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I
(Acts w ose publication is obligatory)
REGULA ION (EC) No 141/2000 OF HE EUROPEAN PARLIAMEN AND OF HE COUNCIL of 16 December 1999
on orphan medicinal products
THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,
H ving reg rd to the Tre ty est blishing the Europe n Community, nd in p rticul r Article 95 thereof,
H ving reg rd to the propos l from the Commission (1),
H ving reg rd to the opinion of the Economic nd Soci l Committee (2),
Acting in ccord nce with the procedure l id down in Article 251 of the Tre ty (3),
Where s:
(1) some conditions occur so infrequently th t the cost of developing nd bringing to the m rket medicin l product to di gnose, prevent or tre t the condition would not be recovered by the expected s les of the medicin l product; the ph rm ceutic l industry would be unwilling to develop the medicin l product under norm l m rket conditions; these medicin l products re c lled ‘orph n’;
(2) p tients suffering from r re conditions should be enti- tled to the s me qu lity of tre tment s other p tients; it is therefore necess ry to stimul te the rese rch, develop- ment nd bringing to the m rket of ppropri te medic - tions by the ph rm ceutic l industry; incentives for the development of orph n medicin l products h ve been v il ble in the United St tes of Americ since 1983 nd in J p n since 1993;
(3) in the Europe n Union, only limited ction h s been t ken so f r, whether t n tion l or t Community level, to stimul te the development of orph n medicin l prod- ucts; such ction is best t ken t Community level in order to t ke dv nt ge of the widest possible m rket nd to void the dispersion of limited resources; ction t Community level is prefer ble to uncoordin ted me s- ures by the Member St tes which m y result in distor-
(1) OJ C 276, 4.9.1998, p. 7. (2) OJ C 101, 12.4.1999, p. 37. (3) Opinion of the Europe n P rli ment of 9 M rch 1999 (OJ C 175,
21.6.1999, p. 61), Council Common Position of 27 September 1999 (OJ C 317, 4.11.1999, p. 34) nd Decision of the Europe n P rli ment of 15 December 1999 (not yet published in the Offici l Journ l).
tions of competition nd b rriers to intr -Community tr de;
(4) orph n medicin l products eligible for incentives should be e sily nd unequivoc lly identified; it seems most ppropri te to chieve this result through the est blish-
ment of n open nd tr nsp rent Community procedure for the design tion of potenti l medicin l products s orph n medicin l products;
(5) objective criteri for design tion should be est blished; those criteri should be b sed on the prev lence of the condition for which di gnosis, prevention or tre tment is sought; prev lence of not more th n five ffected persons per 10 thous nd is gener lly reg rded s the ppropri te threshold; medicin l products intended for life-thre tening, seriously debilit ting or serious nd chronic condition should be eligible even when the prev lence is higher th n five per 10 thous nd;
(6) Committee composed of experts ppointed by the Member St tes should be est blished to ex mine pplic - tions for design tion; this Committee should lso include three represent tives of p tients' ssoci tions, design ted by the Commission, nd three other persons, lso design ted by the Commission, on recommend - tion from the Europe n Agency for the Ev lu tion of Medicin l Products (herein fter referred to s ‘the Agency’); the Agency should be responsible for the dequ te coordin tion between the Committee on orph n medicin l products nd the Committee on propriet ry medicin l products;
(7) p tients with such conditions deserve the s me qu lity, s fety nd effic cy in medicin l products s other p tients; orph n medicin l products should therefore be submitted to the norm l ev lu tion process; sponsors of orph n medicin l products should h ve the possibility of obt ining Community uthoris tion; in order to f cilit te the gr nting or the m inten nce of Community uthoris tion, fees to be p id to the Agency should be w ived t le st in p rt; the Community budget should compens te the Agency for the loss in revenue thus occ sioned;
