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

When you pick up a prescription for insulin or an arthritis drug, you might not realize the pill you’re handed could be a biosimilar-and if it’s labeled as interchangeable, the pharmacist didn’t even need to ask your doctor. This isn’t science fiction. It’s happening right now in pharmacies across the U.S., and it’s changing how millions access life-saving treatments.

What Makes a Biosimilar Different From a Generic?

Think of generics as exact copies of small-molecule drugs like aspirin or metformin. They’re chemically identical to the original brand name. Biosimilars? They’re not copies. They’re highly similar versions of complex biologic drugs made from living cells-like Humira, Enbrel, or Lantus. These drugs are made in living systems (think yeast, bacteria, or animal cells), so even tiny changes in the manufacturing process can affect how they work. That’s why the FDA doesn’t call them "equivalent" like generics. Instead, they’re called "biosimilar," meaning they match the original in safety, purity, and potency-but aren’t identical.

Interchangeability: The Extra Step

Not all biosimilars are created equal when it comes to substitution. Only those with the FDA’s "interchangeable" designation can be swapped out automatically at the pharmacy, just like a generic. To earn that label, a biosimilar must prove it can be switched back and forth with the original drug-multiple times-without increasing risk or reducing effectiveness. That means clinical studies where patients alternate between the reference product and the biosimilar. One study might involve switching three times: biologic → biosimilar → biologic → biosimilar. If the patient’s immune response, drug levels, and side effects stay stable throughout, the FDA may grant interchangeability.

The first interchangeable biosimilar approved was Semglee, an insulin glargine product, in July 2021. Then in August 2023, Cyltezo became the first interchangeable monoclonal antibody biosimilar-targeting conditions like rheumatoid arthritis and psoriasis. As of November 2023, the FDA has approved 10 interchangeable biosimilars out of 41 total biosimilars.

Why It Matters: Cost and Access

Biologics are expensive. Humira, for example, cost over $70,000 per year before biosimilars entered the market. Interchangeable biosimilars typically cost 15-30% less. That’s not just savings for patients-it’s billions saved for insurers and the healthcare system overall. A 2022 RAND Corporation study found biosimilars reduced spending significantly, especially when substitution was automatic. States with laws allowing pharmacists to swap without prescriber approval saw 18.7% higher biosimilar use for insulin, according to a 2023 JAMA Health Forum study.

But here’s the catch: interchangeability doesn’t mean you can swap between two different biosimilars. If your doctor prescribed Cyltezo, and your pharmacy has Hadlima (another adalimumab biosimilar), they can’t automatically switch you to Hadlima-even if both are interchangeable with Humira. The FDA’s rules only allow substitution with the original reference product, not between biosimilars. That creates confusion for pharmacists and patients alike.

State Laws: A Patchwork of Rules

Federal rules say interchangeable biosimilars can be substituted automatically. But state laws decide if they actually are. As of 2023:

• 40 states (including Arizona, California, and New York) allow pharmacists to substitute without asking the doctor.
• 6 states and Washington D.C. only allow substitution if it saves the patient money.
• 4 states (Alabama, Indiana, South Carolina, Washington) plus Puerto Rico require the doctor’s permission every time.

This mess creates real problems. A pharmacist in Arizona might swap your Humira for Cyltezo without telling you. A pharmacist in Alabama can’t do it unless your doctor wrote "dispense as written" on the script. Many pharmacies use software that doesn’t differentiate between state rules, leading to errors. A 2022 survey by the National Community Pharmacists Association found 67% of independent pharmacists were confused about what they could legally do.

What Patients Experience

Some patients report no issues. One user on the Psoriasis Foundation forum said switching from Humira to Hyrimoz saved them $800 a month with no loss in symptom control. Others weren’t told at all-and had reactions. One person reported an allergic response after their pharmacy switched to Hadlima without notice. The problem? Biosimilars can have different inactive ingredients (excipients) than the original drug. While the active part is nearly identical, those extra chemicals can trigger allergies or side effects in rare cases.

A 2022 National Psoriasis Foundation survey showed 63% of patients were satisfied with their biosimilar, but 28% were upset they weren’t informed. That’s a big deal. Informed consent matters. Even if the law doesn’t require it, ethical practice does. Some states, like Arizona, require pharmacists to notify patients in writing and send records to the prescriber within five days. Others don’t.

Pharmacists Are Caught in the Middle

Pharmacists are expected to know federal rules, state laws, insurance policies, and product labels-all while managing busy counters. The American Pharmacists Association offers a 2.5-hour Biosimilars Certificate Program. As of October 2023, over 12,000 pharmacists had completed it. Still, a 2023 survey found pharmacists spent an average of 8.7 hours a year just keeping up with changing rules.

Insurance companies make it harder. About 78% of commercial health plans require automatic substitution for interchangeable biosimilars when state law allows. That means if your plan covers Cyltezo and your state permits substitution, your pharmacy has to switch you-even if you’d prefer to stay on Humira. You can opt out, but you’ll likely pay more out of pocket.

The Big Debate: Should All Biosimilars Be Interchangeable?

There’s a growing push to eliminate the need for switching studies entirely. The Biosimilar Red Tape Elimination Act, introduced in late 2022, would make every FDA-approved biosimilar automatically interchangeable. Supporters say it would cut red tape and speed up savings. The Biosimilars Council backs it. But PhRMA, the big pharma lobby, argues it could risk patient safety. They point to studies showing non-medical switches (like swapping drugs without clinical reason) led to a 20.3% higher discontinuation rate in psoriasis patients, according to a 2021 JAMA Dermatology editorial.

The FDA’s stance is clear: all approved biosimilars are safe and effective. Interchangeability isn’t about quality-it’s about substitution logistics. As Dr. Sarah Yim from the FDA put it in 2023: "Interchangeables are not a higher level of biosimilar. They’re just a different path to the same outcome."

What This Means for You

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

• Your prescription might be switched to a biosimilar without you being told-unless you live in Alabama, Indiana, South Carolina, or Washington.
• Check your medication label. Interchangeable biosimilars will have the same name as the original, but end in a four-letter suffix (like adalimumab-adbm for Cyltezo).
• Ask your pharmacist: "Is this interchangeable?" and "Was this a substitution?"
• If you feel different after a switch-worse symptoms, new side effects-call your doctor immediately.
• You can always ask your doctor to write "dispense as written" or "do not substitute" on your prescription.

The Future: More Biosimilars, More Confusion?

By 2025, 70% of the top 20 biologic drugs by sales will have biosimilar competition. That means more interchangeable options coming-especially for insulin, rheumatoid arthritis, and cancer drugs. But without national standardization, the system will stay messy. Patients will get different experiences depending on where they live. Pharmacists will keep struggling to keep up. And the cost savings? They’re real-but only if the system works smoothly.

Right now, the U.S. is the only country with a formal interchangeability designation. Europe, Canada, and Japan handle substitution differently-often requiring doctor approval. The U.S. model aims for speed and savings. But without better education, clearer rules, and consistent communication, it risks leaving patients and providers behind.