FDA Withdraws 128 Suitability Petitions to Implement PREA. Will FDA Go Further in Its PREA “Clean-Up” Efforts?

In Late February 2007, FDA announced in the Federal Register the withdrawal of approval of 128 suitability petitions in accordance with the Pediatric Research Equity Act of 2003 (“PREA”).  FDA’s notice states:

[T]hese approval decisions are being withdrawn because ANDAs were never submitted and PREA requires that all applications submitted on or after April 1, 1999, for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration contain an assessment of the safety and effectiveness of the drug for the claimed indications in relevant pediatric subpopulations unless the requirement is waived or deferred.

Under PREA and new FDC Act § 505B, Congress granted FDA the authority to require pediatric studies in certain defined circumstances.  Specifically, FDC Act § 505B states that an applicant “that submits an application (or supplement to an application) under section 505 [of the FDC Act] for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration . . . shall submit with the application” the results of pediatric studies assessing “the safety and effectiveness of the drug . . . for the claimed indications in all relevant pediatric subpopulations; and to support dosing and administration for each pediatric subpopulation for which the drug . . . is safe and effective, [unless FDA] concludes that pediatric effectiveness can be extrapolated from adequate and well-controlled studies in adults, usually supplemented with other information obtained in pediatric patients,” or unless FDA defers or partially or fully waives this requirement. 

An ANDA requiring an approved suitability petition for a change to the Reference Listed Drug (“RLD”) in an active ingredient, route of administration, or dosage form meets the PREA criteria triggering a pediatric assessment.  (The only RLD change permitted by a suitability petition that does not trigger PREA is a change in strength.)  However, because of the statutory exception mandating FDA’s denial of a suitability petition requiring clinical studies, FDA can no longer approve suitability petitions for PREA changes unless the Agency fully waives the pediatric assessment requirement.

Because PREA is retroactive to applications submitted on or after April 1, 1999, any suitability petition for a PREA change granted prior to that date can no longer be relied upon today to provide a basis for FDA to approve an ANDA.  To grant such a petition, FDA would have to reassess the change pursuant to a new suitability petition in light of PREA.  FDA’s Federal Register notice concerns only suitability petitions for which ANDAs were never submitted, and is non-controversial.  However, FDA could arguably go one step further in its PREA clean-up efforts and identify post-April 1, 1999 ANDA submissions and approvals that relied on an approved suitability petition no longer valid in light of PREA.  Such a move, while it would be highly controversial and invite intense criticism of FDA, might not be out of the question.