With Orange Book Reform, We’re on the Road to Nowhere

February 1, 2022By Sara W. Koblitz

I don’t mean to be so pessimistic, but 18 months after opening a docket requesting comments on potential “modernizations” for the Orange Book and one year after the passage of the Orange Book Transparency Act, FDA issued its Report on Orange Book reform essentially concluding that that “there is not a consensus view around” Orange Book modernization.  Instead, the FDA Report notes that “the comments received [on the Orange Book docket] provided a variety of different and sometimes competing views on the types of patent information that should be included in, or removed from, the Orange Book,” and “[t]he diversity of viewpoints on these topics indicate a need to examine these issues more closely . . . .”  To that end, FDA announced that it would take the public input it has received and form a working group to address efforts to “modernize the Orange Book, improve transparency, and provide useful information to regulated industry and the public” by…considering the comments that it has supposed to have been considering all along.

Let’s take a step back.  The Orange Book has always been a favorite topic around here (as demonstrated by Kurt Karst’s continued adventures with a hard copy—London most recently), and we were very excited when FDA released the 42nd edition of the Orange Book for 2022 on January 24.  And we were even more excited when that release was followed closely by an FDA Report on the comments submitted to FDA in 2020 and 2021 on the listing of patent information in the Orange Book.  But that Report was a bit of a letdown, as FDA explained that “the comments received provided a variety of different and sometimes competing views” and thus the Agency would not yet take any action.  But none of those “competing views” were novel or unexpected.  This is because generic and innovator sponsors both rely heavily on the Orange Book patent listings but typically for different purposes.  That they would have different opinions—and that combination product sponsors or other stakeholders would have different opinions—on the patents that should be listable in the Orange Book is expected and should have been anticipated by FDA.

Nevertheless, after an interesting history and overview of the origin and use of the Orange Book, FDA described the comments it received on the five areas of interest announced in the Federal Register.  When FDA opened the relevant docket, the Agency asked questions about modernization of the Orange Book generally, as well as about listing of drug product patents, method-of-use patents, REMS patents, and digital application patents.  FDA twice reopened the comment period, including once in response to the Orange Book Transparency Act, to ensure that all commenters had the opportunity submit recommendations as to the types of patent information that should be included in or removed from the Orange Book.  The 24 comments FDA eventually received came from academia, pharmaceutical industry associations, brand and generic drug manufacturers, biopharmaceutical research companies, consulting firms, law firms, intellectual property and drug pricing advocacy groups, biotechnology and trade organizations, information services companies, a pharmacist, and a patient.

FDA addressed each inquiry and responsive comments in turn, but the comments overall were similar—everyone has different ideas.  FDA asked whether and how it could clarify patent listing requirements, and due to the open-ended nature of its questions, the Report explained that FDA received comments on a range of topics with a range of perspectives:

  • Commenters were split on whether the Orange Book should include additional patents, as some argued that additional listings would facilitate generic competition while others argued that expansive listing would unjustly extend monopolies. Another commenter suggested that FDA limit listable patents only “to patents protecting innovations that improve health and have been demonstrated to do so through clinical testing . . . .”  One comment took a different approach and requested that FDA address the conundrum that arises when the current Orange Book listings are manipulated such that listing of ineligible patents prolongs generic approval while omission of eligible patents, and subsequent litigation on those patents, prolongs launch.  Several comments just wanted more information included in the Orange Book about both the patents and the drug products themselves.
  • Digital health and combination product patents received significant attention. It is clear that commenters thought that complex product patent listing needs more clarity, as patent listing requirements for drug-device combination patents are not clear.  However, commenters all had different perspectives about the best way to address these patents.  One commenter, for example, suggested that any component of a drug product that factors into a therapeutic equivalence evaluation should be listed in the Orange Book while several others thought that only patents that reference the drug substance itself should be listed.  Others thought that listing should depend on the scope of FDA’s review of the device component, the clinical use of the device or app, whether the device or app is integral to the drug product, or simply if the patent reasonably could be asserted.
  • Finally, several commenters addressed REMS. Again, commenters were split: Some believed REMS should be listed because the statute does not exclude them from eligibility and some believed that listing them spurs anticompetitive behavior.
  • One comment asked FDA to revise the Orange Book to further discuss the Agency’s position on method-of-use patents and skinny labels.

In response to these comments, FDA convened a working group but declined to provide recommendations to Congress that would help address these issues.  The Orange Book Transparency Act required FDA to summarize these comments in the Report, but it also required FDA to submit a summary of “any actions the Agency is considering taking in response to these comments.”  But FDA proposed no such actions.  Without consensus, and because the comments suggest that “there are a variety of equities and issues to be considered in examining this topic and that some of these issues are still evolving,” FDA provided no plans to further modernize the Orange Book.

For now, FDA “will build upon the efforts of the working group that reviewed the comments and will create a multidisciplinary working group within the Agency to evaluate whether additional clarity is needed regarding the types of patent information that should be included on, or removed from, the Orange Book.”  The Agency however has made no commitments—nor has it even hinted at—revising the Orange Book.  Further, the Report notes that a GAO Report on the Orange Book due to Congress in 2023 “may help inform the Agency’s thinking” on Orange Book issues, which suggests that we should not expect any changes or clarifications in the near future.  With no further action in sight, and with all of this equivocating leads, it seems to us that FDA remains on the Road to Nowhere with respect to Orange Book modernization.