The U.S. Food and Drug Administration (FDA) doesn’t treat biosimilars like regular generics. That’s the first thing you need to understand. A generic aspirin is chemically identical to brand-name aspirin. A biosimilar, on the other hand, is a complex biological molecule - often a protein made in living cells - that’s highly similar, but not identical, to its reference biologic drug. These drugs treat serious conditions like cancer, rheumatoid arthritis, Crohn’s disease, and diabetes. And starting in 2025, the FDA changed how it reviews them - dramatically.
Why Biosimilars Are Different from Generics
Generics are made from simple chemical formulas. You can copy them exactly. Biosimilars come from living systems - yeast, bacteria, or mammalian cells. Even tiny changes in how they’re grown, purified, or stored can affect how they behave in the body. That’s why you can’t just reverse-engineer a biologic like Humira or Enbrel the way you would with a pill. The FDA requires proof of biosimilarity, not identity. This means hundreds of analytical tests comparing the structure, function, and purity of the biosimilar to the original biologic.Before October 2025, sponsors had to run full clinical trials showing the biosimilar worked just as well as the reference drug - often taking three years and costing up to $300 million. That kept most small companies out of the game. Only 28 companies had brought a biosimilar to market in the U.S. as of late 2025, despite over 150 potential candidates identified.
The Big Shift in FDA Guidance (October 2025)
On October 29, 2025, the FDA dropped a bombshell: it no longer routinely requires comparative clinical efficacy studies to approve a biosimilar. That’s huge. The new draft guidance says: if you can prove analytical similarity - meaning your molecule looks, folds, and functions just like the original - and you’ve shown matching pharmacokinetics (how the body absorbs and clears the drug) and low immunogenicity (minimal risk of immune reactions), you may not need a large patient trial at all.The FDA now relies on modern tools: high-resolution mass spectrometry, advanced chromatography, and functional bioassays. These can detect differences at the atomic level. If the data shows the biosimilar matches the reference product across more than 200 quality attributes - and the science behind how those attributes affect safety and effectiveness is well understood - the FDA will accept that as proof.
This change aligns the U.S. more closely with Europe’s EMA, which has approved over 100 biosimilars since 2006. The FDA’s old rules were seen as unnecessarily strict. Now, development time could drop from 8-10 years to 5-7, and costs could fall from $100-300 million to $50-150 million per product.
Interchangeability: What It Really Means
Interchangeability is the holy grail. It means a pharmacist can swap a biosimilar for the brand-name drug without asking the doctor. In the past, the FDA required switching studies - where patients alternated between the reference drug and biosimilar multiple times - to prove no extra risk. That added even more time and cost.In October 2025, the FDA took a radical stance. FDA Commissioner Marty Makary said at a conference: “Every biosimilar should have the designation of interchangeable.” He called interchangeability “a legislative term, not a scientific term.” The agency approved two denosumab biosimilars with interchangeability status that same month - the first time multiple interchangeable biosimilars were approved for the same reference product.
But here’s the catch: federal law still requires a separate application and data package for interchangeability. The FDA can’t just declare all biosimilars interchangeable without Congress changing the law. So while the agency’s scientific position is clear, the legal reality is messy. Some states still have rules blocking automatic substitution unless the product is officially labeled interchangeable. Pharmacists are caught in the middle.
Who’s Winning and Who’s Struggling
Big players like Sandoz, Pfizer, and Amgen dominate the U.S. biosimilar market. Together, they’ve brought 39 biosimilars to market. But small companies? It’s still hard. Only 12 of the 76 approved biosimilars came from firms with fewer than 100 employees. Why? The analytical tools needed - mass spectrometers, automated purification systems - cost millions. Setting up quality control systems takes 12-18 months. The FDA’s own data shows 42% of biosimilar applications get a “complete response letter” asking for more data.Still, the new guidance is helping. Companies like Viatris and Biocon are stepping up. And hospitals are noticing the savings. Mayo Clinic reported a 37% drop in biologic drug costs after switching to biosimilars for cancer treatments - saving $18 million a year. Other health systems are following.
