, A brief history of the name "orphan drugs, vol.22, 2015.

H. Shirkey, Therapeutic orphans, Pediatrics, vol.104, issue.3, pp.583-584, 1999.

&. Who-|, Coming together to combat rare diseases', WHO, p.11, 2018.

, What is a rare disease ?, p.8, 2018.

, Regulation (EC) No 141/2000 of the European Parliament and of the Council on Orphan Drugs, 2018.

, About Rare Diseases | www.eurordis.org', p.8, 2018.

, Orphan Drug Act, 1983.

A. Nitta, Current Status and Challenges of Development for Orphan Drugs in Japan, p.14

, Estimated prevalence of some rare diseases -Public Health -European Commission', Public Health, p.8, 2018.

, Buerger's Disease -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Cystic Fibrosis -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Duchenne Muscular Dystrophy -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Sickle Cell Disease -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, FAQ About Genetic Disorders', National Human Genome Research Institute (NHGRI), p.8, 2018.

, Rett syndrome | Genetic and Rare Diseases Information Center (GARD) -an NCATS Program, p.8, 2018.

, Rett Syndrome -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Creutzfeldt Jakob Disease -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Whipple Disease -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Heavy Metal Poisoning -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Rare Disease Impact Report: Insights from patients and the medical community_ShireReport

S. P. Group, Shire, Microsoft and EURORDIS form Global Commission to accelerate time to diagnosis for children with rare diseases', GlobeNewswire News Room, vol.20, p.14, 2018.

, Committee on Accelerating Rare Diseases Research and Orphan Product Development, Rare Diseases and Orphan Products: Accelerating Research and Development, 2010.

, Craniofrontonasal Dysplasia', NORD (National Organization for Rare Disorders)

, Gaucher Disease -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Xeroderma Pigmentosum -NORD (National Organization for Rare Disorders)', NORD (National Organization for Rare Disorders)

, Market Access for Orphan Drugs: assessing the global landscape, p.106, 2013.

T. Gammie, C. Y. Lu, Z. U. , and -. Babar, Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries, PLoS ONE, vol.10, issue.10, 2015.

M. Herder, What Is the Purpose of the Orphan Drug Act?, PLoS Med, vol.14, issue.1, 2017.

J. H. Reese, FDA Orphan Drug Designation 10, p.36

, Procedure for orphan medicinal product designation -GUIDANCE FOR SPONSORS, Rev 13, p.12

, Orphan medicinal product designation, EMA, 2015.

, Orphan medicines figures, EMA, p.17, 2000.

, Orphan Designation System in Japan, p.12

, Overview of Orphan Drug/Medical Device Designation System, Labour and Welfare: Pharmaceuticals and Medical Devices Jiho. Inc, p.23, 2009.

J. Abraham, &. I. E15definitions, . Biomarkers, P. Pharmacogenomics, G. Data et al., Handbook of Transnational Economic Governance Regimes, pp.1041-1054, 2009.

J. Abraham, ICH E16, Handbook of Transnational Economic Governance, pp.1041-1054, 2009.

J. Abraham and &. I. M3r2, GUIDANCE ON NONCLINICAL SAFETY STUDIES FOR THE CONDUCT OF HUMAN CLINICAL TRIALS AND MARKETING AUTHORIZATION FOR PHARMACEUTICALS', in Handbook of Transnational Economic Governance, pp.1041-1054, 2009.

J. Abraham and &. I. S7a, SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS', in Handbook of Transnational Economic Governance Regimes, pp.1041-1054, 2009.

M. Mcvean, Preclinical Development to IND: Drugs, Biologics, Cellular/Gene Therapies and Vaccines, p.40, 2014.

J. Abraham and &. I. S6r1, PRECLINICAL SAFETY EVALUATION OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS', in Handbook of Transnational Economic Governance Regimes, pp.1041-1054, 2009.

J. Abraham, International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use', in Handbook of Transnational Economic Governance Regimes, pp.1041-1054, 2009.

, Clinical trials in small populations, European Medicines Agency, p.11, 2007.

, Rare Diseases: Common Issues in Drug Development Guidance for Industry, p.8, 2018.

O. , Pediatrics -Best Pharmaceuticals for Children Act and Pediatric Research Equity Act, p.11, 2016.

R. Smith, Regulation (EC) No 764/2008 of the European Parliament and of the Council, Core EU Legislation, pp.183-186, 2015.

, Paediatric investigation plans, European Medicines Agency, vol.17, p.11, 2018.

A. S. Kesselheim, J. Avorn, and A. Sarpatwari, The High Cost of Prescription Drugs in the United States: Origins and Prospects for Reform, JAMA, vol.316, issue.8, pp.858-871, 2016.

, Orphan Drugs in the United States: Growth Trends in Rare Disease Treatments -IQVIA', p.17, 2019.

R. Hyde and D. Dobrovolny, Orphan Drug Pricing and Payer Management in the United States: Are We Approaching the Tipping Point?, Am. Health Drug Benefits, vol.3, issue.1, pp.15-23, 2010.

