orphan drug production


Summary: Production of drugs or biologicals which are unlikely to be manufactured by private industry unless special incentives are provided by others.

Top Publications

  1. Shulman S, Manocchia M. The US orphan drug programme 1983-1995. Pharmacoeconomics. 1997;12:312-26 pubmed
  2. Schieppati A, Henter J, Daina E, Aperia A. Why rare diseases are an important medical and social issue. Lancet. 2008;371:2039-41 pubmed publisher
  3. Boon W, Moors E. Exploring emerging technologies using metaphors--a study of orphan drugs and pharmacogenomics. Soc Sci Med. 2008;66:1915-27 pubmed publisher
  4. Clarke J. Is the current approach to reviewing new drugs condemning the victims of rare diseases to death? A call for a national orphan drug review policy. CMAJ. 2006;174:189-90 pubmed
  5. McCabe C, Tsuchiya A, Claxton K, Raftery J. Orphan drugs revisited. QJM. 2006;99:341-5; discussion 350-1 pubmed
  6. Asbury C. The Orphan Drug Act. The first 7 years. JAMA. 1991;265:893-7 pubmed
    ..Overall, the law has been associated with an increase in orphan product development. The law's costs and benefits to companies, patients, and the public should be examined if future changes are proposed. ..
  7. Wellman Labadie O, Zhou Y. The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?. Health Policy. 2010;95:216-28 pubmed publisher
    ..This study investigates issues associated with the United States Orphan Drug Act...
  8. Orofino J, Soto J, Casado M, Oyagüez I. Global spending on orphan drugs in France, Germany, the UK, Italy and Spain during 2007. Appl Health Econ Health Policy. 2010;8:301-15 pubmed publisher
    ..Mean annual costs per patient of orphan drugs varied widely, with costs being related to the prevalence of the disease for which the product is indicated. ..
  9. Herrling P. Patent sense. Nature. 2007;449:174-5 pubmed

More Information


  1. Hopkins A, Witty M, Nwaka S. Mission possible. Nature. 2007;449:166-9 pubmed
  2. Picavet E, Dooms M, Cassiman D, Simoens S. Drugs for rare diseases: influence of orphan designation status on price. Appl Health Econ Health Policy. 2011;9:275-9 pubmed publisher
    ..In order to gain full insight into orphan drug pricing mechanisms, future research should focus on collecting information about the different factors influencing orphan drug pricing...
  3. Schey C, Milanova T, Hutchings A. Estimating the budget impact of orphan medicines in Europe: 2010 - 2020. Orphanet J Rare Dis. 2011;6:62 pubmed publisher
    ..Furthermore, based on the results of this budget impact forecast, the European orphan drug legislation is not leading to a disproportionate impact on pharmaceutical expenditure. ..
  4. Hotez P, Molyneux D, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs J. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med. 2006;3:e102 pubmed
  5. Herder M. When everyone is an orphan: against adopting a U.S.-styled orphan drug policy in Canada. Account Res. 2013;20:227-69 pubmed publisher
  6. Joppi R, Bertele V, Garattini S. Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU. Eur J Clin Pharmacol. 2013;69:1009-24 pubmed publisher
    ..More stringent criteria to assess OMPs' efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market. ..
  7. Haffner M, Whitley J, Moses M. Two decades of orphan product development. Nat Rev Drug Discov. 2002;1:821-5 pubmed
  8. Maeder T. The orphan drug backlash. Sci Am. 2003;288:80-7 pubmed
  9. Gericke C, Riesberg A, Busse R. Ethical issues in funding orphan drug research and development. J Med Ethics. 2005;31:164-8 pubmed
    ..The limitations of standard economic evaluation tools and other priority setting tools used to inform health policy decision makers on research funding decisions are outlined. ..
