PREA recognizes that, under some circumstances, pediatric assessment may be unnecessary, undesirable, impractical, or delayed, and so the legislation authorizes FDA to grant waivers or deferrals to the pediatric assessments required under the Act. If the applicant requests a waiver or deferral, either full or partial, appropriate and sufficient supporting evidence must be provided. The criteria for granting waivers or deferrals center on safety, the nature of the drug product, and the practicability of the requisite studies. KinderPharm works with our clients to guide them on the FDA guidance so they can comply with PREA by providing a Full Waiver, Partial Waiver of Deferral Submission to the FDA.
Full waivers. Under a waiver, the pediatric assessment does not have to be completed. Three criteria taken directly from PREA are listed in the draft guidance as a basis for FDA granting a waiver, either on their own initiative or at the request of the applicant as follows:
- Necessary studies are impossible or highly impracticable (Federal Food, Drug and Cosmetic Act (FD&C), as amended by PREA, Section 505B(a)(4)(A)(i))
- There is evidence strongly suggesting that the drug or biologic product would be ineffective or unsafe in all pediatric age groups (FD&C, as amended by PREA, Section 505B(a)(4)(A)(ii))
- The drug or biological product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a substantial number of pediatric patients (FD&C, as amended by PREA, Section 505B(a)(4)(A)(iii)).
Partial waivers. The Act also provides for the grant of a partial waiver for specific pediatric age groups. The FDA guidance generally defines the pediatric population as “birth to 16 years, including age groups often called neonates, infants, children and adolescents” (21 CFR 201.57(f)(9)). No actual age ranges are provided, though suggestions have been provided in other documents (2). The guidance states: “For the purposes of satisfying the requirements of PREA, the appropriate age ranges to be studied may vary, depending on the pharmacology of the drug or biological product, the manifestations of the disease in various age groups, and the ability to measure the response to therapy.” This provision means that the drug developer is required to make the case that not all pediatric age groups need to be studied, although some should be.
The guidance supplies the same three criteria for a partial waiver as for full waiver, and adds a fourth requirement as follows:
- The applicant can demonstrate that reasonable attempts to produce a pediatric formulation for that age group have failed (FD&C, as amended by PREA, Section 505B(a)(4)(B)(iv)).
Deferrals. As implied by the name, a deferral delays the submission of the pediatric assessment rather than eliminating it. The Act allows for delay in submitting the pediatric assessment until after the NDA has been submitted, or even until a specific date after approval of the NDA (FD&C, as amended by PREA, Section 505B(a)(3)). FDA is often receptive to this.
Three criteria for a deferral are available as follows:
- The drug or biological product is ready for approval for its use in adults before pediatric studies are complete (FD&C, as amended by PREA, Section 505B(a)(3)(A)(i)).
- Pediatric studies should be delayed until additional safety or efficacy data have been collected (FD&C, as amended by PREA, Section 505B(a)(3)(A)(ii)).
- There is another appropriate reason for the deferral (FD&C, as amended by PREA, Section 505B(a)(3)(A)(iii)). For this deferral, the guidance cites technical difficulties with a pediatric formulation as an example.
Contact us for an assessment of your Pediatric Strategy Plan to determine the best method for your pediatric drug development process.