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(8) experience in the United St tes of Americ nd J p n shows th t the strongest incentive for industry to invest in the development nd m rketing of orph n medicin l products is where there is prospect of obt ining m rket exclusivity for cert in number of ye rs during which p rt of the investment might be recovered; d t protection under Article 4(8)( )(iii) of Council Directive 65/65/EEC of 26 J nu ry 1965 on the pproxim tion of provisions l id down by l w, regul tion or dminis- tr tive ction rel ting to medicin l products (1) is not sufficient incentive for th t purpose; Member St tes cting independently c nnot introduce such me sure
without Community dimension s such provision would be contr dictory to Directive 65/65/EEC; if such me sures were dopted in n uncoordin ted m nner by the Member St tes, this would cre te obst cles to intr - Community tr de, le ding to distortions of competition nd running counter to the single m rket; m rket exclu- sivity should however be limited to the ther peutic indi- c tion for which orph n medicin l product design tion h s been obt ined, without prejudice to existing intellec- tu l property rights; in the interest of p tients, the m rket exclusivity gr nted to n orph n medicin l product should not prevent the m rketing of simil r medicin l product which could be of signific nt benefit to those ffected by the condition;
(9) sponsors of orph n medicin l products design ted under this Regul tion should be entitled to the full benefit of ny incentives gr nted by the Community or by the
Member St tes to support the rese rch nd development of medicin l products for the di gnosis, prevention or tre tment of such conditions, including r re dise ses;
(10) the specific progr mme Biomed 2, of the fourth fr me- work progr mme for rese rch nd technologic l devel- opment (1994 to 1998), supported rese rch on the tre tment of r re dise ses, including methodologies for r pid schemes for the development of orph n medicin l products nd inventories of v il ble orph n medicin l products in Europe; those gr nts were intended to promote the est blishment of cross n tion l cooper tion in order to implement b sic nd clinic l rese rch on r re dise ses; rese rch on r re dise ses continues to be priority for the Community, s it h s been included in the fifth fr mework progr mme for rese rch nd techno- logic l development (1998 to 2002); this Regul tion est blishes leg l fr mework which will llow the swift nd effective implement tion of the outcome of this
rese rch;
(11) r re dise ses h ve been identified s priority re for Community ction within the fr mework for ction in the field of public he lth; the Commission, in its communic tion concerning progr mme of Community ction on r re dise ses within the fr me- work for ction in the field of public he lth h s decided to give r re dise ses priority within the public he lth
fr mework; the Europe n P rli ment nd the Council h ve dopted Decision No 1295/1999/EC of 29 April 1999 dopting progr mme of Community ction on r re dise ses within the fr mework for ction in the field of public he lth (1999 to 2003) (2), including ctions to provide inform tion, to de l with clusters of r re dise ses in popul tion nd to support relev nt p tient org nis tions; this Regul tion implements one of the priorities l id down in this progr mme of ction,
HAVE ADOPTED THIS REGULATION:
Article 1
Purpose
The purpose of this Regul tion is to l y down Community procedure for the design tion of medicin l products s orph n medicin l products nd to provide incentives for the rese rch, development nd pl cing on the m rket of design ted orph n medicin l products.
Article 2
Definitions
For the purposes of this Regul tion:
( ) ‘medicin l product’ me ns medicin l product for hum n use, s defined in Article 2 of Directive 65/65/EEC;
(b) ‘orph n medicin l product’ me ns medicin l product design ted s such under the terms nd conditions of this Regul tion;
(c) ‘sponsor’ me ns ny leg l or n tur l person, est blished in the Community, seeking to obt in or h ving obt ined the design tion of medicin l product s n orph n medicin l product;
(d) ‘Agency’ me ns the Europe n Agency for the Ev lu tion of Medicin l Products.
