On July 23, 2014, the Food and Drug Administration (FDA) issued its response to two citizen petitions submitted by AbbVie Inc. (AbbVie) and Auxilium Pharmaceuticals, Inc. (Auxilium) requesting that FDA initiate notice-and-comment rulemaking under the Administrative Procedure Act (APA) to establish procedures for FDA's assignment of therapeutic equivalence (TE) ratings to New Drug Applications (NDAs) submitted under the Food, Drug, and Cosmetic Act (FDCA) § 505(b)(2) and for public listing of those ratings in the Approved Drug Products with Therapeutic Equivalent Evaluations (the Orange Book). The FDA declined to initiate such rulemaking.
AbbVie and Auxilium argued that TE listings are no longer merely informational or advisory since such listings have been expressly incorporated into state pharmacy practice statues and federal, state and private insurance reimbursement schemes. They argued that this incorporation creates "automatic and significant binding legal consequences under state and federal law" for TE listings. The FDA disagreed with this statement, finding that its listing of TE ratings "neither determines the legal rights of any drug manufacturer or distributor, nor imposes any requirement or restriction upon any person." FDA stated that incorporation of its TE ratings into laws or reimbursement schemes that are not administered by the FDA does not make those rating binding such that notice-and-comment rulemaking would be required. Moreover, inclusion of TE ratings into laws and reimbursement schemes were anticipated and addressed during the FDA's 1979–1980 notice-and-comment rulemaking, which established the TE criteria and put the public on notice that TE ratings would be publicly available. Moreover, there are already procedural mechanisms in place for interested parties to comment on or contest the FDA's TE ratings, such as the citizen petition process and the process described in the Orange Book preface allowing comments on the Orange Book or FDA procedure.
AbbVie and Auxilium also argued that, unlike Abbreviated New Drug Applications (ANDAs) filed pursuant to FDCA § 505(j)(1), the elements of a TE evaluation are not found in the statutes relating to § 505(b)(2) NDAs. This is because "§ 505(b)(2) is not intended for equivalents or duplicates of previously approved drug products." For instance, AbbVie and Auxilium noted that § 505(b)(2) "does not direct the Agency to make findings of pharmaceutical equivalence and bioequivalence in order to approve the product as safe and effective." Instead, a § 505(b)(2) application is required to contain the same information as a full NDA, such as full reports of investigations of safety and effectiveness, not evidence of pharmaceutical equivalence or bioequivalence (both of which are required in order to find TE). FDA disagreed with these arguments, stating that even though the statute does not per se require certain TE requirements for approval, there is no foreclosure that some § 505(b)(2) applications may include information that support such findings. More specifically, "the criteria for evaluating TE … encompass the same type of information FDA assesses under relevant statutory authorities to ensure that products submitted pursuant to 505(b)(2) NDAs meet applicable standards for approval and marketing." Particularly with respect to bioequivalence data, FDA noted that "if a 505(b)(2) NDA applicant relies upon the Agency's previous finding of safety and/or effectiveness for a listed drug …, then a scientific bridge to the listed drug is needed. This scientific bridge often includes a bioequivalence or bioavilability study comparing the systemic exposures of the proposed product with those of the listed drug." This type of information can be "integral to supporting the statutory requirement of safety and effectiveness for 505(b)(2) NDAs."