Rare Pediatric Disease Designation: Complete FDA PRV Voucher Guide

Rare pediatric disease designation is an FDA program that provides sponsors with the opportunity to earn a Priority Review Voucher (PRV) upon approval of a drug or biologic for a rare pediatric disease. Established by the Creating Hope Act of 2012 and incorporated into the FDA Safety and Innovation Act (FDASIA), this designation incentivizes development of treatments for serious conditions affecting children by offering transferable vouchers worth $100 million or more.

For pharmaceutical and biotech companies developing therapies for pediatric populations with rare diseases, the rare pediatric disease designation program represents one of the most valuable FDA incentives available - combining the benefits of faster regulatory review with a substantial financial asset that can be used or sold.

In this guide, you will learn:

• What qualifies a disease and drug for rare pediatric disease designation under FDA regulations
• The specific eligibility criteria including age and prevalence requirements
• How the Priority Review Voucher works and its current market value
• The complete RPDD FDA application process and timeline
• How rare pediatric disease designation compares to orphan drug designation

What Is Rare Pediatric Disease Designation?

Rare pediatric disease designation is a formal FDA program that grants sponsors the opportunity to receive a Priority Review Voucher upon FDA approval of a qualifying product for a rare pediatric disease. A rare pediatric disease is defined as a disease that primarily affects individuals aged birth to 18 years and meets the prevalence criteria for a rare disease (affecting fewer than 200,000 people in the United States).

Key characteristics of rare pediatric disease designation:

• Created by the Creating Hope Act (Section 908 of FDASIA, 2012)
• Administered by FDA's Office of Orphan Products Development (OOPD)
• Available for drugs and biologics treating rare diseases primarily affecting children
• Provides a Priority Review Voucher upon product approval
• The voucher can be used by the sponsor or sold to another company

The rare pediatric disease designation program addresses a critical gap in pediatric drug development. Children with rare diseases often lack treatment options because the small patient populations and specialized development requirements make pediatric rare disease programs economically challenging without special incentives.

RPDD FDA: How the Program Works

The RPDD FDA program operates through a two-stage process: first, sponsors obtain rare pediatric disease designation during development, and second, sponsors receive a Priority Review Voucher upon FDA approval of the designated product.

Rare Pediatric Disease Designation Program Structure

The Two-Stage Process

Stage 1: Rare Pediatric Disease Designation

• Sponsor submits designation request to FDA OOPD
• FDA evaluates disease and drug eligibility criteria
• If criteria met, FDA grants rare pediatric disease designation
• Designation must be obtained before NDA/BLA submission

Stage 2: Priority Review Voucher Award

• Sponsor submits NDA/BLA for designated product
• FDA approves the product for the rare pediatric disease indication
• Upon approval, FDA awards the Priority Review Voucher
• Voucher can be used or sold by the sponsor

What Qualifies as a Rare Pediatric Disease?

FDA defines a rare pediatric disease as a disease that meets ALL of the following criteria:

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Citable Fact: A disease "primarily affects" individuals aged 18 or younger if the disease disproportionately affects this population, meaning the majority of patients or a significant plurality are pediatric patients. FDA evaluates this on a case-by-case basis.

Rare Pediatric Disease Voucher: Understanding Priority Review Vouchers

The rare pediatric disease voucher - formally called the Priority Review Voucher (PRV) - is the primary benefit of the RPDD program. Understanding how PRVs work is essential for sponsors pursuing this designation.

What Is a Priority Review Voucher?

A Priority Review Voucher is a transferable voucher that entitles the holder to a Priority Review designation for any single NDA or BLA submission. Priority Review reduces the FDA review timeline from the standard 10 months to 6 months.

Priority Review Voucher Characteristics:

How Valuable Is a Priority Review Voucher?

PRV vouchers have sold for significant amounts, making the rare pediatric disease designation program highly attractive to sponsors.

Historical PRV Sale Prices:

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Citable Fact: The peak PRV sale price was $350 million in 2015 (United Therapeutics to AbbVie for the Unituxin neuroblastoma voucher). As more vouchers have entered the market, prices have stabilized in the $75-125 million range, though individual transactions vary based on market conditions and buyer needs.

PRV Voucher vs. Standard Priority Review

PRV Voucher Eligibility: RPDD Application Criteria

To qualify for a PRV voucher through the rare pediatric disease designation program, both the disease and the drug product must meet specific criteria.

Disease Eligibility Criteria

Criterion 1: Primarily Affects Pediatric Population

The disease must primarily affect individuals aged birth through 18 years. FDA interprets "primarily affects" to mean:

Criterion 2: Meets Rare Disease Definition

The disease must affect fewer than 200,000 people in the United States, meeting the same prevalence threshold as orphan drug designation.

Criterion 3: Serious or Life-Threatening

The disease must be serious or life-threatening. FDA evaluates seriousness based on:

• Impact on survival
• Degree of morbidity
• Effect on quality of life
• Progressive nature of condition

Product Eligibility Criteria

The drug or biologic must:

Exclusions from PRV Eligibility

Certain products cannot receive a Priority Review Voucher even with RPDD:

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Key Point: A drug that has been approved for an adult indication cannot subsequently receive a PRV for a rare pediatric disease indication, even if it receives RPDD. The PRV is available only when the rare pediatric disease indication is the first approval for that active ingredient.

Pediatric Rare Disease Development: Application Process

The application process for pediatric rare disease designation follows a structured pathway that must be completed before submitting the marketing application.

Step 1: Determine Eligibility Early

Before investing in a RPDD application, verify:

Disease Assessment Checklist:

• [ ] Disease primarily affects individuals 0-18 years
• [ ] US prevalence is under 200,000
• [ ] Disease is serious or life-threatening
• [ ] Disease is not excluded from program

Product Assessment Checklist:

• [ ] Active ingredient has not been previously approved by FDA
• [ ] Product is intended to treat the rare pediatric disease
• [ ] Application will be original NDA or BLA (not supplement)
• [ ] Product is a drug or biologic (not device or diagnostic)

Step 2: Prepare the Rare Pediatric Disease Designation Request

Required Components:

Step 3: Submit to FDA

Step 4: FDA Review and Decision

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Citable Fact: FDA targets a 90-day review timeline for rare pediatric disease designation requests. The actual timeline may extend if FDA requests additional information from the sponsor.

Step 5: From Designation to Voucher

After receiving rare pediatric disease designation:

Development to Approval Pathway:

Step 6: Voucher Redemption or Sale

Once a PRV is awarded:

Rare Pediatric Disease Designation vs. Orphan Drug Designation

Understanding how rare pediatric disease designation compares to orphan drug designation helps sponsors develop optimal regulatory strategies.

Eligibility Comparison

Benefits Comparison

Strategic Considerations: Pursuing Both Designations

Most sponsors pursuing rare pediatric disease designation also seek orphan drug designation for the same product and indication. The programs are complementary:

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Citable Fact: Approximately 85% of products that receive rare pediatric disease designation also have orphan drug designation for the same indication. The combined programs provide both long-term market protection (orphan exclusivity) and immediate financial benefit (PRV).

Comparison Table: Full Program Analysis

Priority Review Voucher Program: Current Status and Future

The Priority Review Voucher program has specific statutory timelines that sponsors should understand.

Program Timeline

PRV Program Statistics

Other Priority Review Voucher Programs

The rare pediatric disease PRV is one of three FDA Priority Review Voucher programs:

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Key Note: Vouchers from all three programs are functionally identical once awarded. A PRV earned through the tropical disease program can be sold and used exactly like a rare pediatric disease PRV.

Common RPDD Challenges and Solutions

Challenge 1: Demonstrating Pediatric Predominance

Problem: Difficulty proving the disease "primarily affects" individuals aged 0-18.

Solutions:

• Compile epidemiological data showing age distribution of affected population
• Document natural history demonstrating pediatric onset
• Reference medical literature on disease demographics
• Provide expert opinion from pediatric disease specialists
• If adults are affected, demonstrate adult cases are rare or atypical

Challenge 2: Previously Approved Active Ingredient

Problem: The drug's active ingredient has been approved for another indication.

Solutions:

• Unfortunately, no workaround exists - PRV eligibility requires first approval
• Consider whether the product qualifies for pediatric exclusivity instead
• Focus on orphan drug designation benefits if PRV not available
• Plan future pipeline products to preserve PRV eligibility

Challenge 3: Timing of Designation Request

Problem: Uncertainty about when to submit RPDD request.

Solutions:

• Submit RPDD request well before planned NDA/BLA submission
• Allow 90-120 days for FDA review and any information requests
• Consider submitting RPDD request after Phase 2 data supports indication
• Coordinate timing with orphan drug designation request

Challenge 4: Prevalence Documentation

Problem: Limited data on pediatric rare disease prevalence in the US.

Solutions:

• Use same prevalence documentation strategies as orphan drug designation
• Commission epidemiological studies if data is insufficient
• Extrapolate from global prevalence data with methodology justification
• Partner with patient advocacy groups for registry data
• Consult with FDA before submission if prevalence is borderline

Key Takeaways

Next Steps

Rare pediatric disease designation offers one of the most valuable regulatory incentives in drug development - a Priority Review Voucher that can be worth over $100 million. For sponsors developing treatments for pediatric rare diseases, pursuing RPDD alongside orphan drug designation maximizes both commercial protection and financial benefit.

Organizations managing regulatory submissions benefit from automated validation tools that catch errors before gateway rejection. Assyro's AI-powered platform validates eCTD submissions against FDA, EMA, and Health Canada requirements, providing detailed error reports and remediation guidance before submission.

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