Biosimilars in the United States: Current Status and Future Implications

Biosimilars in the United States: Current Status and Future Implications

January 19, 2018
6 min read

FDA resources can help prescribers better understand biosimilars

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by Leah Christl, PhD

The Biologics Price Competition and Innovation Act, included within the Affordable Care Act, established an abbreviated licensure pathway for biosimilars in 2010.

Since then, the FDA has approved biosimilars to six of the most widely used biological products on the market: bevacizumab (Avastin, Genentech), etanercept (Enbrel, Amgen), trastuzumab (Herceptin, Genentech), adalimumab (Humira, AbbVie), filgrastim (Neupogen, Amgen) and infliximab (Remicade, Janssen).

As biosimilars become more widely used in medical practice, FDA wants health care providers to better understand these drugs and how they can benefit patients.

We know prescribers have many questions. For instance, we’re frequently asked about “interchangeable” biologic products and how prescribers can be assured that a biosimilar or interchangeable product will be as safe and effective for their patient as its reference product — the product to which the biosimilar was compared during regulatory review.


Strict standards

Our review and approval process requires the manufacturer of a proposed biosimilar to demonstrate that the product is highly similar to the reference product, and that the product has no clinically meaningful differences from the reference product in terms of safety, purity and potency (ie, safety and effectiveness).

A manufacturer developing a proposed biosimilar demonstrates that its product is highly similar to the reference product by extensively analyzing — or characterizing — the structure and function of both the reference product and the proposed biosimilar. Minor differences are acceptable, but biosimilars must pass stringent testing based on state-of-the-art technology.

A proposed biosimilar is shown to have no clinically meaningful differences from a reference product generally through human pharmacokinetic and pharmacodynamic studies, an assessment of clinical immunogenicity and, if needed, additional clinical studies.

Once a biosimilar has been approved by FDA, prescribers can be assured of the safety and effectiveness of the biosimilar, just as they would for the reference product.


Interchangeability requires additional data

An interchangeable biologic product meets all the requirements for biosimilarity mentioned above, as well as additional requirements.

These include showing that the product is expected to produce the same clinical result as the reference product in any given patient. Also, for products that are administered to a patient more than once, data and other information must be provided to evaluate the risk — in terms of safety and decreased efficacy — of alternating or switching between the products.

Although dispensing requirements vary by state, a product that achieves interchangeable status may be able to be dispensed by a pharmacist in place of the prescribed reference product without the need for prescriber authorization.

Currently, there are no interchangeable products approved by FDA.

When FDA carries out a scientific review of a proposed biosimilar, the evaluation does not include a determination of whether the biosimilar is interchangeable with the reference product and whether the biosimilar can be substituted for the reference product at the pharmacy. Substitution of a biosimilar for a reference product is a matter of state pharmacy law and is a decision that is generally outside of FDA’s regulatory role.



Online resources for prescribers

FDA has developed online educational materials for prescribers who have questions or are seeking more information.

These materials provide important definitions of key terms related to biological drugs and biosimilars. They also provide links to relevant online courses, webinars, and presentations.

Through extensive research and interaction with the medical community, FDA has learned many of the questions health care providers have on this subject. They include:

  • Why is a biosimilar different than a generic drug?
  • Are biosimilars approved for all the same indications as the reference product?
  • What is the approval process for biosimilar products?
  • What data are required for approval of a biosimilar or interchangeable product?
  • Do all biosimilar applications include the same types of data?
  • Why do we need an abbreviated approval pathway for biological products?

The site provides answers to these questions and many others, all of which are critical to understanding these complex products.

Next, we want to understand what types of information health care professionals need to properly communicate with their patients about biosimilars.

Greater understanding of biosimilars by patients, as well as health care professionals, can lead to greater acceptance of treatment options that may help reduce their cost of care.


FDA-approved biosimilars

To date, FDA has approved nine biosimilars.

A brief overview of their uses follows.

