FDA Issues Request for Comments on Modernizing Patent Listings in the Orange Book

On June 1, the Food and Drug Administration (FDA) published a notice in the Federal Register announcing that the agency was establishing a public docket for the receipt of public comments regarding the types of patent information published in the FDA’s Orange Book, a collection of FDA-approved drugs and their therapeutic equivalents designed to improve competition from generic drugmakers. While the request for comments only seeks early input on the subject, public responses could influence regulatory action that later changes the types of patents that a branded pharmaceutical manufacturer must disclose to inform generic drugmakers of their infringement liability risk.

Patent information first came to be listed in the FDA’s Orange Book after passage of the Drug Price Competition and Patent Term Restoration (Hatch-Waxman) Act, enacted in part to overturn the Federal Circuit’s 1984 decision in Roche v. Bolar, which effectively prevented pharmaceutical testing by generic drugmakers until after patents covering the branded pharmaceutical expired. Hatch-Waxman required pharmaceutical developers with a new drug application (NDA) approved by the FDA to submit a list of patents covering the drug. This patent listing is important for generic drugmakers filing abbreviated new drug applications (ANDAs) with the FDA to market therapeutically equivalent off-brand drugs. Generic firms filing ANDAs often certify to the FDA that patents listed in the Orange Book are either invalid, unenforceable or will not be infringed by the generic competitor, otherwise known as a Paragraph IV certification. These types of certifications often spawn infringement suits in district court where they, in contrast to many other types of patent infringement suits, tend to result in settlements including a negotiated market entry date for the generic competitor.

Frustrations Develop

Tom Irving, Partner at Finnegan, expressed his enthusiasm at having the opportunity to address aspects of the FDA’s Form 3542, used by NDA applicants to submit patent information, which can lead to uncertainty for counsel representing branded pharmaceuticals. “This is an FDA document, but the people being asked to fill this out are patent professionals who want to make sure that they’re filling out the form correctly,” Irving said. “For many, there’s been a frustration about how to answer the form’s questions which may have been written by an FDA expert and not a patent attorney.” Irving, who has represented drug developers in Orange Book matters for 20 years, noted that increased clarity would also be helpful for ANDA filers by clarifying their infringement liability risks. “I think it helps everyone to modernize the Orange Book and clarify the kind of patent information being submitted,” he added.

Changes to Orange Book Patent Listings Since Hatch-Waxman

The type of patent information that the FDA—which doesn’t itself evaluate the patents submitted by NDA applicants—lists in the Orange Book has changed substantially since the Hatch-Waxman Act was passed in 1984. Under Section 505(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act, NDA applicants are required to identify patents which could be reasonably asserted against those engaging in the use, manufacture or sale of the FDA-approved drug. In the first few years after Hatch-Waxman was passed into law, guidance from the FDA indicated that drug developers seeking FDA approval should submit information on formulation and composition patents, drug ingredient patents and method-of-use patents.

During the early 2000s, the FDA sought to clarify the rules on patent information to be submitted by NDA applicants in response to disputes over whether Orange Book-listed patents met the regulatory requirements under the FD&C Act; a request for clarification was also filed by the Federal Trade Commission (FTC). While a final rule in 2003 required NDA applicants to submit patents claiming a different polymorphic form of the active ingredient of the drug described in the NDA, the agency prohibited the submission of patents claiming packaging, intermediates or metabolites. In its rule, however, the FDA did draw a distinction between packaging like drug containers and drug delivery devices such as metered dose inhalers and transdermal packages.

The most recent revision to the FDA’s patent information listing requirements came in a 2016 final rule which was designed to implement portions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, which amended aspects of the FDA approval process. In part, these rule changes streamlined the process of identifying the basis for which a particular patent is submitted to the FDA or the particular portion of an approved method of use claimed by a patent which doesn’t cover an indication or condition of use in its entirety.

