Amended proposal for a European Parliament and Council Regulation (EC) on orphan medicinal products
27. 6. 2000 EN Official Journal of the European Communities C 177 E/1 II (Preparatory Acts) COMMISSION Amended proposal for a European Parliament and Council Regulation on orphan medicinal products (1) (2000/C 177 E/01) COM(1999) 298 final - 98/0240(COD) (Submitted by the Commission pursuant to Article 250(2) of the EC-Treaty 16 June 1999) (1) OJ C 276, 4. 9. 1998, p. 7. INITIAL PROPOSAL AMENDED PROPOSAL THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION, Unchanged Having regard to the Treaty establishing the European Community, and in particular Article 100A thereof, Having regard to the Treaty establishing the European Community, and in particular Article 95 thereof, Having regard to the proposal from the Commission, Unchanged Having regard to the opinion of Committee, the Economic and Social Acting in accordance with the procedure laid down in Article 189 B of the EC Treaty, Acting in accordance with the procedure laid down in Article 251 of the EC Treaty, Unchanged (1) Whereas some conditions occur so infrequently that the cost of developing and bringing to the market a medicinal product to diagnose, prevent or treat the condition would not be recovered by the expected sales of the medicinal product; whereas the pharmaceutical industry would be unwilling to develop the medicinal product under normal market conditions; whereas these medicinal products are therefore called áorphaní; (2) Whereas patients suffering from rare conditions should be entitled to the same quality of treatment as other patients; whereas it is therefore necessary to stimulate the research, development and bringing to the market of appropriate industry; whereas medications by the pharmaceutical incentives the development of orphan medicinal products have been available in the United States since 1983 and in Japan since 1993; for (3) Whereas, in the European Union, only limited action has been taken so far, whether at national or at Community level, to stimulate the development of orphan medicinal products; whereas such action is best taken at Community in order to take advantage of the widest possible level market and to avoid the dispersion of limited resources; whereas action at Community level is preferable to unco- ordinated measures by the Member States which may result in distortions of competition and barriers to intra- Community trade; C 177 E/2 EN Official Journal of the European Communities 27. 6. 2000 INITIAL PROPOSAL AMENDED PROPOSAL (4) Whereas orphan medicinal products eligible for incentives should be easily and unequivocally identified; whereas it seems most appropriate to achieve this result through the establishment of an open and transparent Community procedure for the designation of potential medicinal products as orphan medicinal products; the (5) Whereas objective criteria for designation should be estab- lished; whereas these criteria should be based on the prevalence of condition for which diagnosis, prevention or treatment is sought; whereas a prevalence of no more than five affected persons per ten thousand is generally regarded as the appropriate threshold; whereas life-threatening, medicinal products debilitating or seriously communicable condition should be eligible even when the prevalence is higher than five per ten thousand; for a seriously debilitating intended the (5) Whereas objective criteria for designation should be estab- lished; whereas these criteria should be based on the prevalence of condition for which diagnosis, prevention or treatment is sought; whereas a prevalence of no more than five affected persons per ten thousand is generally regarded as the appropriate threshold; whereas medicinal products life-threatening, seriously debilitating or serious and chronic condition should be eligible even when the prevalence is higher than five per ten thousand; intended for a Unchanged associations, for designation; whereas (6) Whereas a Committee composed of experts appointed by the Member States should be established to examine this Committee applications representatives of should in addition include the patients’ Commission, and three other persons, also designated by the Commission, on a recommendation from the Agency; whereas the Agency should be responsible for the adequate coordination between the Committee on and the Committee on orphan medicinal products proprietary medicinal products; three be designated by to (7) Whereas patients with such conditions deserve the same quality, safety and efficacy in medicinal products as other patients; whereas orphan medicinal products should therefore be submitted to the normal evaluation process; whereas sponsors of orphan medicinal products should have the possibility of obtaining a Community author- isation; whereas, in order to facilitate the granting of a Community authorisation, fee to be paid to the Agency should be waived at least in part; whereas the Community budget should compensate the Agency for the loss in revenue thus occurred; (7) Whereas patients with such conditions deserve the same quality, safety and efficacy in medicinal products as other patients; whereas orphan medicinal products should therefore be submitted to the normal evaluation process; whereas sponsors of orphan medicinal products should have the possibility of obtaining a Community author- isation; whereas, in order to facilitate the granting or the maintenance of a Community authorisation, fees to be paid to the Agency should be waived at least in part; whereas