HELP subcommittee hearing looks for signs of life in FDA’s biosimilar pathway

A subcommittee hearing on biosimilar implementation was held by the U.S Senate Committee on Health, Education, Labor, and Pensions subcommittee on Primary Health and Retirement Security. The hearing, titled “Biosimilar Implementation: A Progress Report from FDA” addressed the FDA’s efforts to implement its biosimilar approval pathway and inquired as to the cause of the FDA’s delay in providing guidance on the nature of the pathway. The hearing also addressed concerns that the market will not have sufficient confidence in biosimilars as they become more widely available.

Opening statements

Senator William Cassidy (R-La), a physician, chaired the hearing and discussed the fact that since the Biologics Price Competition and Innovation Act (BPCI Act) was passed under Section 7002 of the Patient Protection and Affordable Care Act (ACA) (P.L. 111-148), only one biosimilar has been approved and is on the market. Additionally, the FDA has not issued final guidances on many parts of the approval pathway including: “naming, labeling, interchangeability, and data extrapolation.”


The only witness was Janet Woodcock, the Director of the FDA’s Center for Drug Evaluation and Research (CDER). Woodcock testified that the FDA strongly supports the creation of a meaningful biosimilar pathway and has been working on it since the 1990s. As a rheumatologist, Woodcock acknowledged the significance of biologics in treating diseases like rheumatoid arthritis and commended their success in eliminating the need for things like joint replacements and for increasing the likelihood of disease remission. However, Woodcock also noted that biologics and biosimilars require complex regulation and often have prohibitive costs.


Senator Murphy (D-Conn) acknowledged the promise of biologics but noted that they have led to unprecedented costs for the health care industry. Murphy explained that although biologics constitute less than one percent of prescriptions, expenditures on biologics amount to 28 percent of prescription drug spending, with forecasts of increased spending in the coming years. Murphy suggested that the high cost is due in part to higher cost sharing burdens imposed by insurance companies on biologics. Thus, he explained, the success of biosimilars—which will serve as competitors of reference biologics—is crucial to driving down drug costs.


Cassidy explained that biosimilars raise more complex issues than drugs because of their biologic nature. He noted that, due to the complexity of biologic products, biosimilars can never be deemed truly identical to another biological reference. According to Cassidy, this results in a tension for the FDA, where, although dealing with a biologic, the agency must make certain that a biosimilar has comparable efficiency and effectiveness such that that it can be used in lieu of its reference product. Cassidy explained that while some biosimilars can be deemed interchangeable—meaning the biosimilar can be more safely exchanged with its biologic reference product—biosimilars can only be “similar” and can never be truly identical to a reference.

Reference products

However, not all biosimilars are interchangeable. Those that are not will require specific prescribing and, unlike a generic, cannot be swapped out with the biologic reference product without a separate prescription. However, biosimilars, even when not deemed interchangeable, are still expected to produce the same clinical effect as they biologic they reference. At present, many biosimilars will likely not be deemed interchangeable because of unknowns about immune responses that biologics may cause.

Immune response

Woodcock testified, in response to questions about interchangeability, that biosimilars present complicated risks due to unexpected immune responses. The issues result when switching between a biosimilar and a biologic reference product or another biosimilar. Woodcock explained that, because of their biologic nature, biosimilars are all (on some level) unique and therefore pose a greater risk than generic drugs. Woodcock testified that subtle variation between a biosimilar and a reference drug can cause unwarranted immune responses. Cassidy inquired about the cause of these responses and the problem of demonstrating interchangeability on a biochemical level. Woodcock explained that the problem results from the fact that, while two biologics (a reference and a biosimilar) may seem to be twins, some tiny variation could be perceived by the immune system and result in a harmful immune response. In other words, very small manufacturing changes in a biosimilar drug can lead to negative responses, making the approval and regulatory pathway very complex when compared to the pathway for generic drugs.

Cost savings

Senator Warren (D-Mass) noted that if the pathway starts moving effectively, the ACA pathway for biosimilars could have the potential to save the U.S. $44 billion over the next ten years. However, she also noted that—if the biosimilar market follows the lead of the generic market—cost reductions are not expected to occur until two or more follow-along competitor biosimilars join the market. Thus, Warren warned that drug makers need to “know the rules of the road,” so that competitors can enter the market soon. As result, Warren criticized the FDA for not having issued a draft guidance describing the standard for interchangeability. Warren asked Woodcock why the FDA has not completed this work in five years. After Woodcock responded without directly addressing the question, Warren contrasted the FDA delay to the relative speed of the European Union, which completed its pathway in 2003 and approved its first biosimilar in 2006.


Murphy raised concerns about patient education and the risk that, even if biosimilars reach the market, physicians and consumers may not be willing to prescribe and use biosimilars. Murphy suggested that biologic manufacturers may be encouraged to flood the consumer space with information about why biosimilars are not a safe and effective alternative to their referenced biologic product. Murphy asked Woodcock how to get the truth out. Woodcock, who acknowledged that the responsibility of educating clinicians and consumers fell to the FDA, testified that the FDA was developing a plan of education. Woodcock testified that the FDA was consulting focus group to identify who to reach out to and what the message should be to persuade interested parties regarding the efficacy and promise of biosimilars.

Unnecessary spending

Murphy repeatedly warned Woodcock of the importance of “getting the word out.” Murphy explained that, in the next year, eight of the top 10 drugs could be biologics, which on average cost 22 times that of a traditional drug. Thus, Murphy explained, if biologic advertising was successful in reducing the prescribing of biosimilars, the resulting unnecessary spending would be in the billions. Warren echoed Murphy’s concerns and warned that the if the biosimilar market takes the shape of the generic market, where the majority of physicians retain negative perceptions about generics, public confidence in biosimilar products could be disastrous for prescription drug spending. Murphy explained that the savings and stakes are high because, if biosimilars could achieve the success of generics, which now represent 85 percent of dispensed prescriptions in the U.S., the enormous cost of biologics could be reduced.