  10. Hughes D, Tunnage B, Yeo S. Drugs for exceptionally rare diseases: do they deserve special status for funding?. QJM. 2005;98:829-36 pubmed
    ..Mechanisms are discussed for creating a policy that would reduce geographical inequalities in provision across Europe. ..
  11. Dupont A, Van Wilder P. Access to orphan drugs despite poor quality of clinical evidence. Br J Clin Pharmacol. 2011;71:488-96 pubmed publisher
  12. Cheng M, Ramsey S, Devine E, Garrison L, Bresnahan B, Veenstra D. Systematic review of comparative effectiveness data for oncology orphan drugs. Am J Manag Care. 2012;18:47-62 pubmed
    ..Innovative analytic and policy approaches are needed to develop and implement a decision-making framework for this pharmaceutical category that is consistent with evidence-based medicine and comparative effectiveness research. ..
  13. Simoens S. Pricing and reimbursement of orphan drugs: the need for more transparency. Orphanet J Rare Dis. 2011;6:42 pubmed publisher
    ..Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions...
  14. Miyamoto B, Kakkis E. The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases. Orphanet J Rare Dis. 2011;6:49 pubmed publisher
    ..Our research brings attention to the need for well-defined and practical qualification criteria for the use of surrogate endpoints to allow more access to the AA approval pathway in clinical trials for rare diseases. ..
  15. Brabers A, Moors E, van Weely S, de Vrueh R. Does market exclusivity hinder the development of Follow-on Orphan Medicinal Products in Europe?. Orphanet J Rare Dis. 2011;6:59 pubmed publisher
    ..In the interest of rare disorder patients better understanding of the effect of the market exclusivity incentive on follow-on OMP development is warranted...
  16. Denis A, Mergaert L, Fostier C, Cleemput I, Simoens S. Budget impact analysis of orphan drugs in Belgium: estimates from 2008 to 2013. J Med Econ. 2010;13:295-301 pubmed publisher
    ..Policy options to address the rising budget impact include pricing linked to return on investment, risk-sharing arrangements and re-appraisal of orphan drug status if additional indications are approved. ..
  17. Meekings K, Williams C, Arrowsmith J. Orphan drug development: an economically viable strategy for biopharma R&D. Drug Discov Today. 2012;17:660-4 pubmed publisher
    ..The data support the targeting of rare diseases as an important component of a successful biopharma R&D strategy. ..
  18. Heemstra H, van Weely S, Büller H, Leufkens H, de Vrueh R. Translation of rare disease research into orphan drug development: disease matters. Drug Discov Today. 2009;14:1166-73 pubmed publisher
    ..Consequently, additional incentives should focus on stimulating the specific needs of rare disease research at disease class level...
  19. Mitsumoto J, Dorsey E, Beck C, Kieburtz K, Griggs R. Pivotal studies of orphan drugs approved for neurological diseases. Ann Neurol. 2009;66:184-90 pubmed publisher
    ..As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy. ..
  20. Kesselheim A, Myers J, Avorn J. Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer. JAMA. 2011;305:2320-6 pubmed publisher
  21. Heemstra H, Giezen T, Mantel Teeuwisse A, de Vrueh R, Leufkens H. Safety-related regulatory actions for orphan drugs in the US and EU: a cohort study. Drug Saf. 2010;33:127-37 pubmed publisher
    ..Doctors and pharmacists should therefore be vigilant with regard to the occurrence of a safety-related issue for orphan drugs. ..
  22. Kesselheim A, Myers J, Solomon D, Winkelmayer W, Levin R, Avorn J. The prevalence and cost of unapproved uses of top-selling orphan drugs. PLoS ONE. 2012;7:e31894 pubmed publisher
    ..We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy. ..
  23. Huyard C. How did uncommon disorders become 'rare diseases'? History of a boundary object. Sociol Health Illn. 2009;31:463-77 pubmed publisher
    ..In the definition process of the category of rare diseases, the key actors were the patients and public bodies, not medical professionals or the pharmaceutical industry...