Article 3
Criteria for designation
1. A medicin l product sh ll be design ted s n orph n medicin l product if its sponsor c n est blish:
( ) th t it is intended for the di gnosis, prevention or tre t- ment of life-thre tening or chronic lly debilit ting condi- tion ffecting not more th n five in 10 thous nd persons in the Community when the pplic tion is m de, or
th t it is intended for the di gnosis, prevention or tre t- ment of life-thre tening, seriously debilit ting or serious nd chronic condition in the Community nd th t without
incentives it is unlikely th t the m rketing of the medicin l product in the Community would gener te sufficient return to justify the necess ry investment;
(1) OJ 22, 9.2.1965, p. 369. Directive s l st mended by 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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nd
(b) th t there exists no s tisf ctory method of di gnosis, prevention or tre tment of the condition in question th t h s been uthorised in the Community or, if such method exists, th t the medicin l product will be of signific nt benefit to those ffected by th t condition.
2. The Commission sh ll dopt the necess ry provisions for implementing this Article in the form of n implementing Regul tion in ccord nce with the procedure l id down in Article 72 of Council Regul tion (EEC) No 2309/93 (1).
Article 4
Committee for Orphan Medicinal Products
1. A Committee for Orph n Medicin l Products, herein fter referred to s ‘the Committee’, is hereby set up within the Agency.
2. The t sk of the Committee sh ll be:
( ) to ex mine ny pplic tion for the design tion of medi- cin l product s n orph n medicin l product which is submitted to it in ccord nce with this Regul tion;
(b) to dvise the Commission on the est blishment nd devel- opment of policy on orph n medicin l products for the Europe n Union;
(c) to ssist the Commission in li ising intern tion lly on m tters rel ting to orph n medicin l products, nd in li ising with p tient support groups;
(d) to ssist the Commission in dr wing up det iled guidelines.
3. The Committee sh ll consist of one member nomin ted by e ch Member St te, three members nomin ted by the Commission to represent p tients' org nis tions nd three members nomin ted by the Commission on the b sis of recommend tion from the Agency. The members of the Committee sh ll be ppointed for term of three ye rs, which sh ll be renew ble. They m y be ccomp nied by experts.
4. The Committee sh ll elect its Ch irm n for term of three ye rs, renew ble once.
5. The represent tives of the Commission nd the Executive Director of the Agency or his represent tive m y ttend ll meetings of the Committee.
6. The Agency sh ll provide the secret ri t of the Committee.
7. Members of the Committee sh ll be required, even fter their duties h ve ce sed, not to disclose ny inform tion of the kind covered by the oblig tion of profession l secrecy.
Article 5
Procedure for designation and removal from the register
1. In order to obt in the design tion of medicin l product s n orph n medicin l product, the sponsor sh ll submit n pplic tion to the Agency t ny st ge of the development of
(1) OJ L 214, 24.8.1993, p. 1. Regul tion s mended by Commission Regul tion (EC) No 649/98 (OJ L 88, 24.3.1998, p. 7).
the medicin l product before the pplic tion for m rketing uthoris tion is m de.
2. The pplic tion sh ll be ccomp nied by the following p rticul rs nd documents:
( ) n me or corpor te n me nd perm nent ddress of the sponsor;
(b) ctive ingredients of the medicin l product;
(c) proposed ther peutic indic tion;
(d) justific tion th t the criteri l id down in Article 3(1) re met nd description of the st ge of development, including the indic tions expected.
3. The Commission sh ll, in consult tion with the Member St tes, the Agency nd interested p rties, dr w up det iled guidelines on the required form t nd content of pplic tions for design tion.
4. The Agency sh ll verify the v lidity of the pplic tion nd prep re summ ry report to the Committee. Where ppro- pri te, it m y request the sponsor to supplement the p rticul rs nd documents ccomp nying the pplic tion.
5. The Agency sh ll ensure th t n opinion is given by the Committee within 90 d ys of the receipt of v lid pplic tion.
6. When prep ring its opinion, the Committee sh ll use its best ende vours to re ch consensus. If such consensus c nnot be re ched, the opinion sh ll be dopted by m jority of two-thirds of the members of the Committee. The opinion m y be obt ined by written procedure.
7. Where the opinion of the Committee is th t the pplic - tion does not s tisfy the criteri set out in Article 3(1), the Agency sh ll forthwith inform the sponsor. Within 90 d ys of receipt of the opinion, the sponsor m y submit det iled grounds for ppe l, which the Agency sh ll refer to the Committee. The Committee sh ll consider whether its opinion should be revised t the following meeting.