Request for Comments Includes Questions on REMS, Digital Application Patents

One area of uncertainty at the center of the FDA’s recent request for comments is patents covering elements assuring safe use of a drug or mitigating health risks associated with the use of a specific drug. Such elements may be required by the FDA as part of a risk evaluation and mitigation strategy (REMS), which the agency will order to ensure that the benefits of a drug outweigh its risks. ANDA applicants seeking approval of a generic version of a drug having a REMS in place are subject to the same elements assuring safe use as the original NDA applicant, although ANDA applicants are able to use different and comparable aspects of those elements. Many NDA holders have obtained patents covering the elements for safe use required by a REMS mandated by the FDA and uncertainty as to whether these types of patents need to be submitted for listing in the Orange Book has developed.

In discussing the questions posed in the FDA’s Federal Register notice, Irving expressed a good deal of curiosity regarding both REMS-related and digital application patents. Despite many years of experience regarding patent matters in the pharmaceutical industry, Irving himself hasn’t dealt with many of these patents in his practice. One example of a digital application patent proffered by the FDA’s request for comments covers a mobile application that accepts and records information from an ingestible sensor in a drug product. “These certainly sound like modern patents to me,” Irving commented. “I don’t know how ‘hot button’ the responses to those [REMS and digital applications] questions will be, but it will be fascinating to see how it develops.”

Below are the questions included in the FDA’s Request for Comment:

A. General Questions

1. 1. 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?
   2. 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?
   3. 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?
   4. 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?
   5. Are there other issues related to the listing of patent information that we should consider?

B. Drug Product Patents

1. 1. Are there elements of FDA’s regulatory definition of drug product or dosage form in §?314.3(b) that may be helpful to clarify to assist NDA holders in determining whether a patent claims the finished dosage form of an approved drug product?
   2. What factors should FDA consider in providing any clarifications related to whether device-related patents need to be submitted for listing as a patent that claims the drug? For example, what are the advantages and disadvantages of requiring patents that claim a device constituent part of a combination product approved under section 505 of the FD&C Act to also claim and/or disclose the active ingredient or formulation of the approved drug product (or the drug product class) to fall within the type of patent information that is required to be submitted to FDA for listing in the Orange Book? Also, how, if at all, should this analysis be affected by considerations about whether the device or specific component of device claimed in the patent is “integral” (see 68 FR 36676 at 36680) to the administration of the drug?

C. Method-of-Use Patents

1. 1. What information should FDA consider regarding when a patent that claims a method of using a device constituent part, or only a component of a device constituent part, might or might not meet the statutory standard for submission by the NDA holder for listing in the Orange Book as a method-of-use patent? Should FDA consider whether: (1) The patent claims and/or discloses the active ingredient or formulation of the approved drug product (or the drug product class)?; (2) the device constituent part is described in certain sections of the listed drug labeling?; or (3) use of the device is described in labeling for the listed drug, but the device is not a constituent part of the drug product? Should FDA consider whether the drug product labeling states that the drug is only for use with the specific device? Should FDA also consider device labeling, for example whether the device labeling indicates the device is for use with the specific drug?
   2. What information should FDA consider regarding whether there are circumstances in which a patent claiming the way an approved drug product is administered would meet the statutory standard for submission by the NDA holder for listing in the Orange Book as a drug product patent rather than a method-of-use patent?
   3. What information should FDA consider regarding whether there are circumstances in which a method-of-use patent claiming the way an approved drug product is administered that is not described in FDA-approved product labeling would meet the statutory standard for listing in the Orange Book?

D. REMS-Related Patents

1. 1. What information should FDA consider regarding whether patents that claim how the sponsor has implemented a particular REMS requirement meet the statutory requirement for the type of patent information that is required to be submitted to FDA for listing in the Orange Book? What factors should be considered in making this determination?
   2. Are there other issues related to patents that claim how the sponsor has implemented a particular REMS requirement that FDA should consider with regard to listing patent information in the Orange Book, including any potential impact listing such patents in the Orange Book could have on development of REMS for generic versions of products? For example, does listing patent information in the Orange Book for such patents pose difficulties for ANDA applicants in developing a single, shared system REMS for that product?

E. Patents for Digital Applications

1. 1. If an approved drug product has an associated digital application (e.g., a mobile application that accepts and records information from an ingestible sensor in a drug product), what factors should be considered in determining whether a patent that claims an aspect of that digital application meets the standards for listing in the Orange Book?
   2. Are there other issues related to patents for digital applications associated with approved drugs that should be considered with regard to listing patent information in the Orange Book?