A biosimilar is defined by the FDA as an agent which analytical studies demonstrate as being highly similar to the reference product notwithstanding slight differences in clinically inactive components.¹ It is particularly compelling that over 30 branded biologics—representing more than $50 billion in sales—will lose patent exclusivity between 2011 and 2015.² As a result, and including other factors, the development of biosimilars is expected to grow more than 20% per year moving forward.³ In large part, this growth will be fueled by the introduction of new biopharmaceuticals that target larger patient populations in the presence of competitor medicines, the pressures of increasing reimbursement coverage from payers, and the desire to enhance patient access by reducing high out-of-pocket costs.

The Biologics Price Competition and Innovation Act (BPCIA) was passed as part of the Patient Protection and Affordable Care Act (PPACA) in part to establish an abbreviated regulatory and licensure pathway for biological products with provisions covering exclusivity periods and payments for biosimilars. Similar to the manner in which the Hatch-Waxman Act created an abbreviated drug approval pathway for small molecule drugs (generics) in 1984, the BPCIA is intended to provide a pathway for biosimilar drug approval; however, biologics, and therefore biosimilars, are larger and much more complex entities than small molecule drugs. Furthermore, along with introducing a biosimilar medication approval pathway, the BPCIA also established a 12-year market exclusivity period for biologic products, which served as an important step in paving the way for biosimilars given the long-standing debate between reference biologic makers and generic drug manufacturers regarding exclusivity rights. 

In a recent study of institutional and managed care pharmacists, we found that although biosimilars are generally viewed as having significant potential to provide easier access to treatment, uncertainties remain regarding the value of similar, but not identical, biologic therapies from a safety, efficacy, and overall quality of care perspective.

Gathering Practitioner Opinions
In order to gain a better understanding of how biosimilars are perceived by practicing pharmacists in various health care settings, we developed a survey as part of our post-doctoral fellowship. With help from our fellowship director and current acting dean of the Rutgers Ernest Mario School of Pharmacy, Dr. Joseph Barone, PharmD, FCCP, we electronically surveyed a group consisting of 32 hospital pharmacists and 12 managed care pharmacists in the US. The qualitative survey questions were designed based on the new healthcare reform act of 2010.

In the survey, we examined perceptions about the efficacy, safety, cost, and value of biosimilars. Survey respondents were also queried as to the information that should be required to consider biosimilar agents for formulary positioning as well as their needs for additional guidelines and education.

Limited Awareness
Of perhaps the greatest surprise, at the time of survey, only 40.7% of institutional pharmacists are aware of the BPCIA that created a pathway for approval of biosimilars. Perhaps less surprising, greater than 57% of institutional pharmacists believe that confirmatory clinical trials involving biosimilar agents against the reference product in the indication being sought are necessary to prove its similarity if comparability data is not robust enough to show similarity. Furthermore, over 61% of institutional pharmacists also believe drug switching, or cross-over trials will be required to prove interchangeability of a drug and that there is an important distinction between the clinical meaning and application of biosimilar and interchangeable biologics.

The FDA defines interchangeable biological products as products that are not only biologically similar to the originator or reference product, but also are expected to produce the same clinical result in any given patient. The safety and reduced efficacy risks of switching for biosimilars used repeatedly should not be greater than with repeat doses of the reference product without switching. Thus, interchangeability could allow a pharmacist to automatically substitute the reference product with a biosimilar drug at the point of service without authorization from the health care provider. This is an important distinction and one that is very pertinent for hospital pharmacists, especially when it comes to formulary considerations. Deeming a medication as biosimilar does not necessarily denote that the medication is exactly the same as the originator product and may impact automatic substitution decisions.

Biosimilar Use in Europe
Equally interesting to the concept that a majority of US hospital pharmacists are unaware of the current US government’s activity regarding biosimilar approval is that many of those same pharmacists engaged in pharmacy and therapeutics formulary decisions are likewise unaware of current European legislation addressing biosimilars. 

A Wide Range of Support for Biosimilar Production
In addition to pharmacists and hospital administrations, many health plans support the development of biosimilars, as they believe these agents can provide lower out-of-pocket costs, as well as easier access to treatment for patients (see Figure 1).



