Biosimilars: The Need, The Challenge, The Future

The FDA Perspective

Michael S. Epstein MD, FACG, AGAF; Eli D. Ehrenpreis, MD; Prasad M. Kulkarni MD, FACG


Am J Gastroenterol. 2014;109(12):1856-1859. 

In This Article

The Biosimilar Industry

The pharmaceutical industry's biologics segment began in the 1980s with recombinant versions of endogenous human molecules (i.e., hormones and enzymes) and has evolved to develop more complex products such as mAb. Aptly named 'blockbuster drugs', mAbs have accounted for as much as 19% of the global pharmaceutical market and exceeded $140 billion in sales in 2011. The top 10 revenue-generating drugs in 2011 were Humira, Enbrel, Remicade, Rituxan, Avastin, Lantus, Herceptin, NovoLog, Neulasta, and Lucentis.[12]

The development of biosimilars (also known as follow-on or subsequent entry biologics) was a consequence of the financial success of the biologic therapies and their inevitable ''patent cliff''—a marked drop in sales as they near the expiration of their original patents. The complexity of the structure and the developmental process of biologics make their ''patent cliff'' different from that of chemically synthesized drugs.[13] The BPCI Act provides for 12 years of non-patent market exclusivity for licensed reference products, and this may be extended by 6 months of pediatric exclusivity.

As a result of recent technological innovations, new regulations in the biopharmaceutical industry, and cost concerns, the idea of biosimilars has gathered support.[14] In fact, efforts are already underway to develop a new class of follow-on biologics named ''biobetters'' or ''biosuperiors'', which go beyond mimicking the original biologic to provide improvements through changes in chemistry, alteration in the formulation, and innovative delivery.[15]

The biosimilar industry in the United States has gained momentum more slowly than that in Europe.[16] The EMA (European Medicines Agency) approved its first biosimilar in 2006, a biosimilar version of Amgen's Neupogen in 2010,[17] and the first mAb (Inflectra, a biosimilar of Remicade (infliximab)) in 2013.[18] The FDA has not yet approved a biosimilar under BPCI. However, several large biopharmaceutical companies including Merck BioVentures have intentions to market biosimilars.[19]

Of the 14 or so true biosimilars licensed in Europe, nearly all fall into three biologic analogs: somatropin, epoetin alfa, and filgrastim (Table 2). Most drugs approved to date consist of relatively small molecules. The pharmaceutical industry, although excellent at manufacturing generic versions of small-molecule chemical drugs and small-molecule biosimilars, has demonstrated limited ability in creating large-molecule complex biosimilars that are a perfect copy of their reference product in terms of their size, molecular weight, and three-dimensional structure. This is bound to make regulatory authorities like the FDA put the complex biosimilars through prolonged and rigorous scrutiny. If this happens, it is likely to defeat the very reason why biosimilars were developed in the first place.[20,21] The speed and integrity with which the biosimilar industry meets this challenge will decide its fate in the long run.