Biologic and Biosimilar Drugs: What You Need To Know

Biologic drugs, also called biologics, are the fastest-growing medication class in the United States and include, for example, certain vaccines, insulin and monoclonal antibodies.[1],[2] Biologics are approved for the treatment of numerous conditions, including arthritis, some cancers, chronic skin diseases (such as psoriasis), diabetes, inflammatory bowel diseases (including Crohn’s disease and ulcerative colitis), multiple sclerosis and osteoporosis.[3]

Unlike most drugs available in a pharmacy (which are made from chemical ingredients), biologic drugs are made from living cells or microorganisms, such as animal cells, bacteria or yeasts.[4] Because they are made from living sources, biologics are difficult to manufacture and purify, and different batches of the same biologic can differ slightly from each other.[5] Because biologics are often very expensive, in 2010 Congress passed the Biologics Price Competition and Innovation Act to promote the development of more affordable biologics by creating a shorter approval process for biologic drugs called biosimilars.[6]

Biosimilars are created through similar processes and from comparable natural sources as already-approved biologic drugs, called reference products.[7] However, unlike generic versions of chemical drugs, which are in every way identical to the original brand-name drugs, a biosimilar drug is not an exact copy of the reference product. This is because the production process and the living organisms always slightly differ between the approved biologic and the biosimilar.[8],[9] Importantly, however, according to the Food and Drug Administration (FDA), an approved biosimilar drug is “highly similar to and has no clinically meaningful differences in terms of safety, purity, and potency (safety and effectiveness) from an existing FDA-approved biologic.”[10]

In 2015, filgrastim (NEUPOGEN), a drug that is used in certain cancer patients to lower their risk of infections, was the first reference product for which the FDA approved a biosimilar (ZARXIO). As of August 2024 the FDA had approved 58 biosimilars for many reference products.[11] Other examples of prominent biologic drugs with biosimilar competition include the immunosuppressive drugs adalimumab (HUMIRA) and infliximab (REMICADE, ZYMFENTRA), which are used to treat various autoimmune diseases (including rheumatoid arthritis and Crohn’s disease), and insulin glargine (LANTUS), which is used for the treatment of diabetes. A list of all FDA-approved biologics and biosimilars is available at https://purplebooksearch.fda.gov/.

Similar to the approval process for all drugs, for a biologic to be approved, the manufacturer needs to demonstrate in clinical trials that the product is safe and effective.[12] For a biosimilar, however, the manufacturer does not need to independently demonstrate that the product is safe and effective, only that it is biosimilar (or comparable) to the reference product. This makes the approval process shorter and biosimilars more affordable than their reference product because fewer clinical trials and other studies need to be conducted.[13]

Biosimilars vs. interchangeable biosimilars

Once a biosimilar is approved by the FDA, it can be used in the same way and for the same conditions as the reference product.[14] A reference product may have more than one biosimilar version and a clinician can choose to prescribe one of the less expensive biosimilars instead of a biologic. However, a biosimilar cannot be substituted for the reference product by a pharmacy without a specific prescription unless the biosimilar and the reference product are considered to be interchangeable.

The decision about which biosimilars are interchangeable biosimilars is made at the state level, but most states stipulate that the FDA must have approved the biosimilar as interchangeable first.[15] For a biosimilar to be approved as interchangeable, the FDA requires additional clinical data that demonstrates that the biosimilar is safe and effective when patients switch between the reference product and the interchangeable biosimilar.[16] These so-called “switching studies” are required because of concerns that switching from a biologic to a comparable, but not identical, biosimilar could lead to an increase in unwanted immune responses (immunogenicity), such as the formation of antidrug antibodies, which could affect the efficacy or safety of the treatment.[17]

However, several studies have demonstrated that biosimilars are as safe and effective as interchangeable biosimilars when patients switched to them from a reference product.[18] For instance, a 2020 systematic review of 178 studies that followed about 21,000 patients who had switched from a biologic to a biosimilar drug or vice versa did not find clinically meaningful differences in the efficacy, safety or immunogenicity in those who had switched compared with those who did not switch between a biologic and a biosimilar.[19]

Moreover, in a 2023 systematic review and meta-analysis that included 5,252 patients in studies involving 21 different biosimilars, FDA researchers found no significant differences in safety outcomes (including rate of serious adverse events, deaths and treatment discontinuation) in patients who were switching from a reference biologic to a biosimilar or vice versa compared with those who did not switch.[20],[21] Additionally, this review found that the immune-related adverse events (such as anaphylaxis [a sudden, potentially life-threatening, severe generalized allergic reaction] or antidrug antibodies) were similar between these groups.

For this reason, in June 2024 the FDA proposed loosening requirements such as switching studies for the approval of interchangeable biosimilars. Instead, manufacturers would only need to provide data demonstrating that their product meets the switching standard.[22],[23] The FDA is currently revising its guidelines, but once they are finalized, more biosimilars might be considered interchangeable, a change that could increase competition and lower the cost of some biologics.

