan
medicinal products(cid:146) which (cid:145)holds out advantages in epidemiological, public health and economic
terms(cid:146).

III. ANALYSIS OF THE COMMON POSITION

6. The common position corresponds almost completely to the amended Commission proposal.
Apart from one exception, it thus incorporates all of the European Parliament’s amendments that
were accepted by the Commission.

In some cases, the Council has made textual clarifications or minor changes, which are, however,
consistent with the general
line taken in the European Parliament’s amendments and the
amended proposal.

The Commission has approved all the Council’s amendments.

Amendments accepted unchanged or with minor editorial changes

7. The Council accepted amendment 3 (recital 5) and the corresponding amendment 7 (Article
3(2)), under which the possibility of applying economic criteria when designating a product as an

(1) OJ C 276, 4.9.1998.
(2) OJ C 101, 12.4.1999.
(3) OJ C 175, 21.6.1999.

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orphan medicinal product, initially restricted to communicable diseases, is extended to all serious
and chronic diseases.

8. The Council also accepted amendment 4 (recital 8) and the related amendment 16 (Article 8(1)),
which states that the new form of intellectual property created by the designation of an orphan
medicinal product will not affect other intellectual property rights.

9. Amendment 8 (Article 4(1)) states that the Committee for Orphan Medicinal Products will be a
part of the European Agency for the Evaluation of Medicinal Products. The Council accepted it.

10. The Council accepted amendment 9 (Article 4(3)), which enables members of the Committee for

Orphan Medicinal Products to call upon the services of additional experts if necessary.

11. The Council accepted amendment 10 (Article 4(6)(a)(new)), which is intended to ensure that the
members of the Committee respect the requirements of professional secrecy even after their
duties have ceased.

12. Amendment 11 (Article 5(1)) extends the possibility for a sponsor to apply for designation at any
stage of the development of a medicinal product before an application for market authorisation
is submitted. The Council accepted the amendment.

13. The Council accepted amendment 12 (Article 5(9)(a)(new)), which requires the sponsor to supply

annual reports on the state of development of a designated medicinal product.

14. Amendment 13 (Article 5(9)(b)(new)) is intended to facilitate the transfer of designation rights
from one party to another; this was considered necessary in view of the numerous mergers and
restructuring operations that are a feature of the pharmaceutical industry. The Council accepted
this amendment.

15. The Council accepted amendment 21 (Article 9(1)), which states that medicinal products
designated as orphan medicinal products will be eligible for aid for research for small and
medium-sized undertakings provided under the Fifth Framework Programme for Research and
Technological Development.

Amendment partially accepted

16. The Council accepted the part of amendment 19 (Article 8(5)) that deletes the definition of
(cid:145)similar medicinal product(cid:146) and replaces it by a provision requiring the Commission,
in
consultation with the Agency and interested parties, to adopt a definition as well as a definition
in the form of an implementation regulation, and draw up detailed
of
guidance for the application of Article 8.

(cid:145)clinical superiority(cid:146)

The Council did not accept the part that refers to the drawing up of detailed guidance for
application of the implementation regulation, as it considers it to be already covered by the
reference to the provisions of Article 8 as a whole.

Amendment accepted in principle

17. The Council

incorporated,

(cid:145)the
Commission and the European Parliament(cid:146)) amendment 5 (recital 10), affirming that research
into rare diseases is regarded as a priority by the Commission and the European Parliament.

in a slightly modified form ((cid:145)the Community(cid:146)

instead of

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Amendment not accepted

18. The Council did not adopt amendment 14 (Article 6(2)(a)). The Council considers that the
inclusion in Article 6(1) of a reference to the provisions of Article 51(j) of Regulation (EEC) No
2309/93, which refer to Agency assistance for undertakings in conducting trials, rendered Article
6(2)(a) concerning assistance in the development of a protocol for pre-clinical and clinical trials
redundant. It therefore deleted Article 6(2)(a).