Access to Orphan Medicinal Products in Bulgaria: An Analysis of the Positive Drug List and Individual Access Schemes

Background/Objectives: Orphan medicinal products offer essential treatments for rare diseases, but patient access varies across European Union countries despite a common regulatory framework. In Bulgaria, access is primarily through inclusion in the positive drug list following health technology assessment or via individual access schemes under Ordinance No. 2/2019, which allows for ad hoc reimbursement. This study evaluates the timeliness and extent of Bulgarian patient access to orphan-designated drugs authorized by the European Medicines Agency. Methods: We analyzed European Medicines Agency-authorized orphan drugs between July 2006 and September 2023 using data from the European Medicines Agency, Bulgarian health technology assessment bodies, positive drug list records, and individual access scheme reports. Medians, interquartile ranges, stratified analyses, and permutation/bootstrapping methods were applied. Results: Of the 142 European Medicines Agency-approved orphan drugs, only 41 (28.9%) were included in the Bulgarian positive drug list. The median time to positive drug list inclusion was 828 days, with pre-health technology assessment delays (median 570 days) as the main bottleneck. Health technology assessment evaluations had a median duration of 204 days. Cancer and accelerated-assessment drugs reached health technology assessment faster, while conditional approvals faced longer delays. Twenty-four drugs were accessed through individual schemes; twenty remained outside the positive drug list. Overall, 43.0% of orphan drugs reached Bulgarian patients via either mechanism. Conclusions: Access to orphan drugs in Bulgaria is limited and delayed, mainly due to pre-health technology assessment lags. In light of the forthcoming European Union health technology assessment regulation, Bulgaria must ensure that national processes are capable of rapidly translating centralized assessments into meaningful patient access.