8. The Agency sh ll forthwith forw rd the fin l opinion of the Committee to the Commission, which sh ll dopt decision within 30 d ys of receipt of the opinion. Where, in exception l circumst nces, the dr ft decision is not in ccord- nce with the opinion of the Committee, the decision sh ll be dopted in ccord nce with the procedure l id down in Article 73 of Regul tion (EEC) No 2309/93. The decision sh ll be notified to the sponsor nd communic ted to the Agency nd to the competent uthorities of the Member St tes.
9. The design ted medicin l product sh ll be entered in the Community Register of Orph n Medicin l Products.
10. E ch ye r the sponsor sh ll submit to the Agency report on the st te of development of the design ted medicin l product.
11. To h ve the design tion of n orph n medicin l product tr nsferred to nother sponsor, the holder of the design tion sh ll m ke specific pplic tion to the Agency. In consult tion with the Member St tes, the Agency nd interested p rties, the Commission sh ll dr w up det iled guidelines on the form in which pplic tions for tr nsfer sh ll be m de nd the content of such pplic tions nd ll the p rticul rs of the new sponsor.
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12. A design ted orph n medicin l product sh ll be removed from the Community Register of Orph n Medicin l Products:
( ) t the request of the sponsor;
(b) if it is est blished before the m rket uthoris tion is gr nted th t the criteri l id down in Article 3 re no longer met in respect of the medicin l product concerned;
(c) t the end of the period of m rket exclusivity s l id down in Article 8.
Article 6
Protocol assistance
1. The sponsor of n orph n medicin l product m y, prior to the submission of n pplic tion for m rketing uthor- is tion. request dvice from the Agency on the conduct of the v rious tests nd tri ls necess ry to demonstr te the qu lity, s fety nd effic cy of the medicin l product, in ccord nce with Article 51(j) of Regul tion (EEC) No 2309/93.
2. The Agency sh ll dr w up procedure on the develop- ment of orph n medicin l products, covering regul tory ssis- t nce for the definition of the content of the pplic tion for uthoris tion within the me ning of Article 6 of Regul tion (EEC) No 2309/93.
Article 7
Community marketing authorisation
1. The person responsible for pl cing on the m rket n orph n medicin l product m y request th t uthoris tion to pl ce the medicin l product on the m rket be gr nted by the Community in ccord nce with the provisions of Regul tion (EEC) No 2309/93 without h ving to justify th t the medicin l product qu lifies under P rt B of the Annex to th t Regul tion.
2. A speci l contribution from the Community, distinct from th t provided for in Article 57 of Regul tion (EEC) No 2309/93, sh ll be lloc ted every ye r to the Agency. The contribution sh ll be used exclusively by the Agency to w ive, in p rt or in tot l, ll the fees p y ble under Community rules dopted pursu nt to Regul tion (EEC) No 2309/93. A det iled report of the use m de of this speci l contribution sh ll be presented by the Executive Director of the Agency t the end of e ch ye r. Any surplus occurring in given ye r sh ll be c rried forw rd nd deducted from the speci l contribution for the following ye r.
3. The m rketing uthoris tion gr nted for n orph n medi- cin l product sh ll cover only those ther peutic indic tions which fulfil the criteri set out in Article 3. This is without
prejudice to the possibility of pplying for sep r te m rketing uthoris tion for other indic tions outside the scope of this Regul tion.
Article 8
Market exclusivity
1. Where m rketing uthoris tion in respect of n orph n medicin l product is gr nted pursu nt to Regul tion (EEC) No 2309/93 or where ll the Member St tes h ve gr nted m rketing uthoris tions in ccord nce with the procedures for mutu l recognition l id down in Articles 7 nd 7 of Directive 65/65/EEC or Article 9(4) of Council Directive 75/319/EEC of 20 M y 1975 on the pproxim tion of provisions l id down by l w, regul tion or dministr tive ction rel ting to medicin l products (1), nd without prejudice to intellectu l property l w or ny other provision of Community l w, the Community nd the Member St tes sh ll not, for period of 10 ye rs, ccept nother pplic tion for m rketing uthoris tion, or gr nt
m rketing uthoris tion or ccept n pplic tion to extend n existing m rketing uthoris tion, for the s me ther peutic indi- c tion, in respect of simil r medicin l product.
