On January 5, 2021, President Trump signed into law H.R. 1503, the "Orange Book Transparency Act of 2020," which amends provisions governing the types of patents and exclusivity-related information for approved drugs listed in Orange Book, the Food and Drug Administration (FDA) listing of approved drug products with therapeutic equivalence evaluations. In addition, appropriations bill H.R. 133, “Consolidated Appropriations Act, 2021,” signed into law December 27, carries significant ramifications for the patent and exclusivity information that will be listed in the Purple Book, FDA’s listing of licensed biological products. We analyze these statutory changes below.

Orange Book patent listing clarification

In June 2020, FDA had opened a public docket to solicit comments on the listing of patent information in the Orange Book, specifically seeking feedback on the types of patents currently listed in the Orange Book and the impact that any change to current patent listing practices may have on drug product development; this docket was reopened in October to allow additional time for comment. Former FDA Commissioner Scott Gottlieb had previewed this public comment period in January 2019, when he announced FDA was considering re-examination of the types of pharmaceutical patents that must be listed in the Orange Book, as we analyzed online here.

Now, with the passage of H.R. 1503, Congress has aimed to clarify – in Sections 2(a) and 2(b) of the Act – information related to patent listing and the types of patents that should be listed in the Orange Book.

Previously, 21 USC 355(b) required that NDA holders submit information for “any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug” and that could reasonably be asserted based on a competitor’s manufacture, use, or sale of the drug. In its regulations, FDA had interpreted that statutory provision to require NDA holders to submit information on the following types of patents “drug substance (active ingredient) patents, drug product (formulation and composition) patents, and method of use patents.” 21 CFR 314.53(b). The regulation also clarifies that for patents that claim a method of use, listing is limited to “patents that claim indications or other conditions of use for which approval has been sought or has been granted….” Id.

The new law mostly codifies the language of the regulations distinguishing between drug substance, drug product and method of use patents. Specifically, H.R. 1503 provides that an NDA holder must list patent information for the following patents:

  1. a patent that claims the drug for which the applicant submitted the application and is a drug substance (active ingredient) patent or a drug product (formulation or composition) patent; or
  2. a patent that claims a method of using such drug for which approval is sought or has been granted in the application.

As the revised statutory language mirrors the existing language in the patent listing regulation, it does not appear that the revised law will have any immediate practical impact.

New Orange Book requirements for FDA and drug sponsors

The new law may have a more immediate impact with respect to the listing of exclusivity periods in the Orange Book. H.R. 1503 Sec. 2(c) requires that, for each drug in the Orange Book, FDA “shall specify any exclusivity period that is applicable, for which the Secretary has determined the expiration date, and for which such period has not yet expired.” Under current practice, FDA sometimes lags in identifying certain exclusivity periods in the Orange Book, and the agency has in some cases taken years to make an exclusivity determination for products raising novel or complicated exclusivity issues. For situations where FDA has determined the expiration date of an exclusivity period, the law makes clear that FDA must list the exclusivity period in the Orange Book.

Meanwhile, Sec. 2(d) requires that NDA holders notify FDA within 14 days of a final decision invalidating an Orange Book listed patent by the Patent Trial and Appeal Board (PTAB) or a court (and from which no appeal has been, or can be, taken), and request that FDA remove or amend the patent information in the Orange Book in accordance with the decision. However, FDA cannot remove a patent prior to the expiration of any 180-day exclusivity period that relies on a paragraph IV certification that such patent is invalid.

Currently, FDA regulations require an NDA holder to “promptly” notify FDA after determining that patent information should be withdrawn or amended, including after a judicial finding of invalidity. 21 CFR 314.53(f)(2). This new provision adds requirements for NDA holders that largely mirror requirements that currently exist for generic applicants. See 21 CFR § 314.107(e). However, this provision also brings invalidity decisions from the PTAB within its scope: something that was absent from the current regulations for generic filers. The requirement that NDA holders delist Orange Book patents within 14-days after a finding of invalidity may impact enforcement strategy and settlement negotiations, particularly when there are concurrent district court and PTAB proceedings.

“Patent dance” information to be made public in Purple Book

Analogous to the Orange Book listing for drug products, biological products including biosimilars are listed in the Purple Book, FDA’s “Database of Licensed Biological Products.” Signed into law on December 27, 2020, H.R. 133, the “Consolidated Appropriations Act, 2021,” contains language from the former H.R. 1520, the “Purple Book Continuity Act of 2019,” which significantly changes the role of FDA in biologics regulation landscape. Under the Biologics Price Competition and Innovation Act (BPCIA), biologics license holders and companies seeking to market a biosimilar engage in a statutorily-prescribed exchange of information about the patents to be litigated, often referred to as the “patent dance.” Previously, this exchange of information had been undertaken confidentially between the reference product BLA holder and the biosimilar applicant; however, H.R. 133 requires reference product BLA holders who engage in the patent dance to provide FDA with the patent number and expiration date of each patent identified by the BLA holder in either the original list exchanged with the biosimilar applicant or any supplemental list. The patent information submitted by the BLA holder will then become public information listed in the Purple Book.

While the new law advances transparency regarding the patent coverage for subsequent biosimilar filers, a BLA holder may assert other patents against future filers, and there is the possibility of new patents being obtained. It may also prompt certain challenges to specific patents in the PTAB, affect the scope of potential license negotiations, or encourage potential design-around options.

Also notable in H.R. 133 is the new requirement that FDA specify exclusivity for each biological product included on the list (Sec. 325(a)(9)(A)(iv)). The BPCIA provides 12 years of exclusivity for the first licensure of innovator biological products, meaning FDA may not license a biosimilar application until 12 years after the date on which the reference product was “first licensed” under PHSA 351(a). However, not every BLA is eligible for its own 12-year period of exclusivity.

Presently, FDA draft guidance from August 2014 sets out a complex process for how the agency determines the exclusivity period for a biological product. Adding to this opacity, FDA’s general practice has been to decline to issue any exclusivity determinations for newly approved biological products except in limited circumstances involving regulatory necessity or certain requests, which has been a source of frustration to industry stakeholders. The language of the statute provides that “[f]or each biological product included on the list [Purple Book] the Secretary shall specific each exclusivity period…for which the Secretary has determined such biological product to be eligible….” For situations where FDA has determined that a product is eligible for an exclusivity period, the law makes clear that FDA must list the exclusivity period in the Purple Book .

* * * * *

While the manner in which each of these new laws will be carried out remains to be seen, it appears the new laws will bring increased clarity around the types of patent information that must be included in the Orange Book and Purple Book, and add useful information to the databases themselves.