FDA 4035 FDA Orphan Drug Designation Request Form

Department of Health and Human Services
Food and Drug Administration

FDA ORPHAN DRUG DESIGNATION REQUEST FORM

Form Approved
OMB Control Number: 0910-0167
Expiration Date: January 31, 2021
See OMB Statement on final page.

*Required field

Note: Include in a separate PDF document 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 a copy of the website and the website address. The word "drug" in this
form includes biologics. Additional guidance is available at the FDA Orphan Products website.
1. *Date of Request (mm/dd/yyyy)
2. Designation Request Number (for amended requests only)
Note: Amendment requests should include updated contact information, and address only the deficient portions
of the previous request.

3. Sponsor Contact Information
*Business Country

*Primary Contact Country

*Business Name

*Primary Contact Business Name

Business Address (if different from primary contact)

*Primary Contact Prefix (Mr., Mrs., Ms., Dr., Sir, Mx.)
*Primary Contact Degrees/Credentials
*Primary Contact Name & Title

*Primary Contact Address

Telephone Number (if different from primary contact)

*Primary Contact Office Number

Ext:

Primary Contact Cell Number
Primary Contact Other Number
** FDA recommends that sponsors provide an e-mail address that is FDA
secure. FDA will send the response to this email address. See the FDA
Orphan Products website

FORM FDA 4035 (6/20)

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*Primary Contact Email Address:**

PSC Publishing Services (301) 443-6740

EF

4. Sponsor U.S. Resident Agent Information (if applicable)
Note: A foreign sponsor is required to have a U.S. permanent-resident agent in order to file a request for an orphan
drug designation (See 21 CFR 316.22). For foreign sponsors, FDA will send the response to the email
address of the U.S. Resident Agent.
Business Name
Prefix (Mr., Mrs., Ms., Dr., Sir, Mx.)

Degree/Credentials

U.S. Resident Agent Name and Title

Office Number

Address

Cell Number
Other Number

Email Address:**

5. Product Information
Biologic

Combination Product

Drug

UNII

Chemical Name

*Generic/Descriptive Name (if no generic name, provide a meaningful descriptive name)

Code (other) Name

Trade Name

Provide an explanation as to what makes the product a combination product.

Additional Information

6. Manufacturer

Is the sponsor the manufacturer?
Yes

No

Name
Address

FORM FDA 4035 (6/20)

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Ext:

7. Requested Orphan Disease or Condition. (Identify it with specificity)
Note: Designation is given to a drug / biologic for the treatment, diagnosis, or prevention of a rare disease or
condition, not to proposed drug indication or how a sponsor may wish to study a drug.
Requesting Sponsor Name
This designation request is for:

Treatment

Prevention

Diagnosis

Drug Type/Class

Diagnosis Request: (for Diagnosis only)
Management of Disease
Initial Diagnosis
Proposed Orphan Disease or Condition

8. Description of the Disease or Condition, the Proposed Use of the Drug, and the Reasons why such
Therapy is Needed.

Describe the disease or condition in a few paragraphs. Briefly summarize the proposed use of the drug and the reasons
for its use.

Add Attachment

Note: Attachments are only for tables, charts, illustrations, and photos. Do not attach text or
references. Name attachments for this section starting with the number 8. Click the paper
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9. Scientific Rationale Relevant to the Disease/Condition. The scientific rationale should support a medically

plausible basis for the drug to be effective in the disease/condition (for more information see 21 CFR 316.20(b)(4)).

Briefly describe the product in one paragraph detailing the active ingredient(s), the drug type/class, structure, physical/
chemical properties, route of administration and formulation.

Briefly describe in one paragraph the drug's mechanism of action explaining how the drug works in the relevant disease/
condition.

Note: Limit the data provided in the scientific rationale section to the drug and its use in the disease or condition.
Data describing the use of the drug in other diseases or conditions typically are not relevant in supporting the request.
Note: For a treatment use, the study drug must be administered after the disease/condition has developed. For a
prevention use, the study drug must be administered before the disease/condition develops.
Note: The scientific rationale is best supported by human data that show the clinical benefit of using the drug in
patients with the rare disease or condition. If clinical data for the drug/active moiety in treating, diagnosing, or
preventing the rare disease are available, present the clinical data in this section; preclinical in vitro and in vivo studies
should only be briefly mentioned. Clinical data may include preliminary results as well as case reports.
Note: In absence of human data, the request for orphan drug designation may be satisfactorily supported with
preclinical data using a relevant animal model for the human disease. Animal toxicology data describing the safety of
the drug in animals do not provide efficacy data and are not generally relevant in supporting the scientific rationale.
Only in rare situations, where there is an absence of both human data and a relevant in vivo model, will FDA consider
a combination of alternative data that include the pathogenesis of the disease, a clear description of the drug and its
mechanism of action specific to the disease, and supporting in vitro data.
Has the drug been evaluated in humans with the disease that is the subject of the current orphan drug designation
request?
Yes

No

FORM FDA 4035 (6/20)

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Please provide up to several paragraphs describing only the relevant clinical data to support the scientific rationale.

Has the drug been evaluated in animals with the disease that is the subject of the current orphan drug designation
request?
Yes
No
Please provide up to several paragraphs describing only the relevant animal data to support the scientific rationale.

