This October, the U.S. Food and Drug Administration (FDA) will be celebrating its 40th anniversary of the “Orange Book” as a resource for consumers, health care professionals, drug developers, and Hatch-Waxman litigants. The Orange Book, formally titled “Approved Drug Products with Therapeutic Equivalence Evaluations,” lists drug products that have been approved by FDA under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and have not been withdrawn from sale for safety or efficacy reasons. The Orange Book contains key information for drug developers, including patent and exclusivity information for those drug products, as well as therapeutic equivalence evaluations. According to the Orange Book Preface, “[a]pproved drug products are considered to be therapeutic equivalents if they are pharmaceutical equivalents for which bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling.” The Orange Book can be accessed electronically here.
Modernizing the Orange Book
On May 29, 2020, FDA released a statement that it is making efforts to enhance the utility of the Orange Book. FDA is taking three primary actions: (1) providing a draft guidance for industry on using the current Orange Book, (2) seeking comments on how stakeholders currently use the Orange Book and how it can be improved, and (3) seeking comments on listing patent information in the Orange Book. According to Patrizia Cavazzoni, M.D., acting director of FDA’s Center for Drug Evaluation and Research, each of these actions is meant to ensure the Orange Book “provides as much value as possible to those that rely on it” with “the ultimate goal of improving access to high quality, affordable treatment options for Americans.”
Action 1: Providing Draft Guidance on Orange Book
As part of its modernization efforts, FDA published a draft guidance titled “Orange Book – Questions and Answers.” (See Federal Register Notice). The goal of the guidance is “to assist prospective and current drug product applicants and approved application holders in effectively using the Orange Book.” The draft guidance provides answers to commonly asked questions, including questions about the content and format of the Orange Book, petitioned ANDA drug products, moving products between different sections of the Orange Book, and listing patents in the Orange Book. The public may comment on the draft guidance by August 31, 2020.
Action 2: Soliciting Comments on How the Orange Book Can Be Improved
FDA also established a public docket to solicit comments from “a broad group of stakeholders, including patients, health care providers, drug manufacturers, public policy makers (e.g., Federal and State health agencies), individuals involved in patent litigation (e.g., patent counsel), and any other interested parties, on whether and how the Orange Book can be improved.” (See Federal Register Notice.) In addition to general comments, FDA is seeking responses to the following questions:
- What types of people or entities use the Orange Book?
- What sections of the Orange Book do these different types of people or entities use?
- For what reasons do these people or entities use the Orange Book? What additional information or features (e.g., additional search functions) could be incorporated into the Orange Book to make it more useful?
- Is the information in the Orange Book regarding therapeutic equivalence generally useful?
- How useful is the second letter of a therapeutic equivalence evaluation code?
- How could the therapeutic equivalence information be made more user-friendly or otherwise be tailored to meet the needs of people or entities that use the Orange Book (e.g., the therapeutic equivalence evaluation code)?
- If you use the information regarding therapeutic equivalence, how do you use it?
- Does the information regarding therapeutic equivalence promote drug competition? And if so, how?
- Is there any other information regarding the Orange Book that would be useful for FDA to consider?
Comments are due August 31, 2020.
Action 3: Soliciting Comments on Listing Patent Information in Orange Book
As part of “an Agency-wide effort to modernize the Orange Book,” FDA also established a public docket to solicit comments on “the types of patents currently listed and the potential impact any changes to current patent listing practices may have on drug product development.” (See Federal Register Notice.) FDA posed a number of questions for stakeholders, including
- Do 505(b)(2) and ANDA applicants currently encounter any challenges because certain types or categories of patents are not listed in FDA’s Orange Book
- Given the general increasing complexity of products approved in an NDA (e.g., drug-device combination products, complex delivery systems, associated digital applications), are there any aspects of FDA’s interpretation of the statutory requirement for NDA holders to submit information on a patent that claims the drug or a method of using such drug that are not sufficiently clear? If there is a lack of clarity, how could this be resolved?
- How would NDA holders and prospective 505(b)(2) and ANDA applicants weigh any advantages that may result from listing of additional types or categories of patent in the Orange Book against the potential need to submit additional patent certifications that could result in a delay of approval of a 505(b)(2) application or ANDA?
- If you think FDA should clarify the type of patents that must be listed in the Orange Book, what factors should FDA consider in implementing this clarification? For example, should FDA consider specific factors in evaluating the timeliness of patent information submitted after such clarification?
- Are there other issues related to the listing of patent information that we should consider?
FDA also posed questions on listing drug product patents, method-of-use patents, REMS-related patents, and patents for digital applications. Comments are due August 31, 2020.
Opportunity for Drug Developers and Hatch-Waxman Litigants
FDA’s draft guidance and pursuit of feedback offers drug developers and Hatch-Waxman litigants an opportunity to further their understanding of the Orange Book as well as provide input on changes. The FDA’s May 2020 draft guidance provides drug developers and Hatch-Waxman litigants a consolidated source of insight into FDA’s current views on patent listing and patent listing disputes, among other topics. FDA’s solicitation for comments on how stakeholders use the Orange Book provides drug developers and Hatch-Waxman litigants an opportunity to share their views on how to improve the Orange Book, including what other information or functionality could be helpful and should be included.
Drug developers and Hatch-Waxman litigants perhaps should pay most attention to FDA’s solicitation for comments on listing patent information in the Orange Book. Currently, FDA regulations allow NDA applicants to list patents that claim a drug or method of using a drug for which a claim of patent infringement could reasonably be asserted. See 21 C.F.R. § 314.53(b)(1). The current regulations prevent NDA applicants from listing process/manufacturing patents, patents to intermediates formed in the manufacturing process, and metabolite patents in the Orange Book. These regulations influence the scope of Hatch-Waxman patent infringement disputes and any changes to the FDA regulations might affect the scope of future litigation. FDA’s solicitation for comments on patent listing in the Orange Book provides a unique opportunity for drug developers and Hatch-Waxman litigants to weigh in on an important issue.
As FDA’s 40th anniversary of the Orange Book approaches later this year, we will be keeping a watchful eye on the latest developments.