Market Reality: Why U.S. Adoption Is Still Low
Even with these changes, biosimilars only make up 23% of the market for drugs with alternatives in the U.S. In Europe, it’s 67%. Why the gap?- Patients don’t know what biosimilars are. Only 32% of Americans have heard of them.
- Doctors are cautious. Some still worry about long-term effects, especially for chronic conditions.
- Patient stories are mixed. On Reddit, 63% of users switching to biosimilars for rheumatoid arthritis reported similar results. But 22% noticed more injection site reactions.
- Patent lawsuits delay entry. The FTC says 68% of approved biosimilars face legal battles that push launch dates back years.
Therapeutic areas vary too. Oncology biosimilars have 31% market share - doctors are more comfortable switching when lives are on the line. Autoimmune disease biosimilars? Only 18%. Why? Less urgency, more fear of change.
What’s Next: The Road to 2030
The FDA’s draft guidance is open for public comment until January 27, 2026. Final rules are expected by June 2026. Analysts predict approval rates could jump from 8-10 per year to 15-20. By 2030, biosimilars could capture 40-50% of the market for eligible biologics, saving the U.S. system up to $150 billion annually.The science is ready. The regulatory path is clearer. What’s holding things back now isn’t the FDA - it’s the system around it. Pharmacists need consistent rules. Patients need education. Doctors need reassurance. And Congress needs to fix the legal mismatch around interchangeability.
For now, the message is simple: if you’re a patient on a $70,000-a-year biologic, your options are expanding. The FDA is making it possible. The rest of the system just needs to catch up.
Are biosimilars the same as generics?
No. Generics are chemically identical copies of small-molecule drugs, like aspirin or metformin. Biosimilars are complex biological products made from living cells. They’re highly similar to their reference biologic - but not identical - because biological molecules can’t be perfectly replicated. That’s why biosimilars require much more testing than generics.
Do biosimilars work as well as the original biologic drugs?
Yes, when approved by the FDA. All biosimilars must show no clinically meaningful differences in safety, purity, or potency compared to the reference product. Real-world data from patients with rheumatoid arthritis, cancer, and diabetes show similar effectiveness. Some report minor side effect differences, like more injection site reactions, but serious safety issues are rare.
Can pharmacists automatically substitute a biosimilar for the brand name?
Only if the biosimilar has official FDA interchangeability designation. Even then, state laws vary. Thirty-four states still require prescriber approval before substitution, despite the FDA’s position that all biosimilars should be interchangeable. Pharmacists must follow local rules, which creates confusion for patients and providers.
Why are biosimilars so expensive to develop?
Because they’re made in living cells, not labs. Every batch must be tested for over 200 quality attributes - structure, folding, glycosylation, purity - using expensive tools like mass spectrometers and chromatography systems. Setting up these systems takes years and millions of dollars. The new FDA guidance is reducing this cost, but it’s still far more complex than making a generic pill.
How many biosimilars has the FDA approved so far?
As of late 2025, the FDA has approved 76 biosimilars for use in the U.S. These cover conditions including cancer, rheumatoid arthritis, diabetes, Crohn’s disease, and osteoporosis. Ten of these have received interchangeability designation, including two denosumab biosimilars approved in October 2025.
Is the FDA’s new guidance reliable, or is it too risky?
The FDA’s approach is backed by science. Modern analytical tools can now detect differences in biological molecules with far greater precision than clinical trials ever could. Experts like former FDA Deputy Director Mark Eisner call it the most scientifically sound approach yet. Critics worry about long-term effects in chronic conditions, but the FDA argues that the same analytical standards used for decades to ensure drug safety are now sufficient. The risk is low - and the potential savings are enormous.
What Patients and Providers Should Do Now
If you’re on a biologic drug and costs are a burden, ask your doctor about biosimilar options. They’re not just cheaper - they’re proven effective. If you’re a provider, don’t assume patients are afraid of biosimilars. A September 2025 survey found that 68% of patients’ safety concerns disappeared after a simple conversation with their doctor.For pharmacists, know your state’s substitution laws. If your pharmacy system hasn’t updated its protocols since 2023, it’s time to revisit them. The FDA is clearing the path. It’s up to the system to step through.
