By Kurt R. Karst –It’s been a little more than 2.5 years since Section 505(w) was added to the FDC Act by Section 1134 of the 2012 FDA Safety and Innovation Act (“FDASIA”). Section 505(w), titled “Deadline For Determination on Certain Petitions,” requires FDA to issue a final, substantive determination on a petition submitted pursuant to 21 C.F.R. § 314.161(b) – a so-called “discontinuation petition” – “no later than 270 days after the date the petition is submitted.” The provision, which many believe was included in FDASIA to make the bill compliant with the Statutory Pay-As-You-Go Act of 2010 (see our FDASIA Summary here), applies to any discontinuation petition submitted to FDA on or after July 9, 2012. Unlike Section 505(q) petitions, which FDA must respond to within 150 days of receipt, FDA is not required to report to Congress on the Agency’s track record in responding to discontinuation petitions. (Last December, we reported on FDA’s most recent Report to Congress on 505(q) petitions.) So we took it upon ourselves to assess – and grade – FDA on the Agency’s efforts to meet the statutory deadline. After all, when FDA is not subject to any oversight, the Agency has been known to slip on meeting statutory deadlines. Just consider FDA’s 30-plus-year track record in meeting (or not) the 90-day statutory deadline for ruling on ANDA suitabi

As such, FDA took it upon itself to create such a procedure.FDA’s interpretation of the Hatch-Waxman Amendments is embodied in the Agency’s regulations at 21 C.F.R. § 314.161, which state, in relevant part:(a) A determination whether a listed drug that has been voluntarily withdrawn from sale was withdrawn for safety or effectiveness reasons may be made by the agency at any time after the drug has been voluntarily withdrawn from sale, but must be made:(1) Prior to approving an abbreviated new drug application that refers to the listed drug;(2) Whenever a listed drug is voluntarily withdrawn from sale and abbreviated new drug applications that referred to the listed drug have been approved; and(3) When a person petitions for such a determination under 10.25(a) and 10.30 of this chapter.(b) Any person may petition under 10.25(a) and 10.30 of this chapter for a determination whether a listed drug has been voluntarily withdrawn for safety or effectiveness reasons.

In addition, FDA can withdraw or suspend approval of an ANDA if the RLD is withdrawn from sale for reasons of safety or effectiveness (FDC Act § 505(j)(6)). With respect to an ANDA suspension under FDC Act § 505(j)(6), FDA’s regulation at 21 C.F.R. §314.161(d) provides that the Agency will initiate a proceeding in accordance with 21 C.F.R. § 314.153(b). That regulation lays out the procedures for suspension of an ANDA when the RLD is voluntarily withdrawn for safety or effectiveness reasons.

” It turns out that the answer to that question is a little more complicated to come by that we initially thought. Down the rabbit hole . . . .Often – but not always – FDA makes a determination that a drug was discontinued for safety or effectiveness reasons in response to a so-called “discontinuation petition” submitted to the Agency pursuant to 21 C.F.R. § 314.161(b). FDA may also make such a determination on its own initiative.

As a result, FDA has needed to direct resources away from other important initiatives to attempt to comply with the new shorter deadline.Not included in the Fifth Annual Report (and not required to be) is FDA’s progress with meeting the new 270-day timeframe at FDC Act § 505(w) covering discontinuation petitions submitted pursuant to 21 C.F.R. § 314.161. That provision was also included in FDASIA.

By Kurt R. Karst – Late last Friday, FDA announced that the Agency denied an August 13, 2012 Citizen Petition (Docket No. FDA-2012-P-0895) submitted by Endo Pharmaceuticals Inc. (“Endo”) requesting that the Agency determine that OPANA ER (oxymorphone HCl) Extended-release Tablets approved under NDA No. 021610 were discontinued for safety reasons in light of the availability of a reformulated version of OPANA ER approved under NDA No. 201655, and that FDA refuse to approve any pending ANDAs and suspend and withdraw the approval of any ANDAs citing original OPANA ER as its Reference Listed Drug. The decision, which is apparently the first under the new 270-day timeframe at FDC Act § 505(w) covering discontinuation petitions submitted pursuant to 21 C.F.R. § 314.161, comes less than a month after FDA determined that OXYCONTIN (oxycodone HCl) Controlled-release Tablets approved under NDA No. 020553 were discontinued for safety reasons in light of the availability of a reformulated version of OXYCONTIN approved under NDA No. 022272 (see our previous post here). On the same day FDA announced its decision concerning reformulated OXYCONTIN, the Agency approved abuse-deterrent labeling for the drug.

Just days later, Purdue Pharma, L.P. (“Purdue”), the sponsor of both OXYCONTIN drug products, notified FDA that the company ceased shipment all of the strengths of the original version of OXYCONTIN, and FDAthen moved the drug products to the “Discontinued Drug Product List” section of the Orange Book. Under FDA’s regulations at 21 C.F.R. § 314.161, the Agency must determine whether a listed drug that has been voluntarily withdrawn from sale was withdrawn for safety or effectiveness reasons before approving an ANDA for a generic version of the drug.According to FDA’s notice concerning original OXYCONTIN:FDA has conducted an extensive review of data available to the Agency regarding reformulated OxyContin, including in vitro, pharmacokinetic, clinical abuse potential, and postmarketing study data. The data show that, when compared to original OxyContin, reformulated OxyContin has an increased ability to resist crushing, breaking, and dissolution using a variety of tools and solvents.

The first Citizen Petition (Docket No. FDA-2012-P-0895) requests that FDA determine that Original Formulation Opana® ER was discontinued for reasons of safety and can no longer serve as the basis of approval for an ANDA, that FDA refuse to approve any pending ANDA for a generic version of Original Formulation Opana® ER, and that FDA suspend and withdraw the approval of any ANDA referencing Original Formulation Opana® ER as its basis for approval. The second Citizen Petition (Docket No. FDA-2012-P-0951), which was recently supplemented, primarily concerns the requirements to obtain approval of an ANDA for a generic version of Opana® ER CRF, but also brings Original Formulation Opana® ER into the mix.“FDA has not carried out its responsibility under 21 C.F.R. § 314.161(a) to make a determination sua sponte as to whether Endo discontinued Original Formulation Opana® ER for reasons of safety,” alleges Endo. That regulation requires FDA to determine, prior to approving a pending ANDA that refers to a drug product that is no longer marketed, and “[w]henever a listed drug is voluntarily withdrawn from sale and [ANDAs] that referred to the listed drug have been approved,” whether such discontinuation was for reasons of safety or effectiveness.

The certification and verification statements must disclose when information supporting the petition, supplement, or comment became known to certain parties and must identify the parties in interest.FDASIA § 1135 (along with another petition provision at FDASIA § 1134 that sets a 270-day deadline for FDA to respond so-called discontinuation petitions submitted pursuant to 21 C.F.R. § 314.161) appears to be intended to realize greater savings from generic drug and biosimilar approvals as a result of quicker FDA decisions on citizen petitions. As we’ve noted elsewhere, however, FDC Act § 505(q) petition decisions often are not keyed to generic drug and biosimilar approval decisions.