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Overview of Biologics and Biosimilar Products

 

Advances in medicine have revolutionized care for patients with disease states such as cancer, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and even asthma. These conditions are increasingly treated with biologic medications, which target the causes of disease in ways that were once impossible. Hundreds of millions of patients worldwide have used biologic medications to live healthier, more active lives. The advent of cheaper biosimilars can further expand access to these life-saving products.

As a pharmacist, one must understand the distinctions between conventional medications, biologic medications, biosimilars, and their interchangeability; their journey to the marketplace; and the regulations that affect how they are dispensed. Most importantly, pharmacists must be prepared to educate patients on the appropriate use of these products.

APhA has created this FAQ document to help our members and their patients navigate the rapidly evolving biologic and biosimilar landscape.

What is a biologic?

Most traditional prescription medications (also known as small-molecule drugs) are manufactured through chemical processes. Biological products, however, are generally large, complex molecules made from living cells. Biologics can be used to treat cancer, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis, diabetes, and other conditions.

Therapeutic proteins; monoclonal antibodies; blood, blood components, and their derivatives; allergenic products; and vaccines are examples of biological products. Because biologics are so different from small-molecule drugs, particularly in their manufacturing, the Food and Drug Administration (FDA) has a separate process for reviewing and approving them.

It takes months to manufacture a biologic drug, and every part of the process must be carefully monitored and controlled. Even small changes in the manufacturing process or environment (e.g., temperature changes) can make a big difference in the final product. Because biologics are so complex to develop and manufacture, they are often very expensive.

What is a biosimilar?

Generic medicines are essentially identical copies of brand name drugs. Unlike generic drugs, however, it is impossible to make an exact copy of a biologic. In fact, all biologic medicines vary slightly from one batch to another because they are derived from living cells, which constantly undergo change.

Instead, biosimilars are characterized as highly similar to an FDA-approved biologic, which may also be known as a reference product in this context. While not an exact match, a biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved biological reference product.

FDA may approve more than one biosimilar product for a single reference product. The agency approved the first biosimilar in 2015. Click here to see the latest list of FDA-approved biosimilars.

Pharmacists can find information about all FDA-licensed biologic medications, FDA-licensed biosimilars, and their interchangeability in the agency’s Purple Book database. The database also contains information about all FDA-licensed allergenic, cellular and gene therapy, hematologic, and vaccine products that the agency regulates.

How are biosimilar products named?

Biosimilars may be named in one of three formats.

  • Brand name : Example
  • Core scientific name with manufacturer name : examplemab Medmaker
  • Core scientific name followed by a random four-letter suffix : examplemab-gxrm

May pharmacists substitute a biosimilar for a biologic reference product as they do with generics?

FDA reviews manufacturer data to assess whether a biosimilar is interchangeable with an FDA-approved biologic reference product. Pharmacists may substitute biologics with biosimilars only if FDA has declared that they are interchangeable, subject to state pharmacy laws, which vary from state to state. State law may require dispensing pharmacists to notify the prescriber, communicate with the patient, and complete certain documentation before they can substitute with an interchangeable biosimilar. While pharmacists can consult this helpful resource on state laws and regulations, they should check with their board of pharmacy to confirm they comply with applicable laws.

If FDA has not concluded that the biosimilar is interchangeable with the reference product, pharmacists cannot independently substitute one for the other. In these cases, pharmacists can only dispense biosimilars if the prescriber writes a prescription specifically for it. If a patient struggles to pay for the reference product, pharmacists can inform the patient and prescriber that a cheaper biosimilar is available.

What is FDA’s approval process for biosimilars?

The Biologics Price Competition and Innovation Act (BPCIA) created a pathway that permits a biosimilar biological product to be licensed under section 351(k) of the Public Health Service Act based on less than a full complement of product-specific preclinical and clinical data.

FDA checks for similar purity, structure, and activity and requires that biosimilars, like reference products, are studied in patients. This ensures that the reference product and the biosimilar product are clinically equivalent, with no clinically meaningful differences in safety or effectiveness. FDA allows biosimilar manufacturers to rely on some of the same clinical data that the agency used to approve the reference product.

FDA continues to monitor all biologics, including biosimilars, after they are approved and used by a larger number of patients.

What benefits do biosimilars offer?

It boils down to costs.

A biosimilar is highly similar to and has no clinically meaningful differences from an existing FDA-approved biological reference product. While still expensive, biosimilars may provide cost savings to patients and the health care system. According to IQVIA, biosimilars are projected to save $100 billion in aggregate between 2021 and 2025.

What is an interchangeable biologic?

The Biologics Price Competition and Innovation Act (BPCIA) created a special category of biosimilars called "interchangeable biologics", which must meet additional FDA-approval requirements. FDA does not approve a product as interchangeable unless the manufacturer specifically seeks an interchangeability determination.

The law requires a manufacturer to provide evidence that:

  • The proposed interchangeable product is expected to produce the same clinical result as the reference product in any given patient.
  • If a biological product is administered to a patient more than once, that the risk in terms of safety or reduced efficacy of switching back and forth between an interchangeable product and the reference product is not greater than using the reference product alone.

Once FDA declares that a biosimilar product is interchangeable with the reference product, pharmacists may substitute one with the other without the intervention of the prescriber; however, the laws governing this authority vary by state. While pharmacists can consult this helpful resource on state laws and regulations, theyshould check with their board of pharmacy to confirm they comply with applicable laws.

Is insulin considered a biologic, and does it have biosimilars?

In March 2020, FDA transitioneda small subset of biological products, including insulin, that had been approved as drugs to being regulated as biologics. This paved the way for the development of biosimilar and interchangeable insulin products.

On July 28, 2021, FDA announced that it had approved Semglee (insulin glargine-yfgn), the first interchangeable biosimilar insulin product for the treatment of diabetes. Semglee (insulin glargine-yfgn) is interchangeable with, and can be substituted for, its reference product Lantus (insulin glargine)—a long-acting insulin analog.

It is important to note that only the Semglee (insulin glargine-yfgn) biosimilar is interchangeable with Lantus – not the Semglee (insulin glargine injection) biologic product that was approved by FDA in June 2020. While not currently available, the interchangeable Semglee product is expected to be launched by the end of 2021.

What is APhA’s position on interchangeable biologics?

APhA strongly supports the development of biologics and biosimilars. We also support state biosimilar substitution laws that, unless science dictates otherwise, mirror those for small-molecule drugs.

Specifically, APhA opposes interchangeable biologic product–substitution processes that require authorization, recordkeeping, or reporting more burdensome than generic product substitution processes.Read the policy statement

APhA has also advocated against the use of unique names and/or suffixes for reference biologics and biosimilars. This practice could contribute to confusion about interchangeability, among other concerns.

Additional Resources