Prior to prescribing, please see Drugs@FDA — available at — for product labeling, which includes complete information about approved uses, as well as risk and safety information. Additional information, including links to FDA-approved product labeling, can be found at

  • Adalimumab-atto (Amjevita, Amgen) and adalimumab-adbm (Cyltezo, Boehringer Ingelheim) — both biosimilar to adalimumab (Humira, AbbVie) — are approved for the treatment of patients with rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and plaque psoriasis;
  • Etanercept-szzs (Erelzi, Sandoz/Novartis), biosimilar to etanercept (Enbrel, Amgen), is approved for the treatment of moderate to severe rheumatoid arthritis; moderate to severe polyarticular juvenile idiopathic; active psoriatic arthritis; active ankylosing spondylitis, and chronic moderate to severe plaque psoriasis;
  • Infliximab-dyyb (Inflectra, Pfizer), infliximab-qbtx (Ixifi, Pfizer) and infliximab-abda (Renflexis, Merck) — each biosimilar to infliximab (Remicade, Janssen) — are approved for the treatment of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis and ulcerative colitis;
  • Bevacizumab-awwb (Mvasi, Amgen), biosimilar to bevacizumab (Avastin, Genentech), is used for the treatment of multiple types of cancer, including certain patients with metastatic colorectal cancer, nonsquamous non-small cell lung cancer, glioblastoma, metastatic renal cell carcinoma and cervical cancer;
  • Trastuzumab-dkst (Ogivri, Mylan), biosimilar to trastuzumab (Herceptin, Genentech), is approved to treat certain patients with specific types of breast or metastatic stomach cancer; and
  • Filgrastim-sndz (Zarxio, Sandoz/Novartis), biosimilar to filgrastim (Neupogen, Amgen), is used to help restore a patient’s white blood cells after depletion by a cancer treatment or due to severe chronic neutropenia, and increase a patient’s white blood cells in association with certain medical procedures.

Three of nine biosimilars approved by FDA are on the market: infliximab-dyyb, infliximab-abda and filgrastim-sndz.



Nonproprietary naming

The convention for nonproprietary names of biological drugs can be confusing to prescribers and patients.

Some biological products and all biosimilar products contain a suffix as part of their nonproprietary name. However, some biological products have a prefix as part of this name.

The nonproprietary naming convention for biological drugs has evolved over time and has been standardized such that a suffix containing a unique combination of four lowercase letters will be included in the nonproprietary name for biological products.

With this convention, these letters deliberately have no specific meaning. Their main purpose is to distinguish one product from another. This can help, for instance, to facilitate drug safety monitoring and other research of drug safety issues that needs to be conducted on a product-specific basis.


FDA ‘Purple Book’

Biological products can have complicated names.

In addition, there are a variety of examples of biological products that have similar-sounding nonproprietary names. Such products may have similar or identical FDA-approved uses but, in other cases, the products may have very different uses.

For example, there are two distinct biological products on the market with “aflibercept” as, or as part of, their nonproprietary name.

  • Aflibercept (Eylea, Regeneron) is FDA approved for the treatment of patients with wet age-related macular degeneration.
  • Ziv-aflibercept (Zaltrap, Sanofi Genzyme) is FDA approved for the treatment of certain patients with metastatic colorectal cancer.
  • Alternatively, these products with similar-sounding nonproprietary names share some FDA-approved uses.
  • Filgrastim (Neupogen, Amgen);
  • Tbo Filgrastim (Granix, Sicor Biotech UAB); and
  • Filgrastim-sndz (Zarxio, Sandoz/Novartis).

It is clear from the above examples that a growing field of biosimilars and new biological products adds complexity to understanding these therapies and the treatment options they may provide to patients and prescribers.

FDA’s new educational materials also highlight information about an important reference for biological drugs known as the “Purple Book.” This reference lists every FDA-approved biological product, including biosimilars.

Among many other uses, this reference can help prescribers and patients learn which reference products have one or more FDA-approved biosimilar or interchangeable product. In addition, prescribers should review the specific product labeling — or prescribing information — and approved indications to determine the most appropriate product for their patient.

The driving force behind biosimilars is increased market competition, which may lead to significantly reduced costs for both patients and the U.S. health care system.

The biopharmaceutical industry has shown great interest in developing these products, and FDA expects many more applications for biosimilars to be submitted.


For more information:

Leah Christl, PhD, is associate director for therapeutic biologics in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research. She can be reached at Center for Drug Evaluation and Research, 10001 New Hampshire Ave., Silver Spring, MD 20903.


Disclosure: Christl reports no relevant financial disclosures.