As Prescribed


The US Food and Drug Administration (FDA or Agency) on January 30 signaled what could be an about-face with regard to its role administering the List of Approved Drug Products with Therapeutic Equivalence Evaluation (referred to as the Orange Book). Historically, FDA’s Orange Book role has been solely ministerial. However, over the next year, FDA may begin taking a more active approach to the Orange Book.

FDA announced its potential new Orange Book role in a press release accompanying the publication of a draft guidance, Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic Act (Guidance). The actual Guidance is not particularly remarkable; it largely provides instructions on the content and format of marketing status notifications under Section 506I of the Federal Food, Drug, and Cosmetic Act (FFDCA), a new addition to the statute from the FDA Reauthorization Act of 2017. As a reminder, among other provisions, 506I requires that drug application sponsors provide FDA with: (1) 180-day prior notification before withdrawing an approved drug product from sale; and (2) notification within 180 days of a drug’s approval if that drug will not be available for sale within that same timeframe. Failure to provide the required notifications can result in a product being moved from the active to the discontinued section of the Orange Book.

More interesting, however, is how the Guidance fits into FDA’s larger initiative to increase generic drug competition. FDA Commissioner Scott Gottlieb stated, “Having timely, accurate information about what drugs are being actively marketed helps provide transparency around circumstances where generic competition is lacking. It helps us also better understand circumstances where generic medicines are being approved, but not marketed so that we can better consider any policy reasons why this may be occurring.” Thus, it appears that with the new information provided by Section 506I, FDA will be evaluating the current generic competition landscape.

Commissioner Gottlieb also announced three other potential Orange Book enhancements:

  • First, FDA intends to issue draft guidance on how the FDA evaluates therapeutic equivalence (TE) and assigns TE codes (these codes are published in the Orange Book). The goal is to assist applicants to achieve TE status for pharmacy substitution, including pharmacy substitution of 505(b)(2) products. While FDA has previously awarded TE codes to 505(b)(2) products, such a guidance would clarify FDA’s TE policy for 505(b)(2) applicants. This development is particularly notable, as it may signal an FDA focus on 505(b)(2) products, which have largely been left out of the drug competition conversation to date.
  • Second, FDA intends to issue a draft guidance to provide answers to commonly asked questions on the Orange Book.
  • Finally, FDA will be soliciting public comment on Orange Book use and enhancements. This includes “a re-examination” of whether additional patents should be listed in the Orange Book.

This last enhancement is particularly interesting. As Commissioner Gottlieb said, the enhancement would “help generic developers to assess all intellectual property assertions related to [a reference] product that could potentially block generic entry and determine its approach . . . .” If implemented, this proposal could significantly impact patent strategies for companies in this space, as it might open up a new category of listable patents.

The breadth of FDA’s proposal and its potential impact, however, is not clear.

  • First, while Commissioner Gottlieb provided the specific example of the listing of patents for digital applications that have been approved for use in conjunction with a drug, the proposal could be read more broadly to include other non-drug patents, such as patents for companion diagnostics, as well as other patents that are not currently listed, such as patents directed to the method of making and formulating active pharmaceutical ingredients and non-active product components. In the case of companion diagnostics, given the increasing importance of these tests, the listing of diagnostic patents in the Orange Book would be a potentially significant development for product research and commercialization.
  • Second, FDA’s statutory basis for such a listing requirement is uncertain as the FFDCA only requires the listing of patents that claim the drug or a method of using the drug. Accordingly, changes to the FFDCA may be required to implement FDA’s proposal.
  • Third, there is also the question of whether the listing of additional patents would impact the current Hatch-Waxman patent challenge and 30-month stay framework, as 505(b)(2) and generic drug applicants are only required to submit certifications for patents that claim a drug or a use for the drug.
  • Finally, while FDA’s proposal may provide potential generic drug applicants with greater visibility into potential intellectual property impediments, it is possible that the inclusion of additional patents in the Orange Book may create more uncertainty in whether there are patent protections that would prevent FDA from making a generic drug approval effective.

Overall, FDA’s statements appear to indicate that the Agency will be taking a more proactive role in assessing market access through its management of the Orange Book requirements. Exactly what this role will look like, however, is yet to be seen. Moreover, with the recently announced resignation of Commissioner Gottlieb, the exact timeframe and scope of these changes are unclear. Accordingly, as with many of the novel initiatives emerging from FDA, stakeholders should continue to monitor these developments.