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FDA Designations for Rare Disease Products, Part 3: 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 2 examined 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 added Section 529 to the FD&C Act, establishing the RPDD program and its associated priority review vouchers. In 2016, the Advancing Hope Act provided additional clarifications and definitions for the RPDD program, and the 21st Century Cures Act extended 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 be a rare disease or condition as 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’s guidance on RPDD:

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 a priority 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 application eligible 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 five years 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. Under Section 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 to available 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. Per the 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 a user fee associated with redeeming a PRV, in addition to the other user fees required for marketing applications. For FY 2021, 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 us to find out how we can support your program.

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

Author:

Marissa Berry, PhD, RAC
Manager, Regulatory Strategy

Sources:

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

Rare Pediatric Disease Priority Review Vouchers: Guidance for Industry

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