BPCA Section 11 and Pediatric Labeling; Revised Labeling Carve-Out Citizen Petition Scorecard

By Kurt R. Karst –   

Section 11 of the Best Pharmaceuticals for Children Act (“BPCA”) of 2002 amended the FDC Act to add a new provision, which was reauthorized under the FDA Amendments Act of 2007 and is located at FDC Act § 505A(o), to require the prompt approval of ANDAs when pediatric information protected by patent or exclusivity is added to the labeling of a Reference Listed Drug.  Specifically, FDC Act § 505A(o) states:

A drug for which an application has been submitted or approved under section 505(j) shall not be considered ineligible for approval under that section or misbranded under section 502 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).

In addition, FDA “may require that the labeling of a drug approved under section 505(j) that omits a pediatric indication or other aspect of labeling” include: “(A) a statement that, because of marketing exclusivity for a manufacturer – (i) the drug is not labeled for pediatric use; . . . and (B) a statement of any appropriate pediatric contraindications, warnings, or precautions that the Secretary considers necessary.”

Shortly prior to the enactment of the BPCA in 2002, FDA was petitioned to issue new regulations or amend existing regulations before implementing Section 11 of the BPCA.  Although FDA denied this petition request shortly after the enactment of the BPCA, the Agency left open the possibility of issuing regulations in the future “as part of the continuing implementation process for this statutory provision. . . .”  And in 2006, FDA amended its prescription drug labeling regulations to add 21 C.F.R. § 201.56(d)(5) “to make clear that any risk information from the ‘Contraindications,’ ‘Warnings and Precautions,’ or ‘Use in Specific Populations’ section is ‘pediatric contraindications, warnings, or precautions’ within the meaning of section 11 of the BPCA,” and to “avoid any possible confusion as to what information the agency may require in generic labeling that otherwise omits a pediatric indication or other aspect of labeling pertaining to pediatric use protected by patent or exclusivity.”

FDC Act § 505A(o) has been applied in several instances since the enactment of the BPCA in 2002.  For example, FDA has approved generic versions of GLUCOPHAGE (metformin HCl), AGRYLIN (anagrelide HCl) (here and here), and PRILOSEC (omeprazole) with labeling that omits certain protected pediatric information, but that also includes certain essential pediatric safety information, regardless of pediatric exclusivity.  Moreover, in 2003, FDA responded to a citizen petition in which the Agency stated that it would apply Section 11 of the BPCA with respect to generic versions of ALPHAGAN (brimonidine), and issued a Manual of Policies and Procedures discussing, among other things, the review of generic drug labeling pursuant to Section 11 of the BPCA. 

Given the interest our previous post and scorecard on labeling carve-out issues generated, we thought it would be worthwhile to update the scorecard with a more complete list of petitions and FDA responses and to add a new section on BPCA Section 11 (FDC Act § 505A(o)) petitions (for which there will likely be only a few petitions given the express language in the statute).

Generic Drug Labeling Carve-Out Citizen Petition Scorecard

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/PRC (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 Response, Docket No. FDA-2006-P-0073 (Nov. 18, 2008) – PULMICORT Respules (budesonide inhalation suspension)

• FDA Response, Docket Nos. FDA-2008-P-0343 & FDA-2008-P-0411 (Dec. 4, 2008); PRC and PSA denied as moot (June 16, 2009) – PRANDIN (repaglinide)

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 Nos. FDA-2004-P-0426 and FDA-2003-P-0081; FDA Letter – SKELAXIN (metaxalone)

• FDA Docket No. 2007P-0322 – ACTOS (pioglitazone)

• FDA Docket No. 2007P-0354 – THALOMID (thalidomide)

BPCA Section 11 Pediatric Labeling Citizen Petitions

• FDA Response, Docket No. 2002P-0469 – ALPHAGAN (brimonidine)