Public Citizen Petitions FDA to Amend Generic Drug Labeling Regulations in the Wake of Mensing

August 29, 2011

By Kurt R. Karst –      

On August 29, 2011, Public Citizen announced that it submitted a citizen petition to FDA requesting that the Agency amend its regulations to permit ANDA sponsors to revise their labeling through the Changes Being Effected (“CBE”) and Prior Approval Supplement (“PAS”) procedures.  The petition is in response to the U.S. Supreme Court’s June 23, 2011, 5-4 landmark consolidated decision in PLIVA Inc. v. Mensing (Docket No. 09-993), Actavis Elizabeth, L.L.C. v. Mensing (Docket No.  09-1039), and Actavis, Inc. v. Demahy (Docket No. 09-1501) (and for which rehearing was requested and recently denied), in which the Court invoked the doctrine of impossibility preemption to hold that federal drug regulations applicable to generic drug manufacturers directly conflict with, and thus preempt, state tort-law claims based on drug manufacturers’ alleged failure to provide adequate warning labels for their products (see our previous post here), and in response to FDA’s position (pages 16-17) that the CBE and PAS procedures are not available to ANDA sponsors to add or strengthen label warnings.  (Public Citizen submitted an amicus brief in the Mensing case in support of Respondents.)

The Public Citizen petition makes three requests:

(1)  That FDA amend, through notice and comment rulemaking, its PAS and CBE regulations at 21 C.F.R. § 314.70(a) to specify that subsections (b) and (c) apply to ANDA sponsors.  Such an amendment, says Public Citizen “might also make exceptions to reflect situations in which the agency believes that particular ANDA holders lack an adequate basis to make labeling changes, such as, perhaps, during the first few months after the first ANDA holder enters the market or for an ANDA holder that sells very few prescriptions of a drug (for example, under 1,000 prescriptions per year);”

(2) That FDA amend its regulation at 21 C.F.R. § 314.150(b)(10) (permtting ANDA approval to be withdrawn if a generic drug’s approved labeling differs from that of the RLD) “to specify that this regulation does not apply to ANDA holders permitted to supplement labeling through CBE or PAS procedures;” and

(3) That FDA clarify in its regulations (and specifically 21 C.F.R. § 201.57(c)(6)(i)(A)) “that all ANDA holders are required to report safety concerns to the FDA as soon as they become aware of a clinically significant hazard.”  

Public Citizen’s petition is premised on the contention that despite significant changes in the generic drug market since the 1984 enactment of the Hatch-Waxman Amendments, “FDA regulation of generic labeling has remained substantially unchanged.”  “The regulatory revisions requested here would bring postmarket regulation in line with the realities of the pharmaceutical market and help to ensure that drug labeling provides adequate warnings to patients based on information that comes to light after the drug is approved for marketing,” says the petition.  Moreover, according to Public Citizen, “FDA’s position on the inapplicability of 21 C.F.R. § 314.70 to ANDA holders, and the Supreme Court’s recent decision in PLIVA, which turns on the limitations of the regulatory scheme, threaten the safety of prescription drugs, and accordingly, pose unnecessary risks to patients.”  Amending FDA’s regulations to make the PAS and CBE procedures applicable to ANDA sponsors in response to new risk information would undo the impossibility that the Supreme Court found in Mensing, says Public Citizen.  “In that event, common law could once again complement the FDA’s mandate to monitor drug safety across the full range of drugs, rather than just the decreasing portion occupied by brand-name drugs.” 

Interestingly, Public Citizen contends that its proposed regulatory changes “would not impose an obligation beyond the capacity of generic manufacturers.”  “It is our understanding,” says Public Citizen, “that under current regulations, a generic manufacturer is designated by the FDA to maintain the label of a drug when the name-brand manufacturer of that drug withdraws from the market.  This procedure manifests the FDA’s confidence in the ability of generic manufacturers to perform ongoing pharmacovigilance duties – which makes sense, given their substantial scientific and financial resources, as well as the effort they must already invest to comply with post-approval safety regulations.”  This is presumably a reference to FDA’s practice of unilaterally designating an ANDA as the sole RLD for a multi-source generic drug product where the brand-name drug has been discontinued and is listed in the Discontinued Drug Product List of the Orange Book.  In such cases, FDA has stated time and time again that when an NDA designated as the RLD is discontinued for reasons other than safety or effectiveness “[a]pproved ANDAs that refer to the NDAs . . . are unaffected by the discontinued marketing of the products subject to those NDAs. . . .  If FDA determines that labeling for these drug products should be revised to meet current standards, the agency will advise ANDA applicants to submit such labeling.”  FDA, Notice, Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness, 75 Fed. Reg. 48,352, 48,353 (Aug. 10, 2010) (emphasis added).