Should the Best Pharmaceuticals for Children Act be Amended to Accommodate 505(b)(2) NDA Labeling Carve-outs?
Posted: 16 Mar 2017 05:26 AM PDT
By Kurt R. Karst –
There are many things that are unique to the 505(b)(2) NDA approval pathway. Some are good and some are . . . well, let’s just say that they have proven to be frustrating for some 505(b)(2) applicants. Perhaps one of the most nettlesome aspects of the 505(b)(2) NDA pathway arises by operation (or should we say by lack of operation?) of FDC Act § 505A(o), which is part of the Best Pharmaceuticals for Children Act (“BPCA”).
FDC Act § 505A(o), titled “Prompt approval of drugs under section 505(j) when pediatric information is added to labeling,” and also known as the “Anti-Glucophage Provision” (or Section 11 of the BPCA), allows an ANDA applicant to omit from its labeling certain patent- and/or exclusivity-protected information concerning the pediatric use of a drug, and to include a disclaimer with respect to the omitted information. (Such a disclaimer might state: “Pediatric use information is approved for [COMPANY’S BRAND-NAME DRUG]. However, due to [COMPANY’S] marketing exclusivity rights, this drug product is not labeled with that pediatric information.”) Specifically, FDC Act § 505A(o) states:
(1) GENERAL RULE.— A drug for which an application has been submitted or approved under section 505(j) of this title shall not be considered ineligible for approval under that section or misbranded under section 502 of this title on the basis that the labeling of the drug omits a pediatric indication or any other aspect of labeling pertaining to pediatric use when the omitted indication or other aspect is protected by patent or by exclusivity under clause (iii) or (iv) of section 505(j)(5)(F) of this title.We’ve seen FDC Act § 505A(o) come into play before, and sometimes in court. The provision was at issue in litigation over generic CRESTOR (rosuvastatin calcium) (here and here) and generic ABILIFY (aripiprazole) (see our previous post here).
At this point you may be asking: “Why are you discussing 505(b)(2) NDAs in the context of a provision that concerns only ANDAs?” After all, FDC Act § 505A(o) is titled “Prompt approval of drugs under section 505(j) when pediatric information is added to labeling” (emphasis added), and there’s no indication that FDA raised any concerns with the provision in a report submitted to Congress in July 2016. But that’s precisely the point! FDC Act § 505A(o) does not address 505(b)(2) NDAs. The BPCA neither addresses the carve-out or retention of protected pediatric information from 505(b)(2) product labeling, nor does the BPCA address the use of disclaimers for protected pediatric use information that is carved-out of 505(b)(2) product labeling.
If FDA determines that the protected pediatric information is important safety information, and therefore, must be retained in 505(b)(2) product labeling for reasons of safe use, then a full approval for the affected 505(b)(2) product cannot be issued until pediatric exclusivity has expired. Instead, FDA could issue only a tentative approval, with final approval dependent on the expiration of exclusivity applicable to pediatric labeling information. This is true regardless of how close a 505(b)(2) NDA product may be to an ANDA drug product (and which ANDA could be approved by operation of FDC Act § 505A(o)). For example, a drug product that is essentially a generic version of a brand-name listed drug, but that is submitted under a 505(b)(2) NDA simply by virtue of the sponsor’s use of a so-called “non-exception excipient,” thus precluding ANDA submission (see our previous post here), may be blocked from obtaining final approval because FDC Act § 505A(o) does not accommodate 505(b)(2) NDAs.
With the growing popularity of 505(b)(2) NDAs, which the Tufts Center for the Study of Drug Development recently assessed, the inability of a 505(b)(2) NDA applicant to obtain final approval because of protected pediatric information is on the rise. We sifted through several 505(b)(2) NDA approval packages and found quite a few FDA assessments concerning the ability (or inability) of a 505(b)(2) applicant to omit protected pediatric information. Sometimes FDA concluded that the 505(b)(2) NDA could be approved with a labeling carve-out, and sometimes FDA determined that only tentative approval could be granted because FDC Act § 505A(o) does not apply to 505(b)(2) NDAs. Here’s a rundown of the FDA assessments we found:
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