Orphan Drugs and Rare Diseases
All legal aspects surrounding the orphan drugs and rare diseases in Romania. Prepared in association with Mușat & Asociații, a leading global law firm, this is an extract from The Pharma Legal Handbook: Romania, available to purchase here for GBP 75.
1. What is the definition of Rare Diseases in your country?
Regulation (EC) no. 141/2000 on orphan medicinal products (“Regulation no. 141/2000”), which is directly applicable in Romania, specifies that a medicinal product could be designated by the European Medicines Agency as an orphan medicine when:
(i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 persons in the Community when the application is made; or
it is intended for 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
(ii) there is 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.
The Romanian legislation on the health technology assessment (HTA) of medicinal products provides for the definition of rare diseases, in the context of evaluating the medicines in view of their inclusion in the national reimbursement list.
According to the HTA legislation, rare diseases are conditions which are affecting not more than 5 in 10,000 persons in the European Union or which are life-threatening, chronic debilitating or serious and chronic conditions of the body.
The Government created a national health insurance program for rare diseases, which provides for the treatment of patients diagnosed, amongst others, with degenerative / inflammatory-immune neurological diseases, imperfect osteogenesis, Fabry disease, Pompe disease, tyrosinemia, Mucopolysaccharidosis type II (Hunter syndrome), Mucopolysaccharidosis type I (Hurler syndrome), congenital afibrinogenemia, primary immunodeficiency syndrome, bullous epidermolysis, systemic sclerosis, evolving digital ulcers, amyotrophic lateral sclerosis, cystic fibrosis, Prader Willi syndrome, idiopathic pulmonary fibrosis, Duchenne muscular dystrophy, hereditary angioedema and Leber hereditary optic neuropathy.
2. Does the designation of ‘Orphan Drug’ exist in your country? (Does it correspond with the definition of Rare Diseases?)
Pursuant to the national legislation, the designation of a medicine as an orphan drug should be performed by the European Medicines Agency in accordance with Regulation no. 141/2000.
The definition of “orphan medicines” does not correspond with the definition of “rare diseases”, because the rare diseases could be treated also with certain medicines which do not have an orphan designation. In this respect, the HTA legislation provides that an INN could fall under the “orphan” or the “rare disease” categories, as follows:
- INNs with orphan status, designated as such by the European Medicines Agency; or
- INNs for rare diseases, whose orphan designation was removed by the European Medicines Agency or which did not have an orphan designation, used for the treatment, prevention or diagnosis of certain conditions which are affecting not more than 5 in 10,000 persons in the European Union or which are life-threatening, chronic debilitating or serious and chronic conditions of the body.
3. What is the regulatory framework for the authorization of an Orphan Drug? (Is this regulatory framework based on Rare Disease status or can it alternatively be based on Orphan Drug foreign status?)
The Romanian legislation specifies that the authorisation and designation of a medicinal product as orphan drug should be performed at the EU centralized level, and not at a national level.
The European Medicines Agency is the main authority in this field, responsible for the scientific evaluation of marketing authorisation applications for orphan medicines under the EU centralised authorisation procedure. If a medicine has an orphan drug status at the EU centralized level, this status will be acknowledged by the Romanian authorities.
The authorisation and the designation of orphan medicines should be carried out in accordance with Regulation no. 141/2000 and Regulation (EC) no. 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (the „Regulation no. 726/2004”).
The EU procedure for the designation of an orphan medicine involves, amongst others, the filing of an application dossier with the European Medicines Agency and the issuance of on opinion by the Agency’s Committee for Orphan Medicinal Products, based on which the European Commission will adopt its decision. The designated medicine will be included in the Community Register of Orphan Medicinal Products. The marketing authorisation for these medicines should be issued afterwards by the European Medicines Agency.
While the Romanian authorities do not approve the orphan drug status, they could acknowledge the rare disease status under the HTA procedure and/or in the national health programs.
4. Does your country have provisions for relaxed clinical trial/scientific evidence requirements in respect of Orphan Drugs as compared to other drugs?
The Romanian legislation does not provide for relaxed clinical trial/scientific evidence requirements in respect of orphan medicinal products. The matters pertaining to the marketing authorisation of orphan drugs should be handled by the European Medicines Agency, in accordance with the EU legislation.
