Orphan drugs designation

Several gene therapies have received orphan drug designation these are treatments for cystic fibrosis, Gaucher disease, and metastatic brain tumor. 

G. Other considerations Serono conducted the comparative study to demonstrate that Rebif is clinically superior to Avonex. No other path was available for Serono to have the product licensed by the FDA before mid-2003 because Avonex carried an orphan drug designation based on its superior safety profile over Betaseron, the first interferon beta to be licensed for multiple sclerosis. Based on the results of the Rebif versus Avonex study, the FDA determined that Rebif is clinically superior to Avonex. While recognizing that the safety profile associated with Rebif is not as favorable as the safety profile of Avonex, the FDA has determined that the severity and frequency of such adverse events do not render Rebif unUcensable under Section 35 of the Public Health Service Act. Further, under the orphan drug regulations, if Serono demonstrates that Rebif is superior to Avonex based on efficacy, Serono does not have to show that Rebif is safer than, or as safe as, Avonex. 

EU Orphan Drug designation. European Medicines Agency (EMEA). INTERNET SITE, 2005 August 26. 

But if pharmaceutical companies focused exclusively on these major diseases, millions of people with very serious but less widespread conditions would be left without help or hope. The solution, of course, is for the government to provide incentives that supplement the potential sales value of an important treatment for a relatively obscure disease, thus encouraging development in the absence of market blockbuster potential. In the United States, the mechanism for that encouragement is orphan-drug designation. 

Statement requesting Orphan-Drug designation for specific rare disease... 

A statement that the sponsor requests orphan-drug designation for a rare disease or condition, which shall be identified with specificity... 

The information requested from respondents represents, for the most part, an accounting of information already in the possession of the applicant. It is estimated, based on frequency of requests over the past five years, that 171 persons or organizations per year will request orphan-drug designation and none will request formal recommendations on design of preclinical or clinical studies. 

Response 2) We disagree with the comment because some sponsors have more experience with submitting Orphan-Drug Designation applications/ requests and, therefore, may require less human resource hours to compile all... 

The estimated 130h pertains to Sec. Sec. 316.20,316.21, and 316.26. These apply primarily to initial applications/requests seeking orphan-drug designation. Many applications/requests received in the Office of Orphan Products Development contain multiple volumes include an exact duplicate copy of the original and may include 50 or more documented references. Additional information is requested when an application/request is denied. The sponsor usually supplies the requested information in the form of an amendment. 

Withdrawal of exclusive approval or revocation of orphan-drug designation by FDA under any provision of this part or... 

Content and Format of a Request for Orphan Drug Designation... 

If the sponsor of a drug that is otherwise the same as an already-approved orphan drug seeks orphan drug designation for the subsequent drug for the same rare disease or condition, an explanation of why the proposed variation may be clinically superior to the first drug is required. 

Size of patient population. This refers not only to those in the parent country, but in other countries as well. Considerations of closely related subsets of patients must be considered because it is not possible to obtain orphan drug designation in the United States if the drug can be used by a closely related subgroup of patients [e.g. one type of epileptics vs. another or a large number of moderately ill who can readily benefit from a drug as well as a small number (under 200000) of severely ill patients with a particular disease],... 

It is important to note that medical foods and medical devices were not eligible for orphan drug designation or for the marketing exclusivity provisions of the Act. The Act was originally designed for unprofitable and unpatentable medicines only. 

In 1984, an amendment to the Act changed the standard for orphan drug designation from profitability to prevalence, which was set at less than 200 000 patients in the United States. The requirement of unprofitability was dropped from the Act. 

In 1985, another amendment to the Act made it possible for patented and patentable medicines to receive orphan drug designation (a pre-marketing classification) and orphan drug status (a post-NDA approval classification). 

In 1988, a further amendment established the time period for filing for orphan drug designation. This clarified that the designation must be prior to filing the NDA. 

Within the Act itself, the four major benefits are (1) the period of marketing exclusivity, which may be considered as a type of patent (2) the tax benefits on clinical trials between the date of orphan drug designation and NDA approval and (3) the FDA s Office of Orphan Products Development grants to support clinical trials on orphan drugs. A fourth benefit of protocol assistance, from the FDA, was always available for important new drugs (as well as others) and is important, but not necessarily new. Nonetheless, it is useful to call attention to this provision. 

A current trend is that more biotechnology products (see Chapter 2.11) are applying for orphan drug designation. The main reason for this phenomenon is that biotechnology patents are so difficult to obtain and orphan drug protection is valuable, while the inventors wait to see if a strong patent will issue. 

It is often important to establish that a company s medicine for which it desires an orphan drug designation differs from another medicine. There are a number of principles that will help a company establish a difference. 

Different chemical structures. If it is unequivocally shown that two structures differ and it makes a biological or clinical difference, both will be given orphan drug designation. However, if the chemical difference is minor (e.g. one amino acid difference in a protein or the terminal carbohydrate portion of a large molecule) and no clinical differences can be shown, they will usually be viewed as the same product. 

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