  24. Haffner M, Torrent Farnell J, Maher P. Does orphan drug legislation really answer the needs of patients?. Lancet. 2008;371:2041-4 pubmed publisher
  25. McCabe C, Claxton K, Tsuchiya A. Orphan drugs and the NHS: should we value rarity?. BMJ. 2005;331:1016-9 pubmed
  26. Yin W. Market incentives and pharmaceutical innovation. J Health Econ. 2008;27:1060-1077 pubmed publisher
    ..Tax credits can stimulate R & D; yet because they leave revenue margins unaffected, tax credits appear to have a more limited impact on private innovation in markets with smaller revenue potential. ..
  27. Trouiller P, Battistella C, Pinel J, Pecoul B. Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts. Trop Med Int Health. 1999;4:412-20 pubmed
    ..However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'. ..
  28. Tambuyzer E. Rare diseases, orphan drugs and their regulation: questions and misconceptions. Nat Rev Drug Discov. 2010;9:921-9 pubmed publisher
    ..This article provides an industry perspective on some of the common questions and misconceptions related to orphan drug development and its regulation, with the aim of facilitating future progress in the field...
  29. Maurer S. Choosing the right incentive strategy for research and development in neglected diseases. Bull World Health Organ. 2006;84:376-81 pubmed
    ..The efficiency of pay-as-you-go methods depends on sponsors' willingness to withdraw funding from failed drug discovery programmes. ..
  30. Orfali M, Feldman L, Bhattacharjee V, Harkins P, Kadam S, Lo C, et al. Raising orphans: how clinical development programs of drugs for rare and common diseases are different. Clin Pharmacol Ther. 2012;92:262-4 pubmed publisher
    ..We conclude that small studies of appropriate design can support US FDA approval of new medicines for rare diseases...
  31. Buckley B. Clinical trials of orphan medicines. Lancet. 2008;371:2051-5 pubmed publisher
  32. Putzeist M, Mantel Teeuwisse A, Llinares J, Gispen de Wied C, Hoes A, Leufkens H. EU marketing authorization review of orphan and non-orphan drugs does not differ. Drug Discov Today. 2013;18:1001-6 pubmed publisher
    ..Differences in deficits were found, but similarities in the way ODs and non-ODs were reviewed and marketing approval decisions were taken, underline that regulatory standards are equally high. ..
  33. Côté A, Keating B. What is wrong with orphan drug policies?. Value Health. 2012;15:1185-91 pubmed publisher
  34. Luisetti M, Balfour Lynn I, Johnson S, Miravitlles M, Strange C, Trapnell B, et al. Perspectives for improving the evaluation and access of therapies for rare lung diseases in Europe. Respir Med. 2012;106:759-68 pubmed publisher
  35. Rinaldi A. Adopting an orphan. EMBO Rep. 2005;6:507-10 pubmed
  36. McCabe C, Tsuchiya A, Claxton K, Raftery J. Assessing the economic challenges posed by orphan drugs: a comment on Drummond et al. Int J Technol Assess Health Care. 2007;23:397-401; author reply 401-4 pubmed
  37. Stolk P, Willemen M, Leufkens H. Rare essentials: drugs for rare diseases as essential medicines. Bull World Health Organ. 2006;84:745-51 pubmed
    ..In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme. ..
  38. Winters D. Expanding global research and development for neglected diseases. Bull World Health Organ. 2006;84:414-6 pubmed
  39. Kettler H, Modi R. Building local research and development capacity for the prevention and cure of neglected diseases: the case of India. Bull World Health Organ. 2001;79:742-7 pubmed
    ..Further studies are required on how Indian companies would respond to push and pull incentives originally designed to persuade multinational corporations to do more R&D on neglected diseases. ..
  40. Hughes Wilson W, Palma A, Schuurman A, Simoens S. Paying for the Orphan Drug System: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments?. Orphanet J Rare Dis. 2012;7:74 pubmed publisher
    ..The authors believe that this could, therefore, facilitate the approach for all stakeholders. ..
