Interpreting the BPCIA – Is the “Patent Dance” Mandatory?

Background

Biologics are a type of therapeutics derived from, or made by, the biological processes of a living organism, such as human cells, animals, microorganisms, or yeast.1 Examples of biologics include some vaccines, blood or blood components, hormones, and antibodies. Unlike standard chemical drugs, which are relatively small molecules, biologics are often large and complex molecules that are not easily produced through synthetic manufacturing pathways. Due to their production mechanism, it is difficult to create biological products that are exactly identical to the the biologic therapeutic molecule that has already received FDA approval, known as the reference molecule or reference product.

The Biologics Price Competition and Innovation Act (BPCIA), or Bio-similars Act, was enacted on March 23, 2010, as a component of the Patient Protection and Affordable Care Act. The Bio-similars Act was designed to create an abbreviated approval pathway for producers of biological products that are known to be sufficiently bio-similar, or interchangeable, with a therapeutic biological product that has already been approved by the FDA.2  These products need to be highly similar to an already approved biological product; however, they do not need to be identical.3 Minor differences in clinically inactive components are allowable in bio-similar products.4 By contrast, the Hatch Waxman Act, which provides an abbreviated approval pathway for generic drugs, applies only to chemical drugs, which must be both functionally and molecularly identical to the original drug.5 The purpose of the Bio-similars Act is to reduce the price of biologics, encouraging the development of competitive bio-similars. As the act allows producers to rely on the studies, clinical trials, and data completed by the reference product producer, bio-similars are expected to retail at approximately 20-30% less than their reference molecule counterparts, helping the U.S. save an estimated $250 billion per year on healthcare costs.6

The European Union developed a framework for bio-similar approval by 2006, and the European Medicines Agency has since approved 21 bio-similar drugs.7

The bio-similar approval process has been slower in the United States – the first bio-similar drug was approved on March 6, 2015, for Zarxio, produced by Sandoz.8 Zarxio is bio-similar to Neupogen, produced by Amgen.9 Neupogen stimulates proliferation and differentiation of white blood cells, and was originally approved in 1991.10 However, the approval of Zarxio has been subject to immediate litigation. As biologics are expensive to research and produce, producers of reference therapeutics have strong interests in protecting their exclusive rights to market their therapy for as long as possible. These initial decisions will shape the bio-similar market in the US, and as such, will likely be heavily contested.

The Amgen-Sandoz Fight

The BPCIA, along with the abbreviated approval process, introduced a scheme for resolving patent disputes for bio-similar products. Commonly referred to as the “patent dance”, 42 U.S.C. §262(l) creates a schedule whereby the bio-similar applicant and the reference product sponsor exchange information regarding the application for the bio-similar; in particular, the parties exchange information regarding patents that may be the subject of litigation regarding the proposed bio-similar product.11 This information exchange may then culminate in two rounds of litigation: an “immediate patent infringement action” on agreed-upon patents, followed by a second round when the bio-similar applicant gives notice to the reference product producer “not later than 180 days before the date of the first commercial marketing” of its proposed bio-similar.(42 U.S.C. §262(l)).12  Once the reference product sponsor receives notice of commercial marketing, it may seek a preliminary injunction on any patents that it identified during its information exchanges with the applicant.12

The FDA accepted Sandoz’s application in July 2014. At that time, Sandoz wrote to Amgen that it would not participate in the “patent dance”, and, importantly, claimed that this letter served as notice of commercially marketing the product, therefore (according to Sandoz) starting the 180 day clock for commercial marketing of the bio-similar.13

Amgen immediately filed a motion in the District Court for the Northern District of California for a preliminary injunction to stop Sandoz from commercially launching Zarxio (licensed by the FDA on March 6, 2015), arguing that Sandoz failed to comply with the requirements of the BPCIA, and should therefore be enjoined from entering the market with its bio-similar version of Neupogen.14 Amgen additionally sought an order to compel Sandoz to comply with the “patent dance” provisions, and a declaratory judgment that Sandoz could not provide notice of commercial marketing until the FDA approved the product.

Is the “patent dance” mandatory?

Amgen argued that the patent dance provisions are mandatory, citing to language like “shall” and “required” in each of the steps the parties would take under §262(l). However, Judge Seeborg found that the BPCIA is an optional safe harbor for applicants, and “contain[s] no stick to force compliance”, should that bio-similar applicant choose the potential of immediate litigation. 15

Of particular importance, Judge Seeborg found that the 180-day notice provision is not dependent on approval of the bio-similar by the FDA, stating that “had Congress intended to make the exclusivity period [180 days longer], it could not have chosen a more convoluted method of doing so.” 16

Given that this statutory interpretation is an issue of first impression before the court, and the extraordinary importance of the notice provisions under the BPCIA in determining the length of a reference product holder’s monopoly, an appeal will likely follow.

  1. U.S. Food and Drug Administration, FDA approves first bio-similar product Zarxio, FDA.GOV,  (March 6, 2015), http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm
  2. U.S. Food and Drug Administration, Bio-similars, FDA.GOV,  (March 25, 11:00 pm), http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/default.htm.
  3. Id.
  4. Id.
  5. David Fazzolare, Obtaining Early Bio-similar Patent Certainty in the Aftermath of Sandoz v. Amgen, mbbp.com,  (March 25, 11:00 pm), http://www.mbbp.com/resources/iptech/biosimilar-patents.html.
  6. Carly Helfand, Novartis gets bragging rights on first U.S. biosim. But will its Neupogen copy sell?, fiercepharma.com,  (March 6, 2015), http://www.fiercepharma.com/story/novartis-gets-bragging-rights-first-us-biosim-will-its-neupogen-copy-sell/2015-03-06.
  7. Generics and Bio-similars Initiative, Bio-similars approved in Europe, gabionline.net,  (February 27, 2015), http://www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe.
  8. U.S. Food and Drug Administration, FDA approves first bio-similar product Zarxio, FDA.GOV,  (March 6, 2015), http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436648.htm
  9. Id.
  10. Id.
  11. Elaine Blaise, Order in Amgen v. Sandoz Provides First Judicial Interpretations of the BPCIA Patent Dispute Resolution Provisions, jdsupra.gov,  (March 20, 2015), http://www.jdsupra.com/legalnews/order-in-amgen-v-sandoz-provides-first-65848/.
  12. Id.
  13. Id.
  14. Thomas Wintner, District Court Rules Against Amgen’s Motion for Preliminary Injunction to Prevent Marketing of Sandoz’s Bio-similar Zarxio, globalipmatters.com,  (March 20, 2015), http://www.globalipmatters.com/2015/03/20/district-court-rules-against-amgens-motion-for-preliminary-injunction-to-prevent-marketing-of-sandozs-biosimilar-zarxio?utm_source=Mondaq&utm_medium=syndication&utm_campaign=View-Original.
  15. Amgen v. Sandoz, No. 14-cv-04741-RS (N.D. Cal. Mar. 19, 2015).
  16. Id.

Comments are closed.