In this respect is it noteworthy that according to Regulation no. 141/2000, the sponsor of an orphan medicine could request advice from the EMA on the conduct of the various tests and trials intended to demonstrate the quality, safety and efficacy of the respective medicinal product, before filing the marketing authorization application for the product in question.
5. Is there an expedited pathway for Orphan Drugs?
According to the EU legislation, the medicines authorised at centralized level, including orphan drugs, could undergo an accelerated assessment if they are of major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation.
The European Medicines Agency could perform such accelerated assessment in accordance with EU Regulation no. 726/2004. The authorisation timeframe would be reduced from 210 days to 150 days as of the filing of a valid application.
The Romanian legislation does not provide for an expedited pathway for the marketing authorisation of orphan medicines at national level, since such authorisation is granted by the European Medicines Agency at the EU centralized level.
6. Are foreign marketing authorizations recognized in your jurisdiction for Orphan Drugs? If yes, marketing authorizations from which countries are recognized?
As a rule, in order to be placed on the Romanian market, medicinal products should have a marketing authorisation issued by the National Agency of Medicines and Medical Devices at national level or by the European Medicines Agency at centralized level.
In case of orphan drugs, the marketing authorisation issued by the European Medicines Agency at EU centralized level is recognized in Romania. The marketing authorisation for orphan medicines issued by other countries are not recognized at local level.
7. Can Orphan Drugs be reimbursed? If so, is there a specific reimbursement procedure for Orphan Drugs?
Medicinal products could be reimbursed in the Romanian health insurance system if the following conditions are met: (1) they have a valid marketing authorisation; (2) their price for Romania is approved by the Ministry of Health and (3) they are included in the national list of reimbursed medicines, approved by the Romanian Government based on the health technology assessment (HTA) performed by the National Agency of Medicines and Medical Devices. These rules are applicable also to orphan drugs.
The HTA legislation stipulates specific conditions for orphan drugs, which could improve their chances to have a favourable HTA decision. For example, the HTA norms provide for the prioritization of the evaluation of orphan drugs and for special evaluation criteria for them.
If the National Agency of Medicines and Medical Devices issues a favourable HTA decision, the medicines in question should be included in the reimbursement list.
8. How are the prices of Orphan Drugs regulated?
The competent authority which approves the prices of medicinal products in Romania is the Ministry of Health. The Ministry approves the prices of prescription-only (Rx) medicines, as well as of the prices of over-the-counter (OTC) medicines released based on medical prescription.
By law, the pricing rules applicable to innovative medicinal products are also applicable to orphan medicines. The norms issued by the Ministry of Health provide, amongst others, that: (i) the manufacturer price for Romania should be lower than or (at most) equal to the lowest price of the same medicinal product in 12 (twelve) comparison countries; (ii) the price should be approved by the Ministry of Health within 90 days as of receiving the price application dossier; and (iii) the price is valid for 1 (one) year.
Further to the approval of the manufacturer price, the maximum wholesale and retail prices are calculated by the Ministry of Health according to a special formula, by considering the maximum applicable wholesale and pharmacy margins set forth by the applicable regulations. The approved prices are published in the national price catalogues.
Every year, the marketing authorisation holders and/or their representatives should submit a price correction dossier with the Ministry of Health for updating the price of each medicine placed on the Romanian market. The updated price will be valid also for 1 (one) year.
9. In case of reference price based on a basket of countries, what countries are included?
As per the Romanian legislation, the 12 (twelve) reference countries taken into account when establishing the price for medicinal products are Czech Republic, Bulgaria, Hungary, Poland, Slovakia, Austria, Belgium, Italy, Lithuania, Spain, Greece and Germany.
10. Have there been any significant legal/judicial developments in relation to Orphan Drugs in your country?
In July 2020, the Ministry of Health issued an order for approving new HTA evaluation criteria, which provides certain favourable rules for orphan drugs and for advanced therapy medicinal products. These new rules significantly improve the chances of the orphan drugs and of the advanced therapy medicinal products to become reimbursed in the national health insurance system.
11. Are there proposals for reform or significant change to the regulation of Orphan Drugs? If yes, when are they likely to come into force?
The Romanian authorities intend to issue a new pricing methodology. This reform might impact the pricing and the reimbursement of orphan drugs in Romania.
Therefore, it is advisable for the pharmaceutical companies acting in this field to closely monitor the legal developments in Romania.