U. S. , Department of Health and Human Services Food and Drug Administration and Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER), 'Expanded Access to Investigational Drugs for Treatment Use -Questions and Answers Guidance for Industry, Quest. Answ, p.25, 2016.

J. P. Jarow, S. Lemery, K. Bugin, S. Khozin, and R. Moscicki, Expanded Access of Investigational Drugs: The Experience of the Center of Drug Evaluation and Research Over a 10-Year Period, Ther. Innov. Regul. Sci, vol.50, issue.6, pp.705-709, 2016.

K. E. Young, I. Soussi, M. Hemels, and M. Toumi, A comparative study of orphan drug prices in Europe, J. Mark. Access Health Policy, vol.5, issue.1, 2017.

P. Mincarone, Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements, Public Health Genomics, vol.20, issue.1, pp.1-8, 2017.

&. Eucerd, . Eucerd, . Of, . European-union, . Of et al.,

, Beneluxa initiative | BeNeLuxA, p.17, 2019.

A. Ct, Service médical rendu (SMR) Le médicament a-t-il suffisamment d'intérêt clinique pour être pris en charge par la solidarité nationale ?, p.2

T. Kirchmann, H. Kielhorn-schönermark, P. P. Matthias, and . Schönermark, White Paper: Orphan Drugs in Germany -lessons learned from AMNOG, best and worst practices and strategic implications, p.19, 2017.

, EURORDIS -The Voice of Rare Disease Patients in Europe, p.17, 2019.

C. Ema, &. Guideline, . Compassionate, . Of, and . Products, , vol.726, 2004.

G. Balasubramanian, S. Morampudi, P. Chhabra, A. Gowda, and B. Zomorodi, An overview of Compassionate Use Programs in the European Union member states, Intractable Rare Dis. Res, vol.5, issue.4, pp.244-254, 2016.

H. I. Hyry, J. Manuel, T. M. Cox, and J. C. Roos, Compassionate use of orphan drugs, Orphanet J. Rare Dis, vol.10, 2015.

, Early access to medicines in Europe: Compassionate use to become a reality, EURORDIS position, 2017.

&. Qu and &. Qu, une autorisation temporaire d'utilisation? -ANSM : Agence nationale de sécurité du médicament et des produits de santé'

, Les Recommandations Temporaires d'Utilisation : Principes généraux -ANSM : Agence nationale de sécurité du médicament et des produits de santé'

, Medicinal Products Act (Arzneimittelgesetz -AMG)'. [Online, p.18, 2019.

, Italian Council of State Improves Access to Investigational Medicines, Inside EU Life Sciences, vol.24, p.19, 2017.

H. Mamiya, Update of Drug Pricing System in Japan, p.18

, Pharmaceutical Administration and Regulations in Japan, p.20, 2017.

, The Pharmaceutical Industry in Figures Key Data, EFPIA European Federation of Pharmaceutical Industries and Associations, 2018.

O. Of and . Commissioner, Office of Medical Products and Tobacco, 2019.

, Investigational New Drug (IND) Application', 2019.

C. and B. E. Fda, Center for Biologics Evaluation and Research -Transfer of Therapeutic Products to the Center for Drug Evaluation and Research (CDER, p.19, 2019.

C. Fda and C. , Expedited Programs for Serious Conditions -Drugs and Biologics, p.40, 2017.

, PRIME: a two-year overview, EMA, p.14, 2016.

, Enhanced early dialogue to facilitate accelerated assessment of PRIority Medicines (PRIME), EMA/CHMP/57760/2015, Rev, EMA Committee for Medicinal Products for Human Use, p.19, 2018.

, PRIME eligibility requests 2019 Deadlines for submission and timetable for assessment EMA/737186/2017, EMA, 2018.

, European Medicines Agency Guidance for applicants seeking access to PRIME scheme EMA, EMA, 2015.

, Guideline on the scientific application and the practical arrangements necessary to implement the procedure for accelerated assessment pursuant to Article, Regulation (EC), vol.14, issue.9, 2004.

, Assessment of request for accelerated assessment of initial Marketing Authorisation applications 30-day timetable, 2017.

V. P. and S. S. Ema, Better processes to facilitate earlier authorisation, vol.21, p.23, 2016.

, Strategy of SAKIGAKE', p.23, 2019.

J. and P. D. , Quality Overall Summary Grounds for Revision, 2006.

, Application for Accreditation of Foreign Manufacturers

I. Harmonised and . Guideline, ETHNIC FACTORS IN THE ACCEPTABILITY OF FOREIGN CLINICAL DATA E5(R1, 1998.

, Pharmaceutical and Food Safety Bureau Ministry of Health, Labour and Welfare, p.11, 2007.

, Drugs Reviews | Pharmaceuticals and Medical Devices Agency, p.23, 2019.

K. Sarnola, R. Ahonen, J. E. Martikainen, and J. Timonen, Policies and availability of orphan medicines in outpatient care in 24 European countries, Eur. J. Clin. Pharmacol, vol.74, issue.7, pp.895-902, 2018.

