Table 1.

Summary of rare disease policy and regulatory frameworks across 11 countries

	France	Germany	UK	Canada	Bulgaria	Turkey	Argentina	Mexico	Brazil	China	Taiwan
National Policy	Two plans implemented; Launch of third plan underway	Adopted; implementation underway	Plan adopted for all 4 UK nations; implementation underway	Adopted; implementation underway	Approved; limited implementation	Draft guideline passed; implementation delayed	Approved; awaiting implementation	No uniform plan	In early implementation stage	None	Adopted; implementation underway
Authorization Process	Central EU authorization COMP OD Designation	Central EU authorization COMP OD Designation	Central EU authorization COMP OD Designation	Accelerated review available	Central EU authorization COMP OD Designation	No defined OD designation	ANMAT regulates conditions for drug approval Streamlined authorization available for US or EU-approved drugs OD registration process in place	Accelerated review available Process in place for OD classification	Accelerated review available; timelines vary No special registration process for ODs	Delays in OD drug approval despite fast-track program No distinction between ODs and regular drugs	Accelerated review available Process in place for OD classification
Early Access Programs	Processes in place for ODs with and without market authorization	Granted during the third phase of the clinical trial and when the product’s safety and efficacy are guaranteed.	Early Access to Medicines scheme approved, but not specific to RD	No plan for early access; Patients may apply to the Special Access Program in special circumstances	No legal provision for early access	Program available for patients with unmet medical needs meeting defined criteria	Program for free access to drugs from other countries in place	No programs in place	No legislation or programs in place Unregistered medicines can be imported upon request	ODs yet to be authorized may be available through donation programs	No formal NP in place, but policies implemented Unregistered medicines can be imported upon request
Current Access to Treatment	Market authorization required ODs can only be prescribed in RD competence centers (+500 in France) No OD-specific funding	Several initiatives exist to improve access to ODs No OD-specific funding	NICE HST review process for ultra-orphan drugs Scotland’s New Medicine Fund allocated £80 M for ODs	ODs assessed through same HTA process as other drugs Provincial Drug Plans-special provisions for ODs	Access to ODs improved markedly over last 4 years Special considerations for HTAs of ODs 10% of annual NHIF budget allocated to ODs	Pathways for access are defined No OD-specific funding	Comprehensive RD patient care: Act 26.689 not yet implemented Refund system provides financial support to Social Health Service for select drugs	Limited information available No OD-specific funding	Limited access through public health system No OD-specific funding	No special access considerations No OD-specific funding	Special access considerations Several drugs approved recently Separate budget not covered by NHI
Diagnosis Programs	Neonatal screening available for 4 pathologies (2 RDs) Inequality in access to tests	Newborn screening available for 14 conditions Screening and genetic testing mandatory, but no specific RD policies	The UK Rare Disease Strategy does not specifically contain early diagnosis programs Expansion of RD testing in newborns as of 2015	Provincial newborn screening programs vary in number and conditions Health Ministers to implement screening programs for 22 conditions	National program for early diagnosis expected to be fully funded/operational by 2016	Few public diagnosis centers Neonatal screening for 3 RDs through Ministry of Health Genetic testing at universities; testing abroad possible	Legislation passed, but no programs in place	No early diagnosis initiatives Limited newborn screening Early Diagnosis Clinic under development	Newborn screening available for 6 RDs Main rare diseases research centers is located in the Federal University of Rio Grande do Sul,for diagnosis	No national screening and/or diagnostic programs available	Improved screening and diagnosis in development Nation-wide newborn screening program for 26+ diseases