the Community budget should compensate the Agency for the loss in revenue thus occurred; (8) Whereas experience in the United States and Japan shows that the strongest incentive for industry to invest in the development and marketing of orphan medicinal products is the prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered; whereas data protection under Article 4(8)(a)(iii) of Council Directive 65/65 is not sufficient that purpose; whereas market exclusivity should however be limited to the therapeutic indication for which orphan medicinal product desig- nation has been obtained; whereas, in the interest of patients, the market exclusivity granted to an orphan medicinal product should not prevent the marketing of a similar medicinal which is safer, more effective or otherwise clinically superior; incentive for (8) Whereas experience in the United States and Japan shows that the strongest incentive for industry to invest in the development and marketing of orphan medicinal products is the prospect of obtaining market exclusivity for a certain number of years during which part of the investment might be recovered; whereas data protection under Article 4(8)(a)(iii) of Council Directive 65/65 is not incentive for that purpose; whereas Member sufficient States this measure without a Community dimension as such a provision would be contradictory to Directive 65/65/EEC; whereas if such measures were adopted in an uncoor- dinated manner by the Member States, this would create obstacles to intra-Community trade, leading to distortions of competition and running contrary to a single market; independently introduce cannot acting 27. 6. 2000 EN Official Journal of the European Communities C 177 E/3 INITIAL PROPOSAL AMENDED PROPOSAL has designation to whereas market exclusivity should however be limited to the therapeutic indication for which orphan medicinal obtained, without product prejudice rights; whereas, in the interest of patients, the market exclusivity granted to an orphan medicinal product should not the marketing of a similar medicinal which prevent could be of significant benefit to those affected by the condition; been intellectual property existing Unchanged (9) Whereas of sponsors orphan medicinal products designated under this Regulation should be entitled to full benefit of any incentives granted by the 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; these grants (10) Whereas the specific programme Biomed 2, of the Fourth Framework Programme for research and technological support development research on the (1994-1998), treatment of rare diseases, including methodologies for rapid schemes for the development of orphan medicinal products and inventories of available orphan medicinal in to promote the estab- Europe; whereas lishment of cross national cooperation in order to implement basic and clinical research on rare diseases; research on rare diseases continue to be a whereas priority for the Commission, as it has been in the Commission’s Fifth Framework Programme (1998-2002) for research and technological development; whereas this Regulation establishes a legal framework which will the allow the swift and effective implementation of outcome of this research; (10) Whereas the specific programme Biomed 2, of the Fourth Framework Programme for research and technological supported research on the development (1994-1998), treatment of rare diseases, including methodologies for rapid schemes for the development of orphan medicinal products and inventories of available orphan medicinal in Europe; whereas these grants were to promote the estab- lishment of cross national cooperation in order to implement basic and clinical research on rare diseases; whereas research on rare diseases continues to be a priority for the Community, as it has been included in the Programme (1998-2002) for research and technological development; whereas this Regulation establishes a legal framework which will allow the swift and effective implementation of the outcome of this research; Commission’s Framework Fifth Unchanged in its the Commission, (11) Whereas rare diseases have been identified as a priority area for Community action within the framework for action in the field of public health (COM(93) 559 final); whereas communication concerning a programme of Community action on rare diseases within the framework for action in the field of public health (COM(97) 225 final) has decided to give rare diseases priority within the public health framework; whereas the Commission has proposed a European Parliament and Council Decision adopting a programme of Community action 1999-2003 on rare diseases in the context of the framework for action in the field of public, including actions to provide information, to deal with clusters of rare diseases in a population and to support relevant patient organisations; whereas this Regulation carries out one of laid down in this the priorities programme of action. C 177 E/4 EN Official Journal of the European Communities 27. 6. 