Reports Detail FDA’s 505(q) Citizen Petition Response Track Record; Section 505(q) May Have Some Unintended Consequences, FDA Says (Part I)

By Kurt R. Karst –      

Reports FDA submitted to Congress on the Agency’s implementation of FDC Act § 505(q) recently became available and show that only a few applications have been delayed by certain citizen petitions covered by the law, and that the Agency is timely responding, one way or another, to many of the covered citizen petitions.  The reports also show, however, that FDA is wrestling with implementing some of the statutory provisions and is concerned about some unintended consequences.  This is Part I of a two-part post on those reports. 

FDC Act § 505(q) was added to the law by § 914 of Title IX of the FDA Amendments Act of 2007 (“FDAAA”), Pub. L. No. 110-85 (2007), as amended by § 301 of Pub. L. No. 110-316 (2008), and is intended to prevent the citizen petition process from being used to delay approval of ANDAs and 505(b)(2) applications.  Briefly, FDC Act § 505(q) provides that FDA shall not delay approval of a pending ANDA or 505(b)(2) application as a result of a citizen petition submitted to the Agency pursuant to 21 C.F.R. § 10.30 (citizen petition) or § 10.35 (petition for stay of action), unless FDA “determines, upon reviewing the petition, that a delay is necessary to protect the public health.”  Under FDC Act § 505(q), which FDA has interpreted to apply only to certain petitions submitted to the Agency after September 27, 2007, “[FDA] shall take final agency action on a petition not later than 180 days after the date on which the petition is submitted.”  FDA may not extend the 180-day period “for any reason,” including consent of the petitioner, and may summarily deny a petition submitted with the primary purpose of delaying ANDA or 505(b)(2) application approval. 

FDC Act § 505(q) does not apply to all citizen petitions.  Excluded from the new law are petitions that relate “solely to the timing of the approval of an application pursuant to subsection (j)(5)(B)(iv)” (i.e., 180-day exclusivity), and petitions that are made by an ANDA or 505(b)(2) sponsor “that seeks only to have [FDA] take or refrain from taking any form of action with respect to that application.”  Petitions subject to FDC Act § 505(q) must include a specific certification identified in the new law, and petition supplements and comments must include a specific verification statement.  FDA Law Blog vigilantly follows 505(q) petitions and our FDC Act § 505(q) Citizen Petition Tracker has been a big hit.  (It beats wading through Regulations.gov to find a particular citizen petition or FDA petition response.)

In January 2009, FDA published a draft guidance document titled “Citizen Petitions and Petitions for Stay of Action Subject to Section 505(q) of the Federal Food, Drug, and Cosmetic Act.”  (See our previous post here.)  The draft guidance describes FDA’s interpretation of FDC Act § 505(q), including how FDA determines if § 505(q) applies to a particular petition, and whether such a petition would delay approval of a pending ANDA or 505(b)(2) application.  According to a December 2010 Federal Register notice, FDA is in the process of finalizing the guidance.

Both FDAAA and FDC Act § 505(q) include separate provisions requiring FDA to report on how to encourage early citizen petition submission and on the Agency’s experience with implementing the law.  Specifically, FDAAA § 914(b) states that “[n]ot later than 1 year after the date of the enactment of this Act [(i.e., September 27, 2008)], the Secretary of Health and Human Services shall submit a report to the Congress on ways to encourage the early submission of petitions under section 505(q). . . .”  FDC Act § 505(q)(3) requires FDA to submit an annual report to Congress that specifies, “(A) the number of applications that were approved during the preceding 12-month period; (B) the number of such applications whose effective dates were delayed by petitions referred to in paragraph (1) during such period; (C) the number of days by which such applications were so delayed; and (D) the number of such petitions that were submitted during such period.”

FDA’s February 9, 2009 report, which is the focus of today’s post, is titled “Encouraging Early Submission of Citizen Petitions and Petitions for Stay of Agency Action,” and fulfills the requirement under FDAAA § 914(b).  The report describes several FDA initiatives to encourage early submission of certain petitions so that the petitions can be received in time to avoid a delay in ANDA or 505(b)(2) application approval.  Although FDA has already implemented some of these initiatives, such as the establishment of the Agency’s Individual Product Bioequivalence Recommendations database and the Paragraph IV Certifications list (both of which are specific to ANDAs), other initiatives are still under consideration.  In particular, FDA is still considering whether it is appropriate to answer a 505(q) petition raising bioequivalence issues for a particular drug product with a very brief response when a draft bioequivalence guidance has already been published or when a petition is submitted to FDA more than a certain number of days after the Agency publishes a final bioequivalence guidance.  According to FDA:

