Abstract Background Although some jurisdictions have implemented particular adjustments to accommodate often-expensive orphan drugs in their healthcare systems, availability of these drugs remains complex. This study investigates alternative financing models and early access schemes for orphan drugs in the context of the Belgian healthcare system. Methods Three focus group discussions were held with a panel of eleven experts from the Belgian Drug Reimbursement Committee, the Colleges for Orphan Drugs, the pharmaceutical industry, physicians, ethicists and pharmacists. Retrieved data were pseudonymised, analysed and coded according to the Qualitative Analysis Guide of Leuven. Results Experts disfavoured the insulated fund as well as private insurance for financing orphan drugs, as, respectively, isolation of a separate budget and a mostly profit-driven mechanism would contradict the Belgian fundamental principle of solidarity. Moreover, an insulated fund could, albeit on a smaller scale, reproduce the same budgetary constraints as the general reimbursement system. As the Special Solidarity Fund is intended for urgent care and exclusively accommodates financial needs subject to eligibility criteria, its design would not allow general financing of orphan drugs. Overall, implementation of an alternative financing model was not endorsed, instead, improving the current reimbursement system was preferred. Suggestions mentioned were; increased collaboration and transparency, robust and quality real-world evidence but also digitalization of data. Alleviating administrative burden and simplifying the admission process of compassionate use program, medical need program and early treatment reimbursement should be prioritized to facilitate early access. Furthermore, a legal framework for off-label use could stimulate proper implementation. Efforts on collaboration of expertise centres and coordination of orphan drug databases across Europe could foster a robust data network to support orphan drug availability in individual ...