2000 INITIAL PROPOSAL AMENDED PROPOSAL 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 bringing to the market of designated orphan medicinal products. Article 2 Scope and definitions For the purpose of this Regulation: - medicinal product means a medicinal product for human use, as defined in Article 2 of Directive 65/65/EEC, - orphan medicinal a medicinal product designated under the terms and conditions of this Regu- lation, product means - sponsor means any legal or natural person, established in the Community, seeking to obtain the designation of a medicinal product as orphan medicinal product, - sponsor means any legal or natural person, established in the Community, seeking to obtain or who has obtained the designation of a medicinal product as orphan medicinal product, - Agency means the European Agency for the Evaluation of Unchanged Medicinal Products. Article 3 Criteria for designation if A medicinal product its shall be designated as orphan 1. medicinal product the sponsor can establish that medicinal product is intended for the diagnosis, prevention or treatment of a condition affecting less than five per ten thousand persons in the Community at the application is made and that there exists no satisfactory method of diagnosis, prevention or treatment of the considered if condition that has been authorised in the Community or, such method exists, that it can reasonably be expected that the medicinal product will be safer, more effective or otherwise clinically superior. the time that 2. Notwithstanding paragraph 1, a medicinal product may also be designated as orphan medicinal product if its sponsor can establish that the medicinal product is intended for a life- threatening, or seriously debilitating communicable condition is unlikely that, without in the Community and that incentives, in the Community would generate sufficient return to justify the necessary investment. the medicinal product the marketing of it if A medicinal product its shall be designated as orphan 1. medicinal product the sponsor can establish that medicinal product is intended for the diagnosis, prevention or treatment of a condition affecting less than five per ten thousand persons in the Community at the application is made and that there exists no satisfactory method of diagnosis, prevention or treatment of the considered if condition that has been authorised in the Community or, such method exists, the medicinal product will be of significant benefit to those affected by the condition. the time that that 2. Notwithstanding paragraph 1, a medicinal product may also be designated as orphan medicinal product if its sponsor can establish that the medicinal product is intended for the life-threatening, diagnosis, prevention or seriously debilitating or a serious and chronic condition in the Community and that it is unlikely that, without incentives, the marketing of the medicinal product in the Community would generate sufficient return to justify the necessary investment. treatment of a 27. 6. 2000 EN Official Journal of the European Communities C 177 E/5 INITIAL PROPOSAL AMENDED PROPOSAL 3. The Commission shall, in consultation with the Member States, the Agency, and interested parties, draw up detailed guidance for the application of this Article. Unchanged Article 4 Committee for Orphan Medicinal Products A Committee for Orphan Medicinal Products, hereinafter 1. referred to as áthe Committeeí, is hereby set up. A Committee for Orphan Medicinal Products, hereinafter is hereby set up within the 1. referred to as áthe Committeeí, European Agency for the Evaluation of Medicinal Products. 2. The task of the Committee shall be: Unchanged (a) to examine any application for designation of a medicinal product as orphan medicinal product which is submitted to it in accordance with this Regulation, (b) upon request, lishment product policy for the European Union, to advise the Commission on the estab- an orphan medicinal and development of (c) to assist the Commission in international liaison on matters relating to orphan medicinal products, particularly the United States and Japan, and in liaisons with patients support groups. The Committee shall consist of one member nominated 3. by each Member State, three members nominated by the Commission to represent patient 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 shall be chosen by reason of their role and experience in treatment of or research into rare diseases. The Committee shall consist of one member nominated 3. by each Member State, three members nominated by the Commission to represent patient organisations and three members nominated by the Commission on the basis of a the recommendation from the Agency. The members of Committee shall be appointed for a term of three years which shall be renewable. Where necessary they may seek the assistance of an expert. The Committee shall elect its Chairman for a term of 4. three years, renewable once. Unchanged 5. The representatives of the Commission and the Executive Director of the Agency or his representative may attend all meetings of the Committee. The Agency 6. Committee. shall provide the Secretariat of the 7. Members of the Committee shall be required, even after their duties have ceased, not to disclose information of the kind covered by the obligation of professional secrecy. Article 5 Procedure for designation 1. In order to obtain the designation of a medicinal product as orphan medicinal product, the sponsor shall submit, an application to the Agency. 1. In order to obtain the designation of a medicinal product as orphan medicinal product, the sponsor shall submit, at any stage of the development of the medicinal product before an application for marketing authorisation is made, an application to the Agency. C 177 E/6 EN Official Journal of the European Communities 27. 6. 2000 INITIAL PROPOSAL AMENDED PROPOSAL The application shall be accompanied by the following 2. particulars and documents: Unchanged (a) name or corporate name and permanent address of the sponsor, (b) the name of the active ingredient(s) (c) proposed therapeutic indication, Unchanged (d) the justification that Article 3 paragraph 1 or 2 is applicable. The Commission shall, in consultation with the Member the Agency and interested parties, draw up detailed in which applications 3. States, guidance on the format and content for designation are to be presented. 