The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) established a framework for FDA approval of biosimilars. It also provided a system for litigation of patent disputes involving those products. Recently on November 19, 2020, FDA issued guidance entitled, “Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the Biologics Price Competition and Innovation Act of 2009”*.
The BPCIA requires that for approval a biosimilar must be demonstrably “highly similar to the reference product, notwithstanding minor differences in clinically inactive components.” There should also be “no clinically meaningful differences in terms of safety, purity, and potency.” The statute further provides that this standard can be met through analytical studies, animal studies, and clinical studies, with a focus on the assessment of immunogenicity. As Biologics are produced through natural processes or isolated from natural sources, any change in cell lines and variations in cell feed etc. can result in a product that varies both in structure and purity from the reference product. Moreover, multiple purification and stabilization requirements enhance the complexity of the process needed to produce an approved product.
Innovators are known to file multiple ‘follow-on’ patent applications to further extend a product’s patent protection. And few of them have become the master builder of patent-thickets. Some of the Biologic drugs are protected by 1000+ patents and/or pending patent applications, certain of these patent filings occur late in the life cycle of a drug product. Though the practice of creating a ‘thicket’ of patents is all across it is particularly problematic in the biosimilar space, as various aspects including processes for manufacturing, multiple indications, delivery methods, delivery devices, and aspects relating to side effects, impurities, etc. are covered in number of patents. Moreover, not all of these are listed in the Purple book and generic manufacturer have to struggle to understand the complete landscape.
A bill for Biologic Patent Transparency Act (S.659 and H.R. 4850**) was introduced in House last year which requires the holder of a license to market a biologic drug to disclose all patents believed to be covering that drug. The bill also directs the Department of Health and Human Services (HHS) to make such information publicly available.
The holder of a market approval license for a biologic product shall submit a list to HHS of all patents that the holder reasonably believes would be infringed by an unauthorized person making, using, offering to sell, selling, or importing that product. The license holder shall update HHS as to any relevant patents granted after the initial submission and as to listed patents that were later invalidated or rendered unenforceable.
If a patent that should have been listed was not timely disclosed to HHS, the patent holder may not sue for infringement of that patent.
HHS shall publish an easily searchable list of all biologics that have received market approval or for which an application for approval has been filed. The list shall contain information including (1) the official and proprietary name of the product, (2) the patents the license holder has listed under this bill, (3) whether various market exclusivity periods apply to the product, and (4) information about whether the product is interchangeable with another biologic product.
In Humira® (Adalimumab) class action lawsuit the practice of establishing so called patent-thickets for biologic products has been questioned as a potentially abusive way of preventing biosimilar competition. In this lawsuit AbbVie was accused of violating federal antitrust laws, state antitrust laws, and consumer protection laws regarding Humira®. The Plaintiffs, who were indirect purchasers of Humira®, alleged that AbbVie obtained and asserted patents to gain power to elbow its competitors out of and maintain its position in the U.S. Humira® market. Plaintiffs further alleged that AbbVie repeatedly and aggressively asserted “swaths of invalid, unenforceable, or non-infringed patents without regard to the patents’ merits.”
The Court order stated that the alleged anticompetitive conduct described by Plaintiffs was not an antitrust violation. “AbbVie has exploited advantages conferred on it through lawful practices and to the extent this has kept prices high for Humira® [adalimumab], existing antitrust doctrine does not prohibit it.”
Though the Humira® “patent thicket” antitrust case was dismissed by the Court, the Biologic Patent Transparency Act proposal (must be passed by both the House and Senate in identical form and then be signed by the President to become law) if sees light of the day, may drain the swamp.
*The question and answer (Q&A) format is intended to inform prospective applicants and facilitate the development of proposed biosimilars and proposed interchangeable biosimilars, as well as to describe FDA’s interpretation of certain statutory requirements added by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). This draft guidance document provides new Q&As. It does not replace the draft guidance document entitled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2),” issued December 12, 2018.
**“H.R. 4850 — 116th Congress: Biologic Patent Transparency Act.” www.GovTrack.us. 2019. November 21, 2020 https://www.govtrack.us/congress/bills/116/hr4850