tyle='margin-left:1.0in;text-align:justify;text-indent: -.25in;line-height:150%;mso-list:l14 level1 lfo10;tab-stops:list 1.0in'>1.      the original holder gives consent

2.      the sponsor is unable to supply sufficient amounts of the drug; or

3.      the second applicant can show that their product is safer, more effective or clinically superior.[66] 

Unlike the U.S. regulations, marketing exclusivity can be reduced to six years if after five years the criteria for designation are no longer met or the profits being made on the product are considered unreasonable.[67]  The American Orphan Drug Act does not provide for any penalties or guidelines to revoke any of the incentives offered.  Other economic incentives provided by the European Union’s Act include funds for examination fees and the possibility of other member states to waive their fees for applications to place the orphan drugs on their domestic markets.[68]

            Japan has had a financial support system in place since 1973 that focused on researching orphan drugs that has been amended in 1993.[69]  In Japan, the same rules are applied to orphan medical devices as well orphan drugs.  Orphan status is given to drugs that are:

1.      used to treat severe diseases effecting less that 50,000 patients in Japan,

2.      alternative treatments are not available, or greater effectiveness and/or safety are expected; and

3.      the development of the drug is highly probable. 

Once a drug receives designation, it is eligible to receive: grants, tax reductions, guidance to facilitate development, accelerated procedures on new drug approval applications, a ten year period of exclusivity of the collected data from practical medical use and a ten year term for re-examination.[70]

The pharmaceutical industry participates in a strong worldwide market and rare diseases are a global concern.  The availability of drugs, pharmaceutical production and consumption is linked to developments that occur worldwide as well as domestically. “The introduction of new products and the expansion of foreign markets have kept domestic production growing” therefore it is important to encourage involvement in world markets and harmonize procedures.[71]  The majority (83.5%) of the world market is distributed among North America (36.5%), Europe (29%), and Japan (15.8%).[72]  As discussed earlier, many of the nations are instating similar plans to promote R&D for rare diseases modeling the American Orphan Drug Act.

The pharmaceutical industry is seeking a harmonization by offering ten years of marketing exclusivity for all countries and it is trying to extend these rights to any registration data, including indications of older drugs.[73]  The U.S. should provide additional incentives or the FDA should offer more guidance on marketing on the global market.  Also, there should be efforts to gain mutual recognition of approvals from other countries, as Australia does for orphan drug approved in the U.S.  There should also be harmonization to permit companies to import drugs that are marketed in a different country upon authorization.

V. ALTERNATIVES, OTHER INCENTIVES AND PROGRAMS

The U.S. Orphan Drug Act primarily focuses on the pharmaceutical companies and inciting them to produce orphan drugs.  The Act, as it is, has proven to significantly increase the revenue a company can make on an orphan drug and harness’s these financial incentives to induce companies to invest. Corporate responsibility and public image should be promoted and there should be less emphasis on profitability. In addition to offering financial incentives through the Orphan Drug Act, Congress should also encourage academic researchers and others outside of just the for-profit pharmaceutical industry to develop more drugs and provide them with more incentives, funding and grants. 

Since pharmaceuticals companies are so profitable in general, it has been proposed that they should set aside a fraction of their revenues for development of rare diseases and assist governments in providing access and implementing health programs.[74]  The industry should also work with organizations such as WHO, World Bank and NGOs to build up collaborative policies. Major pharmaceutical companies should aid the WTO to set up exceptions to permit underdeveloped countries to produce or import generic drugs instead of prohibiting them. At the November 1999 conference entitled “Increasing Access to Essential Drugs in a Globalized Economy” called for “compulsory research obligations, such as requirements that companies reinvest a percentage of pharmaceutical sales into R&D, either directly or through public or private sector R&D programs.”[75]

Sometimes the pharmaceutical industry is more concerned about profits and business, forgetting that they play a vital role in the health and fitness of people. The “industry should consider its social responsibilities and not just its profits.”[76]  There are other things a company should be concerned about, such as their public image.  If a pharmaceutical researcher has come across a cure for a rare disease, why not share it and help those that need it? The argument provided by the pharmaceutical industry is, “Giving away our medicines away in general is an unsustainable and unrealistic answer because, at the end of the day, we must earn adequate return on our investment in order to fund future research.” It seems selfish and almost cruel to withhold a possible antidote from someone suffering from a rare disease.  Pharmaceuticals should be encouraged to make donations, either by their own morality or by incentives offered through the government.  Displaying good corporate responsibility is valuable for a company's image in the long run. If clients and patients perceive a company as moral and genuinely interested in the public good, they are more likely to maintain a relationship and invest in that corporation. Tax incentives over the past 20 years and corporate giving amounted to 6 billion.[77] This is a practice that should be continued and encouraged.

