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The Federal Circuit’s Recent “Safe Harbor” Ruling Could Impact Biosimilars Drug Development
By: Christine Norris
A recent Federal Circuit case, Momenta v. Amphastar, involves the Hatch-Waxman 271(e)(1) safe harbor, and is rousing the biologics and biosimilars industry. In particular, the court held in Momenta, that section 271(e)(1) does apply to certain post-approval activities.
As background, Momenta Pharmaceuticals, Inc. and Sandoz Inc. filed for a preliminary injunction against Amphastar Pharmaceuticals, Inc., International Medication Systems, Ltd., Watson Pharmaceuticals, Inc. and Watson Pharma, Inc. in the U.S. District Court for the District of Massachusetts alleging infringement of U.S. Patent No. 7,575,886. The ‘886 patent generally claims processes for analyzing heterogeneous populations of sulfated polysaccharides. Momenta alleged that Amphastar infringed the claimed processes when developing and manufacturing of batches of generic Lovenox (enoxaparin), a low-molecular-weight complex polysaccharide, for commercial sale. (Momenta used the claimed processes to gain approval of its own generic enoxaparin one year earlier.) The district court granted Momenta a preliminary injunction, concluding that Amphastar’s testing falls outside the scope of the safe harbor.
Momenta appealed the decision to the Federal Circuit, which held that Amphstar’s activities fell within the safe harbor provision, even if (1) the alleged infringement took place after FDA approval and (2) the derived information was not submitted to the FDA. The Court distinguished this case from Classen v. Biogen IDEC, which involved post-marketing studies to determine the relationship between the timing of childhood vaccinations and the risk of developing certain immune-mediated disorders. The Court in Momenta stated that
[t]his case, however, fits well within Classen because the information submitted is necessary both to the continued approval of the ANDA and to the ability to market the generic drug. Here, the submissions are not “routine submissions” to the FDA, but instead are submissions that are required to maintain FDA approval. . . . Failure to comply with these requirements could result in suspension or revocation of Amphastar’s ANDA approval to market the drug.
We also note that, unlike in Classen where the patented studies performed were not mandated by the FDA, the information here is not generated voluntarily by the manufacturer but is generated by FDA requirements the manufacturer is obligated under penalty of law to follow. Under such circumstances, the information can be said to have been gathered solely for submission to the FDA and not, as in Classen, primarily for non-FDA purposes…
The facts in Momenta raise deep concerns in the biosimilars community. FDA approval of a generic “biosimilar” product using the new abbreviated Biosimilars pathway requires a demonstration of “biosimilarity” between a previously approved “reference product” and a follow-on “biosimilar” product. The FDA is still in the process of interpreting and providing guidance for the biosimiliarity requirements created by the Biologics Price Competition and Innovation Act of 2010. However, it is important to note that the FDA’s “sameness” requirements at issue in Momenta are similar to the FDA’s draft requirements for a demonstration of biosimiliarty.
Unlike small-molecule pharmaceuticals, biologics are complex macromolecules whose safety and efficacy is highly dependent on manufacturing processes. Given the complex nature of biologics, biosimilarity can be difficult to determine and can vary greatly on a product by product basis. A Biosimilar Applicant may undertake significant research to develop complex compliance testing and innovative analytical technologies, much like Momenta’s claimed invention. Patents covering such manufacturing processes, compliance monitoring technologies and other platform technologies are also likely to play a key role in biosimilars litigation. Momenta’s expansive interpretation of the 271(e)(1) safe harbor may create a disincentive for the biotech community to invest in and patent analytical technologies, if not other biologics innovations.
It is important to note that Classen v. Biogen IDEC is up on appeal to the U.S. Supreme Court, which has asked for the U.S. solicitor general to weigh in. The conflicting rulings in Classen and Momenta may further prompt the justices to take the case and resolve the dispute over the scope of 271(e)(1) safe harbor. In the meantime, the biosimilars abbreviated approval pathway is available for use. The FDA has received numerous preliminary investigational new drug (PIND) meeting requests, held PIND meetings with sponsors; received several INDs.
Questions or Comments? Click to Contact Christine Norris
Are Biosimilars the Next Generation of Small Drug Manufacturers?
By: Leslie Tector
New reports suggest that while generic drug makers are aggressively consolidating in the United States and United Kingdom, smaller generic drug manufacturers’ viability is threatened, forcing them to seek niche therapeutic areas. Manufacturing biosimilar biologicals may be an answer for the smaller generic drug companies, due to several factors. First, while manufacturing complexities create market entry barriers, recent shortages of the biologics supply in the U.S. have increased the market demand. Also, low margins are causing large manufacturing companies to exit the biologics market. Furthermore, the patents for many top selling biologics will expire in the next 3 to 5 years, creating an opportunity for new market entrants. Finally, the new abbreviated approval pathway for biosimilars in the U.S. may be more conducive to the needs of smaller firms: efficient approval process, lower development costs, and protection for first generation biologics.
Background
In an effort to encourage biosimilar innovation, the Patient Protection and Affordable Care Act (“PPACA”), passed in 2010, amended the Public Health Services Act, providing an abbreviated marketing approval pathway for biosimilar biologics. According to the PPACA, biosimilar biologics are products that are similar to biologics previously approved by the U.S. Food and Drug Administration (“FDA”), and which have no differences in safety, purity and potency, in comparison to the originator biologics.
Prior to the passage of the PPACA, in the U.S. there was no abbreviated process specifically dedicated to follow-on biological products that allowed for an applicant to rely on safety and efficacy information of previously FDA approved biologics. In the past, the abbreviated approval process available for manufacturers of biologics was under the Food Drug and Cosmetic Act (“FDCA”), and was applicable only to a small subset of biologics regulated as drugs under the FDCA. However, the abbreviated new drug approval pathways have proven to be burdensome and difficult for biologics manufacturers to use, due to the differences in the properties of chemical drug products and biologics.
Under PPACA, the new abbreviated approval process for follow-on biologics sets forth general approval requirements, as well as requirements to show that the biosimilar is “interchangeable” with the predecessor biologics. Furthermore, the FDA has the ability to waive data submission requirements related to analytic, animal and chemical studies. In addition, time frames have been established as to when a follow-on biologic application can be considered, following the approval of the original reference biologic. The PPCA also extends the exclusivity period by 6 months for biologics that receive marketing approval for treatment of pediatric populations, which again may encourage development for the pediatric treatments. For follow-on biologicals that are “interchangeable” with the reference products, a one-year exclusivity right is granted to the first generation biosimilar, with time periods built-in to that, in the case of a patent dispute.
Most recently, separate legislation provides for implementation of biological product user fees, to allow for increased resources for faster review by the FDA. Only time will tell whether the new abbreviated pathways will help or hinder the smaller firms that specialize in this niche area.