2. This period m y however be reduced to six ye rs if, t the end of the fifth ye r, it is est blished, in respect of the medi- cin l product concerned, th t the criteri l id down in Article 3 re no longer met, inter alia, where it is shown on the b sis of v il ble evidence th t the product is sufficiently profit ble not
to justify m inten nce of m rket exclusivity. To th t end, Member St te sh ll inform the Agency th t the criterion on the b sis of which m rket exclusivity w s gr nted m y not be met nd the Agency sh ll then initi te the procedure l id down in
Article 5. The sponsor sh ll provide the Agency with the inform tion necess ry for th t purpose.
3. By w y of derog tion from p r gr ph 1, nd without prejudice to intellectu l property l w or ny other provision of Community l w, m rketing uthoris tion m y be gr nted, for the s me ther peutic indic tion, to simil r medicin l product if:
( ) the holder of the m rketing uthoris tion for the origin l orph n medicin l product h s given his consent to the second pplic nt, or
(b) the holder of the m rketing uthoris tion for the origin l orph n medicin l product is un ble to supply sufficient qu ntities of the medicin l product, or
(c) the second pplic nt c n est blish in the pplic tion th t the second medicin l product, lthough simil r to the orph n medicin l product lre dy uthorised, is s fer, more effective or otherwise clinic lly superior.
4. The Commission sh ll dopt definitions of ‘simil r medi- cin l product’ nd ‘clinic l superiority’ in the form of n imple- menting Regul tion in ccord nce with the procedure l id down in Article 72 of Regul tion (EEC) No 2309/93.
5. The Commission sh ll dr w up det iled guidelines for the pplic tion of this Article in consult tion with the Member St tes, the Agency nd interested p rties.
(1) OJ L 147, 9.6.1975, p. 13. Directive s l st mended by Council Directive 93/39/EEC (OJ L 214, 24.8.1993, p. 22).
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Article 9 nd the development nd v il bility of, orph n medicin l products. Th t inventory sh ll be upd ted regul rly.Other incentives
1. Medicin l products design ted s orph n medicin l prod- ucts under the provisions of this Regul tion sh ll be eligible for incentives m de v il ble by the Community nd by the Member St tes to support rese rch into, nd the development nd v il bility of, orph n medicin l products nd in p rticul r id for rese rch for sm ll- nd medium-sized undert kings
provided for in fr mework progr mmes for rese rch nd tech- nologic l development. 2. Before 22 July 2000, the Member St tes sh ll communi- c te to the Commission det iled inform tion concerning ny me sure they h ve en cted to support rese rch into, nd the development nd v il bility of, orph n medicin l products or medicin l products th t m y be design ted s such. Th t infor- m tion sh ll be upd ted regul rly. 3. Before 22 J nu ry 2001, the Commission sh ll publish det iled inventory of ll incentives m de v il ble by the Community nd the Member St tes to support rese rch into,
Article 10
General report
Before 22 J nu ry 2006, the Commission sh ll publish gener l report on the experience cquired s result of the pplic tion of this Regul tion, together with n ccount of the
public he lth benefits which h ve been obt ined.
Article 11
Entry into force
This Regul tion sh ll enter into force on the d y of its public - tion in the Official Journal of t e European Communities.
It sh ll pply s from the d te of doption of the implementing Regul tions provided for in Article 3(2) nd Article 8(4).
This Regul tion sh ll be binding in its entirety nd directly pplic ble in ll Member St tes.
Done t Brussels, 16 December 1999.
For t e European Parliament For t e Council
T e President T e President
N. FONTAINE K. HEMILÄ