The US Food and Drug Administration (FDA) has released a long-anticipated guidance document intended to explain how a new incentive program known as the Rare Pediatric Disease Priority Review Voucher system works.
Created in 2012 under the Food and Drug Administration Safety and Innovation Act (FDASIA), the Rare Pediatric Disease Priority Review Voucher is modeled closely off a similar program known as the Tropical Disease Priority Review Voucher system.
The tropical disease voucher system was established under the Food and Drug Administration Amendments Act of 2007 (FDAAA). Under the system, companies that receive approval for a tropical disease treatment are eligible to receive a transferrable voucher that allows the bearer to receive priority review status for any future product. Products undergoing priority review are generally given an approval decision—positive or negative—within six months (instead of the usual 10 months) after the applicant's filing date.
But the tropical disease voucher system hasn't been used much, in part because it's somewhat restrictive. As FDA explains in its guidance document on the voucher, "The sponsor redeeming the voucher must notify FDA of their intent to submit a human drug application with a priority review voucher at least 365 days prior to submission of the human drug application for which a priority review voucher will be used to obtain a priority review." That advance review time makes it impractical for many companies, which may not be willing to purchase a voucher until they know their product will be able to be submitted to FDA.
In contrast, the rare pediatric voucher offers the exact same benefits—namely, an accelerated review process for a drug owned by the bearer of the voucher—but is able to be used just 90 days after a company notifies FDA of its intent to use the voucher. In addition, the pediatric voucher may be transferred an unlimited number of times. Tropical disease vouchers can only be transferred once (though legislation to change that is under consideration in Congress).
The rare pediatric vouchers are specifically intended for sponsors of products approved to treat patients with "certain rare pediatric diseases." While incentives exist for orphan drugs in general, legislators were of the opinion that additional incentives needed to be put in place for companies to study their products in children with rare diseases. Those populations are especially rare and often quite challenging to recruit into studies.
Both vouchers cost $2,562,000 to use in addition to any other fees payable to FDA. Those fees are meant to pay for the additional cost FDA incurs by accelerating its review of the drug, which requires additional staff resources.
The pediatric voucher's relative ease of use is already being seen as a major benefit by some companies. BioMarin, the first company to receive a rare pediatric voucher after its drug Vimizim was approved, recently sold the voucher to Sanofi and Regeneron for $67.5 million.
Though the first rare pediatric voucher has been awarded, FDA had yet to release guidance regarding the parameters of the program. Specifically: Under what process would it award the vouchers, and which products were eligible for the award?
Then, in July 2014, FDA announced that the guidance would soon be released under a larger plan set to clarify various aspects of pediatric drug development.
Guidance and Definitions
The guidance, Rare Pediatric Disease Priority Review Vouchers, published on 17 November 2014, contains thorough explanations of several key definitions.
For example, FDA notes that Section 529 of FDASIA defined a "rare pediatric disease" as a disease that:
- “primarily affects individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents,” which we interpret as meaning that greater than 50% of the affected population in the U.S. is aged 0 through 18 years; and
- is “a rare disease or condition” as defined in section 526, which includes diseases and conditions that affect fewer than 200,000 persons in the United States (U.S.) and diseases and conditions that affect a larger number of persons and for which there is no reasonable expectation that the costs of developing and making available the drug in the U.S. can be recovered from sales of the drug in the U.S.
The definition is notable in that it defines "pediatric" as a patient younger than 18 years of age. FDA has traditionally defined a pediatric patient as someone younger than 16 years of age.
As FDA explains, a drug may be eligible for the voucher in two ways. The first, as explained in the statute, is if more than 50% of the population affected by a rare disease is under the age of 19. The second is if there is a distinct subset of the rare disease population that is "primarily comprised of individuals aged 0 through 18 years."
FDA's guidance contains information on how to calculate the prevalence of diseases depending upon whether the product intended for use is a therapeutic drug or a vaccine, diagnostic or preventative drug.
The guidance also directs sponsors interesting in obtaining a rare pediatric voucher to request their product receive "rare pediatric disease designation" at the same time they request orphan drug designation or fast track designation—both prior to the sponsor filing an application for drug approval with FDA. The agency is not bound to any deadlines for replying to requests, it said.
"Sponsors who choose not to submit a rare pediatric disease designation request may nonetheless receive a priority review voucher if they request such a voucher in their original marketing application and meet all of the eligibility criteria," FDA explained. The designation, therefore, is entirely voluntary.
Accordingly, "Even if sponsors have requested and received rare pediatric disease designation, they should include a request for a rare pediatric disease priority review voucher in their original NDA/BLA submission (either in the initial package sent or up until the point of NDA/BLA filing)," FDA said.
Comments on the guidance are due by 16 January 2015.
Rare Pediatric Disease Priority Review Vouchers (FR)