Health problems affect people physiologically, psychologically, socially, and economically, and they may prevent people from continuing their lives functionally.1 Rare diseases may seen rare in society, however they are one of major health problems as life-threatening, serious, genetic,2 chronic,3 complex,4 and demanding5 conditions. Rare diseases are usually genetic in origin—such as cancer, autoimmune diseases, and degenerative and proliferative diseases—except for rare diseases originating from infection and infestation.2
Although the definition of “rare disease” varies, diseases that affect fewer than 200,000 people in the United States (US), 50,000 people in Japan, and 2,000 people in Australia are considered “rare”.3,6 The World Health Organization (WHO), according to a report published in 2013, considers a disease to be “rare” if it affects fewer than five people per 10,000.3
In general, rare diseases range in prevalence from one to eight people per 10,000.6 An estimated 25 million people in the US, 30 million people in Europe, and 400 million people worldwide are affected by rare diseases.3 Although each rare disease affects a small number of people, 6–10% of the overall population is affected3 by a rare disease.3
World epidemiological data are constantly changing. Although a new rare disease is discovered almost every week, its status may change from being considered a rare disease2 to being described as a common disease.2
On the one hand, because rare diseases occur in unusual forms and often entail comorbidities, they are difficult to diagnose. On the other hand, no diagnostic methods or diagnostic possibilities are available for many rare diseases. Also, the number of doctors who can diagnose and treat rare diseases is very limited. Therefore, appropriate treatment is difficult to obtain, and patients sometimes spend many years facing treatment uncertainty.4,7
Estimates suggest a total of 8,000–10,000 rare diseases.8 Drugs have been approved to treat approximately 300 of these diseases. In other words, no appropriate treatment is available for approximately 95% of rare diseases.9
Orphan Drugs
An “orphan drug” is a drug especially developed to treat a rare medical condition. The high costs of drug development and pharmaceutical companies’ reluctance to develop drugs for very small patient populations make the public sector’s participation in the orphan drug market critical.10
The Orphan Drug Act was adopted in 1983 in the US to facilitate the research, development, and commercialization of drugs to treat rare diseases that are largely ignored.11 Orphan drug legislation and policy have succeeded in promoting the progression of treatments for rare diseases. Since these policies’ implementation, more orphan drugs have been licensed in the US.12,13
Market access to orphan drugs faces several challenges, including delays in the process from European Medicines Agency (EMA) approval to reimbursement. In some European countries, reimbursement takes longer for orphan drugs than other drugs. The main reason for this difference is that European countries, unlike the US, include health technology assessment (HTA) processes. A limited number of HTAs on orphan drugs14 are available, and negative results are generally obtained when standard HTA procedures are applied to orphan drugs.15,16
In a study that covered August 2000 to December 2004, only 18 of 255 orphan drugs (7.1%) in Europe were approved. Meanwhile, 153 out of 193 drugs (79.3%) for which applications had been submitted to the EMA during the same periods received license approval.17
The Orphan Drug Market
Marketing authorization for a drug does not mean that the drug is available in all countries within the European Union.18 Marketing authorities determine commercialization status in each country. The necessary procedures are then applied to determine a drug’s reimbursement conditions and price.19 In most countries, access to orphan drugs is only possible if it is included on the country’s reimbursement list. Figure 1 compares the number of orphan drugs on the market that are unavailable in European countries.14
Rare Diseases and Orphan Drugs in Turkey
Inevitably, the problems with rare diseases throughout the world are also experienced in Turkey. Rare diseases occur frequently in Turkey due to disease burden, consanguineous marriages, and different ethnic structures.18 In Turkey, the Ministry of Health on the Pricing of Medicinal Products for Human Communiqué (2007) defined “orphan drugs” as drugs for the treatment of a disease affecting a population of more than 100,000.20 It could be said that the definition of the prevalence of rare diseases in Turkey is very low compared to the European Union and United States.21
The number of rare disease specialists, insufficient knowledge or experience, and expensive treatment processes are leading problems. The preparation of regulation on rare diseases and orphan drugs is expected to facilitate more concrete steps in diagnosis, treatment, and disease prevention for both researchers or physicians and patients.22
To determine specific orphan drug legislation in Turkey, since the beginning of 2010, the Turkey Pharmaceuticals and Medical Devices Agency (TİTCK)—formerly known as the Pharmaceutical General Directorate—has conducted detailed studies.23 The main purpose of the agency’s Draft Guidance Document (still not public) was to encourage research on treatments for rare diseases, develop appropriate treatment alternatives, provide incentives for placing these treatments on the market, and determine orphan drug identification criteria as well as authorization requirements.21
In Turkey, the TİTCK is following orphan drug operations in three ways. A drug:
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can be licensed and available for purchase on the market;
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can be currently not licensed in Turkey but available by prescription if approved in the US or the EU, efficacy and safety grounds are provided, and a clinical trial protocol is available;
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can be available for patients approved under the compassionate use program or with early access to a humanitarian medication to be clinically administered.11,21
In Turkey, in accordance with the Regulation on Medicinal Products for Human Use Permit, the Ministry of Health completes a preliminary examination within 210 days of the date an application is submitted. If the drug complies with legal regulations, its application is finalized. The same regulation also states that it can issue licenses if it cannot provide absolute evidence for sufficient effectiveness and safety in rarely indicated indications for an orphan drug application.24
A protocol has been signed between the Turkish Ministry of Health and the Turkish Pharmacists’ Association (TEB) to supply drugs from abroad that are otherwise unavailable in Turkey, whether licensed or unlicensed. According to this protocol, the provision for the supply of units from abroad was created by the TEB, which serves as an economic operator. The association’s Ankara-based units have branches in Istanbul, Izmir, and Adana. Drugs for rare diseases claimed to have been purchased abroad through this unit are sent to patients and their relatives.25 Like the TEB, the Social Security Pharmaceutical Department of the Social Security Center, Ibn Sina, Pharmaceutical Warehouse within the Social Security Institution (SGK) supplies drugs from abroad26.
This study aimed to analyze the accessibility, reimbursement status, licensed status, and Anatomical Therapeutic Chemical (ATC) codes of drugs considered “orphan” by the EMA in Turkey. In addition, orphan drug data taken on a box basis and the budget allocated to these drugs were calculated according to the years. Accordingly, the study’s findings evaluated orphan drug policy and drugs’ access statuses.