What You Can Do

If you require treatment with a biologic drug, discuss with your clinician whether you can safely switch to a more affordable biosimilar for the same condition. The fact that biosimilars tend to be more affordable does not mean that these products are less effective, and research has shown that they are as safe as their reference products. The potential cost savings will vary depending on the specific biologic drug and biosimilar. It is important to keep in mind that biologics and biosimilars, like all drugs, can vary in their effectiveness as compared with other possible treatments and in some instances may be associated with serious adverse events. Discuss with your clinician whether a biologic drug, a biosimilar or another type of drug is the best treatment option for your condition.
 

References

[1] Food and Drug Administration. Biological product innovation and competition. April 10, 2024. https://www.fda.gov/drugs/biosimilars/biological-product-innovation-and-competition. Accessed August 5, 2024.

[2] Food and Drug Administration. Biosimilars. Overview for health care professionals. August 1, 2024. https://www.fda.gov/drugs/biosimilars/overview-health-care-professionals. Accessed August 5, 2024.

[3] Food and Drug Administration. Biosimilar basics for patients. August 1, 2024. https://www.fda.gov/drugs/biosimilars/biosimilars-basics-patients. Accessed August 5, 2024.

[4] Ibid.

[5] Food and Drug Administration. Biosimilars. Overview for health care professionals. August 1, 2024. https://www.fda.gov/drugs/biosimilars/overview-health-care-professionals. Accessed August 5, 2024.

[6] Food and Drug Administration. Implementation of the biologics price competition and innovation act of 2009. February 12, 2016. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009. Accessed August 5, 2024.

[7] National Cancer Institute. Biosimilar drug. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biosimilar-drug. Accessed August 5, 2024.

[8] Barbier L, Ebbers HC, Declerck P, et al. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review. Clin Pharmacol Ther. 2020;108(4):734-755.

[9] Triplitt C, Hinnen D, Valentine V. How similar are biosimilars? What do clinicians need to know about biosimilar and follow-on insulins? Clinical Diabetes. 2017;35(4):209-216.

[10] Food and Drug Administration. Review and approval. Biologics. December 13, 2022. https://www.fda.gov/drugs/biosimilars/review-and-approval. Accessed August 5, 2024.

[11] Food and Drug Administration. Biosimilar product information. July 22, 2024. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information. Accessed August 5, 2024.

[12] Triplitt C, Hinnen D, Valentine V. How similar are biosimilars? What do clinicians need to know about biosimilar and follow-on insulins? Clinical Diabetes. 2017;35(4):209-216.

[13] Food and Drug Administration. Review and approval. Biologics. December 13, 2022. https://www.fda.gov/drugs/biosimilars/review-and-approval. Accessed August 5, 2024.

[14] Food and Drug Administration. 9 things to know about biosimilars and interchangeable biosimilars. June 20, 2024. https://www.fda.gov/drugs/things-know-about/9-things-know-about-biosimilars-and-interchangeable-biosimilars. Accessed August 5, 2024.

[15] Triplitt C, Hinnen D, Valentine V. How similar are biosimilars? What do clinicians need to know about biosimilar and follow-on insulins? Clinical Diabetes. 2017;35(4):209-216.

[16] Food and Drug Administration. Review and approval. Biologics. December 13, 2022. https://www.fda.gov/drugs/biosimilars/review-and-approval. Accessed August 5, 2024.

[17] Barbier L, Ebbers HC, Declerck P, et al. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review. Clin Pharmacol Ther. 2020;108(4):734-755.

[18] Food and Drug Administration. FDA updates guidance on interchangeability. Reference products. June 20, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-guidance-interchangeability. Accessed August 5, 2024.

[19] Barbier L, Ebbers HC, Declerck P, et al. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review. Clin Pharmacol Ther. 2020;108(4):734-755.

[20] Herndon TM, Ausin C, Brahme NN, et al. Safety outcomes when switching between biosimilars and reference biologics: a systematic review and meta-analysis. PLoS One. 2023;18(10):e0292231.

[21] Food and Drug Administration. Safety outcomes when “switching” between biosimilars and reference products. December 5, 2023. https://www.fda.gov/drugs/spotlight-cder-science/safety-outcomes-when-switching-between-biosimilars-and-reference-products. Accessed August 5, 2024.

[22] Food and Drug Administration. FDA updates guidance on interchangeability. Reference products. June 20, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-guidance-interchangeability. Accessed August 5, 2024.

[23] Food and Drug Administration. Draft guidance document. Considerations in demonstrating interchangeability with a reference product: Update. June 21, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-demonstrating-interchangeability-reference-product-update. Accessed August 5, 2024.