For Industry

Tips for Submitting an Orphan Drug Designation Request

1. Requirements: Eight (8) items of information are required in the orphan drug designation request, they are found in 21CFR 316.20.  Please number the responses in your request from 1 through 8 to match the CFR.  There is no required application form; however, sponsors may use the common EMA/FDA Application form as part of their designation request.

2. Content:  While all eight items will be reviewed, the request 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 measures and can not be substituted for one another.  Also see Frequently Asked Questions (FAQ).

The request must contain a copy of every reference used to document prevalence, and used to support the scientific rationale for the use of the drug or biologic in the treatment of the rare disease.   References obtained from public websites must include the website address.  A complete set of references will facilitate the review process.

3. Regulatory Status and Marketing History:  Please note that 21 CFR 316.20(b)(7) requires the sponsor of an orphan-drug designation request to submit a "summary of the regulatory status and marketing history of the drug".  Information provided by the sponsor relating to item 7 is often incomplete.  This information is relevant to confirm your drug meets the statutory and regulatory requirements for orphan drug designation.  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 designation request.  In that case, amend the orphan designation request by providing a copy of the NDA/BLA (or supplement) acknowledgement letter received from the FDA reviewing division.  See Section 526(a)(1) of the Federal Food, Drug and Cosmetic Act (21 U.S.C 360bb(a)(1) ("A request for [orphan-drug] designation...shall be made before the submission of an application under Section 505(b) for the drug").  See also 21 CFR 316.23(a) (A sponsor may request orphan-drug designation at any time in  its drug development process prior to the time that sponsor submits a marketing application for the drug for the same rare disease or condition".)

In the event that the product is approved in another country, list the countries where it is approved and for how long.  In this case, it is helpful to provide copies of this information under a separate tab. (Tabs are discussed below.)

4. Self-Certification:  In order to ensure the summary provided under 21CFR 316.20(b)(7) is complete, please certify in the designation request whether or not you ever submitted a marketing application for the same active moiety for the same rare disease or condition prior to the time you submitted this designation request.  Therefore, in your designation request, please self-certify that "SPONSOR NAME has not previously submitted a marketing application to the FDA for the same active moiety for the same rare disease or condition prior to the submission of this request for orphan drug designation."

 5. Request Format:  Format your request 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 are cited numerically with superscripts.  In this case, provide the bibliography with the corresponding numeric superscripts, 1 through "n."  References must be separated by a tabbed divider rather than blank or colored sheets of paper placed between the references.  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 designation request is being developed, renumbering of the references is not necessary.  Provide the bibliography (listed alphabetically) directly after the designation request, 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 request such as an investigator's brochure, provide the document behind a tab labeled accordingly.

Proper formatting of your orphan designation request is very important.  The FDA reviewer needs to be able to "walk through" your request with ease.

6. Hard Copy Submissions:  Submit the original and one photocopy of the request in separate binders or report covers to the Office of Orphan Products Development.  The photocopy needs to be an exact duplicate of the original request.  If there is a cover letter with the original, there needs to be a copy of the cover letter with the duplicate.  No correspondence should arrive loose, or out of the binder or report cover.  An example of a useful type of report cover is a letter-size (8.5x11 inches) pressboard report cover, side bound, with metal fasteners.  They are inexpensive and readily available, and they fit in standard filing cabinets.  It helps to label the front of reach report cover or binder with the name of the sponsor, drug/biological, indication, and date of the designation request.

7. CD Submissions:  As an alternative to a hard-copy submission noted above, an orphan designation request may be submitted on a compact disk (CD) with a signed original cover letter.  A pdf copy of the signed letter must be on the disk.  Place copies of the referenced materials in a separate directory from the cover letter and orphan designation request.  Thumb/flash drives and email attachments will not be accepted.  See Corresponding with the OOPD Drug Designation Programs for CD requirements.

8. Address:  Address the cover letter for an orphan drug designation request to: 

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

9. Tracking Your Submission:  You can track receipt of your orphan designation request by using an express mail company or tracking options for U.S. mail.  Within about 2 weeks of receiving an orphan designation request, OOPD will send the sponsor (or designated agent) a letter acknowledging receipt of the designation request or an email acknowledging receipt of an amendment to a previously submitted request.  New requests typically take 120 to 150 days to review.

If you have any questions, please call 301-796-8660 or email:  


Page Last Updated: 06/15/2017
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