Coordination of Care	131 centers of reference and 501 centers of competence are in place	RD expert centers and networks for cross-border research in place	UK Strategy for Rare Diseases Calls for specialist centres to deliver coordinated care, 150 providers of highly specialized services	Centers of Expertise in specific rare diseases; some linked to research across sites with adult clinics No national coordinating body for all RD Centers of Expertise	Not in place RD committee not yet operational	Few centers with specialized services; mostly university hospitals and research centers	Planned: Act 26.689 Cibersalud launched to strengthen specialist networks “Hiptour” patient-lead initiative provides medical guidance to HCPs	No developed centers, but functionally active network of 12 civil organizations Lysosomal Storage Disease Network: diagnosis, treatment, support	National policy initiated with accreditation of specialized health centers in progress;	No comprehensive specialist centers Centers for specific RDs located in Beijing and Shanghai Most mature treatments for hematologic RDs	No comprehensive specialist centers 10+ RD genetic counseling centers approved Some NPs implemented but coordinated care not fully developed
Research	300+ funded clinical research projects Funding allocated for basic and clinical research Banque Nationale de Données Maladies Rares national database launched European/international collaborations developed	28 RD organizations supported by Ministry of Education and Research BMBF funding 12 research projects; €23 million allocated for 3 years Cross-border research projects No central coordinated RD registry	Collaborative initiatives with pharmaceutical companies for patient-centered research exist UK10K project on RD genetics Public Health England intends to build national RD registry	Canadian Institutes for Health Research funds basic and translational research Proposed formal inclusion of RD research in CIHR, Genome Canada, and IRDiRC	Growing awareness but few research initiatives in place Centralized patient registry approved but not yet operational	No initiatives, networks, or cross-border collaborations No national registries, but Turkey participates in European registries Comprehensive national epidemiological survey underway	No national initiatives in place Some research conducted with support from patient organizations, research grants, or private initiatives Legislation passed, but registries still under development	No funded research projects or initiatives Development of RD patient database in progress	Few incentives; no long-standing initiatives; Initiative in 2014 by the National Council of Scientific and Technological Development (CNPq), which screened and funded 15 research projects devoted to rare diseases (diagnosis and treatment) Bill to secure RD research funding under review No national registries Patient groups collect data DORA program and FEMEXER RD database in development	CARDPT national research program initiated in 2013 Cross-border initiatives gaining momentum No national centralized patient database/registry Registry launched at local level in 2013 Patient group-developed database in progress	No RD-specific national registry National disability registry in place and hemophilia registry in development
Patient Engagement	Established patient organizations are engaged and play a role in RD policy	Established patient organizations are engaged and play a role in RD policy	Established patient organizations play active role Stakeholder engagement by Rare Disease UK and Specialized Healthcare Alliance	Patient group support and advocacy facilitated by CORD National Strategy launched with Rare Alliance Canada	Patient organizations actively engaged Implemented support and education programs and played a role in the launch of 13 RD registries	Little information available	Patient organizations play active role Collaborations with government aided implementation of RD legislation and programs	Patient organizations play an important, active role	Patient organizations play an important role	Patient advocacy groups limited but localized RD groups raise awareness/promote legislation Chinese Organization for Rare Disorders active in RDI	Strong patient support/advocacy groups active in RD policy TFRD helped pass 2000 Rare Disease Control and ODA
Gross National Income per Capita (2015)	40,580	45,790	43,340	47,500	7220	9950	13,640	9710	9850	7820	22,723
Healthcare Spending (% GDP)	11.5	11.3	9.1	10.4	8.4	5.4	4.8	6.3	8.3	5.5	6.6
Average Wealth Healthcare Rank	1.8	2.3	2.3	2.8	7.8	6.5	7.0	7.3	6.5	5.0	8.8

Abbreviations Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; BMBF Bundesministerium für Bildung und Forschung, Federal Ministry of Education and Research; CARDPT China Alliance for Rare Disease Prevention and Treatment; CIHR Canadian Institutes of Health Research; CORD Canadian Organization for Rare Disorders; EU European Union; DORA Doenças Raras, rare diseases; FEMEXER Federación Mexicana de Enfermedades Raras, Mexican Federation for Rare Disorders; HTA Health technology assessment; IRDiRC International Rare Diseases Research Consortium; NHI National Health Insurance; NHIF National Health Insurance Fund; NICE National Institute for Health and Care Excellence; NP national plan; OD orphan drug; RD rare disease; RDI Rare Diseases International; TFRD Taiwan Foundation for Rare Disorders