The rationale for such an approach is that the petitioner already had an opportunity to raise these issues in the context of a proposed product specific guidance.  Whether or not anyone raises an issue in the context of a bioequivalence guidance, where someone disagrees with FDA's bioequivalence recommendations issued in a final guidance and chooses to raise those issues in a petition, the objections can be raised shortly after the publication of a final guidance because the petitioner should have been aware of both the draft and the final guidance.  An exception to this could be if the petition contains material new information not previously considered by the agency.

Another brief response option FDA is considering concerns 505(q) petitions involving ANDAs containing Paragraph IV certifications.  According to FDA:

Another possible means to encourage the early submission of 505(q) petitions that involve ANDAs with paragraph IV certifications – or more precisely, discourage their late submission – is to establish a policy under which FDA may, if appropriate, issue only a brief response to a petition that raises any issues pertaining to the approval of an ANDA if the petition is submitted more than a certain number of days after the filing of the first substantially complete ANDA using a particular listed drug as the basis of its submission and containing a paragraph IV certification.  Again, a possible exception that FDA could invoke would be situations where the agency determines that a petition contains material new information not previously considered.

Implementing both brief response options FDA discusses in the report or issuing a summary denial of a petition pursuant to FDC Act § 505(q)(1)(E) could be difficult because of some “potential statutory impediments.” 

Under FDC Act § 505(q)(1)(E), FDA can summarily deny a petition if: (1) the Agency determines the petition was submitted with the primary purpose of delaying the approval of a pending ANDA or 505(b)(2) application; and (2) the petition does not obviously raise valid scientific or regulatory issues.  The provision also states that FDA “may issue guidance to describe the factors that will be used to determine . . . whether a petition is submitted with the primary purpose of delaying the approval of an application.”

Because both of the preconditions stated above must be met for FDA to summarily deny a 505(q) petition, the Agency believes the statutory standard “would be extremely difficult to meet.  In fact, we are not aware of a single case since the enactment of FDC Act § 505(q) in which FDA has invoked FDC Act § 505(q)(1)(E) to deny a citizen petition.  “Although a petition may not raise persuasive scientific or regulatory issues when those issues have been reviewed by FDA, a petition can easily raise valid scientific or regulatory issues,” says FDA in the report, making it nearly impossible for the Agency  to divine intent to delay.  FDA acknowledges that the Agency “could issue guidances describing petitions filed under certain circumstances that would give rise to the presumption that a petition was filed with the primary purpose to delay approval of an ANDA or 505(b)(2) application,” but “given the statutory standard in 505(q)(1)(E) for summary denial of petitions, the agency does not believe issuing a guidance on delay would allow the summary denial of petitions under this provision.  Without any significant impediment to filing a late petition, such as summary denial, it may be difficult to encourage the early submission of petitions under 505(q).”  Moreover, “if FDA was able to issue a summary denial or brief response to a petition, the agency would still want to have an adequate internal record that the merits of any relevant substantive issues had been addressed in the consideration of affected applications.”

FDA concludes the 2009 report by noting that with only one year of experience with § 505(q) under the Agency’s belt, it is premature to determine the impact of FDC Act § 505(q), and “particularly whether petitions that may delay approval of an application are being discouraged overall.”  (This is a question that a subsequent annual report appears to answer.)  The Agency also notes some potential “unintended consequences” (a couple of which are deemed “areas of concern” in a later annual report):

• Many 505(q) petitions have been filed by companies that hold ANDA applications or have applications pending before FDA, rather than by innovator companies that hold the NDA referenced by an ANDA or 505(b)(2) applicant.  These petitions raise issues about the standards for approval for applications that, if approved, might compete with the petitioner's approved or pending application.

• Petitions that are filed early may not be subject to 505(q) and its 180-day response deadline because, when the petition is submitted, an ANDA or 505(b)(2) application may not be pending.

• Early response to one petition may give rise to a new petition raising additional issues or a petition for reconsideration. These new petitions could cause additional work and delay approval of ANDAs or 505(b)(2) applications. 

In Part II of this post, which will be posted tomorrow, we’ll take a look at the two annual reports FDA has submitted to Congress detailing the Agency’s experience with 505(q) citizen petitions.