A. De-varax, M. Letellier, G. Börtlein, and . Alcimed, Study on orphan drugs, p.39, 2005.

, Patient Support Services -Sanofi Genzyme, p.24, 2019.

, Pfizer Supports Patients Affected by Rare Diseases | Pfizer: One of the world's premier biopharmaceutical companies, p.24, 2019.

S. Ministère-des, L. De, and . Santé, Les maladies rares -Qu'est-ce qu'une maladie rare ?', Ministère des Solidarités et de la Santé, p.4, 2019.

S. Ministère-des, L. De, and . Santé, L'offre de soin', Ministère des Solidarités et de la Santé, p.4, 2019.

. Ministère, . Solidarités, L. A. De, and . Santé, Arrêté du 25 novembre 2017 portant labellisation des réseaux des centres de référence prenant en charge les maladies rares, vol.15, p.4, 2017.

. Dicom_jocelyne and . Dicom_jocelyne, Référentiel des indications des spécialités pharmaceutiques inscrites sur la liste en sus', Ministère des Solidarités et de la Santé, p.4, 2019.

M. Ministère-du-travail, M. Sports, and . Budget, Circulaire DSS/1C/DGS/PP2/DHOS/E2 no 2010-24 du 25 janvier 2010 relative à la validation des prescriptions initiales de médicaments désignés comme orphelins financés en sus des presta-tions d'hospitalisation, vol.15, 2010.

A. Ars and . Omedt, Les médicaments orphelins Comment les prescrire ? Comment les dispenser ?, 2012.

M. T. Lopes, V. H. Koch, V. Sarrubbi-junior, P. R. Gallo, and M. Carneiro-sampaio, Difficulties in the diagnosis and treatment of rare diseases according to the perceptions of patients, relatives and health care professionals, Clinics, vol.73, 2018.

, The History of Gaucher Disease', National Gaucher Foundation, vol.25, 2018.

S. Nestler-parr, Challenges in Research and Health Technology Assessment of Rare Disease Technologies: Report of the ISPOR Rare Disease Special Interest Group, Value Health, vol.21, issue.5, pp.493-500, 2018.

E. F. Augustine, H. R. Adams, and J. W. Mink, Clinical Trials in Rare Disease: Challenges and Opportunities, J. Child Neurol, vol.28, issue.9, pp.1142-1150, 2013.

, Overcoming the Challenges of Rare Disease Drug Development', 2018.

M. Abou-el-enein, A. Elsanhoury, and P. Reinke, Overcoming Challenges Facing Advanced Therapies in the EU Market, Cell Stem Cell, vol.19, issue.3, pp.293-297, 2016.

C. Schey, T. Milanova, and A. Hutchings, Estimating the budget impact of orphan medicines in Europe: 2010 -2020', Orphanet J. Rare Dis, vol.6, p.62, 2011.

, EvaluatePharma Orphan Drug Report, p.24, 2018.

K. N. Meekings, C. S. Williams, and J. E. Arrowsmith, Orphan drug development: an economically viable strategy for biopharma R&D, Drug Discov. Today, vol.17, pp.660-664, 2012.

, Orphan incentives, European Medicines Agency, vol.17, 2018.

I. U. and -. R. Orphanet, Orphanet: Orphan drugs in Japan, p.24, 2019.

I. U. and -. R. Orphanet, Orphanet: Orphan drugs in the United States, p.24, 2019.

, Inventory of Union and Member State incentives to support research into, and the development and availability of, orphan medicinal products, 2015.

A. K. Hall and M. R. Carlson, The current status of orphan drug development in Europe and the US', Intractable Rare Dis, Res, vol.3, issue.1, pp.1-7, 2014.

H. Takeda, Incentives and Regulatory Considerations in Orphan Drug/Medical Device Development -Situation in Japan, p.24, 2014.

, Drug Repositioning: Concept, Classification, Methodology, and Importance in Rare/Orphans and Neglected Diseases, J. Appl. Pharm. Sci, pp.157-165, 2018.

P. Minghetti, E. P. Lanati, J. Godfrey, O. Solà-morales, O. Wong et al., From Off-Label to Repurposed Drug in Non-Oncological Rare Diseases: Definition and State of the Art in Selected EU Countries, Med. Access Point Care, vol.1, 2017.

E. H. Davies, E. Fulton, D. Brook, and D. A. Hughes, Affordable orphan drugs: a role for not -for-profit organizations, Br. J. Clin. Pharmacol, vol.83, issue.7, pp.1595-1601

J. J. Hernandez, Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in Repurposing Approved Drugs As Cancer Therapeutics, Front. Oncol, vol.7, 2017.

C. Fda, Guidance for Industry Applications Covered by Section 505(b)(2), p.24, 1999.

, European Medicines Agency post-authorisation procedural advice for users of the centralised procedure, p.291

S. Murteira, A. Millier, Z. Ghezaiel, and M. Lamure, Drug reformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications, J. Mark. Access Health Policy, vol.2, issue.1, p.22813, 2014.

J. Zhu, Orphan Drugs in Asia, p.159, 2017.

I. U. and -. R. Orphanet, Orphanet: Orphan drugs In Third World, p.24, 2019.