By: Davidta Brown, Senior Staff Editor
In 21st century medicine, pharmaceuticals have come to include compounds derived through novel and complex methods. Some of the most recent innovations have been in the form of biologics, therapeutic compounds produced through biological processes.1 Biologics are derived from living cell lines which may be bacterial, yeast, animal, or human in nature.2 The applications of these treatments are wide in range; biologics have been employed as therapies for rheumatoid arthritis, multiple sclerosis, and various forms of cancer.3 Since insulin became the first biologic to be approved by the FDA in 1982, a wave of biologically derived molecules entered the pharmaceutical market through the 1980s and 1990s.1 The coming years mark the expiration of the patents of many of these innovative biologics, creating a manufacturing opportunity that is familiar in several respects, and original in many others.
With the patent expiration of the original biologics comes the creation of a market for other manufacturers to produce similar therapies, just as the expiration of the patent on a brand name drug provides an opportunity for other companies to offer a generic. The term “biosimilar” implies a relationship between two substances that is analogous to that between a branded and a generic product. However, unlike generic drugs, biosimilars are not produced through chemical synthesis, and so it is virtually impossible to ensure a compound that is structurally identical to the original biologic.1 The impending flood of competition in the biologics market, as well as an international push for more affordable healthcare, brings into focus these and other qualities that distinguish biosimilars from generics and makes their increased prevalence a unique prospect.2
Potential manufacturers of biosimilars may face production difficulties due to the distinctness of biological compounds. Much like during the introduction of the first biologics, manufacturers must invest significantly in the analysis of these large and complex molecules. The original biologic and the resulting biosimilar must both be characterized structurally, which is no easy feat.1 This and all the other stages of the biosimilar production process contribute to steep manufacturing costs that may effectively drive pharmaceutical companies away from the industry.3
For years, the structural dissimilarity between biosimilars and their original compounds has presented difficulties in establishing FDA approval protocols. The traditional Abbreviated New Drug Application is for generics that are essentially indistinguishable from the brand name drug in active ingredient and clinical behavior. With the exception of the few biosimilars that have been approved under the Hatch-Waxman Act, as generics similar but not identical to their reference product, biosimilars have had no abridged pathway for approval, a significant roadblock for any potential manufacturer.1
Fairly recent legislation, specifically an amendment to the Public Health Service Act, intends to address this regulatory conflict by creating an abbreviated pathway for the approval of biosimilars, as long as manufacturers provide data proving that the originator drug and the biosimilar have no clinically significant differences in safety, purity, or potency.4 The revisions, which were included in the Affordable Care Act of 2010 and which are referred to as the Biologics Price Competition and Innovation Act (BPCI Act), share an objective with the Hatch-Waxman Act by welcoming competition in the biosimilar market.4 Of clinical relevance, the legislation also establishes standards for the classification of “similarity” between follow-on biologic and original. According to the guidelines, in order for a compound to be deemed biosimilar, it must not possess any biological or clinical differences from its original counterpart, although its chemical features may vary. 2
The lack of structural homogeneity between biosimilar and biologic also presents a conflict in naming new biosimilars, since the International Nonproprietary Name system currently used for generics could lead to the same name being used for structurally distinct compounds.3 A universal naming system for biosimilars is critical to Phase IV post-marketing studies of biosimilars. Slight differences in the structures of related biosimilars may translate to notable clinical differences, and the exact compound given to each patient must be recorded.3 The debate as to the most appropriate system for naming follow-on biologics is ongoing.
Of specific concern to clinicians is the therapeutic interchangeability of the biosimilar compound and the original biologic. Physicians, community pharmacists, and Pharmacy & Therapeutics (P & T) committees need to be assured that exchanging one biosimilar for another will not compromise safety or efficacy.1 The BPCI Act also seeks to address this concern by establishing high standards for therapeutically interchangeable biosimilars. Manufacturers of the interchangeable treatments must prove that their compounds can produce the same results as the reference biologic in a randomized sample of the population, and that there is little to no risk in switching between original and biosimilar.4
While many favor the increased manufacture of biosimilars to bring more treatment options to the market and lower healthcare costs, opposition to the idea has been presented by several biotechnology manufacturers and their lobbyists.5 These voices of dissent are often the producers of the original biologics soon to go off patent, for whom the increased competition means loss of business and reduced recovery of the investments made in research and development. As the major source of innovation in the pharmaceutical industry, whether of biologics or traditional drugs, it is important that manufacturers find sufficient incentive to invest in new treatments. The patent system helps to ensure that innovators are rewarded for their creativity and effort. However, some biologic manufacturers have sought to defend their interests with legislature as well. In order to maintain some market exclusivity, they apply their influence to state government in the hopes of creating laws that would conflict with the provisions of the ACA.5 Only time can tell how these lobbying efforts will affect the growing biosimilar industry.
As is to be expected with the introduction of any new treatment, the most overarching apprehensions to the flood of biosimilars soon to enter the healthcare field are related to their unfamiliarity. Physicians and pharmacists could reasonably be skeptical of their clinical efficacy in comparison to biologics, and patients comfortable with their medications may be hesitant to switch to something with a different name or from another manufacturer, even if it’s more cost effective. However, in most respects, increased competition in the field of pharmaceuticals is not a wholly foreign experience. The same decision-making principles that have been applied by pharmacists, physicians, and P & T committees when exchanging generics for branded drugs could also be used for biosimilars and biologics. If anything, the new change can be welcomed as an opportunity to see if the lessons of the past can be applied to the future and if innovation finds a warmer reception the second time around.
- Gebhart F. Preparing for biosimilars. Drug Topics: Voice of the Pharmacist. Available from: http://drugtopics.modernmedicine.com/drug-topics/news/preparing-biosimilars. Published July 2013. Accessed January 29, 2014.
- Cai XY, Wake A, Gouty D. Analytical and bioanalytical assay challenges to support comparability studies for biosimilar drug development. Bioanalysis. 2013; 5:517-520
- Farfan-Partet MI, Gerkens S, Lepage-Nefkens I, Vinck I, Hulstaert F. Are biosimilars the next tool to guarantee cost-containment for pharmaceutical expenditures? Eur J Health Econ. 2013. doi: 10.1007/s10198-013-0538-4
- US Food and Drug Administration. Implementation of the Biologics Price Competition and Innovation Act of 2009. Available at: http://www.fda.gov/Drugs/GudianceComplianceRegulatoryInformation/ucm215089.htm. Accessed January 30, 2014.
- PCMA, NCPA blast biosimilars legislation. Drug Topics: Voice of the Pharmacist. Available from: http://drugtopics.modernmedicine.com/drug-topics/news/user-defined-tags/biosimilars/pcma-ncpa-blast-biosimilars-legislation. Published February 2013. Accessed January 30, 2014.