Biosimilars are biologic drugs that are similar to an already established “reference” or “innovator” biologic drug product and can be manufactured when an original biologic drug product’s patent expires. Reference to the innovator product is an integral component of approval for a biosimilar. The U.S. Food and Drug Administration (FDA) requires licensed biosimilar and interchangeable biologic products to meet the agency’s rigorous standards of safety and efficacy.
Laws and Definitions
According to the FDA,1 a biologic product may be demonstrated to be biosimilar if data show that, among other things, the product is “highly similar” to an already-approved biologic product. The biosimilar also must show it has no clinically meaningful differences from the innovator product in terms of safety and effectiveness. Only minor differences in clinically inactive components are allowable in biosimilar products.
The Affordable Care Act amended the Public Health Service Act to create an abbreviated licensure pathway for biologic products that are demonstrated to be “biosimilar to” or “interchangeable with” an FDA-licensed biologic product. This pathway is provided in the part of the law known as the Biologics Price Competition and Innovation Act.
A phrase used to describe the biosimilar creation—“the process is the product”—illustrates that it is critical to understand the biosimilar development process.2 Biosimilars are derived from many sources, including humans, animals, microorganisms, or yeast. Some, such as blood cells or stem cells, are extracted from living beings. Others are produced using advanced genetic technology. If the host cells, cell culture process, or purification methods are different, there may be clinically significant alterations in the safety and effectiveness of the drug.
Regulatory Guidance
Recently, the FDA clarified its views through regulatory guidance. The FDA suggested that manufacturers of biosimilar drug products would be allowed to extrapolate innovator data to support the approval of all indications the branded product is approved for. While they may reduce the overall resources required in bringing a biosimilar to market, other aspects of the guidance were not as favorable to these stakeholders. The guidance also suggested that the FDA does not believe the current technology is evolved enough to truly establish the interchangeability of a biosimilar with a branded product.3
The World Health Organization has stated, “The approach established for generic medicines is not suitable for development, evaluation, and licensing of similar biotherapeutic products since biotherapeutics consist of relatively large and complex proteins that are difficult to characterize.”4
Indeed, biosimilars are not generics. “It is important to note that a biosimilar is not just like a generic drug,” according to Leah Christl, PhD, Associate Director for Therapeutic Biologics in the FDA’s Office of New Drugs. “Because of the differences in complexity of the structure of the biologic and the process used to make a biologic, biosimilars are not as easy to produce as generics, which are copies of brand-name drugs.”5
Thus, uncertainties about interchangeability and their implications for biosimilar development remain to be resolved. In the meantime, federal regulators are charged to determine whether a biosimilar product is sufficiently similar clinically to an innovator biologic drug to merit the same approval for use.
Cost Considerations
Questions about interchangeability aside, it is predicted that biosimilars will save patients money. Biosimilars are expected to save $13 billion over the next 10 years, according to the Congressional Budget Office. The initial promise of biosimilars was that they would save patients 30% to 40%. (As a point of reference, generic drugs, which have 85% of the U.S. pharmaceutical market, cost about 80% to 85% less than their corresponding brand-name products, according to the FDA.3)
Unfortunately, bringing biosimilars to market is proving far more complex than anticipated, and therefore, 10% to 20% less than the cost of the branded medication is a more reasonable expectation. In Europe, biosimilars have often been associated with only a 10% discount from the brand-name product.3
Express Scripts, a pharmacy benefits manager, has stated that biosimilars will provide $250 billion in U.S. health-care savings over the next decade if 11 biologics gain biosimilar competition,6 but the RAND Corporation projects much lower savings—about $44 billion—from the introduction of biologics.7
Another class of new biologic drugs is called “biobetter drugs.” A biosimilar drug is a mere structural imitation; a biobetter drug possesses some molecular modification that constitutes an improvement over the original innovator drug. Such improvements may range from a longer half-life (allowing for less frequent dosing) to more potency with less toxicity. Biosimilar drugs and biobetter drugs offer the very real possibility of quality alternatives and even enhanced treatments at better prices.
More Key Issues
Another important question is, will biosimilar drugs stymie innovation in research and development? Clearly, there must be a return on investment for original biologic medication, and it can take hundreds of millions of dollars to prove a drug’s efficacy and bring it to market. The cost of discovery is staggering, but the cost of copying, even though biosimilars are not chemically exact copies, is significantly less.
There must be a balance between encouraging the development of new, lifesaving, or life-improving drugs and their cost. Whether biosimilars will help in achieving such balance remains to be seen. ■
Disclosure: Dr. Boxer reported no potential conflicts of interest.
References
1. U.S. Food and Drug Administration: Biosimilars. Available at www.fda.gov. Accessed June 23, 2015.
2. Thelwell C, Longstaff C: Biosimilars: The process is the product. The example of recombinant streptokinase. J Thromb Haemost 12:1229-1233, 2014.
3. Howell P: How much cheaper will biosimilars be? March 2, 2012. Available at www.fiercepharma.com. Accessed June 23, 2015.
4. Expert Committee on Biological Standardization: Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs). Geneva, Switzerland, World Health Organization, 2009. Available at www.who.int. Accessed June 23, 2015.
5. U.S. Food and Drug Administration: Biosimilars: More treatment options are on the way. March 6, 2015. Available at www.fda.gov. Accessed June 23, 2015.
6. Milman J: The cheaper cancer drug that could pave the way for much more affordable medicine. The Washington Post. January 5, 2015.
7. RAND Corporation: Biosimilar medications could create billions in health care savings. November 3, 2014. Available at rand.org. Accessed June 23, 2015.
Dr. Boxer is Visiting Professor of Urology and Scholar in Residence (Business of Science Center) at the David Geffen School of Medicine at UCLA. He is also Professor of Clinical Urology at the University of Wisconsin–Madison.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO.
