✅ What is Orphan Drug Designation

Under the Orphan Drug Act and associated regulations (21 CFR §316), the FDA may designate a drug or biological product as an “orphan drug” if it is intended to treat, diagnose or prevent a “rare disease or condition” (affecting fewer than 200,000 persons in the U.S., or if >200,000, the drug is unlikely to be profitable). 
Benefits of designation include:

• Eligibility for tax credits for qualified clinical testing. 
• Potential waiver of certain FDA user fees.
• Eligibility for seven years of market exclusivity post-approval in the U.S. when applicable. 

📝 Eligibility Criteria & Key Considerations

Before submitting, sponsors should check:

• The drug (or biologic) is for a rare disease/condition (i.e., fewer than 200,000 persons in the U.S., or a disease affecting >200,000 but for which the costs of developing and making the drug would not be recoverable). 
• The drug is intended for that indication (treatment, diagnosis or prevention). 
• If the same drug is already approved for the same condition, then there must be a “clinically superior” rationale for the new use. 
• The designation request should preferably be submitted before filing for marketing approval (e.g., NDA or BLA) though it can be at various stages. 

🇺🇸 Submission Routes

You may submit the orphan designation request via one of three methods: 

1. Through the CDER NextGen Portal (for electronic submission)
2. Emailing the required information to orphan@fda.hhs.gov (if submitting electronically)
3. Mailing hard-copy documents to:

   Office of Orphan Products Development  
   Attention: Orphan Drug Designation Program  
   Food and Drug Administration  
   WO32-5295  
   10903 New Hampshire Avenue  
   Silver Spring, MD 20993-0002
   ``` :contentReference[oaicite:11]{index=11}
   

If you send via email, encrypted/secure email is strongly recommended for proprietary or confidential info. 

📄 What to Include: Required Information

Under the regulations (21 CFR §316.20) and FDA guidance, a request must contain certain content.

Key required elements include:

• Statement that you are requesting orphan‐drug designation and specify the disease/condition. 
• Sponsor’s name, address, contact person. 
• The drug’s name (generic, trade, or a meaningful descriptive name if neither exists). 
• Description of the rare disease or condition and the proposed use of the drug. 
• Description of the drug: active moiety, structural features, physical/chemical/biological properties. 
• If the drug is the same as an already approved drug for the same condition, explanation of why it may be clinically superior. 
• Summary of regulatory status and marketing history (if any). 
• Documentation demonstrating that the disease affects fewer than 200,000 persons or meets the >200,000 but unrecoverable cost test. 
• Supporting authoritative references (literature) for the disease prevalence, the drug’s rationale, etc. 

Also note that the request should be complete; the FDA may issue a deficiency letter if required information is missing. 

📋 Useful Form and Resources

• The FDA provides Form FDA 4035 – Orphan Drug Designation Request Form to assist sponsors. 
• Guidance document: “Designating an Orphan Product: Drugs and Biological Products”. 
• FAQs for orphan drug designation requests. 

🕒 What to Expect After Submission

• The FDA will acknowledge receipt of the submission. 
• The FDA reviews the request and may issue a deficiency letter if the submission lacks required information. 
• If approved, the FDA sends a designation letter. If not eligible, a denial letter is sent. 
• Once designated, the sponsor is eligible for the orphan incentives described above.

🧠 Practical Tips for Sponsors

• Submit early: Getting orphan designation before filing for approval is advisable.
• Prepare strong data: Demonstrate the rarity of the disease, the rationale for the drug, and, if necessary, clinical superiority.
• Use Form 4035: Helps ensure you include all required information.
• Ensure secure communications: Especially if submitting proprietary/trade-secret information by email.
• Track your submission: If emailed, use read receipt or confirmation; if mailed, consider tracking.
• Avoid missing data: A complete submission reduces risk of deficiency and delays.
• Keep copies: Retain full documentation of your submission for your records.
• Plan ahead for review: Orphan designation does not mean approval — it is a parallel regulatory process.

🧾 FDA Orphan Drug Designation Request – Submission Checklist

It follows FDA’s 21 CFR §316.20 requirements and the Form FDA 4035 structure.

Sponsor Name: ___________________________________________
Drug Name / Code: _________________________________________
Proposed Indication (Rare Disease/Condition): ________________
Date of Submission: ______________________________________
Contact Person: __________________________________________
Email / Phone: ___________________________________________

🧩 Section 1: Administrative Information

⚗️ Section 2: Description of the Drug

🧬 Section 3: Description of the Disease or Condition

💊 Section 4: Scientific Rationale for Use

🧪 Section 5: Regulatory and Market History

⚖️ Section 6: Same Drug / Clinical Superiority Justification

(Complete only if a similar drug is already approved for the same indication.)

📚 Section 7: Supporting Documentation

📤 Section 8: Submission Details

🕒 Post-Submission Follow-Up

🧾 References & Guidance Documents

• FDA Form 4035 – Orphan Drug Designation Request Form
• Guidance for Industry: Designating an Orphan Product: Drugs and Biological Products
• 21 CFR Part 316 – Orphan Drugs Regulations
• OOPD Contact: orphan@fda.hhs.gov

🗂️ Sponsor Notes

Use this checklist internally before submission to ensure completeness and compliance with FDA OOPD requirements. Incomplete or missing elements may result in a deficiency letter or delayed review.