Are there any in vitro or other supportive data?
Yes
No
Please provide up to several paragraphs describing the in vitro or other supportive data to support the scientific rationale.

Note: Attachments are only for tables, charts, illustrations, and photos. Do not attach text or
references. Name attachments for this section starting with the number 9. Click the paper
clip on the left toolbar to view and delete attachments.
10. Clinical Superiority. Has the same drug already been approved for that same use? (For more information see
21 CFR 316.3(b)(3).

Add Attachment

Yes

No

If no, go to Orphan Subset.

Note: The approved drug need not have previously been granted orphan designation to be considered the same
drug (for more information see 21 CFR 316.3(b)(14)).
Note: Preliminary information or data for your proposed product should be provided to support a foundation for
the hypothesis that your proposed product is clinically superior to the previously same approved drug(s). If
applicable, cite all supporting publications and include them in the references.
Note: A major contribution to patient care (MC-to-PC) is intended to be a narrow category in which each
determination is on a case-by-case basis. Factors that the FDA cannot consider when determining whether a
drug makes a MC-to-PC include: cost of therapy and compliance to therapy.
If yes, provide a plausible hypothesis for clinical superiority based on greater effectiveness, greater safety in a
substantial portion of the target population, or a major contribution to patient care, over all previously approved
same drugs. List these drug(s) including brand name(s) and formulation(s).

Add Attachment

FORM FDA 4035 (6/20)

Note: Attachments are only for tables, charts, illustrations, and photos. Do not attach text or
references. Name attachments for this section starting with the number 10. Click the paper
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11. Orphan Subset. Is the request for an orphan subset of a common disease or condition? (For more information
see 21 CFR316.3(b)(13)).
Yes

No If no, go to Regulatory Status / Marketing History

Note: An orphan subset is not based on the plan to study the drug for a select indication, cost of the drug, clinical
trial eligibility, or disease grade or stage.
Note: An explanation for an orphan subset should include an analysis as to why the drug could not be used in
the remaining population with the disease or condition.
If yes, provide an explanation to support that a feature (e.g., mechanism of action, toxicity profile, prior clinical experience)
of the drug would restrict its use to the desired orphan subset of the common disease or condition.

12. Regulatory Status / Marketing History. (For more information see 21 CFR 316.20(b)(7)).
Provide the regulatory status of the drug in the U.S. Include the following:
• preIND / IND or NDA / BLA numbers if available. Provide the indication that is associated with each one.

•
•

Any relevant regulatory determinations if the drug is a combination product.
Any orphan drug designations you may hold for the drug in other uses.

Note: Do not include a listing of all orphan drug designations for the proposed drug and/or use held by other sponsors.

In order to assure that the regulatory section is complete, please self-certify whether or not you ever submitted a
marketing application to the FDA for the same drug for the same rare disease or condition prior to the time you submitted
this designation request.
Sponsor Self - Certification
Sponsor has not previously submitted a marketing application to the FDA for the same drug for the same rare
disease or condition prior to the submission of this request for orphan drug designation.
Agree

Disagree

Briefly provide the regulatory history outside the US. Include

•
•

A list of the approvals and investigations of the drug outside the US.
Whether you have submitted an European Medicines Agency (EMA) designation request for the same drug, for the
same disease or condition. If so, provide the current status of the request.

13. Population Estimate. Document that the number of people affected by the disease or condition for which the

drug is to be developed is less than 200,000 persons. “Prevalence” is defined as the number of persons in the United
States who have been diagnosed as having the disease or condition at the time of the submission of the request for
orphan-drug designation (for more information see 21 CFR 316.20(b)(8) and 21 CFR 316.21(b)).

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Note: Provide all calculations and cite references used to make the population estimate.
Note: Estimate should be current at the time of the submission of the orphan drug designation request. US
Census Bureau data can be used to update any population estimate.
Note: When a range of estimates exists, FDA accepts only the largest estimate unless a justification is provided
why another estimate is more accurate.
Note: If the drug is intended for diagnosis or prevention of a rare disease or condition, provide the estimated
number of people to whom the drug will be administered annually.
Note: If a disease is an acute condition (i.e., less than one year duration) incidence may be used as an estimate
of the population. However, note that if the disease is a relapsing/remitting disease where each episode is acute
in duration, a prevalence estimate may still be required.
Note: If using data from a claims database or foreign data, clearly explain how such data are generalizable to the
US population and the limitations of the data.
Note: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program is one
recommended resource for determining cancer statistics in the United States. A complete prevalence is required.
Is the current population estimate of the disease / condition or orphan subset less than the 200,000 threshold to qualify for
orphan drug designation?
Yes
No (If no, go to Documentation for No Cost Recovery)
Population Estimate: Provide all calculations and cite references used to make the estimate.

Documentation for No Cost Recovery: (for more information see 21 CFR 316.21(c)). Note: Complete this
section only if the number of people affected by the disease or condition for which the proposed drug is
greater than 200,000.
Provide documentation for No Cost Recovery

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Note: Attachments are only for tables, charts, illustrations, and photos. Do not attach text or
references. Name attachments for this section starting with the number 13. Click the paper
clip on the left toolbar to view and delete attachments.
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FORM FDA 4035 (6/20)

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