A biosimilar is a biological product that is similar to a reference biologic (usually the original product) and for which there are no clinically meaningful differences in terms of safety, purity, and potency.

• Let’s look at an example: Amjevita (adalimumab-atto) was the first biosimilar approved for Humira (adalimumab) used to treat rheumatoid arthritis and psoriasis, among other uses.
• In this case, Humira is the reference (original) product that fulfilled the adalimumab clinical studies and was approved by the FDA.

Biosimilars are expected to help the U.S. healthcare system and consumers save money, although biosimilar products are usually still very expensive. According to the RAND Corporation, biosimilars could help save the U.S. health system close to $54 billion on biologics spending through 2026.

As of June 2023, there are 41 biosimilars approved by the U.S. Food and Drug Administration (FDA). More more information, see: Table of biosimilars currently approved in the United States

What is a Biologic?

If a biosimilar is a biologic, then what is a biologic? Biological products can include a wide range of products including:

• vaccines
• blood components
• gene therapy
• tissues
• proteins, like monoclonal antibodies and cell signaling proteins.

Unlike most chemically-derived small-molecule drugs, biological products are generally derived from a living organism, such as humans, animals, microorganisms or yeast. Clinically, they are used to treat patients with cancer, kidney diseases and autoimmune diseases, such as rheumatoid arthritis and Crohn's disease.

For example, Enbrel (etanercept) or Humira (adalimumab) are referred to as “large-molecule” drugs because they are larger and more complex in structure than small-molecule drugs (like ibuprofen).

Biologic products are very expensive, often in the tens-of-thousands of dollars per year, due to costs linked to complicated development and manufacturing. Often, patients will need to access these medications through a specialty pharmacy.

Related: Specialty Pharmacy and Medicines: A One-to-One Approach

Are Biosimilars Exactly The Same As The Biologic?

Biosimilars are just that; "similar" because they do not have to be exact copies of the active ingredient, as with small-molecule drug generics.

A biosimilar is not considered a “generic” in the same way that a traditional, small molecule drug (for example: ibuprofen or acetaminophen) is determined to be a generic.

In 2010, the U.S. signed into law an abbreviated approval pathway for biologics to encourage production, create competition, increase treatment options and reduce healthcare costs. Under the new law, a biological product may be demonstrated to be “biosimilar” if data show that the product is “highly similar” to an already-approved biological product.

The law, known as the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), aligns with the FDA’s long standing-policy of permitting appropriate reliance on drug science that has already been established, thereby saving time, resources and unnecessary duplication of animal testing or human clinical trials.

How Are Biosimilars Named?

In January 2017 the FDA issued a guidance on naming conventions for biosimilars. According to the guidance the nonproprietary name designated "will be a proper name that is a combination of the core name and a distinguishing suffix that is devoid of meaning and composed of four lowercase letters."

In the current naming convention, the FDA has designated guidelines for approved biosimilar nonproprietary names that incorporate four lowercase letters (a suffix).

FDA has stated drug companies can propose up to 10 suffixes for each new biosimilar.
Currently, the licensed biosimilars have gained the unique 4-letter suffix, but the older reference product may not have a suffix, for example; for example: adalimumab (Humira).

Some older biosimilars are linked with the manufacturer (filgrastim-'sndz' for Sandoz), and some random (infliximab-dyyb); going forward they will be random and not linked with the manufacturer's name.

Can Pharmacists Automatically Substitute a Biosimilar for a Reference Brand?

Yes, but ONLY for FDA-approved biological products specifically designated as interchangeable, as found in The Purple Book database. According to the FDA, automatic substitution can happen once a product is deemed interchangeable.

If the product has been determined to be interchangeable, then it is "biosimilar" to the reference product AND will produce the same clinical result as the reference product in any given patient. Interchangeable also means the original biologic and the new biosimilar can be switched back and forth in a patient without a risk of diminished safety or efficacy.

However, if needed, biosimilars can be dispensed by a pharmacist in place of another biological product if a physician or other healthcare professional specifically prescribes the biosimilar product by name.

Some examples of approved interchangeable biosimilars include:

• Semglee (insulin glargine) was approved as an interchangeable biologic with Lantus in July 2021. It was the first interchangeable biosimilar approved in the US, as well as the first interchangeable insulin product, meaning your pharmacist can automatically substitute it for Lantus.
• Rezvoglar (insulin glargine-aglr) Kwikpen from Eli Lilly was approved as the second biosimilar to Lantus in Dec. 2021. In Nov. 2022, the FDA approved it as the second interchangeable biosimilar insulin product to Lantus.
• Cyltezo (adalimumab-adbm) was deemed interchangeable with Humira in Oct. 2021.
• Cimerli (ranibizumab-eqrn), anti-VEGF therapy, was approved as an interchangeable biosimilar to Lucentis in August 2022. It is used for intravitreal injection (into the back of the eye) to treat all of the same five indications as Lucentis, including the wet form of age-related macular degeneration.

Pharmacists will know which biological products are approved as interchangeable by the FDA, and can check The Purple Book database to find these products.

What is the Purple Book?

The Purple Book database is the go-to resource for pharmacists and other health care providers interested in making an interchange between a reference biologic and a biosimilar. It is found online on the FDA website.

Similar to The Orange Book used to compare generic products to their brand name counterparts, The Purple Book database has been developed by the FDA to list each reference biological product and the corresponding biosimilar and interchangeable biological product.

Biosimilars designated as interchangeable will have no clinically important differences from the original product. Variation in formulation, delivery device, indications, and routes of administration may be acceptable.

Additional biosimilar product information can also be accessed here on the FDA website.