Provider Education: Understanding Biosimilar Differences

When a doctor prescribes a biologic for rheumatoid arthritis, Crohn’s disease, or cancer, they’re using a complex medicine made from living cells - not a simple chemical compound. These drugs have changed lives. But now, a new kind of option is showing up: biosimilars. And if you’re a provider, you need to know how they’re different - not just from the original biologic, but from plain old generics.

What Exactly Is a Biosimilar?

A biosimilar is a biological product that’s highly similar to an FDA-approved reference biologic. It’s not a copy. It’s not a generic. It’s something in between. The FDA requires manufacturers to prove no clinically meaningful difference in safety, purity, or potency. That means the biosimilar works the same way in the body. But because biologics are made from living organisms - like cells grown in labs - tiny variations are unavoidable. Think of it like two handmade wooden chairs from the same craftsman. They look nearly identical, function the same, and feel the same. But if you examine them under a microscope, you’ll see slight differences in grain or finish. That’s biosimilarity.

The first FDA-approved biosimilar in the U.S. was Zarxio, a version of filgrastim, launched in 2015. Since then, 46 biosimilars have been approved as of November 2023. They’re used in oncology, rheumatology, endocrinology, and more. The goal? Lower costs without lowering care. Medicare Part B data from 2022 shows biosimilars cost 28% less on average than their reference products. Over the next decade, the Congressional Budget Office estimates biosimilars could save the U.S. healthcare system $150 billion.

Biosimilars vs. Generics: The Big Difference

This is where confusion starts. Most providers know generics. They’re chemically identical copies of brand-name pills - like metformin or lisinopril. The FDA only requires bioequivalence studies: prove the generic gets into the bloodstream the same way and at the same rate as the original. That’s it. One or two small studies. Usually under 100 people.

Biosimilars? Not even close. They require a whole different level of proof. Manufacturers must run analytical tests comparing molecular structure, functional assays, animal studies, and at least one clinical trial - often involving hundreds of patients. Sometimes two. The goal isn’t just to match blood levels. It’s to prove the immune system reacts the same way. That’s because biologics can trigger immune responses. Even small differences in how they’re made can affect immunogenicity - the risk of the body seeing the drug as foreign and attacking it.

Here’s the hard truth: 63% of U.S. physicians in a 2016 survey couldn’t correctly explain this difference. That’s not just a knowledge gap. It’s a barrier to adoption. Providers who don’t understand this risk rejecting biosimilars out of fear - not science.

Why So Much Hesitation Among Providers?

It’s not just about complexity. It’s about trust. In a 2021 survey of 500 U.S. pharmacists, only 22% felt very confident explaining biosimilar differences to patients. Among oncologists, 40% weren’t sure biosimilars would work as well as the original biologic before training. Even after training, 57% still worried about using biosimilars for conditions not directly tested in trials - a concept called “extrapolation.”

Extrapolation means if a biosimilar works for rheumatoid arthritis, and the reference product is also approved for psoriatic arthritis, the biosimilar can get approved for psoriatic arthritis too - without running a separate clinical trial for that condition. The FDA allows this only if the mechanism of action is the same and the disease processes are similar. But many providers don’t buy it. They think, “If they didn’t test it, how do I know?”

Real-world data is changing that. In Europe, where biosimilars have been used for over 15 years, studies show no increase in adverse events when switching from reference products to biosimilars. The American College of Rheumatology now gives a strong recommendation for biosimilar use in rheumatoid arthritis, based on 37 clinical trials with over 12,500 patients.

Interchangeable Biosimilars: The Next Level

There’s a special category called “interchangeable” biosimilars. These have passed an extra hurdle: they’ve been tested in multiple switches between the biosimilar and the reference product - sometimes back and forth several times - with no loss of safety or effectiveness. Only a handful have received this designation so far, like Semglee (insulin glargine) and Fycompa (perampanel).

