Biosimilar Approval: How the FDA Reviews Biologic Alternatives in 2026

When you hear "generic drug," you probably picture a small, cheap pill that does the same thing as the brand-name version. But when it comes to biologics-complex drugs made from living cells like antibodies or proteins-that simple idea doesn’t work. You can’t just copy them like a photocopy. That’s where biosimilars come in. They’re not generics. They’re highly similar, scientifically proven alternatives to expensive biologic drugs, and the FDA’s approval process for them just got a major update in late 2025.

Why Biosimilars Are Different from Generics

Generics are exact chemical copies of small-molecule drugs. Think aspirin or metformin. Their structure is simple, stable, and easy to replicate. Biosimilars? They’re made from living organisms-cells, proteins, antibodies. Even tiny changes in how they’re grown, purified, or stored can affect how they work in the body. That’s why a biosimilar isn’t identical to its reference product. It’s highly similar-with no clinically meaningful differences in safety, purity, or potency.

The FDA requires proof of this similarity through a mountain of data: analytical tests, animal studies, pharmacokinetic (PK) studies, and sometimes clinical trials. Before October 2025, most biosimilar applications needed a full comparative efficacy study-often taking 2-3 years and costing upwards of $200 million. That kept many smaller companies out of the game. Now, that’s changing.

The Big Shift: FDA’s October 2025 Guidance

On October 29, 2025, the FDA released a landmark draft guidance titled Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies. This wasn’t a minor tweak. It was a rewrite of the rulebook.

Here’s what changed: The FDA no longer routinely requires comparative clinical efficacy studies. If a biosimilar candidate meets three key conditions, those large, expensive human trials may no longer be needed:

1. The drug is made from a single, well-characterized cell line and is highly purified.
2. The link between its molecular structure and how it works in the body is well understood (like with adalimumab or trastuzumab).
3. A pharmacokinetic study in humans can show the drug behaves the same way in the body as the original.

This is huge. Analytical tools today-like mass spectrometry and advanced chromatography-can now detect differences at the atomic level. The FDA says these tools are so precise that they can predict clinical outcomes better than traditional trials for many drugs. That means faster approvals, lower costs, and more competition.

Interchangeability: What It Means and Why It Matters

There’s another layer: interchangeability. This is the designation that allows pharmacists to swap a biosimilar for the original drug without asking the doctor. It’s a legal term, not a scientific one. But until 2025, the FDA required extra “switching studies”-where patients alternate between the reference drug and biosimilar-to prove no added risk.

That’s gone. FDA Commissioner Marty Makary said at the GRx+Biosims 2025 conference: “Every biosimilar should have the designation of interchangeable.” He called the old requirement a bureaucratic hurdle, not a scientific one. In October 2025, the FDA granted interchangeability status to two denosumab biosimilars at once-the first time that happened for the same reference product.

But here’s the catch: States still control pharmacy substitution rules. Thirty-four states have laws that make it harder than it should be. Even if the FDA says a biosimilar is interchangeable, a pharmacist in some states can’t switch it without a doctor’s OK. That’s slowing down adoption.

Who’s Making Biosimilars-and Who’s Not

As of late 2025, the FDA has approved 76 biosimilars. But only 12 came from companies with fewer than 100 employees. Why? Because the analytical requirements are still intense. You need labs that can run hundreds of tests on protein structure, glycosylation patterns, and impurity profiles. That’s expensive. Only big players like Sandoz, Pfizer, and Amgen have had the resources to play.

But now, with the new guidance, smaller companies are lining up. Wilson Sonsini’s analysis predicts development costs could drop from $100-300 million to $50-150 million. Timelines could shrink from 8-10 years to 5-7. That’s a game-changer for startups. The Biosimilars Council has already seen 87 consultations with small developers since 2023.

Still, some molecules are tougher. Antibody-drug conjugates-like those used in cancer treatment-are harder to characterize. The relationship between their structure and how they work isn’t as clear. For those, the FDA still says: “We may need clinical data.” So it’s not a free pass for everything.

Market Reality: Why Biosimilars Are Still Underused in the U.S.

Europe has had biosimilars since 2006. They now make up 67% of the market for biologics. In the U.S.? Only 23%. Why the gap?

• Physician hesitation: Many doctors still don’t trust biosimilars, even when data shows they’re safe.
• Patient fear: A 2025 Arthritis Foundation survey found 41% of patients were worried about switching. Most of those fears faded after talking to their doctor.
• Patent thickets: Biologic manufacturers use legal tactics to delay biosimilar entry. The FTC found 68% of approved biosimilars faced patent lawsuits that pushed back launch dates.
• Lack of awareness: Only 32% of patients know what a biosimilar is, according to the National Biosimilars Survey.

But hospitals are seeing results. Mayo Clinic reported a 37% drop in biologic drug costs after switching to biosimilars for cancer treatments-saving $18 million a year. That’s real money.

What’s Next? The Road to 2030

The U.S. biosimilar market was worth $18.7 billion in 2024. Experts project it’ll hit $62.3 billion by 2029. That’s a 27% annual growth rate. The FDA’s new guidance could push annual approvals from 8-10 to 15-20. By 2030, McKinsey forecasts biosimilars could capture 40-50% of the market.

That could mean $150 billion in annual savings for the U.S. healthcare system. But it won’t happen unless three things change:

1. States update their pharmacy substitution laws to match the FDA’s stance.
2. Doctors and patients get educated-real talk, not marketing.
3. Patent litigation is addressed. Right now, legal battles are the biggest barrier, not science.

The FDA’s October 2025 guidance is a scientific win. But policy and perception still lag. The tools are here. The data is solid. Now, it’s about making sure patients get access-not just paperwork.

How to Get Started with Biosimilars

If you’re a developer looking to bring a biosimilar to market:

• Start early with the FDA. Schedule a Biologics Product Development (BPD) meeting. The first fee is due within 7 days of approval.
• Invest in analytical tech. You’ll need mass spectrometry, chromatography, and bioassays to test over 200 quality attributes.
• Focus on well-characterized targets first-like monoclonal antibodies for rheumatoid arthritis or diabetes.
• Use the FDA’s Biosimilars Community Resource Center. It had over 12,000 visitors in October 2025.

For patients and providers: Ask your doctor if a biosimilar is an option. Ask your pharmacist if it’s interchangeable. And don’t assume it’s “less effective.” The science says otherwise.

Final Thoughts

The FDA’s 2025 update isn’t just a regulatory tweak-it’s a shift in how we think about biologic drugs. Science has caught up. We no longer need to prove biosimilarity through massive human trials when we can see the molecules with enough precision to predict how they’ll behave. The question now isn’t whether biosimilars work. It’s whether we’ll let them reach the patients who need them.

The savings are real. The science is solid. The only thing left to fix is the system holding them back.