The Skinny on “Skinny Labeling” – A Generic Drug Labeling Carve-Out Citizen Petition ScorecardSeptember 16, 2008
Over the past several months, FDA has responded to or companies have submitted citizen petitions to FDA requesting that the Agency refrain from approving ANDAs for generic drugs with less than complete labeling – so-called “skinny labeling.” That got us thinking – what is the scorecard on labeling carve-out citizen petitions? Below, after a brief discussion of the topic, is a listing of labeling carve-out citizen petitions that FDA has responded to or that are pending before the Agency. We will update the lists from time to time as new FDA petition responses are issued and new petitions are submitted to FDA.
In the report accompanying the 1984 Hatch-Waxman Amendments, Congress stated that a generic applicant:
need not seek approval for all of the indications for which the [Reference Listed Drug (“RLD”)] has been approved. For example, if the [RLD] has been approved for hypertension and angina pectoris, and if the indication for hypertension is protected by patent, then the application could seek approval for only the angina pectoris indication.
This view was codified in FDC Act § 505(j)(2)(A)(v), which states that an ANDA must contain “information to show that the labeling proposed for the new drug is the same as the labeling approved for the [RLD] except for changes required because of differences approved under a [suitability petition] or because the new drug and the [RLD] are produced or distributed by different manufacturers.” In addition, FDA’s implementing regulations at 21 C.F.R. § 314.94(a)(8)(iv) state:
Labeling (including the container label and package insert) proposed for the drug product must be the same as the labeling approved for the [RLD], except for [certain differences] . . . . Such differences between the applicant’s proposed labeling and labeling approved for the [RLD] may include. . . omission of an indication or other aspect of labeling protected by patent or accorded exclusivity under [FDC Act § 505(j)(5)(D)].
However, FDA’s regulations at 21 C.F.R. § 314.127(a)(7) further provide that to approve an ANDA that omits an aspect of labeling protected by patent or exclusivity, FDA must find that the “differences do not render the proposed drug product less safe or effective than the listed drug for all remaining, non-protected conditions of use.”
In Bristol-Myers Squibb Co., v. Shalala, 91 F.3d 1493 (D.C. Cir. 1996), the U.S. Court of Appeals for the District of Columbia Circuit held that FDA may approve an ANDA for a generic drug even though the labeling of the generic product does not include one or more indications that appear in the labeling of the RLD upon which the ANDA is based. Similarly, in Sigma Tau Pharma. Inc. v. Schwetz, 288 F.3d 141 (4th Cir. 2002), the U.S. Court of Appeals for the Fourth Circuit held that FDA did not violate the Orphan Drug Act when the Agency approved generic CARNITOR (levocarnitine) where the labeling omitted an indication protected by orphan drug exclusivity.
FDA Citizen Petition Responses Permitting a Labeling Carve-Out
- FDA Response, Docket Nos. 2001P-0495, 2002P-0191, 2002P-0252 (June 11, 2002) – ULTRAM (tramadol HCl)
- FDA Response, Docket No. 2001P-0495 (Mar. 31, 2003) – ULTRAM (tramadol HCl)
- FDA Response, Docket No. 2003P-0321 (Apr. 6, 2004) – REBETOL (ribavirin)
- FDA Response, Docket No. 2005P-0383 (Dec. 1, 2006) – OXANDRIN (oxandrolone)
- FDA Response, Docket No. 2006P-0410 (Mar. 13, 2008) – ETHYOL (amifostine)
- FDA Response, Docket No. FDA-2007-P-0169 (Apr. 25, 2008) – MARINOL (dronabinol)
- FDA Response, Docket No. FDA-2008-P-0304 (June 18, 2008) – ALTACE (ramipril)
- FDA Response, Docket No. FDA-2008-P-0069 (July 28, 2008) – CAMPTOSAR (irinotecan HCl)
FDA Citizen Petition Responses Denying a Labeling Carve-Out
- FDA Response, Docket No. 2003P-0518 (Sept. 20, 2004) – RAPAMUNE (sirolimus)
Pending Labeling Carve-Out Citizen Petitions
- FDA Docket No. 2007P-0354 – THALOMID (thalidomide)
- FDA Docket No. 2007P-0322 – ACTOS (pioglitazone)
- FDA Docket No. FDA -2008-P-0343 – PRANDIN (repaglinide)
If there is a single take away message from FDA’s various petition responses over the years it is that 21 C.F.R. § 314.127(a)(7) is controlling. FDA will permit skinny labeling when the omission of protected RLD labeling information does not render the proposed generic drug product less safe or effective than the RLD for all remaining, non-protected conditions of use. Conversely, if FDA believes that a labeling carve-out would render the proposed generic drug product less safe or effective than the RLD, then the Agency will not permit a labeling carve-out.