Biosimilars in the United States: Current Status and Future Implications
Biosimilars in the United States: Current Status and Future Implications
July 26, 2017
5 min read

Physicians cautiously optimistic as they gain knowledge of biosimilars

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Gregg Silverman
Gregg Silverman

Although research has shown that biosimilars complement the biologic armamentarium for managing chronic diseases, concerns regarding their implementation have caused apprehension among physicians. Issues surrounding their efficacy and interchangeability, as well as how they will be named and prescribed, have left many physicians cautiously optimistic about their introduction to the U.S. marketplace.

One thing is certain, however: Biosimilars are here, and physicians should arm themselves with knowledge to better prepare themselves and their patients for the future.

“Physicians are teachers and counselors,” Gregg Silverman, MD, professor of medicine at the New York University School of Medicine, told Healio. “We need to be well informed so we can provide the best information to our patients, and there is much to learn about biosimilars that may be relevant to patient care.”

Healio spoke with experts to better understand the range of hot topics surrounding biosimilars. Here is what you should know.


Biosimilars are biologic agents that are highly similar — but not identical — to originator biological medications, and minor differences in protein structure due to posttranslational carboxylation can affect immunogenicity, or the immune response to the agent. Consequently, the potential for patients to develop antidrug antibodies and lose their immune response to a treatment is troubling.

According to Silverman, patient responses to any biologic agent vary, and this includes biosimilars. Therefore, it is important to consider the fact that while one patient may respond positively to a biologic, another patient with the same chronic disease may not benefit at all. This could be due to the differences in the disease process itself, or differences in the composition of the therapeutic compound and the sugars that are attached. Even a minor variation can act as a potential antigen, which could cause an allergic response to the agent. On one hand, this could cause a patient to have an immune response to a biologic agent that could cause lower efficacy either immediately, or slowly over time.

“In the extreme, this could trigger a bad immune response that could present as an asthmatic response, anaphylaxis, or even serum sickness with renal and joint injury. Thereby, treatment with a biologic agent, because it is essentially a foreign protein, could even create a disease that may seem like a chronic ailment that requires treatment. But in the process of getting a biosimilar approved, it is not feasible to require the kind of large enrollment, long-term trial that is needed to fully assess the relative risk of triggering such types of rare but potentially catastrophic responses. This is just one of the concerns we must consider as we learn about biosimilars and weigh their benefit-to-risk ratios,” he said.



Interchangeability for biologic products is a separate designation by the FDA. In January 2017, the organization issued draft guidance on interchangeability of biosimilar agents. According to the document, interchangeability will be determined on “a case-by-case basis” due to the complex nature of biologics, and may be affected by factors like the product’s complexity, the indications for the reference product and the potential for complications with the immune system. And although most FDA-approved biosimilars have been compared head-to-head with their originator compounds in what are known as “switching studies,” biosimilars are not expected to be studied against one another in this same manner, according to Stephen B. Hanauer, MD, AGAF, FACG, Clifford Joseph Barborka Professor and professor in medicine in the division of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine. “While each biosimilar has been compared to the originator in head-to-head studies, the FDA biosimilar pathway does not require individual biosimilars to be compared with each other,” Hanauer said. Therefore, the concept of switching from one biosimilar to another has generated concern among physicians for several reasons.

Stephen B. Hanauer, MD
Stephen B. Hanauer


According to David T. Rubin, MD, Joseph B. Kirsner Professor of Medicine and chief of the section of gastroenterology at the University of Chicago Medicine, if a patient is switched from a stable medication to another biosimilar, they may develop antidrug antibodies that can limit the biosimilar’s efficacy and cause an infusion or injection site reaction. He also noted a delay in a patient’s receipt of the drug could occur if a patient is switched from an originator drug to a biosimilar.

David T. Rubin, MD
David T. Rubin


“If these drugs are delayed, you run a high risk of losing response to them because part of how they continue working is when there is a stable amount of drug in the blood,” Rubin said. “So, if there is a delay logistically in switching, this is a real-world example where we might run into trouble and that is different than the clinical trials where everything is under good control.”

Communication regarding switching is a major cause for concern due to the potential for adverse effects. And, while there is no federal law regarding transparency between the pharmacist and the physician and patients, according to Rubin, there are state-mandated laws that each physician should familiarize themselves with so they know whether they will be informed of a switch in treatment.


“... [Switching biosimilars] should not just happen without clear communication,” Rubin said. “[We should be informed] not just that they are doing it, but also why they are doing it, and if it is because of cost we should know. If it is because they have some contract behind the scenes with a rebate that gives them financial preference in this particular insurance company, I think we should be aware and know what that is and there should be full disclosure.”

Naming conventions

Given the concerns regarding switching and interchangeability, establishing naming conventions that allow for post-marketing surveillance and help physicians identify which product their patient is taking is crucial to the successful implementation of biosimilars.

To that end, the Biologics Prescribers Collaborative (BPC), established in 2014, aims to ensure the policies enacted regarding biosimilars promote the safest use of these products, as well as all biologics.

Dennis R. Cryer
Dennis R. Cryer

According to Dennis R. Cryer, MD, one of the co-conveners of the BPC and chief medical officer of CryerHealth, the collaborative works closely with more than a dozen prescribing associations to generate a voice and physician perspective on policies surrounding biologics and biosimilars. An area of specific interest for the group is biosimilar naming.

“We’ve taken the approach that every biologic — whether an originator or biosimilar — should have a unique identifier added to the core drug substance name,” he told Healio. “We prefer the idea of a suffix attached to the drug name, and we prefer they be memorable to reduce confusion, avoid errors and improve knowledge of who is getting what among patients, physicians and pharmacists. The main goal is safety.”

In January 2017, the FDA issued a draft guidance stating that all biologic products — both new and previously licensed — would receive “proper” names. According to their plan, a unique 4-letter suffix is applied to a “core name” for all originator, related and biosimilar products. As of today, no biologic agent has met the FDA requirement for interchangeability. – by Casey Tingle and Stacey L. Adams

Disclosures: Cryer reports no relevant financial disclosures. Hanauer reports receiving consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Hospira, Janssen, Merck, Pfizer, Samsung, Takeda and UCB. Rubin reports consulting for and his institution has received grant support from AbbVie, Janssen, Takeda, Pfizer and Amgen. Silverman reports consulting and advising for Genentec, Roche, Eli Lilly, Pfizer, CelGene and Bristol-Myers Squibb.


Biosimilars forum: Overview. Available at: Accessed Oct. 16, 2016.

For more information:

Dennis R. Cryer, MD, can be reached at

Stephen B. Hanauer, MD, AGAF, FACG, can be reached at Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611; email:

David T. Rubin, MD, can be reached at the University of Chicago Medicine, 5841 S. Maryland Ave., Chicago, IL 60637; email:

Gregg Silverman, MD, can be reached at the New York University School of Medicine, 550 1st Ave., New York, NY 10016; email: