Pediatric Study Planning Should Occur Early In Drug Development, FDA Says

Sponsors of drugs for serious or life-threatening diseases should discuss pediatric study plans with FDA at pre-IND and end-of-Phase I meetings, the agency recommends in a draft guidance.

"For products for life-threatening diseases, the review division will provide its best judgment at the end-of-Phase I meetings on whether pediatric studies will be required" under the Pediatric Research Equity Act "and, if so, whether the submission will be deferred until after approval," the guidance states.

"Studies of drugs or biological products for diseases that are life-threatening or severely debilitating in pediatric patients and that lack adequate therapy could begin earlier than studies of other products because the urgency of the need for the products may justify early trials," FDA said.

Such pediatric studies may begin as early as Phase I or II, "when the initial safety data in adults become available."

FDA announced release of the guidance, "How to Comply with the Pediatric Research Equity Act," in a Sept. 7 Federal Register notice.

The document discusses the requirements of PREA, which was signed into law in December 2003 and codifies FDA's authority to require sponsors to conduct pediatric studies (¹ (Also see "FDA Pediatric Study Bill Clears Senate, Will Sunset With Exclusivity Grants" - Pink Sheet, 28 Jul, 2003.), p. 4). The agency will continue to offer companies the opportunity to qualify for six months of pediatric exclusivity for required studies.

PREA requires all NDAs, BLAs or supplements for a new active ingredient, new indication, new dosage form or dosing regimen, or new route of administration to contain a pediatric assessment unless the sponsor obtains a waiver or deferral.

The law also requires sponsors of currently marketed products to conduct pediatric studies under certain circumstances.

However, this guidance applies only to new products, indications or dosages. Issues "related to already marketed drug and biological products for which the sponsor is not seeking one of the enumerated changes may be addressed in future guidance," FDA said.

The guidance offers recommendations on the timeline for development of a pediatric study plan, noting that applicants are "encouraged to submit their pediatric plans to the agency as early as possible in the drug development process."

"For products that are not intended for treatment of life-threatening or severely debilitating illnesses, applicants are encouraged to submit and discuss the pediatric plan no later than the end-of-Phase II meeting," the guidance states. "Information to support any planned request for a waiver or deferral of pediatric studies also should be submitted as part of the background package."

The guidance describes how to apply for a waiver, partial waiver or deferral of pediatric studies, as well as the criteria for granting waivers or deferrals.

Pediatric studies may be eligible for waiver if they are impossible or highly impracticable, or if the product's indication "has extremely limited applicability to pediatric patients because the pathophysiology of these diseases occur for the most part in the adult population," the guidance states. Examples of such adult-only conditions include age-related macular degeneration, Alzheimer's disease, infertility, Parkinson's disease and certain types of cancer.

PREA authorizes FDA to waive the pediatric study requirements in one or more age groups requiring a pediatric formulation if the sponsor demonstrates that attempts to produce a formulation for that particular age group have failed.

"FDA believes that this partial waiver provision will generally apply to situations where the applicant can demonstrate that unusually difficult technological problems prevented the development of a pediatric formulation," the guidance states.

"The agency may seek appropriate external expert opinion (e.g., from an advisory committee) to assess whether a waiver should be granted."

FDA estimates that each year it will receive 106 pediatric-use assessments containing data on safety and effectiveness of a drug product for the relevant pediatric populations, as well as 160 requests for deferral and 110 requests for full or partial waiver.