An exemplary model of such corporate giving is Merck.  Merck discovered a treatment for river blindness during development and research.  While investigating a heartworm treatment for animals, researchers found a drug that would prevent tropical river blindness. The drug was already produced but no one was buying the product despite the great need.  The government also provided no aid because of the lack of a market so Merck just donated the medicine. Since then 51 million treatments have been distributed.  Now the Merck project is managed in cooperation with United Nation agencies, WHO and the Task Force for Child Survival and Development.[78]  Other organizations should look to Merck as a role model and take responsibility upon themselves to offer or donate medications which they have available. As George W. Merck, the Chairman and CEO of Merck wisely stated, “We try never to forget that medicine for the people.  It’s not for the profits.  The profits follow, and if we have remembered that, they never failed to appear.”[79]

Additionally, there are alternatives for putting a drug on the market to treat rare diseases. In the United States, the regulations of FDA permit physicians to prescribe approved medications for other uses aside from than their intended indications. This practice is known as “off-label use”.[80] This method allows a physician to use an FDA approved drug to treat a patient for a symptom that the drug was not initially approved for.  A manufacturer is allowed to continue producing the drug for its approved use as well as for the additional uses that were not initially foreseen.  This way the product is still available to patients and the manufacturer does not have to wait and go through the FDA approval process for the new use. The FDA does have certain restrictions on how information can be distributed by companies to inform physicians about these alternative uses.[81]  The information can be disseminated through means such as studies published in scientific journals about the safety, effectiveness or benefits of "off label" uses for marketed drugs, biologics and medical devices. This information can only be distributed for "off-label" uses which have been, or will be, studied and submitted for FDA approval. It must also be both reliable and balanced. The FDA should be flexible with these restrictions if an approved drug is found to also treat orphan disease but has not been intended for that use yet.[82]

­­­­­­­­­­­­­

For additional references, see:

Ø      http://www.fda.gov/orphan/

Ø      http://www.rarediseases.org/

Ø      http://ord.aspensys.com/diseases.asp

Ø      http://orphanet.infobiogen.fr/

 

Examples of rare diseases:

Ø      Anorexia Nervosa

Ø      Anthrax

Ø      Carpal Tunnel Syndrome

Ø      Dysthymia

Ø      Endomyocardial Fibrosis

Ø      Growth Hormone Deficiency

Ø      Huntington's Disease

Ø      Meningioma

Ø      Rubella

Ø      Werner Syndrome

 

Some Orphan Drugs Approved this Year:

Ø      Zevalin for the treatment of B-Cell non-Hodgkin's lymphoma

Ø      Gleevec for the treatment of gastrointestinal stromal tumors

Ø      Remodulin for the treatment of pulmonary arterial hypertension



[1] Gary A. Pulsinelli, The Orphan Drug Act: What’s Right With It, 15 Santa Clara Computer & High Tech.L.J. 299, 304 (1999).

[2] David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 126 (2000).

[3] This also raises the issue of whether resources that are allocated to R&D of diseases which affect a greater number of the population should be reduced in order to include R&D for rare diseases.

[4] M. Lisa Swoboda The Ethics of Pharma-Economics: An Examination of the Limit of Corporate Responsibility in the Pharmaceutical Industry, 1, 4 (April 2, 1999).

[5] Id.

[6] Pulsinelli at 299, 304.

[7] Swoboda at 4.

[8] Black’s Law Dictionary 919 (7th ed. 2000).

[9] Rohde at 127.

[10] Generics are drugs which are marketing under their chemical name without advertising. For example the drug Diazedpam is a generic name for the commonly advertised brand name sedative Valium.  See http://medterms.com/script/main/art.asp?li=MNI&ArticleKey=10127.

[11] Swoboda at 5.

[12] Rohde at 125, 126.

[13] Swoboda at 1,5.

[14] Rohde at 125, 126.

[15] David B. Clissold,  Prescription for the Orphan Drug Act: The Impact of the FDA’s 1992 Regulations and the Latest Proposals for Reform, 50 Food & Drug L.J. 125, 130 (1995) See also  David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 127 (2000).

[16] John Henkel, How TV Launched the Orphan Drug Law, FDA Consumer Magazine (June 1999), available at http://www.fda.gov/fdac/features/1999/399_orph.html#tv.

[17] Id.

[18] Id.

[19] Id.

[20] Id.

[21] Gary A. Pulsinelli, The Orphan Drug Act: What’s Right With It, 15 Santa Clara Computer & High Tech.L.J. 299, 305 (1999).