4. The Agency shall verify the validity of the application and prepare a summary report to the Committee. Where appro- priate, the to supplement the particulars and documents accompanying the application. it may request sponsor 5. The Agency shall ensure that an opinion is given by the Committee within 60 days of the receipt of a valid application. 5. The Agency shall ensure that an opinion is given by the Committee within 90 days of the receipt of a valid application. 6. When preparing its opinion, the Committee shall use its best endeavours to reach a consensus. If such a consensus cannot be reached, the opinion shall consist of the position of the majority of members. The opinion may be obtained by written procedure. 6. When preparing its opinion, the Committee shall use its best endeavours to reach a consensus. If such a consensus the opinion shall be adopted by a cannot be reached, majority of the Committee. The opinion may be obtained by written procedure. the members of two-thirds of the Committee is 7. Where the opinion of the application does not satisfy the criteria set out in Article 3 paragraph 1, the Agency shall forthwith inform the sponsor. Within 30 days of receipt of the opinion, the sponsor may submit detailed grounds for appeal, which the Agency shall refer consider whether its opinion should be revised at the following meeting. to the Committee. The Committee shall that Unchanged 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, exceptionally, the draft decision is not in accordance with the opinion of the Committee, the decision shall be adopted in accordance with the procedure laid down in Article 72 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 designated medicinal product shall be entered in the 9. Community Register of Orphan Medicinal Products. 27. 6. 2000 EN Official Journal of the European Communities C 177 E/7 INITIAL PROPOSAL AMENDED PROPOSAL 10. Each year the sponsor shall provide the Agency with a report on the state of development of the designated medicinal product. 11. In order to secure the transfer to another sponsor of the designation of an orphan medicinal product, the holder of that designation shall submit a specific application to the Agency. In consultation with the Member States, the Agency and the interested parties, the Commission shall draw up detailed guidance concerning the form in which transfer applications must be submitted and also the contents of such applications. Article 6 Protocol assistance Unchanged 1. The sponsor of an orphan medicinal product may, prior to the submission of an application for marketing author- isation, request advice from the Agency on the conduct of the various tests and trials necessary to demonstrate the quality, safety and efficacy of the medicinal product. The Agency shall draw up a procedure on the devel- 2. opment of orphan medicinal products, which shall cover in particular: (a) assistance in the development of a protocol and for the follow up of clinical investigations; (a) assistance in the development of a protocol for pre-clinical and clinical trials during the development phase and for the follow up of clinical investigations; (b) regulatory assistance for the definition of the content of the application for authorisation within the meaning of Article 6 of Council Regulation (EEC) No 2309/93. Unchanged Article 7 Community marketing authorisation 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 any part of the Annex to that Regu- lation. 2. A special contribution from the Community, distinct from that provided for in Article 57 of Regulation (EEC) No 2309/93, will be allocated every year to the Agency. This contribution will be used exclusively by the Agency to waive, in part or in total, the fees payable under Community rules 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. C 177 E/8 EN Official Journal of the European Communities 27. 6. 2000 INITIAL PROPOSAL AMENDED PROPOSAL 3. The marketing authorisation granted for an orphan medicinal product shall cover only those therapeutic indi- cations which fulfil the criteria set out in Article 3. This is without prejudice to the possibility to apply for a separate marketing authorisation for other indications outside the scope of this Regulation. Article 8 Market exclusivity 1. Where a marketing authorisation is granted pursuant to Regulation (EEC) No 2309/93 in respect of an orphan the Community and the Member States medicinal product shall not, for a period of ten years, accept another application for a marketing authorisation, nor grant a marketing author- isation or extend an existing marketing authorisation, for the same therapeutic indication, in respect of a similar medicinal product. 