FDA Designations For Rare Disease Products, Part 3: Rare Pediatric Disease Designation | Premier Consulting (2022)

Published On: March 25, 2021

Table Of Contents hide

1 Criteria to obtain the designation

2 Criteria to obtain the benefit

(Video) FDA Orphan Drugs Program and Financial Incentives for CDER Medical Products- June 10, 2019

3 Timeline and maintenance for RPDD

4 Benefit of rare pediatric disease designation

This is the third installment in a four-part blog series highlighting FDA designations for products with rare disease indications: orphan drug designation (ODD), rare pediatric disease designation (RPDD), and humanitarian use device (HUD) designation.Part 2examined orphan drugs, and in Part 3, we take a detailed look at the rare pediatric disease designation.

The RPDD program focuses on pediatric patients with rare diseases and unmet needs. Its purpose is to stimulate the development of new drugs for rare pediatric diseases by offering additional incentives for obtaining FDA approval of such products beyond the incentives offered by the ODD program.

The Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012 addedSection 529 to the FD&C Act, establishing the RPDD program and its associated priority review vouchers. In 2016, theAdvancing Hope Actprovided additional clarifications and definitions for the RPDD program, and the21stCentury Cures Actextended the sunset provisions for the program.

Criteria to obtain the designation

A rare pediatric disease is one that is serious or life-threatening in which the serious or life-threatening manifestations primarily affect patients from birth to 18 years, including neonates, infants, children, and adolescents. It must also bea rare disease or conditionas described in the FD&C Act, with a prevalence of fewer than 200,000 people in the United States.

There are three major criteria that a drug or biological product must meet to obtain RPDD:

  1. The drug must be intended for the prevention or treatment of a rare pediatric disease.
  2. Adequate documentation or prevalence data must demonstrate that the intended pediatric disease or condition is rare.
  3. There must be supportive data suggesting that the drug may be effective in the rare pediatric disease or condition.

The FDA requires a lesser level of data suggesting drug efficacy than it does for orphan drug requests. Per the FDA’sguidance on RPDD:

(Video) In the Spotlight: Recent FDA Updates and Guidance for Rare Disease Drug Development

In vitro data supporting the mechanism of action of the drug in the disease or in a related disease may suffice for rare pediatric disease designation, whereas that level of data would not generally suffice for orphan drug designation.

Criteria to obtain the benefit

The FDA may award the sponsor of an RPDD product that receives NDA or BLA approval apriority review voucher(PRV), which can be either redeemed to expedite the review of subsequent NDA or BLA for another product* or sold to another sponsor for use in the same manner. For a sponsor to receive a PRV upon approval of a rare pediatric disease product application (a marketing application for a drug with RPDD), the NDA or BLA must be a human drug application that meets several criteria:

  • The application must be for a drug or biological product that is for the prevention or treatment of a rare pediatric disease and that contains no active ingredient (including any ester or salt of the active ingredient) that has been previously approved in any other application under relevant sections of the FD&C Act and the Public Health Service Act (PHS Act)
  • The FDA must deem the applicationeligible for priority review(i.e., the product treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness)
  • The application must be submitted under Section 505(b)(1) or 505(b)(2) of the FD&C Act (for an NDA) or Section 351(a) of the PHS Act (for a BLA)
  • The application must rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population
  • The original rare pediatric disease product application must not seek approval for an adult indication
  • The application must be approved after September 30,2016, the date the Advancing Hope Act of 2016 was enacted.

Timeline and maintenance for RPDD

Sponsors should request RPDD at the same time as or within two weeks of submitting a request for ODD or fast-track designation. ODD requests can be submitted to the Office of Orphan Products Development (OOPD) at any time prior to submission of an NDA or BLA, and fast-track requests can be submitted to the appropriate review division as early as the time of original IND submission or any time thereafter up until the pre-NDA or pre-BLA meeting. Regardless of whether requests are submitted at the same time as the orphan drug or fast-track request, each RPDD request should be a separate proposal submitted to the OOPD.

If a sponsor submits a timely request for RPDD, the FDA should make a decision on the request no later than 60 days after submission. It is worth noting that, while the FDA is willing to accept RPDD requests submitted at a different time from the orphan drug designation or fast-track designation request, the 60-day response deadline does not apply to these requests. It is also important to note that RPDDs are not listed on any public FDA databases (unlike ODDs, which are public information). Sponsors may still choose to disclose the granting of RPDD for their products via news releases or other means.

While there are no apparent requirements for maintaining an RPDD prior to NDA or BLA submission, the sponsor of a rare pediatric disease product application must submit a report to the FDA no later than fiveyears after its approval that addresses specific questions regarding the first four post-approval years. This report should contain several pieces of information:

  • The estimated population in the U.S. with the rare disease or condition for which the product was approved (both the overall population and the population ages 0 through 18 years)
  • The estimated demand for the product in the U.S.
  • The actual amount of product distributed in the U.S.

Benefit of rare pediatric disease designation

The benefit of RPDD is a sponsor’s eligibility to receive a PRV, though the sponsor can receive additional benefits through another incentive program like ODD. UnderSection 529 of the FD&C Act, the FDA may award a PRV upon approval of an RPDD product, provided the sponsor requests the PRV in the original NDA or BLA.

As noted above, the PRV can be either redeemed by the sponsor of the RPDD product to expedite the review of subsequent NDA or BLA for another product or sold to another sponsor for use in the same manner. According toavailable sales information, PRVs have been sold for prices ranging from $80 million to $130 million since February 2017.

A major caveat to keep in mind for the RPDD is the program’s sunset provisions, as the program has a termination date unless it is extended. Perthe FDA’s website,

On December 27, 2020, the Rare Pediatric Disease Priority Review Voucher Program was extended. Under the current statutory sunset provisions, after September 30, 2024, FDA may only award a voucher for an approved rare pediatric disease product application if the sponsor has rare pediatric disease designation for the drug, and that designation was granted by September 30, 2024. After September 30, 2026, FDA may not award any rare pediatric disease priority review vouchers.

It is also important to note that there is auser feeassociated with redeeming a PRV, in addition to the other user fees required for marketing applications. For FY2021, the fee for redeeming a PRV is $1,360,879.

Premier Consulting has a long history of helping sponsors attain special designations like RPDD and map the most time- and cost-efficient development plan for regulatory and post-marketing success.Contact usto find out how we can support your program.

(Video) COMP Workshop Support for development of orphan medicines

*Note that redeeming a PRV does not guarantee approval of the product receiving priority review.

(Video) Developing a Rare Disease Policy in India


CFR – Code of Federal Regulations Title 21

The United States Code

Designating an Orphan Product: Drugs and Biological Products

FDA’s Orphan Drug Modernization Plan

Clarification of Orphan Designation of Drugs and Biologics for Pediatric Subpopulations of Common Diseases

Regulatory Explainer: Everything You Need to Know About FDA’s Priority Review Vouchers

(Video) The FDA's Role in Gene Therapy

Rare Pediatric Disease Priority Review Vouchers: Guidance for Industry


What is rare pediatric disease designation? ›

Criteria to obtain the designation

A rare pediatric disease is one that is serious or life-threatening in which the serious or life-threatening manifestations primarily affect patients from birth to 18 years, including neonates, infants, children, and adolescents.

What is rare disease designation? ›

What is a rare disease? The Orphan Drug Act defines a rare disease as a disease or condition that affects less than 200,000 people in the United States.

What is FDA orphan drug designation? ›

The FDA has authority to grant orphan drug designation to a drug or biological product to prevent, diagnose or treat a rare disease or condition. Orphan drug designation qualifies sponsors for incentives including: Tax credits for qualified clinical trials. Exemption from user fees.

What are the criteria for orphan drug designation? ›

The Orphan Drug Act defines a rare disease or condition as one (a) that affects fewer than 200,000 persons in the United States or (b) for which there is no reasonable expectation that the cost of developing a drug and making it available in the U.S. will be recovered from sales in the country.

How much is a priority review voucher worth? ›

What Other Types of Vouchers Exist?
Medical Countermeasure Priority Review Voucher User Fee
Fiscal YearVoucher Fee
FY 2018$2,830,579
FY 2019$2,457,140
FY 2020$2,167,116

What is orphan designation number? ›

A status assigned to a medicine intended for use against a rare condition. The medicine must fulfil certain criteria for designation as an orphan medicine so that it can benefit from incentives such as protection from competition once on the market.

What are examples of rare diseases? ›

Rare diseases come in many forms and include some cancers, auto-immune diseases, metabolic conditions and inherited malformations.
Some examples of rare diseases are:
  • cystic fibrosis.
  • muscular dystrophy.
  • spina bifida.
  • haemophilia.

How long does orphan designation take? ›

The evaluation process takes a maximum of 90 days from validation. For information on how to apply, see how to apply for orphan designation.

How long does orphan designation last? ›

With orphan designation, the FDA grants a seven-year market exclusivity for that medicine that applies specifically to that designated orphan use, but this exclusivity does not preclude generic competition for other non-orphan approved uses of that drug, nor for orphan uses for which the exclusivity has expired.

Is orphan drug designation valuable? ›

A Rise in Orphan Drug Designation (ODD) Approvals

The increase in approvals is leading industry experts to value the global orphan drug market at $300 billion by 2026, more than 20% of global prescription drug sales3, up from $132 billion in 2019.

Does orphan drug designation expire? ›

New chemical entity (NCE) exclusivity expires after five years (sometimes four); orphan drug exclusivity ends after seven years; and even Reference Product exclusivity expires eventually – after a whopping 12 years.

How many orphan drug designations are there? ›

Between 1983 and 2019, a total of 5099 drugs and biologics received orphan drug designation. Designations more than doubled between the 1980s and 1990s, almost doubled between the 1990s and 2000s, and almost tripled in number between the 2000s and 2010s.

How do I submit an orphan drug designation request? ›

Orphan Drug Designation Application

Requests for an orphan drug designation can be submitted through the FDA Form 4035. The FDA will complete a review of the orphan drug designation request within 90 days of its receipt.

Are orphan drugs excluded from 340B? ›

Orphan drugs are not covered outpatient drugs for us as a 340B entity, but Medicaid still views them as a covered outpatient drug.

Does Medicare cover orphan drugs? ›

Medicare Plans' Coverage of Orphan Drugs—Stand-Alone PDPs and MA-PDs. The coverage rate (percentage of plans covering a drug) for orphan drugs among Medicare prescription drug plans is high. On average, an orphan drug is covered by 84 percent (standard deviation: 24 percent) of stand-alone PDPs.

How long does FDA priority review take? ›

Priority Review means that FDA aims to take action on an application within six months, compared to 10 months under standard review. A Priority Review designation directs attention and resources to evaluate drugs that would significantly improve the treatment, diagnosis, or prevention of serious conditions.

What is a drug voucher program? ›

These programs provide direct financial assistance to patients who need help paying for prescription medications and qualify for the programs' medical and financial requirements. Patients can apply directly for these programs, or physicians or pharmacists may apply on a patient's behalf.

How many priority review vouchers have been awarded? ›

From fiscal year 2009, when the first PRV was awarded, through fiscal year 2019, FDA awarded 31 PRVs, mostly for drugs to treat rare pediatric diseases. Of the 31 PRVs awarded by FDA,17 were sold to another drug sponsor for prices ranging from about $67 million to $350 million, according to available data.

When can you apply for orphan drug designation? ›

The orphan designation is part of the approval process

In fact, the orphan application can be filed anytime in the drug development process before NDA/BLA submission, even prior to IND filing.

What are examples of orphan diseases? ›

Orphan and rare diseases include more familiar conditions such as cystic fibrosis, Lou Gehrig's disease and Tourette's syndrome, as well as less familiar conditions such as Duncan's Syndrome, Madelung's disease and acromegaly/gigantism. The prevalence of rare diseases is often an estimate and may change over time.

What is considered an orphan disease? ›

An orphan disease is defined as a condition that affects fewer than 200,000 people nationwide.

What is the rarest disorder known to man? ›

According to the Journal of Molecular Medicine, Ribose-5 phosphate isomerase deficiency, or RPI Deficinecy, is the rarest disease in the world with MRI and DNA analysis providing only one case in history.

What percentage is considered a rare disease? ›

The study challenged the estimate that rare diseases affect between 6% and 8% of the global population. The authors instead found that rare diseases affect between 3.5% and 5.9%, or nearly 300 million people worldwide, based on the point prevalence estimates for 67.6% of rare diseases included in the study.

Do orphan drugs need Phase 3 trials? ›

Orphan drug trials are generally single arm (no placebo arm), nonrandomized, and open label. Safety Phase 1 trials are not usually required, and Phases 2 and 3 can be combined when the patient population is very low.

Can orphan drug designation be revoked? ›

(b) For an approved drug, revocation of orphan-drug designation also suspends or withdraws the sponsor's exclusive marketing rights for the drug but not the approval of the drug's marketing application.

Are orphan drugs profitable? ›

Pharmaceutical companies are seeking “orphan” status to develop blockbuster drugs used to treat other common medical conditions. They reap the benefits of orphan status – subsidies, tax credits, and waivers – while generating billions of dollars in profits.

What is orphan exclusivity? ›

Orphan Drug Exclusivity Is Product & Disease Specific

It blocks approval of the same product for the same disease. Orphan Exclusivity bars any sponsor from making the same drug for the same disease – even if the sponsor does not rely on the innovator's data.

Are orphan drugs FDA approved? ›

Development of Medical Devices for Rare Diseases

Since 1990, the FDA's Center for Devices and Radiological Health (CDRH) has approved 78 medical devices for orphan indications under the Humanitarian Device Exemption program.

What is FDA fast track approval? ›

Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

What is FDA exclusivity? ›

Exclusivity is a period of time when a brand-name drug is protected from generic drug competition. There are different exclusivities for different situations. Exclusivity is designed to promote a balance between new drug innovation and generic drug competition.

How do I submit an orphan drug Annual Report? ›

Contact orphan@fda.hhs.gov to: Request a meeting. Submit an orphan drug, rare pediatric disease or humanitarian use device designation request. Submit changes to your contact information.

What is drug designation? ›

When a drug is designated for a particular intended use, the sponsor of the drug obtains seven (7) years of exclusive marketing rights upon approval (or conditional approval) of the drug for that intended use.

What are examples of orphan drugs? ›

An orphan drug can be defined as one that is used to treat an orphan disease. For example, haem arginate, used to treat acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria [12], is an orphan drug.

What does Pdufa stand for? ›

The Prescription Drug User Fee Act (PDUFA) was created by Congress in 1992 and authorizes FDA to collect fees from companies that produce certain human drug and biological products.

What is an IND submission? ›

Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

Is Humira an orphan drug? ›

Adalimumab (Humira; AbbVie) was approved as a nonorphan drug first in 2002 and then as an orphan drug in 2008; it has 6 nonorphan indications and 7 orphan indications, and it rang up $13.7 billion in US sales in 2018.

Is Botox an orphan drug? ›

Botox, stocked in most dermatologists' offices, started out as a drug to treat painful muscle spasms of the eye and now has three orphan drug approvals. It's also approved as a mass market drug to treat a variety of ailments, including chronic migraines and wrinkles.

Is stelara an orphan drug? ›

Ustekinumab (as sponsored by the innovator drug company) has been granted orphan drug designation by the FDA for “treatment of type 1 diabetes mellitus patients with residual beta-cell function” in November 2010, for “treatment of pediatric Crohn's disease (0 through 16 years of age)” in May 2016, for “treatment of ...

Can you get paid for having a rare disease? ›

Children with rare diseases can qualify for SSI benefits if their family's income meets the guidelines. In order to medically qualify for disability benefits because of your rare disease, you have to meet the criteria set forth for your condition in the Blue Book.

Does Medicare cover rare diseases? ›

One model for paying for rare diseases is Medicare coverage for end-stage renal disease (ESRD) and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease).

What is orphan drug pricing? ›


Orphan drug costs are a concern. For example, orphan drugs have an average annual cost of $32,000, and more than a third of drugs with orphan indications cost more than $100,000 annually. However, high cost therapies are generally prescribed for a small portion of patients.

How are rare diseases diagnosed? ›

In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25–35%) of undiagnosed patients, often with actionable findings.

What is the rarest disability? ›

According to the Journal of Molecular Medicine, Ribose-5 phosphate isomerase deficiency, or RPI Deficinecy, is the rarest disease in the world with MRI and DNA analysis providing only one case in history.

Is lupus considered a rare disease? ›

Nine out of ten lupus patients are women. The disease takes many forms and its symptoms vary considerably from one individual to another. Other populations particularly affected are West Indians and African-Americans'.

