Congress enacted the Biologics Price Competition and Innovation Act (BPCIA) in 2009 to create a framework for the introduction of biosimilar and interchangeable drugs into the US market. Like the predecessor Hatch-Waxman Act, which regulates market entry of generic small molecule drugs, the BPCIA outlines a process whereby companies can gain an abbreviated approval of more complex protein-based drugs if the drug is highly similar to one already on the market. Four companies have announced submission of applications to the FDA for approval of their biosimilars. These include biosimilars for Neupogen (filgrastim) and Neulasta (peg-filgrastim), Remicade (infliximab) and Epogen (epoetin). On March 6, the FDA approved the first biosimilar, Zarxio (filtrastim).
For this first crop of biosimilars, a key issue has been the procedure for patent disputes. Both the Hatch-Waxman and BPCIA processes include a mechanism for the “copycat” drug to enter the market before the patents covering the original drug have expired. This process includes challenging and proving non-infringement, invalidity or unenforceability of the unexpired patents in federal court. The Hatch-Waxman process sets out a fairly short timeline whereas the BPCIA process is significantly longer.
The BPCIA provisions prescribe pre-litigation steps for the companies controlling the original biologic and the biosimilar to exchange product and patent information. This process can consume more than six months between the filing of the biosimilar application with the FDA and the start of patent litigation. The BPCIA also includes provisions for litigating some of the patents in an initial lawsuit and then addressing others through preliminary injunction and later litigations at 180 days prior to commercial launch of the biosimilar.
As the first biosimilars make their way through the system, this complex process has made for some false starts, particularly because biosimilar companies may file declaratory actions. In June 2013, the Northern District of California dismissed a declaratory action related to a biosimilar for Enteracept (enbrel) as premature because the action was brought before the biosimilar application was filed with the FDA, thus the applicant had not complied with the BPCIA framework. In a District of Massachusetts case involving a biosimilar of Remicade, the defendant brought a motion to dismiss the declaratory action on similar grounds and in October 2014, the biosimilar company voluntarily dismissed the case. Similarly, the Southern District of New York dismissed a declaratory judgment case against a third party holding patents related to a biosimilar antibody drug, reasoning that an actual case or controversy did not exist until the biosimilar company had completed the BPCIA process and entered the market.
In October 2014, a new ground of controversy arose in the biosimilar litigation arena. In a case involving a biosimilar of Neupogen, the biosimilar company refused to provide its FDA application and manufacturing processes to the company marketing the branded drug, asserting that these steps of the BPCIA were not mandatory. This issue is currently pending in the Northern District of California.
So, at almost five years out from the BPCIA’s enactment, is the process working as intended? These initial starts and stops and the complexity of the litigation process suggest that it may take some time before everything falls into place.