Source: https://www.fdalawblog.net/2011/09/citizen-petition-requests-rulemaking-process-for-505b2-nda-therapeutic-equivalence-rating-decisions/
Timestamp: 2019-04-24 16:31:22+00:00

Document:
The submission of 505(b)(2) applications for certain versions of transdermal testosterone gel drug products – specifically ANDROGEL and TESTIM – was the subject of two FDA Citizen Petition responses (here and here). In each case, FDA determined that proposed generic transdermal testosterone gel drug products containing new or different inactive ingredients must conduct skin transfer, hand-washing, and possibly showering studies, and that such studies are outside the scope of an ANDA submission.
Although “A” TE codes are typically associated with generic versions of a brand-name drug approved under an ANDA, a drug product approved under a 505(b)(2) application may also be assigned an “A” rating to a listed drug (which was approved either under a “full” 505(b)(1) NDA or a 505(b)(2) application). Some examples of A-rated 505(b)(2) drug products from the current edition of the Orange Book include Pamidronate Disodium (NDA No. 021113), Fluorescein Sodium (NDA No. 022186), Nicardipine HCl (NDA No. 022276), and Azithromycin (NDA No. 050809).
Much has changed in the world since FDA’s 1980 final rule (45 Fed. Reg. 72,582 (Oct. 31, 1980) amending 21 C.F.R. § 20.117(a)(3) to make available “a list of FDA-approved prescription drug products, together with therapeutic equivalence evaluations of products in the List that are available from more than one source” (i.e., the Orange Book). Too much, in fact, according to Abbott.
the List neither determines nor adjudicates the legal rights of any drug manufacturer or distributor; it does not impose any requirement or restriction upon any person; it does not interpret or apply the act in a manner that creates any obligation on any person; it makes no recommendation as to which products persons should purchase, prescribe, or dispense, or conversely, which products should be avoided.
To the extent that the List sets forth FDA's evaluations of the therapeutic equivalence of drug products that have been approved, it contains FDA’s advice to the public and to the States regarding an important public health matter. These evaluations do not constitute determinations that any products are in violation of the act or that any products are preferable to others. These are nonregulatory evaluations that are based on the application of certain criteria to information contained in FDA files. Most of the reasons cited by the comments for demanding an evidentiary hearing (for example, determinations of effectiveness and bioequivalence) concern determinations that were made by FDA in clearly defined proceedings when there existed the right to an evidentiary hearing. Thus, the notice and comment procedure used in adopting this List is sufficient.
First, TE listings are now far more than advisory. They have been expressly incorporated into state pharmacy practice statutes that control which drug products pharmacists may dispense and, therefore, which drug products patients receive when filling prescriptions at the pharmacy. TE listings also directly affect federal, state, and private insurance reimbursement schemes, and are expressly relied upon in Medicare Part B, among other federal laws. These listings materially impact the economic rights of competing drug sponsors. Thus, TE listings have automatic and significant binding legal consequences under state and federal law.
Second, TE listings for § 505(b)(2) drugs can in no way be characterized as merely the product of information already “contained in FDA files” that is based upon findings made in the course of the § 505(b)(2) approval process. The Agency can perhaps make a plausible case for characterizing TE listings for duplicate drugs approved under abbreviated new drug applications, or “ANDAs,” as merely a summary of the statutory findings that FDA makes in approving such drugs under § 505(j)(1) of the FDCA. But even if so, FDA cannot make the same case for § 505(b)(2) drugs because the elements of a TE evaluation cannot be found in § 505(b)(2) (or any other statutory provision applicable to § 505(b)(2) drugs).
Abbott’s Citizen Petition is not the first time TE ratings with respect to 505(b)(2)-approved drug products have caused controversy. In May 2009, FDA, in responding to a Citizen Petition, affirmed its decision to grant an AP rating for Nicardipine HCl (NDA No. 022276). Several years ago, FDA also had to address TE ratings with respect to Levothyroxine Sodium drug products approved under FDC Act § 505(b)(2).

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