Even though pricing advantages will invariably drive the adoption of newly approved biosimilars, a lack of understanding of how such adoption will take place remains. Many pharmacists have concerns regarding the long-term use of biosimilar agents and feel that information such as bioequivalence data, long-term efficacy and safety data, drug characteristic data, head-to-head trials, and long-term health outcomes data is important to have available when making coverage decisions (see Figure 2). When biosimilar agents do come onto the market, pharmacists expect most agents will have to be vetted through cost control methods such as prior authorization or managed care pharmacy step-edit processes.



FDA Draft Guidance 
Following the conduct of this survey, the FDA did release a draft guidance document on biosimilar approval in February 2012 called Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. As expected, the agency expressed the need for strong analytical characterization of the biosimilar medication in order to show high similarity to the reference product, and thus reduce the number of questions surrounding safety and efficacy. The FDA also has the authority to waive any clinical studies, but in the draft guidance, the agency states an explicit expectation to require clinical studies for immunogenicity. The need for head-to-head clinical studies will be determined on a case-by-case basis; however, if the manufacturer can show the biosimilar medication is highly similar through comparative analytical and pharmacokinetic/pharmacodynamic data, there will be a lower risk of clinical differences. 

Furthermore, the FDA is taking a totality-of-evidence approach when evaluating biosimilar medications and key points remain under debate, including the amount of clinical trial data required, the amount of scientific data required for interchangeability, and the naming and labeling of biosimilar products—including whether unique International Nonproprietary Names (INN) would be required for approved biosimilar medications. Future revisions and additions to the FDA’s guidance likely will help clarify these points. 

Using Real World Case Studies
While the survey results represent a relatively small sample size, the responses show uniformity in certain areas of concern. Even though the questions are qualitative as opposed to quantitative, the data does reflect that significant questions remain regarding the bioequivalence, safety, and efficacy of biosimilars. Unsurprisingly, the majority of respondents indicated they would like more information regarding biosimilars, including additional guidance and regulation from the FDA regarding the type and amount of clinical trial data needed for biosimilar approval, as well as more technical information surrounding comparability exercises and assays.

Once biosimilar medications begin entering the marketplace, cost savings are likely to be immediately realized in the institutional setting. A case example from Skane University Hospital in Sweden showed that transitioning to Omnitrope—the first biosimilar approved in Europe—upon its release in 2009 from the original biologic, Somatropin, would lead to a cost savings of €600,000 ($750,000) moving forward.⁴ 

Although such examples are encouraging, biosimilar acceptance in the US would be just the beginning of what would likely introduce a host of other logistical and operational challenges. Simply stocking biologic medications, which include many agents used in the treatment of cancer, can be a challenge. Regardless, the direction of biologic therapy use clearly demonstrates the need for such accommodations to be made in the near future.

References

1. Biologics Price Competition and Innovation Act (BPCIA) provisions of the Patient Protection and Affordable Care Act (PPACA). www.gpo.gov/fdsys/delivery/getdoc.action?dbname=111_cong_bills&docid=f:h3590enr.txt.pdfAccessed June 25, 2012
2. Grogran K. Biosimilar Sales to Soar in next Five Years—Datamonitor. PharmaTimes.com. March 29, 2011. www.pharmatimes.com/Article/11-03-29/Biosimilar_sales_to_soar_in_next_five_years_-_Datamonitor.aspxAccessed June 25, 2012.
3. Bruce F, Schofield I. US FDA should look to the EU for guidance on biosimilars, Regulatory Affairs Pharma. November 8, 2010.
4. Befrits G. Biosimilars in Sweden. Presented at the 10th EGA International Symposium. April 19, 2012. 

Jiten Rana, PharmD, is an acute care staff pharmacist at Riverview Medical Center in Red Bank, New Jersey and a 2010 graduate of the Rutgers University School of Pharmacy. He recently completed a post-doctoral fellowship with Rutgers University in the field of regulatory affairs and has work experience in several therapeutic areas including immunology, hepatitis, and other infectious diseases. Jiten’s work within regulatory affairs covers US, EU, and Latin America regulations, orphan drug regulation, and biosimilars. 

Dannis Chang, PharmD, is a 2010 graduate of the University of Southern California School of Pharmacy and recently completed a post-doctoral fellowship with Rutgers University in the field of US and global clinical development and scientific affairs. His experiences in the biopharmaceutical industry comprise multiple therapeutic areas including oncology, hematology, and immunology.