Is Parkinson's considered a rare disease? ›

Parkinson disease affects more than 1 million people in North America and more than 4 million people worldwide. In the United States, Parkinson disease occurs in approximately 13 per 100,000 people, and about 60,000 new cases are identified each year.

Are most rare diseases genetic? ›

While most rare diseases are genetic in origin, many causes are not well understood. Even if the cause of a rare disease is identified, researchers may still not understand how the disease functions or how to properly treat it.

What are the 10 genetic disorders? ›

Genetic Disorders
  • Genetic Disorders. Sickle Cell Disease.
  • Cystic fibrosis. Cystic Fibrosis Liver Disease.
  • Brain, Nerves and Spine. Huntington's Disease.
  • Cleft lip and palate. Cleft Lip and Palate.

Which disease has no cure? ›

cancer. dementia, including Alzheimer's disease. advanced lung, heart, kidney and liver disease. stroke and other neurological diseases, including motor neurone disease and multiple sclerosis.

What disease causes you to age rapidly? ›

Overview. Progeria (pro-JEER-e-uh), also known as Hutchinson-Gilford syndrome, is an extremely rare, progressive genetic disorder that causes children to age rapidly, starting in their first two years of life. Children with progeria generally appear normal at birth.

What is Kabuki syndrome? ›

What is Kabuki syndrome? Kabuki syndrome is a rare congenital disorder, meaning that a child is born with the condition. Children with Kabuki syndrome usually have distinctive facial features, mild to moderate mental impairment and growth problems.

What is the most common autoimmune disease? ›

The most common autoimmune disorders in the United States are Crohn's disease, type 1 diabetes, multiple sclerosis (MS), rheumatoid arthritis, Hashimoto's thyroiditis, celiac disease, and psoriasis.

What race is lupus most common in? ›

Although lupus affects people of all ages, it's most often diagnosed between the ages of 15 and 45. Race. Lupus is more common in African Americans, Hispanics and Asian Americans.

What color is Rare Disease Day? ›

Being part of a global chain of lights in recognition of Rare Disease Day is one example. You can be part of it either by helping to light up monuments and buildings near you in Rare Disease Day colors (blue, green, pink and purple).

Is Parkinson's inherited from mother or father? ›

Parkinson's disease can run in families as a result of faulty genes being passed to a child by their parents. But it's rare for the disease to be inherited this way.

What are the five 5 signs of Parkinson disease? ›

Parkinson's signs and symptoms may include:
  • Tremor. A tremor, or rhythmic shaking, usually begins in a limb, often your hand or fingers. ...
  • Slowed movement (bradykinesia). ...
  • Rigid muscles. ...
  • Impaired posture and balance. ...
  • Loss of automatic movements. ...
  • Speech changes. ...
  • Writing changes.
8 Jul 2022

What are the 3 hallmark signs of Parkinson's disease? ›

The hallmark symptoms of Parkinson's disease are tremors and slow, rigid movements. Small changes in a person's movements and behavior can signal the onset of Parkinson's disease before diagnosis.


1. Innovative Product Regulatory Strategies and Considerations for Medical Devices and IVDs
(Brandwood CKC)
2. Integrated Assessment of Marketing Applications and Integrated Review Documentation Workshop
(U.S. Food and Drug Administration)
3. No Opportunity Unturned: Optimizing Orphan Drug Development
(Premier Research)
4. Commercial and Regulatory Success in Accelerated Gene Therapy Development
5. Business of Biotech: Trends in Life Science Funding & Exits
(Yale Innovation & Entrepreneurship)
6. PF Research Update (2021)
(Pulmonary Fibrosis Foundation)

You might also like

Latest Posts

Article information

Author: Foster Heidenreich CPA

Last Updated: 07/30/2022

Views: 5784

Rating: 4.6 / 5 (76 voted)

Reviews: 91% of readers found this page helpful

Author information

Name: Foster Heidenreich CPA

Birthday: 1995-01-14

Address: 55021 Usha Garden, North Larisa, DE 19209

Phone: +6812240846623

Job: Corporate Healthcare Strategist

Hobby: Singing, Listening to music, Rafting, LARPing, Gardening, Quilting, Rappelling

Introduction: My name is Foster Heidenreich CPA, I am a delightful, quaint, glorious, quaint, faithful, enchanting, fine person who loves writing and wants to share my knowledge and understanding with you.