Back in February  2012, the U.S. FDA had released three draft guidance documents related to implementation of the Biologics Price Control and Innovation Act of 2009 (BPCIA). The guidance addressed questions regarding implementation of biosimilars, scientific considerations in demonstrating biosimilarity, and quality considerations. Since that time, many new questions have emerged, including issues around IP and biosimilar patents.
 
The ACI’s 6th Annual Summit on Biosimilars this past June included the panel “Following the Rules of the BPCIA: A Cheat Sheet for Managing the Complicated Timing and Logistics of the Statutory IP Exchange Process.” The session provided an overview on several topics, including making the decision to navigate the pathway comparing and contrasting the biosimilars pathway under the statute to 505(b) (2) and BLA pathways including timing, costs, IP litigation considerations, and exclusivities; exploring the implications of the new “Purple Book” listing biologics that may serve as reference products for biosimilars and interchangeable; and understanding the importance of Patent Term Extension in a biosimilars scenario.
 
Siegmund (“Sige”) Gutman, chair of the Life Sciences Patent practice with Proskauer Rose LLP participated in the panel. Sige discusses the key takeaways from this panel highlighting issues and concerns, and how best to address them. –KB
 
Contract Pharma: Please summarize the key issues and concerns from the panel “Following the Rules of the BPCIA: A Cheat Sheet for Managing the Complicated Timing and Logistics of the Statutory IP Exchange Process.”

Siegmund Gutman: The overarching issue addressed by the panel is how reference product sponsors and biosimilar developers alike should deal with the legal uncertainties surrounding the BPCIA, given its complexity and the fact that the courts have not had many opportunities to consider it. That said, the courts have begun to answer questions surrounding the BPCIA and its application.

For example, in a case between Amgen and Sandoz—which has not yet been decided as of July 14—the U.S. Court of Appeals for the Federal Circuit is considering whether the BPCIA’s so-called “patent dance” is mandatory or whether biosimilar developers may “opt” out of it. Additionally, the courts have considered whether a biosimilar developer may challenge a patent by filing a declaratory judgment action before filing an application with FDA. On this question, the courts have thus far not allowed a biosimilar developer to do so. Perhaps in view of this, some biosimilar developers have sought to challenge patents in administrative proceedings before the U.S. Patent and Trademark Office, e.g., through inter partes reviews.     

CP: What are the key issues around IP and biosimilar patents?

SG: One issue is how to challenge patents that may cover various aspects of a biosimilar product, including, for example, its active ingredient that may be an antibody or protein, formulations, methods of use, and methods of manufacture. As discussed above, one of the ways in which biosimilar developers have challenged patents is through the use of administrative patent office proceedings, such as inter partes reviews.

CP: How is the legal system currently supporting both innovation and competition?

SG: One way is by providing different mechanisms that can address both innovation and competition.  For example, Congress can pass a law that takes into account both innovation and competition, and the courts can construe the law in a way that takes into account Congress’s intent. Various aspects of the BPCIA, passed by Congress in 2010, are now making their way through the legal system.

CP: What are the concerns with Federal and State biosimilars substitution laws?

SG: Some have expressed the view that biosimilar substitution laws must, for example, allow for the reporting of any adverse events that may be associated with a particular product and notification to the patient’s physician of which product has been dispensed. Others hold the view that certain biosimilar substitution laws may decrease substitution by and uptake of biosimilars. 

CP: What are some of the regulatory, pricing, and safety lessons learned so far with biosimilars?

SG: The lessons learned to date are limited. FDA has so far approved only one biosimilar, Sandoz’s Zarxio, which has not yet been launched. Zarxio is a recombinant protein and not a monoclonal antibody, so it is unclear whether any lessons learned from FDA’s approval of Zarxio can be extended to other types of biosimilars. Additionally, it recently has been reported that Hospira obtained a public contract in France by offering prices for its biosimilar to Remicade that amounted to a 45% discount. 
  
CP: How does the 505(b)(2) abbreviated pathway work? What are the concerns/benefits?

SG: According to FDA, a 505(b)(2) application “is one for which one or more of the investigations relied upon by the applicant for approval ‘were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted,’’’ citing 21 U.S.C. 355(b)(2). Examples of information that a 505(b)(2) applicant can rely on that is “not conducted by or for the applicant and for which the applicant has not obtained a right of reference” include published literature and FDA’s previous finding of safety and effectiveness for an approved drug. 505(b)(2) applications can be used for, among other things, changes to dosage form, strength, and route of administration, and substitution of an active ingredient in a combination product. 

As stated by FDA, “the filing or approval of a 505(b)(2) application may be delayed due to patent or exclusivity protections covering an approved product. Section 505(b)(2) applications must include patent certifications described at 21 CFR 314.50(i) and must provide notice of certain patent certifications to the NDA holder and patent owner under 21 CFR 314.52.”  On the other hand, an approved 505(b)(2) application may itself be entitled to its own exclusivity. FDA explains that “a 505(b)(2) application may itself be granted three years of Waxman-Hatch exclusivity if one or more of the clinical investigations, other than BA/BE studies, was essential to approval of the application and was conducted or sponsored by the applicant…A 505(b)(2) application may also be eligible for orphan drug exclusivity…or pediatric exclusivity.” For biosimilars, the 505(b)(2) approval pathway is available for a limited range of biologics that had been previously approved under a New Drug Application (NDA).

Siegmund (“Sige”) Gutman is chair of the Life Sciences Patent practice, a partner in the Litigation Department, and a member of the Patent Law and Intellectual Property Groups with Proskauer.
 
The views expressed do not represent the firm or any of its clients and is not intended to offer legal advice.

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Kristin Brooks has been Associate Editor at Contract Pharma since 2004.