Five Things Every Biotech Company Must Know About Biosimilars

The new US legislation will forever alter the commercial landscape for biologics.
Jun 01, 2010
Volume 23, Issue 6

Jonathan Harris
Healthcare reform has passed, and with it comes the long awaited establishment of an abbreviated pathway by which generic versions of branded biologics, often called follow-on biologics (FOBs), may obtain FDA approval. The legislation creating this pathway is one of the most significant developments affecting the regulatory and patent rights of biotech companies in US history, and, barring its reversal or repeal, will forever alter the commercial landscape for biologic therapeutics.


Initially, Congress considered three pieces of the FOB legislation:

  • Hatch-Enzi: introduced by Orinn Hatch (R-UT), Michael B. Enzi (R-WY), and Kay R. Hagan (D-NC) on July 13, 2009;
  • Eshoo-Barton: proposed by Anna Eshoo (D-CA), Joseph Barton, (R-TX), and Jay Insless, (D-WA) on July 17, 2009; and
  • Waxman: H.R. 1427, proposed by Henry Waxman, (D-CA) on March 11, 2009.

Most industry insiders characterized Hatch- Enzi and Eshoo-Barton as pro-innovator and Waxman as pro-generic. Hatch-Enzi, the only proposal to ultimately survive, passed with the healthcare reform bill.

There are five key things every innovator and generic company should know about this recently enacted legislation.


Notwithstanding that Senator Hatch had a hand in crafting Hatch-Enzi, he did not seek to recreate the Hatch-Waxman regulatory regime. In fact, Hatch-Enzi contains several differences from Hatch-Waxman.

First, Hatch-Enzi does not include a counterpart to the Approved Drug Products with Therapeutic Equivalence Evaluations or Orange Book. This means applicants for approval of FOBs have no ready access to a similar list of patents subject to regulatory patent infringement litigation. Although the Hatch-Waxman Act forbids Orange Book listing and subsequent regulatory litigation over methods of manufacture patents, which cover the steps for making drug products and formulations, no such bar exists under Hatch-Enzi. Thus, innovators may and likely will assert method of manufacture patents in FOB-related regulatory actions for patent infringement.

Second, Hatch-Enzi provides innovator exclusivity of at least 12 years, which is significantly longer than Hatch-Waxman. This critical difference will encourage innovators to stagger their patent protection and potentially delay generic FOB filings.

Third, under Hatch-Enzi, a 30-month litigation stay of FDA approval of FOB applications is unavailable, which will undoubtedly influence the timing and pace of regulatory litigation. If, on the one hand, innovator exclusivity is absent or nearing its end, innovators likely will file early motions for preliminary injunction to block FOB launch or seek to expedite the litigation to obtain favorable rulings before potential launch dates. On the other hand, if a substantial portion of the innovator exclusivity period remains, generic companies must strategically balance the possibility that an early court decision clears the path for launch after exclusivity expiration against the waiting period necessary to recapture the expense associated with early research and development efforts and litigation.


The absence of an Orange Book along with the nature of biologics will likely prompt innovators to create and maintain patent thickets as a way to fend off generic challenges. Without the Orange Book, innovators need not limit regulatory patent infringement litigation to patents covering their reference products. Furthermore, because the environment in which synthesis of active proteins occurs can lead to unwanted mutations in nucleotide sequences and breakdowns in biological processes, patents covering the various ways to make biologics might impair generic design-around efforts.

Innovators would, therefore, do well to pursue an extensive patent filing strategy. Patents covering methods of manufacture will become critical components in the innovator's arsenal for stemming the tide of generic competition. Evaluative methods, for example, methods for determining dissimilarities between active FOB proteins and the active proteins of reference products also may play an important role. Innovators can seek to use this information to defeat approval of pending FOB applications based on biosimilarity and interchangeability standards. Finally, innovators may wish to stagger design-around protection in an effort to block subtle changes in nucleotide sequences.

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