Orphan Drugs and Rare Diseases
Keen to learn more about orphan drugs & rare diseases in Bulgaria? Read on! Prepared in association with Kinstellar and PharmDedict, this is an extract from The Pharma Legal Handbook: Bulgaria, available to purchase here for GBP 75.
1. What is the definition of Rare Diseases in your country?
Under the Medicinal Products in Human Medicine Act (“MPHMA”), a “rare diseases” is defined as a disease characterized by an incidence not higher than 5 per 10,000 individuals.
2. Does the designation of ‘Orphan Drug’ exist in your country? (Does it correspond with the definition of Rare Diseases?)
The term “Orphan Drug” is reflected under Bulgarian law as “A medicinal product intended for treatment, prevention and diagnosis of rare diseases”. According to the MPHMA, these are products which:
- are intended for the diagnosis, prevention or treatment of life-threatening diseases or chronic diseases with a progressive course affecting no more than 5 out of 10,000 people on the territory of the country, or
- are intended for the diagnosis, prevention or treatment of life-threatening diseases and of chronic conditions that seriously damage health (diseases with a high share of disease-related inability to work and disability), evidence being attached that the sale of the product does not provide a satisfactory level of return that would justify the required investment in scientific research and development operations without further incentives for the author of the product, and
- when there is no satisfactory method for diagnosis, prevention or treatment of the respective condition or, if one exists, the proposed medicinal product has significantly more advantages the existing method and it is of significantly bigger benefit for the those affected by the said condition.
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?)
There is no specific procedure for authorisation of Orphan Drugs in Bulgaria and for authorisation of such products the MPHMA refers to (i) Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (the “Orphan Drugs Regulation”) for the designation of a product as an Orphan Drug; and (ii) Regulation (EC) No 726/2004 of the European Parliament and of the Council1 (“Regulation (EC) 726/2004”) regarding the marketing authorisation of Orphan Drugs.
More specifically, in order to be marketed in Bulgaria, an Orphan Drug shall have received a market authorisation by the European Medicines Agency (“EMA”) through a centralised procedure under Regulation (EC) 726/2004.
4. Does your country have provisions for relaxed clinical trial/scientific evidence requirements in respect of Orphan Drugs as compared to other drugs?
There are no provisions for relaxed clinical trial/scientific evidence requirements in respect of Orphan Drugs effective in Bulgaria.
5. Is there an expedited pathway for Orphan Drugs?
EMA has implemented an adaptive pathways approach for authorisation of Orphan Drugs. The adaptive pathways approach is a scientific concept for medicine development and data generation which allows for early and progressive patient access to a medicine.
The adaptive pathways approach is based on three principles:
- iterative development, which either means:
- approval in stages, beginning with a restricted patient population then expanding to wider patient populations;
- confirming the benefit-risk balance of a product, following a conditional approval based on early data (using surrogate endpoints) considered predictive of important clinical outcomes;
- gathering evidence through real-life use to supplement clinical trial data;
- early involvement of patients and health-technology-assessment bodies in discussions on a medicine’s development.
6. Are foreign marketing authorizations recognized in your jurisdiction for Orphan Drugs? If yes, marketing authorizations from which countries are recognized?
In general, any Orphan Drug that has received market authorization by the EMA would also be recognized in Bulgaria. This, means that Orphan Drugs from each Member State may receive market authorization in Bulgaria. There is no separate register for the Orphan Drugs authorised in Bulgaria.
7. Can Orphan Drugs be reimbursed? If so, is there a specific reimbursement procedure for Orphan Drugs?
There is no specific procedure for reimbursement of Orphan Drugs in Bulgaria.
As a general rule, the reimbursement status of a medicinal product is determined by the National Council on Prices and Reimbursement of Medicinal Products (“NCPRMP”).
In order to be reimbursed a medicinal product (including an Orphan Drug) has to be included in the Positive Drug List (“PDL”) by the NCPRMP.
Only medicinal products which have received market authorisation may be included in the PDL. The medicinal products included in the PDL receive a ceiling price defined by the NCPRMP. Another requirement is the product to be reimbursed by a public health insurance fund in at least five of the following countries: Belgium, Greece, Estonia, Latvia, Lithuania, Poland, Portugal, Romania, Slovakia, Denmark, Italy, Slovenia, Hungary, France, Finland, Czech Republic, Spain. The above requirement applies also for Orphan Drugs with the specific that it may not only be reimbursed by a public health insurance fund but also paid by with other public funds.
The medicinal product should also be suitable for the respective disease (rare disease). Assessment on certain aspects of the medicinal products is also conducted such as effectiveness, efficiency, safety, pharmaco-economic parameters, effect on budget.
The medicinal products included in the PDL are paid with public funds.
8. How are the prices of Orphan Drugs regulated?
The prices of medicinal products included in the PDL, including Orphan Drugs, are regulated by the NCPRMP.
The price of the medicinal products included in the PDL is defined on the basis of the following elements:
- Manufacturer price;
- Wholesale price;
- Retail price;
- Value added tax;
- Reference prices and margins.
9. In case of reference price based on a basket of countries, what countries are included?
Please see above p. 7 above.
10. Have there been any significant legal/judicial developments in relation to Orphan Drugs in your country?
No significant legal/judicial developments in relation to Orphan Drugs have been introduced in Bulgaria.
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?
No proposals for reform or significant change to the regulation of Orphan Drugs in Bulgaria have been introduced.
- Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency