Squeezing All The Juice From the Orange Book: FDA Issues Guidance and Seeks Comment

By Sara W. Koblitz & Kurt R. Karst

Much to our delight, the Orange Book is getting quite a bit of attention from FDA in 2020.  And why not?!?  After all, the Orange Book is celebrating its 40th anniversary this year.  There was even a special “BPCIA Orange Book Transition Edition” published in March.  And here at the FDA Law Blog we too have been celebrating the Orange Book.  Although COVID-19 has temporarily prevented us from continuing our popular Orange Book World Tour (see here, here, here, here, and here for example), we will soon be publishing the “Orange Book Archive” so that folks have easy access to all of the old editions.

With the publication of three (!!!) notices in the Federal Register today, FDA is finally taking the steps to make the Orange Book more accessible that the Agency promised in February 2019.  As part of FDA’s “transparency initiative,” today’s Federal Register notices provide a little bit of Orange Book love for newbies and experienced Orange Book users alike.  For newbies, FDA published the long-promised guidance, “Orange Book: Questions and Answers,” while the old pros were asked a series of questions about general Orange Book improvements and patent listings.

For those less familiar, the Orange Book is an incredibly handy tool in drug development.  Its formal name is the “Approved Drug Products With Therapeutic Equivalence Evaluations,” and it lists drug products approved by FDA (other than those determined to have been withdrawn from sale for safety or effectiveness reasons) and patent and exclusivity information related to approved drug products.  It also contains therapeutic equivalence evaluations for approved multisource prescription drug product, which are frequently used for purposes of drug substitution and containment of health care costs.  The print edition of the Orange Book contains a detailed “Preface,” which explains the Orange Book in detail.

In a new guidance, “Orange Book: Questions and Answers,” the Orange Book staff put together a list of frequently asked questions with respect to the content and format of the Orange Book, “Petitioned” ANDAs (ANDAs with a suitability petition), the Active and Discontinued sections of the Orange Book, and patent listings.  The guidance explains that some products are notably absent from Orange Book specifically those products discontinued prior to 1987, products with tentative approval, DESI drugs, BLAs, and marketed drugs not subject to an NDA or ANDA (i.e. compounded drugs or OTC monograph drugs).  The guidance explains the frequency of Orange Book updates, how to access data files, how to move products from the Active to Discontinued section of the Orange Book, and how to timely update or remove patent listings.  The guidance also provides details on notifying FDA that a product is or will be withdrawn from sale under section 506I of the FDCA.

For those who have already mastered the Orange Book basics, FDA has some questions.  Specifically, FDA has opened two dockets: one soliciting comments on improving the Orange Book generally and one soliciting comments on the listing of patent information in the Orange Book.  The Federal Register notice soliciting general comments on the Orange Book is part of FDA’s Drug Competition Action Plan.  It provides a detailed explanation of the contents of the Orange Book and an interesting history of the updates FDA has made to it since 1985.  Then, as part of FDA’s “continued effort to provide more accessible and useful information in the Orange Book,” FDA announces questions to guide FDA’s priorities in enhancing the Orange Book.  These questions focus on the users and uses of the Orange Book, information or features that would make it more useful, the utility of the therapeutic equivalence codes and related information, and any other information that users would like to provide.

Finally, the third effort, soliciting comments on the listing of patent information in the Orange Book, is intended to address very important considerations with respect to generic competition.  As we recently discussed (in an only tangentially related blog post), only patents listed in the Orange Book are eligible for the Hatch-Waxman “patent dance” and are considered artificially infringed upon the filing of an ANDA.   FDA regulations limit the types of patents that can be listed in the Orange Book to drug substance (ingredient) patents, drug product (formulation or composition) patents, and method-of-use patents.  Process patents, packaging and container patents, and patents claiming intermediates or metabolites are not eligible for listing.  But not all patents that are relevant to drug products fit neatly into one of these categories: in particular, device patents for combination drug-device products and REMS patents.  FDA has avoided addressing these types of questions for at least 15 years, and the First Circuit recently intervened in one case.

Not prepared to let anyone steal its thunder, FDA seems poised to update its Orange Book listing requirements to address combination products and REMS patents.  FDA notes in the Federal Register notice that it is “aware that some NDA holders have submitted patents for listing in the Orange Book, including certain types of device-related patents and REMS-related patents, for which there may be uncertainty regarding whether these are in fact the type of patents that must be submitted.”  Because there are benefits and challenges in the listing and omission of certain patents—specifically including the opportunity to challenge a patent while applications are under review and the possibility of a 30-month stay, FDA wants stakeholder input on:

  • The listing of patents that claim a device constituent part of a combination product approved under section 505 of the FDCA (e.g. a drug delivery device);
  • The listing of patents that claim a device whose use is referenced in approved drug labeling;
  • The listing of patents associated with an established REMS; and
  • The listing of patents associated with digital applications (e.g. clinical decision support software, software as a medical device).

FDA also includes 14 specific questions for stakeholders to address.

FDA is providing stakeholders with a great opportunity to provide insight and advice on potential revisions to the Orange Book.  Given that FDA has ignored some of these issues for a decade and a half, these solicitations present a rare opportunity to shape the Orange Book.  Indeed, those who want to “squeeze all of the juice” out of the Orange Book should definitely submit comments in response.  Comments on both the solicitations and the Questions and Answers guidance are due on September 1, 2020.