Why does this matter? Because in 42 U.S. states, pharmacists can substitute an interchangeable biosimilar for the reference product without asking the prescriber - just like they do with generics. But here’s the catch: if the biosimilar isn’t interchangeable, the prescriber must specifically write “dispense as written” or “no substitution.” And EHR systems? Many still don’t track the difference. A 2022 AMCP survey found 78% of U.S. hospitals struggle with documentation in their electronic records. That means a patient might get a biosimilar, but the chart doesn’t show it. That’s dangerous for monitoring side effects or managing insurance.

Who’s Leading in Adoption - And Who’s Falling Behind?

Adoption isn’t even across specialties. Rheumatologists are at the front: 68% use biosimilars regularly. Oncologists are close behind at 52%. But endocrinologists? Only 29%. That’s despite insulin biosimilars being available since 2015. Why? Because endocrinologists manage patients with complex, long-term conditions. They’re cautious. And patients are often on stable regimens. Switching feels risky.

Meanwhile, pharmacists are the unsung heroes. In 76% of U.S. hospitals, pharmacists lead biosimilar education. They run lunch-and-learns, update formularies, train nurses, and fix EHR issues. At UCSF Medical Center, pharmacist-led education cut provider hesitation from 58% to 12% in just six months. At the University of Pittsburgh, a three-phase approach - foundational knowledge, specialty-specific training, then ongoing support - boosted provider confidence to 89% within six months.

Education Is the Missing Link

Studies show a direct link between education and confidence. Before training, only 40.1% of providers were sure biosimilars worked as well as originators. After 12 training sessions over four months, that jumped to 92%. That’s not a small gain. That’s life-changing for patients.

The FDA has built a full Teaching Resource Guide with 12 modules, available in nine languages. It covers everything: regulatory pathways, immunogenicity, extrapolation, billing, and EHR setup. But awareness is low. Only 38% of U.S. physicians in one survey said they were “extremely familiar” with the FDA’s definition of biosimilarity. Younger providers? They’re even less familiar - 40% less than experienced clinicians.

Real education isn’t a one-time webinar. It’s ongoing. It’s built into pharmacy school curricula. It’s part of oncology fellowships. It’s discussed in grand rounds. The Association of American Medical Colleges plans to embed biosimilar education into 95% of medical school programs by 2025. That’s progress. But we need more.

What You Need to Know Right Now

• Biosimilars are not generics. They require far more testing and proof of similarity.
• Minor differences in inactive ingredients are allowed - but not in the active part that affects safety or effectiveness.
• Extrapolation is scientifically valid, but requires clear communication with patients.
• Interchangeable biosimilars can be substituted at the pharmacy without prescriber approval - in states that allow it.
• EHR systems often fail to track biosimilars correctly. You must manually verify documentation.
• Provider confidence jumps dramatically with targeted education - especially when led by pharmacists.

If you’re prescribing biologics, you’re already on the front lines of cost-saving care. Biosimilars aren’t a threat. They’re a tool. Used right, they expand access to life-changing treatments for patients who couldn’t afford them before. But only if providers understand them.

What’s Next?

The market is growing fast. Global biosimilar sales hit $12.3 billion in 2022, up 18% from the year before. But the U.S. still lags behind Europe, where biosimilars make up 65% of eligible biologic prescriptions. The gap? Education. In Europe, concerted efforts by regulators, manufacturers, and providers built trust over time. The U.S. is catching up - slowly.

The FDA plans to update its Teaching Resource Guide in 2024 with more real-world evidence data. That’s critical. Providers want to know: “What’s happened to real patients who switched?” Not just trial results. Real outcomes. Real side effects. Real savings.

Start here: Talk to your hospital pharmacist. Ask if they have a biosimilar education program. If not, suggest one. Review the FDA’s free resources. Attend a webinar. Read one study. Don’t wait for someone else to fix the knowledge gap. You’re the one who prescribes. You’re the one who explains. And your understanding - right now - can change how thousands of patients are treated.