The recently enacted “Purple Book Continuity Act of 2019” went into effect as of June 25, 2021.  The FDA must proactively update the Purple Book information every 30 days with an alphabetical list of licensed biologics, including the date of marketing application approval and the marketing/licensure status.  Additionally, there is now a potentially higher price for reference product sponsors for biologic drugs to enter the patent dance under the BPCIA and assert their patents against potential competitor biosimilar manufactures.

Prior to enactment of  H.R. 1520, the “Purple Book Continuity Act of 2019,” the FDA published the “Purple Book” reference guide for biologic drugs under section 351(a) or 351(k) of the Public Health Service Act (PHS) with information on whether biologic drug products have been determined by the FDA to be biosimilar to (or interchangeable with) the reference biological product and the date a biological product was licensed for marketing under section 351(a) or 351(k) of the PHS.  The Purple Book also indicated the date of expiration of applicable exclusivity if the FDA evaluated the biological product for reference product exclusivity under section 351(k)(7).  The Purple Book was only updated periodically by the FDA.

The recent enactment now adds a new layer of complexity for parties strategizing how to enter the patent dance under the BPCIA.  The reference product sponsor must provide the FDA with the expiration dates of all patents listed in the patent list sent to the subsection (k) applicant pursuant to 42 U.S.C. § 262(l)(3) and any supplemental lists pursuant to 42 U.S.C. § 262(l)(7) within 30 days of providing the subsection (k) applicant with such lists.  The FDA will then publish the patent expiration dates on the searchable Purple Book database in its recurring monthly updates.

The new regulation will likely ensure that the Purple Book listing will be closely watched by parties looking to develop their own biosimilar versions of licensed biologics.  As a result, a reference product sponsor may choose to forgo asserting some or all of their patents in order to avoid publication of expiration dates in what would amount to an easily accessibly compilation of the relevant patent estate.  This prospect could change the calculus for reference product sponsors in terms of the number and type of patents that they assert.  For example, a reference product sponsor may want to limit the number of patents asserted against a party in order to avoid revealing their hand to follow on competitors that may implement a design around strategy.  It remains to be seen whether the new regulation will have an impact on the desire to wield the better part of expansive portfolios against competitors, for example AbbVie’s recent challenge to Alvotech reported here.

As of the date of this post, the Purple Book lists patents and expiration dates in connection with AbbVie’s Humira® product and Genentech’s Avastin® and Lucentis® products.  Notably, most of the listed patents relate to methods of manufacturing rather than formulations, treatment methods, and other aspects relevant to biosimilar manufacturers.

Despite progress, there is still room to improve on the new regulations from the viewpoint of public transparency.  For instance the Purple Book counterpart for small molecule drugs, “The Orange Book”, requires NDA applicants and holders to provide the patent number and expiration date of any patent which claims the drug or method of using such drug and which a claim of patent infringement could reasonably be asserted (21 U.S. Code § 355(b)).  Recent changes to the Orange book came through the Orange Book Transparency Act of 2020.  NDA holders are now required to notify the FDA of invalidation of a patent within 14 days so the Orange Book listing can be amended as necessary.

The trend for both the Purple Book and Orange Book is moving towards increased public transparency.  The major impetus for the new regulations is to increase the number of lower cost drug options on the market, for example by shedding more light on the patent mine field that awaits some would-be competitors trying to enter the market.  However, it may take several years to see any impact, if at all, on the number of generic drugs and biosimilars entering the market.