1. Where a marketing authorisation is granted pursuant to Regulation (EEC) No 2309/93 or when all Member States have granted marketing authorisations according to the procedures for mutual recognition foreseen in Articles 7 and 7a of Directive 65/65/EEC or Article 9(4) of Directive 75/319/EEC in respect of an orphan medicinal product and without law on intellectual prejudice property or any other provision of Community law, the Community and the Member States shall not, for a period of ten years, accept another application for a marketing author- isation, nor grant a marketing authorisation or extend an existing marketing authorisation, for the same therapeutic indi- cation, in respect of a similar medicinal product. to the provisions of the This period may however be reduced to six years if, at 2. the end of the fifth year, a Member State can establish that the criteria laid down in Article 3 are no longer met in respect of the medicinal product concerned or that the price charged for the medicinal product concerned is such that it allows the earning of an unreasonable profit. To this end, the Member State shall initiate the procedure laid down in Article 5. Unchanged By derogation to paragraph 1, and without prejudice to 3. intellectual property law or any other provision of Community law, a marketing authorisation may be granted, for the same therapeutic indication, to a similar medicinal product if: (a) the holder of the marketing authorisation of the original orphan medicinal product has given his consent to the second applicant, or (b) the holder of the marketing authorisation of 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 to the safer, the second medicinal product, although similar orphan medicinal product already authorised, more effective or otherwise clinically superior. is At 4. the end of orphan medicinal product Community Register of Orphan Medicinal Products. the period of market exclusivity, the removed from the shall be 27. 6. 2000 EN Official Journal of the European Communities C 177 E/9 INITIAL PROPOSAL AMENDED PROPOSAL For the purpose of 5. productí means one which consists of: this Article, a ásimilar medicinal including isomers and mixture of - the same chemical active substance or active moiety of the isomers, substance, derivatives, complexes, provided that and toxicological activities of the latter are qualitatively and quantitatively identical to those of the original product, the pharmacological non-covalent esters, other - a substance with the same biological activity (including those that differ from the original substance in molecular structure, source material and/or manufacturing process) said provided that the pharmacological to substance is qualitatively and quantitatively identical that of the original product, activity of - a substance with the same radiopharmaceutical activity (including those with a different radionuclide, ligand, site of labelling or molecule-radionuclide coupling mechanism) provided that its diagnostic or therapeutic indications are identical to those of the original product. The Commission shall, in consultation with the Member the Agency and interested parties, draw up detailed 6. States, guidance for the application of this Article. Article 9 Other incentives The Commission shall adopt definitions of 5. ásimilar medicinal productí and of áclinical superiorityí in the form of an implementing Regulation, in accordance with the procedure laid down in Article 72 of Regulation (EEC) No 2309/93, at the latest one year after the adoption of the present regulation. The Commission shall, in consultation with the Member the Agency and interested parties, draw up detailed including the 6. States, guidance for the application of implementing Regulation. this Article, 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 the research, development and availability of orphan medicinal. 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 the research, development and availability of orphan medicinal products and in particular aid for research for Small and Medium Enterprises provided under the Fifth Framework Programme for Research and Tech- nological Development. 2. Within six months of the adoption of this Regulation, the Member States shall communicate to the Commission detailed information about the measures they have enacted to support the research, development and availability of orphan medicinal products. This information shall be updated on a regular basis. 2. Within six months of the adoption of this Regulation, the Member States shall communicate to the Commission detailed information about any measures they may have enacted to support the research, development and availability of orphan medicinal products. This information shall be updated on a regular basis. 3. Member States shall also consider waiving, in part or in total, the fees to be paid in respect of applications to place orphan medicinal products on the market. Deleted C 177 E/10 EN Official Journal of the European Communities 27. 6. 2000 INITIAL PROPOSAL AMENDED PROPOSAL 4. Within one year from the adoption of this Regulation, the Commission shall publish a detailed inventory of all available by the Community and the incentives made Member States to support the research, development and avail- ability of orphan medicinal products. This inventory will be updated on a regular basis. 3. Within one year from the adoption of this Regulation, the Commission shall publish a detailed inventory of all available by the Community and the incentives made Member States to support the research, development and avail- ability of orphan medicinal products. This inventory will be updated on a regular basis. Article 10 General report Unchanged Within six years of the entry into force of this Regulation, the Commission shall publish a general report on the experience acquired as a result of the application of this Regulation. Article 11 Entry into force This Regulation shall enter into force on the thirtieth day following its publication in the Official Journal of the European Communities. This Regulation shall be binding in its entirety and directly applicable in all Member States