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Understanding Biologics and Biosimilars


For some patients, a seismic wave of change is preparing to wash over the autoimmune landscape. Already in Europe, Canada and Australia, among other locations, patients are experiencing the effects of a shift away from biologic to biosimilar prescription drugs, and that change is now coming to the United States. CVS recently announced that effective April 1, 2024, Humira®, a reference biologic used to treat many autoimmune conditions including rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis, will be removed from their major national commercial template formularies and only Humira biosimilars will be covered.

So, what does this mean? What are biosimilars, and how do they differ from biologics? What, if anything, do you need to do? If you don’t know, you’re certainly not alone.

In a recent Autoimmune Association survey, 36% of patients reported they were on a biologic drug to treat their condition. And 38% of all patients reported they did not know what a biosimilar was. While the terminology may be unfamiliar, most people are familiar with the concepts. Discovered in 1921 and animal-sourced until 1982, insulin was first introduced as a biosynthetic “human” insulin made via recombinant DNA. Then in 2021, the FDA approved a biosimilar for insulin. Neither biologics nor biosimilars are anything new. But they are revolutionary in what they can accomplish and the way they work.

Defining Biologics and Biosimilars

Biologics are generally defined as a class of drugs that are produced using a living system, such as a microorganism, plant cell, or animal cell.  They are designed to zero in on parts of the immune system that trigger inflammation. These are in contrast to small molecule drugs such as ibuprofen or aspirin that are chemically synthesized; while their structure is known, most biologics are complex mixtures that are not as easily replicated, identified, or characterized. They typically have tens of thousands of molecules, whereas a chemical drug is limited.

Unlike chemically compounded drugs, which are generally available in pill form, these medications are usually administered with a needle, either injected under the skin or infused into a vein.

Since biologics essentially employ your immune system, they offer a targeted treatment option, as they are designed to interact with the immune system in specific ways. The targets have increased exponentially with new genetic information and new understanding of disease processes which indicate there will be exciting scientific breakthroughs in the future. Biologic treatments are transformative for some patients with psoriasis, rheumatoid arthritis, and inflammatory bowel diseases like Crohn’s disease, and even some cancers.

There are differences in how biologics are made as well. The production process of small molecule drugs is relatively well defined as they are chemically manufactured, which allows these drugs to be produced in uniform large quantities. But a biologic is not as readily replicable.  Because the manufacturing uses living cells, it is impossible to guarantee that each batch of a biologic will be identical to the last, which means every dose of a biologic has slight variations.

Because they are so difficult to manufacture, and the approval process costly and exhaustive, they are expensive. In 2022, biologics accounted for a substantial proportion of healthcare expenditures. In the US, they make up only 2% of prescriptions but account for 37% of net drug spending.

A biosimilar is a biological medicinal product that is nearly identical to the original product, but created by a separate manufacturer. According to the Food and Drug Association (FDA), a biosimilar is a biologic that is highly similar to another biologic that is already FDA-approved (known as the original biologic, or reference drug). It is normal and expected for biosimilars and original biologics to have minor differences between batches of the same medication.

Safety and Effectiveness of Biosimilars

When we asked patients about their concerns, more than 40% wanted to know if biosimilars were safe, and what the approval process looked like.

First, there is the approval of the reference product, which entails a well-established, exhaustive process of evaluation and clinical review. This can take several years and involves lengthy and expensive clinical trials. Biosimilars, however, have a different pathway. According to the FDA, since the goal of a biosimilar development program is to demonstrate bio-similarity between the proposed biosimilar and its reference product, not to independently establish the safety and effectiveness of the proposed biosimilar, the process may be abbreviated. This generally means that biosimilar manufacturers do not need to conduct as many expensive and lengthy clinical trials, which subsequently means that the approval process is less costly.

While not specifically “generic” due to the composition and manufacture, the FDA states there are no significant differences in structure or efficacy, and they are made from the same types of sources (e.g., living cells or microorganisms). The investigative process includes analytical studies, which provide the foundation of biosimilar development. These studies provide data to support the structural and functional similarity of the proposed product to the reference product and to evaluate the impact of any differences identified. Animal studies are used to provide toxicology and pharmacology information along with clinical study or studies that prove the biosimilar moves through the body in the same way and provides the same effects as the reference product. An immunogenicity assessment evaluates a patient’s immune response to the proposed biosimilar. Other comparative clinical studies are sometimes conducted after the completion of other studies to address any remaining uncertainty about whether the proposed biosimilar has any clinically meaningful differences from the reference product.

This means you can expect the same safety and effectiveness from the biosimilar throughout treatment as you would the reference product.

Differences Between Biologics and Biosimilars

Biosimilars are generally less costly to manufacture due to two primary reasons. Unlike the reference drug, which took a significant investment to discover, biosimilar companies do not bear the burden of that cost.  Nor do they bear the overall burden of extensive clinical trials and testing.

Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe, Canada, and Australia to cut costs and increase access. Unfortunately, it may be some time before we know definitely if the consumer will see any out-of-pocket cost savings.

Because the pricing and approval structures are different, there is no apples-to-apples comparison to be had in terms of market transition. However, there are some lessons learned for patients who are anticipating what the future may hold if they do, indeed, have to move from a biologic to a biosimilar.

According to a 2023 study that highlighted a systematic review using statistical methods to address the risk of switching patients between reference biologics and biosimilars, there were no differences in the safety profiles or immunogenicity rates in patients who were switched and those who remained on a reference biologic or a biosimilar. This is supported by repeated studies around the world – for most patients, there is minimal risk.

Effectively Transitioning from a Biologic to a Biosimilar

Several factors seem to make a difference in the overall efficacy of uptake. According to a 2022 study published in Rheumatology International, communicating with your healthcare provider is essential. It can prevent what is called the ‘nocebo’ effect, defined as the “worsening of symptoms induced by any negative attitude from a non-pharmacological therapeutic intervention.” Essentially, when approaching the drug with a negative attitude and apprehension, it’s possible to experience a lack of or decrease in efficacy.

Patient support is another factor that appears to help. Described as encouragement from family members and healthcare providers, patient support is also an important component of uptake. For example, one individual interviewed during the study mentioned the positive effect of words of support from her son.

So, if you find yourself facing a potential change in medication, it’s reassuring to know that millions of people have successfully done so in the past and likely there will be no issues with the transition. However, it’s essential for patients to be proactive and as always, they should work with their health care provider to monitor their symptoms carefully and practice the tenants of shared decision-making. It’s also important to approach any potential changes with an open mind and a positive attitude for optimum results.

Additional Educational Resources

 Keep an eye out for an upcoming video series that will explore and clarify the similarities and differences between biologics and biosimilars. Follow our social media channels or subscribe to our emails to be alerted when this educational video series is available.

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