  41. Kanters T, de Sonneville Koedoot C, Redekop W, Hakkaart L. Systematic review of available evidence on 11 high-priced inpatient orphan drugs. Orphanet J Rare Dis. 2013;8:124 pubmed publisher
    ..Despite the often heard claim that RCTs are not feasible for orphan drugs, we found that an RCT was available in 60% of orphan drugs investigated. Cost-effectiveness and budget impact analyses for orphan drugs are seldom published. ..
  42. Kanavos P, Nicod E. What is wrong with orphan drug policies? Suggestions for ways forward. Value Health. 2012;15:1182-4 pubmed publisher
  43. Owen A, Spinks J, Meehan A, Robb T, Hardy M, Kwasha D, et al. A new model to evaluate the long-term cost effectiveness of orphan and highly specialised drugs following listing on the Australian Pharmaceutical Benefits Scheme: the Bosentan Patient Registry. J Med Econ. 2008;11:235-43 pubmed publisher
    ..The success of a generic drug registry model based on the BPR will be enhanced by addressing a number of operational issues identified during the implementation of this project. ..
  44. Ridley D, Grabowski H, Moe J. Developing drugs for developing countries. Health Aff (Millwood). 2006;25:313-24 pubmed
    ..In a well-functioning market, the voucher would speed access to highly valued treatments. Thus, the voucher could benefit consumers in both developing and developed countries at relatively low cost to the taxpayer. ..
  45. Dear J, Lilitkarntakul P, Webb D. Are rare diseases still orphans or happily adopted? The challenges of developing and using orphan medicinal products. Br J Clin Pharmacol. 2006;62:264-71 pubmed
    ..In this article we review OMPs and the incentives for their development and discuss the challenges presented by funding these treatments. ..
  46. Drummond M, Wilson D, Kanavos P, Ubel P, Rovira J. Assessing the economic challenges posed by orphan drugs. Int J Technol Assess Health Care. 2007;23:36-42 pubmed
  47. Heemstra H, Leufkens H, Rodgers R, Xu K, Voordouw B, Braun M. Characteristics of orphan drug applications that fail to achieve marketing approval in the USA. Drug Discov Today. 2011;16:73-80 pubmed publisher
    ..Sponsors, therefore, should engage in dialogue with the FDA and thoughtfully design pivotal clinical trials in accordance with FDA guidance documents. ..
  48. Villa S, Compagni A, Reich M. Orphan drug legislation: lessons for neglected tropical diseases. Int J Health Plann Manage. 2009;24:27-42 pubmed publisher
    ..Second, small-sized companies, which have played a successful role in the development of orphan drugs for rare diseases, may also represent a good business strategy for the case of tropical diseases. ..
  49. Griggs R, Batshaw M, Dunkle M, Gopal Srivastava R, Kaye E, Krischer J, et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009;96:20-6 pubmed publisher
  50. Haffner M. Adopting orphan drugs--two dozen years of treating rare diseases. N Engl J Med. 2006;354:445-7 pubmed
  51. Heemstra H, de Vrueh R, van Weely S, Büller H, Leufkens H. Predictors of orphan drug approval in the European Union. Eur J Clin Pharmacol. 2008;64:545-52 pubmed publisher
    ..Further research should be directed towards studying the quality of the clinical development program of those designated orphan medicinal products not reaching approval status. ..
  52. Denis A, Mergaert L, Fostier C, Cleemput I, Simoens S. A comparative study of European rare disease and orphan drug markets. Health Policy. 2010;97:173-9 pubmed publisher
  53. Braun M, Farag El Massah S, Xu K, Cote T. Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years. Nat Rev Drug Discov. 2010;9:519-22 pubmed publisher
    ..The implications of such findings for future development and marketing of therapies for rare diseases are discussed. ..