For Industry

Tips for Submitting an Application for Orphan Designation

  1. The required information to be included in the application is found under 21 CFR 316.20(b), shown as (8) items. Number the items in your application 1 though 8 and respond to the eight items as described. Creative numbering is not helpful.

    21 CFR 316.20(b) is accessed through “How to Apply for Orphan Drug Designation.”

  2. While all eight items will be reviewed, the application will be reviewed most critically in two areas: scientific rationale (Item 4) and population prevalence (Item 8). Do not confuse prevalence with incidence. They are different entities and can’t be substituted for one another.

    The application must contain a copy of every reference used in the application to document prevalence. While most references are from published sources, this also includes information obtained from websites. Provide a hard copy of the reference obtained from the Internet, plus the website address.

    It will facilitate the review process if the application contains a copy of every reference used to support the scientific rationale for the use of the drug/biological in the treatment of the rare disease.

  3. Information provided by the sponsor relating to Item 7 is often incomplete. Provide the IND or NDA/BLA numbers if they are available to you.

    Sometimes sponsors submit an NDA/BLA after they have requested orphan designation, but before the Office of Orphan Products Development has made a determination on their application. In that case, amend the application for orphan designation by providing a copy of the NDA/BLA (or supplement) acknowledgment letter that you received from the FDA Reviewing Division.

    In the event that the product is approved abroad, list the countries where it is approved and for how long. In this case, it is helpful to provide copies of the package insert(s) under separate tab. (Tabs are discussed below.)

  4. Format your application so that it is user friendly. After addressing the eight required items, provide a bibliography displayed in a related fashion as shown in the text of your document. This is described below. Usually references within the application are cited numerically with superscripts. In this case, provide the bibliography with the corresponding numeric superscripts, 1 through “n.” References need to be separated by a tabbed divider—colored sheets of paper placed between references are not functional. Place a copy of the first reference cited behind tab “1,” and so on.

    Some sponsors prefer to mention their references by author directly after the cited work, for example (Abel E, Shaw FG, Elder GF, et al. 1997). An advantage to this method is that as the text of the application is being developed, renumbering of the references is not necessary. Provide the bibliography (listed alphabetically) directly after the application, followed by the tabbed references. In this case, the references will be arranged alphabetically. In the example used above, the first tab will read, “Abel et al 1997.”

    In the event there are additional documents included in the application such as the investigator’s brochure, provide the document behind a tab, in this case labeled, “Investigator’s Brochure.”

    Proper formatting of your application is very important. The reviewer of the application needs to be able to “walk through” your application with ease.

  5. Submit the original and one photocopy of the application in separate binders or report covers to the Office of Orphan Products Development. The photocopy needs to be an exact duplicate of the original application. If there is a cover letter with the original, there needs to be a copy of the cover letter with the duplicate. Also, no correspondence should arrive loose, or out of the binder or report cover. An example of a useful type of report cover is the “ACCO 25973” with metal fasteners. They are inexpensive and readily available, plus they fit in standard filing cabinets nicely. It helps to label the front of each report cover or binder with the name of the sponsor, drug/biological, indication, and date of application.
  6. Submit the application (one original and one photocopy) for orphan designation to:

    Gayatri R. Rao, M.D., J.D.
    Director, Office of Orphan Products Development
    10903 New Hampshire Avenue
    WO 32-5295
    Silver Spring, MD 20993

If you have any questions, please call Jeff Fritsch R.Ph. at (301) 796-8682

Page Last Updated: 03/27/2017
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