Groups Challenge FDA’s PLAN B Approval

April 18, 2007

On April 12, 2007, the Association of American Physicians & Surgeons (“AAPS”), Concerned Women for America, Family Research Council, and Safe Drugs For Women filed a complaint in the U.S. District Court for the District of Columbia against FDA seeking declaratory and injunctive relief concerning the Agency’s August 24, 2006 approval of a supplemental NDA for PLAN B (levonorgestrel) Tablets, 0.75mg.  FDA’s PLAN B approval permitted Over-the-Counter (“OTC”) use of the drug in women 18 years and older and maintained prescription status for women 17 years old and younger, and was made after the Agency solicited comment on the novel issues presented by the PLAN B switch.

The AAPS complaint asks the court to:

  • Vacate FDA’s approval of PLAN B for OTC distribution;
  • Declare that FDA lacks authority to approve the same drug product for simultaneous OTC-prescription distribution;
  • Declare that FDA lacks authority to bifurcate a drug product’s OTC versus prescription status based on the patient’s age;
  • Declare that FDA lacks authority to create a hybrid “third class” of behind-the-counter drug beyond the FDC Act’s OTC and prescription classes;
  • Declare that FDA failed to conduct the required rulemakings necessary to authorize OTC distribution of PLAN B; and
  • Declare that FDA unlawfully approved PLAN B for OTC distribution under improper pressure from Senators Clinton and Murray.

AAPS contends that “the methodologies used and the workproduct prepared by the staff at Defendant FDA’s Reproductive Health Division diverge from accepted scientific and regulatory methods.”  For example, AAPS alleges that FDA did not consider safety data in overweight women, smokers, and adolescents, and only considered acute safety data without assessing the chronic impacts of the drug.

The complaint also alleges that FDA’s PLAN B approval violates the Administrative Procedure Act (“APA”) and the Pediatric Research Equity Act of 2003 (“PREA”).

Under FDA’s “meaningful difference” policy, the Agency has interpreted the FDC Act to allow marketing of the same active ingredient in products that are both prescription and OTC, assuming some meaningful difference exists between the two that makes the prescription product safe only under the supervision of a licensed practitioner.  Historically, these “meaningful differences” have been active ingredient, indication, strength, route of administration, or dosage form.  The PLAN B approval added age as a sixth parameter.  AAPS contends that “[b]y failing to convene a rulemaking to add its new, patient-based ‘age’ parameter to the its prior, drug-based, five-parameter interpretation of the meaningful-difference test, FDA amended a rule without the required notice-and-comment rulemaking” in violation of the APA.

PREA requires sponsors of marketing applications to include in their application (unless the requirement is waived or deferred) an assessment and relevant data for each relevant pediatric age group to enable FDA to assess the drug’s safety and efficacy for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective.  AAPS contends that:

[FDA] premised [its] authority to approve OTC status only for women 18 and over, without requiring PREA data, on the SNDA’s changing the Plan B labeling only for non-PREA subpopulations (i.e., “adults” aged 18 and older).  Contrary to Defendants’ premise, PREA does not include such rigid age ranges, and puberty extends beyond the eighteenth birthday for a significant pediatric subpopulation of young women. . . .   Because PREA applies past the eighteenth birthday for systemically absorbed hormonal drugs like Plan B, the Plan B SNDA required not only dosage and administration data to support all indications for all pediatric subpopulations (i.e., regardless of Rx versus OTC distribution), but also safety and efficacy data to support the OTC indication for pediatric subpopulations past their eighteenth birthday but still within puberty and/or adolescence.  [The] data submitted to support Plan B’s age-bifurcated Rx-to-OTC switch did not satisfy PREA’s (and thus FFDCA’s) requirements.

FDA’s PLAN B approval has been controversial.  It seems unlikely, however, that the AAPS complaint -despite some novel arguments- will result in FDA withdrawing approval.

Categories: Drug Development