[22] Gary A. Pulsinelli, The Orphan Drug Act: What’s Right With It, 15 Santa Clara Computer & High Tech.L.J. 299 (1999).

[23] Rohde at 133.

[24] Robert A. Bohrer, A Tale of Two Proteins: The FDA’s Uncertain Interpretation of the Orphan Drug Act, 12 Harv.J.L.&Tech. 365, 367 (1999).

[25] Orphan Drug Act, Pub. L. No. 94-414, §526(a)(2), 96 Stat. 2049 (1982).

[26] Pulsinelli at 306.

[27] Rohde at 129.

[28] Pulsinelli at 306.

[29] Id. at 307.

[30] Id. at 312.

[31] Id. at 310.

[32] Id. at 307.

[33] Id. at 312.

[34] Id. at 310.

[35] Id. at 310.

[36] David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 133 (2000).

[37] Id. at 129.

[38] Id. at 129.

[39] David B. Clissold,  Prescription for the Orphan Drug Act: The Impact of the FDA’s 1992 Regulations and the Latest Proposals for Reform, 50 Food & Drug L.J. 125, 130 (1995)

[40] Id. at 130.

[41] Id. at 130.

[42] Gary A. Pulsinelli, The Orphan Drug Act: What’s Right With It, 15 Santa Clara Computer & High Tech.L.J. 299 (1999).

[43] Id.

[44] Id. at 130.

[45] David B. Clissold,  Prescription for the Orphan Drug Act: The Impact of the FDA’s 1992 Regulations and the Latest Proposals for Reform, 50 Food & Drug L.J. 125, 130 (1995).

[46] Joseph A. Levitt & John V. Kelsey, The Orphan Drug Act Regulations and Related Issues, 48 Food & Drug L.J. 525, 526 (1993).

[47] Id. at 525.

[48] Micheal J. Bernstein, Bills would boost research funding for rare disorders through NIH and FDA (October 21, 2002), available at http://www.ama-assn.org/sci-pubs/amnews/pick_02/gvsb1021.htm

[49] Id.

[50] David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 133 (2000).

[51] Paola Minghetti, et al., A Proposal to Improve the Supply of Orphan Drugs, 42 (1) Pharmacological Research 33, 35 (2000).

[52] Rohde at 131.

[53] Raises the issue of whether mortality rates for orphan disease should be lower compared to other diseases.

[54] David R. Francis, Orphan Drugs Cure Rare Diseases at www.nber.org/digest/may02/w8677.html (For an updated listing of products obtaining designation and a listing of marketing approvals see http://www.fda.gov/orphan/designat/index.htm).

[55] David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 135 (2000).

[56] Id.

[57] David D. Rohde, The Orphan Drug Act: An Engine of Innovation? At What Cost?, 55 Food & Drug L.J. 125, 136 (2000).

[58] James Love, Paying for Health Care R&D: Carrot and Sticks, MSF/DND Working Group, 182 (2001).

[59] Rinat Ariely, The Rise of Biopharmaceutical Orphan Drug Adoption, Frost & Sullivan (December 2001) available at www.inpharm.com/intelligence/frost071201.html.

[60] Paola Minghetti, et al., A Proposal to Improve the Supply of Orphan Drugs, 42 (1) Pharmacological Research 33, 35 (2000).

[61] Id.

[62] Id.

[63] Arrigo Schieppeti et al., Modulating the profit motive to meet needs of the less-developed world, 358 The Lancet 1638 – 1640 (Nov. 10, 2001).

[64] Minghetti at 35.

[65] Minghetti.

[66] Id.

[67] Id.

[68] Id.

[69] Id.

[70] Minghetti.

[71] Kanavos at 57.

[72] Kanavos at 57.

[73] Love at 183.

[74] Schieppati at 1640.

[75] Love at 185.

[76] Schieppati at 1640.

[77] M. Lisa Swoboda The Ethics of Pharma-Economics: An Examination of the Limit of Corporate Responsibility in the Pharmaceutical Industry, 1, 3 (April 2, 1999).

[78] Id.

[79] Id.

[80] Definition provided at http://medterms.com/script/main/art.asp?li=MNI&ArticleKey=4622. 

[81]  FDA Proposes Rules For Dissemination Information On Off-Label Uses, HHS News, June 5, 1998, available at http://www.fda.gov/bbs/topics/NEWS/NEW00643.html.

[82] For further discussion on “off label” uses, See Steven R. Salbu, Off Label Use , Prescription and Marketing of FDA Approved Drugs: An Assessement of Legislative and Regulatory Policy, 51 Fla. L. Rev. 181 (1999).