It’s PANDA-monium at FDA

August 17, 2021By Sara W. Koblitz

Meet the newest category of drug applications: the PANDA.  A PANDA, or the Pre-Hatch-Waxman Abbreviated New Drug Application, refers to abbreviated drug applications submitted and approved under sections 505(b) and 505(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) prior to the enactment of the Hatch-Waxman Amendments in 1984, as FDA announced in the Federal Register last week.  Drugs approved as PANDAs are, for all intents and purposes, follow-on drugs approved based on FDA’s previous findings of safety and efficacy for a given drug, but, because they were not submitted under section 505(j) of the FDCA, they are not technically “Abbreviated New Drug Applications (ANDAs).”  Nonetheless, FDA has been calling them ANDAs and listing them in the Orange Book as ANDAs for years, but recent changes to the Orange Book have spurred some confusion.  Thus, FDA divided them into their own category and is now seeking Comments on whether the 505(b) or the 505(j) regulatory scheme should apply.

While generic drugs as we know them are a creation of the 1984 Hatch-Waxman Amendments, the Federal Register Notice explains that FDA first introduced the concept of an ANDA in 1968 to facilitate approval of Drug Efficacy Study Implementation (DESI) drugs.  By 1970, products evaluated as DESI drugs ultimately determined to be effective for one or more indications could be eligible for approval as ANDAs if they were similar or related to DESI drugs even if the drug products had not been marketed under a 505(b) New Drug Application (NDA).  However, because they are not necessarily the same as any previously approved drugs, the title “ANDA” is a bit of a misnomer.  Yet some of these ANDAs, which FDA is now calling PANDAs, still are marketed today, and, despite the misnomer, are listed in the Orange Book as ANDAs.

Because PANDAs are listed in the Orange Book as ANDAs but are not duplicates of any FDA-approved 505(b) drugs, there has been confusion about whether they can serve as Reference Listed Drugs (RLDs) for new ANDAs or 505(b)(2) NDAs.  As ANDAs, the PANDAs are not listed RLDs in the Orange Book; they are only Reference Standards (RS) and therefore cannot be relied on for FDA’s findings of safety and effectiveness.  While this was not an issue when FDA did not distinguish RLDs from its associated RS in the Orange Book (and therefore these PANDAs were listed as RLDs), it became confusing when FDA revised the Orange Book in 2017 to separately identify a RLD and a RS.  To address this confusion, FDA has decided to designate PANDA products as RLDs in an effort to provide “clarity both to prospective 505(j) ANDA applicants seeking to make generic versions of these products, and to applicants of 505(b)(2) applications that there is a finding of safety and effectiveness for these products that may be relied upon for approval.”  This approach, FDA explains, is consistent with its efforts to “advance competition and increase patient access to more affordable medicines.”

FDA already has started adding RLD designations for PANDAs to the Orange Book and will continue to do so “as expeditiously as resources permit.”  In the interim, ANDA applicants may also submit Controlled Correspondence to FDA seeking to designate a PANDA as a RLD.  FDA also provided a list of PANDA products currently identified as an ANDA in the Orange Book for reference.  FDA emphasizes, however, that this effort expressly excludes antibiotic drug products originally submitted under FDCA § 507.

The Federal Register Notice also solicits input from PANDA holders or other interested stakeholders related to FDA’s post-approval regulation of PANDAs.  Because PANDAs were submitted to FDA under section 505(b) and approved under 505(c)—which typically apply to NDAs—but are nonetheless treated as ANDAs, FDA recognizes ongoing confusion as to which regulatory scheme might apply for purposes of postmarketing reporting requirements, labeling updates, patent listing, exclusivity eligibility, and drug-safety related requirements or procedures; indeed, PANDA holders have typically elected which regulatory scheme to follow.  FDA therefore seeks industry comment on whether “there are regulatory or policy reasons for treating PANDAs differently from other 505(b) Application.”  Specifically, FDA asks for Comments on regulatory or policy rationales for treating PANDAs differently from other 505(b) applications in certain respects, in particular with respect to:

  • Labeling requirements and updates, including safety-related information;
  • Patent listing requirements;
  • Eligibility for exclusivity; and
  • Certain safety-related requirements, such as the postmarket studies and clinical trials, safety-labeling change requirements, and REMS requirements.

Further, FDA requests Comment on:

  • Factors FDA should consider in determining a reasonable amount of time for PANDA holders to make changes to their practices, if applicable;
  • Any additional steps FDA should take to highlight for PANDA holders that their ANDA is a PANDA;
  • Any additional steps, beyond the Orange Book, that FDA should take to aid other interested persons in identifying PANDAs;
  • Any necessary modifications to the PANDA list for accuracy; and
  • Any other issues FDA should consider in assessing the regulatory framework for PANDAs under the FDCA.

FDA will accept Comments on its PANDA proposal—submitted to the docket in black and white (see what I did there?)—until December 13, 2021.

Categories: Hatch-Waxman