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

When you pick up a prescription for insulin or an autoimmune drug like Humira, you might not realize your pharmacist could swap it for a cheaper version without asking your doctor. That’s not a mistake-it’s interchangeability. But only if the biosimilar has been officially labeled as interchangeable by the FDA. And not every state lets them do it.

What Makes a Biosimilar Interchangeable?

A biosimilar isn’t just a cheaper copy of a biologic drug. It’s a highly complex version made from living cells, not chemicals. That’s why it’s not like a generic pill. Generics, like generic ibuprofen, are exact chemical duplicates. Biosimilars are similar-but not identical-because living systems (like yeast or hamster cells) are used to make them. Tiny differences in manufacturing can change how the drug behaves in your body.

The FDA created a special category called interchangeable biosimilar to let pharmacists swap it out automatically, just like generics. But to get that label, the manufacturer has to prove more than just similarity. They need to show that switching back and forth between the original drug and the biosimilar doesn’t increase risk or reduce effectiveness. That means running studies where patients are switched multiple times-say, from Humira to a biosimilar, then back to Humira, then again to the biosimilar-and tracking safety and response over time.

As of November 2023, the FDA has approved 41 biosimilars. Only 10 of them have the interchangeable designation. The first was Semglee, an insulin glargine product approved in July 2021. The first interchangeable monoclonal antibody biosimilar was Cyltezo, approved in August 2023. These aren’t "better" biosimilars-they’re just ones that passed an extra hurdle for substitution.

Why Doesn’t the U.S. Just Make All Biosimilars Interchangeable?

Some experts argue we should. The Biosimilar Red Tape Elimination Act, introduced in late 2022, proposed removing the switching study requirement and automatically granting interchangeability to all FDA-approved biosimilars. The Biosimilars Council supports this, saying it would speed up cost savings. But PhRMA, the big drugmaker lobby, opposes it, arguing that switching without proof could risk patient safety.

The FDA disagrees with the idea that all biosimilars are the same when it comes to substitution. They maintain that interchangeability is about the process of switching, not the quality of the drug. All approved biosimilars-interchangeable or not-are just as safe and effective as the original. But only the interchangeable ones have been tested for multiple switches.

In Europe, Canada, and Japan, there’s no formal interchangeability designation. Substitution is usually up to the doctor or pharmacist, often with rules about informing the patient. The U.S. is the only country that built a legal pathway for automatic substitution at the pharmacy counter.

State Laws Are a Mess

Even if a biosimilar is FDA-interchangeable, your pharmacist might not be allowed to swap it. Forty states let pharmacists substitute without asking the doctor first. But six states and Washington D.C. only allow it if the patient pays less. Four states-Alabama, Indiana, South Carolina, and Washington-require the prescriber to approve the switch every time.

Pharmacists are stuck in the middle. A 2022 survey found 67% of independent pharmacists were confused about state rules. One pharmacist on Reddit wrote: "In California, I check if it’s cheaper. In Arizona, I don’t. My pharmacy software doesn’t know the difference."

Arizona’s law is strict: pharmacists must notify the patient, record the exact brand and manufacturer, tell the doctor within five days, and keep records for seven years. Other states have different rules. And every state lets doctors block substitution by writing "dispense as written" or using a DAW code on the prescription.

Cost Savings Are Real-But Not Always Immediate

Biosimilars typically cost 15-30% less than the original biologic. Semglee, the interchangeable insulin, captured 17.3% of the insulin market within six months. Non-interchangeable biosimilars only reached 9.8% in the same time. That’s a big gap.

A 2023 JAMA Health Forum study showed states with automatic substitution laws had 18.7% higher biosimilar use for insulin. Insurance companies are pushing for it too-78% of commercial plans now require automatic substitution when state law allows it.

But savings aren’t guaranteed. Some patients end up paying more if their plan doesn’t cover the biosimilar as well. Or if the pharmacy doesn’t know how to process the claim correctly.

What Patients Are Saying

On patient forums, stories are mixed. One person with psoriasis said switching from Humira to Hyrimoz saved them $800 a month with no side effects. Another said their pharmacy swapped Humira for Hadlima without telling them-and they had an allergic reaction to an inactive ingredient.

A 2022 National Psoriasis Foundation survey found 63% of patients were satisfied with their biosimilar. But 28% were upset they weren’t told about the switch. That’s a big issue. Biologics are powerful drugs. Patients want to be part of the decision.

What Pharmacists Need to Know

Pharmacists aren’t expected to be biologics experts-but they do need to know the rules. The American Pharmacists Association offers a 2.5-hour Biosimilars Certificate Program. As of October 2023, over 12,000 pharmacists have taken it.

They need to check:

• Is the biosimilar FDA-designated as interchangeable?
• What does my state law say?
• Did the doctor block substitution?
• Is the patient’s insurance covering the switch?
• Do I need to notify the patient or doctor?

On average, pharmacists spend nearly nine hours a year just learning the rules. That’s time they could spend counseling patients.

The Future: More Biosimilars, More Confusion?

By 2025, 70% of the top 20 selling biologics will have biosimilar competitors. Insulin, Humira, Enbrel, Remicade-these are all up for grabs. Interchangeable versions will likely follow.

But the system is still broken. Patients don’t know if they’re getting a biosimilar. Pharmacists are overwhelmed. Doctors aren’t always informed. And the federal government hasn’t stepped in to fix the state-by-state mess.

The FDA is working on streamlining the switching study rules. But until Congress or the states create uniform rules, interchangeability will remain a patchwork of confusing laws, good intentions, and real-world consequences.

What This Means for You

If you’re on a biologic:

• Ask your doctor if your prescription can be switched to a biosimilar.
• Ask your pharmacist: "Is this the original drug or a biosimilar? Is it interchangeable?"
• Check your pharmacy’s notification policy. Are you being told about the switch?
• Monitor your symptoms. If you feel different after a switch, tell your doctor immediately.
• Know your insurance plan’s rules. Some won’t cover the biosimilar unless you switch.

Biosimilars are saving billions. But automatic substitution isn’t magic. It needs transparency, education, and clear rules-before more patients get caught in the middle.