When Can Biosimilars Be Automatically Substituted? Understanding Interchangeability in the U.S.

When you walk into a pharmacy to pick up your insulin or rheumatoid arthritis medication, you might not realize that what you’re handed could be a biosimilar-and that it might have been swapped in without your doctor’s knowledge. This isn’t a glitch in the system. It’s the result of a specific FDA designation called interchangeability. And it’s changing how millions of Americans access life-saving biologic drugs.

What Exactly Is an Interchangeable Biosimilar?

An interchangeable biosimilar isn’t just any biosimilar. It’s a special category created by the U.S. Food and Drug Administration (FDA) under the Biologics Price Competition and Innovation Act (BPCIA) of 2009. This designation allows pharmacists to swap out the original biologic drug-like Humira or Lantus-with a biosimilar version without needing to check back with the prescriber. It’s automatic. Just like how generic pills replace brand-name drugs under the Hatch-Waxman Act.

But here’s the catch: not all biosimilars are interchangeable. In fact, as of November 2023, out of 41 FDA-approved biosimilars, only 10 have earned this status. The first was Semglee, an insulin glargine biosimilar approved in July 2021. The first interchangeable monoclonal antibody was Cyltezo, approved in August 2023, which can replace Humira without a doctor’s order.

Interchangeability doesn’t mean the biosimilar is better. It just means the FDA has confirmed that switching back and forth between the reference product and the biosimilar won’t increase safety risks or reduce effectiveness. That’s a much higher bar than standard biosimilarity, which only requires proof that the biosimilar is highly similar to the original.

Why Is Interchangeability So Hard to Get?

Unlike generic drugs, which are chemically identical copies of small-molecule medications, biosimilars are made from living cells. Think of them like handmade replicas of a complex sculpture-no two are exactly alike. That’s why the FDA demands extra proof before allowing automatic substitution.

To qualify as interchangeable, a manufacturer must run switching studies. These involve giving patients multiple rounds of the reference drug and the biosimilar, switching between them at least twice. Researchers then track whether this back-and-forth causes any unexpected side effects, changes in immune response, or drops in effectiveness. The data must show no clinically meaningful differences after these switches.

The FDA’s guidance, updated in January 2023, requires statistical proof that the biosimilar performs just as reliably as the original-even after multiple switches. This isn’t just about matching one dose. It’s about proving consistency over time, across different patients, in different conditions.

Compare that to the European Union, where no formal interchangeability designation exists. In Europe, substitution decisions are left to doctors or pharmacists, and there’s no requirement for switching studies. The U.S. is the only country with this specific legal pathway.

State Laws Are a Mess

Even if the FDA says a biosimilar is interchangeable, that doesn’t mean it can be automatically swapped everywhere. Each state has its own rules.

Forty states, including Arizona and California, allow pharmacists to substitute interchangeable biosimilars without contacting the prescriber. But even in those states, there are hoops to jump through. In Arizona, pharmacists must notify the patient, record the exact product and manufacturer, send a notice to the doctor within five business days, and keep records for seven years.

Six states and Washington D.C. only allow substitution if it saves the patient money. Four states-Alabama, Indiana, South Carolina, and Washington-require the prescriber’s explicit approval before any substitution can happen. And in some places, pharmacists have to check whether the patient’s insurance plan mandates substitution.

This patchwork creates real confusion. A 2022 survey by the National Community Pharmacists Association found that 67% of independent pharmacists struggled to keep up with state-specific rules. One pharmacist on Reddit wrote: “In California, I have to check if it’s lower cost, but in Arizona I don’t. My pharmacy system doesn’t differentiate between states.”

Interchangeable vs. Non-Interchangeable: What’s the Real Difference?

Let’s be clear: every FDA-approved biosimilar-interchangeable or not-is safe and effective. The FDA insists that all biosimilars meet the same high standards for quality, purity, and potency as the original biologic. The only difference is who gets to decide when to switch: the doctor, or the pharmacist.

Non-interchangeable biosimilars still offer big cost savings-typically 15% to 30% less than the reference product, according to a 2022 RAND Corporation study. But they can’t be swapped automatically. That means if your doctor prescribes Humira, you’ll get Humira, unless you or your doctor specifically asks for a biosimilar.

Interchangeable biosimilars, on the other hand, can be substituted without any action from the prescriber. That’s why they’re driving faster adoption. In the insulin market, Semglee captured 17.3% of the market within six months of launch. Non-interchangeable biosimilars took much longer to reach similar levels.

What Do Patients Really Think?

Patient experiences vary. Some are thrilled with the savings. One person on the Psoriasis Foundation forum wrote: “My dermatologist switched me from Humira to Hyrimoz. I saved $800 a month with no change in effectiveness.”

Others aren’t so happy. Another patient reported an adverse reaction after their pharmacy automatically substituted Hadlima for Humira without telling them. Turns out, they were allergic to an excipient-a non-active ingredient-in the biosimilar.

A 2022 survey by the National Psoriasis Foundation found that 63% of patients were satisfied after switching to a biosimilar. But 28% were upset they weren’t notified. That’s a big issue. Patients have a right to know what they’re taking, especially when it’s a complex biologic.

And then there’s the concern about treatment persistence. Dr. Kevin Winthrop, a professor at Oregon Health & Science University, pointed to a study showing psoriasis patients switched to biosimilars were 20.3% more likely to stop treatment altogether. Could it be side effects? Lack of communication? Or just the psychological impact of being switched without consent?

What’s Next for Interchangeable Biosimilars?

The market is growing fast. By 2026, biosimilars could capture nearly half of the $168 billion global biologics market, according to Evaluate Pharma. But regulatory uncertainty is slowing things down.

There’s a bill in Congress-the Biosimilar Red Tape Elimination Act (H.R. 9500)-that wants to scrap the switching study requirement. Proponents, including the Biosimilars Council, argue it would speed up access and lower prices. Opponents, like PhRMA, warn it could compromise safety.

Meanwhile, the FDA is working on streamlining its guidance. A 2023 draft proposal suggests reducing the burden of switching studies, possibly allowing data from one product to support interchangeability for others in the same class.

Pharmacists are getting better trained. The American Pharmacists Association has certified over 12,450 pharmacists in biosimilars as of October 2023. But the learning curve is steep. Pharmacists now spend an average of 8.7 hours a year just keeping up with changing laws.

What Should You Do as a Patient?

If you’re on a biologic drug, here’s what you need to know:

• Ask your doctor if a biosimilar is an option-and whether it’s interchangeable.
• Check your prescription. If your doctor writes “dispense as written” or uses a DAW code like “DAW 1,” substitution is blocked.
• Always ask your pharmacist: “Is this the same drug my doctor prescribed?”
• If you’re switched without warning, call your doctor. Report any new side effects.
• Know your state’s laws. If you live in Alabama or Washington, your pharmacist can’t substitute without your doctor’s OK.

You don’t have to accept automatic substitution. You have the right to refuse. And you have the right to be told when a change happens.

Final Thoughts

Interchangeability is a powerful tool. It’s designed to lower costs and expand access to biologics that can cost over $20,000 a year. But it’s not a simple swap. It’s a complex system built on science, law, and patient rights.

The U.S. has created a unique path-one that no other country follows. And while it’s working for some, it’s confusing for others. The goal should be clear: safe, affordable access to biologics, with transparency and choice at the center.

The next few years will decide whether interchangeability becomes a cornerstone of American healthcare-or a regulatory headache that holds back progress.