FDA Listing for Biosimilars: How They Are Evaluated and Approved

When you hear the word biosimilar, you might think it’s just another name for a generic drug. But that’s not true. Biosimilars aren’t copies like generics-they’re highly similar versions of complex biologic medicines, made from living cells. The FDA doesn’t give them a simple rating like A, B, or C. Instead, they go through a deep, science-heavy process to prove they’re safe and effective. If you’re wondering how the FDA decides which biosimilars can be sold in the U.S., here’s how it actually works.

What Makes a Biosimilar Different From a Generic

Generics are simple chemical copies of brand-name drugs. You can make them in a lab using the same ingredients every time. Think of them like baking cookies from a recipe-same flour, sugar, butter, same result.

Biosimilars are nothing like that. They’re made from living organisms-cells, proteins, antibodies. Even tiny changes in how they’re grown, stored, or handled can change how they work in the body. That’s why a biosimilar isn’t an exact copy. It’s a highly similar version, with no clinically meaningful differences in safety or effectiveness. The FDA requires proof of this similarity through over 200 different analytical tests.

The FDA’s Step-by-Step Approval Process

The FDA doesn’t approve biosimilars the same way it approves new drugs. Instead, it uses a special pathway called 351(k), created by the BPCIA in 2010. Here’s how it works:

1. Analytical studies: Scientists compare the biosimilar to the original biologic using advanced tools like mass spectrometry and capillary electrophoresis. They look at molecular structure, purity, and how the protein folds. The goal? At least 95-99% similarity across critical quality attributes.
2. Animal studies: These test for toxicity and how the body reacts. The FDA can skip this step if the analytical data is strong enough.
3. Human studies: Pharmacokinetic (how the body processes the drug) and pharmacodynamic (how the drug affects the body) studies are done in 50-100 healthy volunteers. These are usually crossover trials-patients get both the biosimilar and the reference drug at different times.
4. Immunogenicity testing: This checks if the body reacts to the drug with unwanted immune responses. This is critical because biologics can trigger antibodies that reduce effectiveness or cause side effects. Testing lasts 24-52 weeks.

The FDA looks at all this data together-the “totality of evidence.” If everything lines up, they approve the product. No large-scale clinical trials with thousands of patients are needed, unlike for brand-new biologics.

The FDA Purple Book: The Official List

You won’t find biosimilars listed in the same place as generics. The FDA’s Purple Book is the only official source for approved biologics and their biosimilars. As of October 2025, it includes 387 reference biologics and 43 approved biosimilars.

Each entry shows:

• The reference product name
• The biosimilar’s brand and generic name
• Approval date
• Exclusivity period
• Whether it’s designated as “interchangeable”

Since June 2021, the Purple Book also includes patent information that reference product makers must submit. This helps biosimilar companies plan their launches and avoid legal delays.

Interchangeable vs. Biosimilar: What’s the Difference?

Not all biosimilars are interchangeable. In fact, only 17 out of the 43 approved biosimilars have this status as of late 2025.

An interchangeable biosimilar meets an even higher bar. The FDA requires proof that switching between the reference product and the biosimilar won’t increase risk or reduce effectiveness. This means:

• It must produce the same clinical result in any patient
• Switching back and forth multiple times must be safe
• No additional safety risks compared to staying on the reference product

Only interchangeable biosimilars can be automatically substituted by pharmacists without a doctor’s permission-just like generics. The rest require a specific prescription.

Why the FDA’s Process Is Stricter Than Other Countries

The European Medicines Agency (EMA) has approved over 118 biosimilars as of 2025. The FDA has approved only 43. That’s not because the U.S. is behind-it’s because the FDA demands more.

According to Dr. Steven Kozlowski, former director of FDA’s Office of Biotechnology Products, the U.S. requires deeper analytical characterization than Europe. That means more tests, more data, and more time. The median approval time in the U.S. is 3.2 years. In Europe, it’s 2.1 years.

But here’s the trade-off: the FDA’s approach has led to zero biosimilar-specific safety signals in over nine years of post-market monitoring. Adverse event rates for biosimilars are statistically identical to their reference products-0.8 per 10,000 patients versus 0.7 for the originals.

Real-World Challenges for Developers

Getting a biosimilar approved isn’t just hard-it’s expensive. The analytical phase alone costs $120-180 million and takes 10-12 months of full-time work by specialized teams. Companies need experts in 10-15 advanced lab techniques.

The biggest reason biosimilar applications get delayed? Insufficient analytical data. Especially for complex molecules like monoclonal antibodies, which have intricate sugar structures (glycosylation) that are hard to replicate exactly.

Even after approval, many biosimilars don’t hit the market right away. Patent lawsuits delay launches. Of the 43 approved biosimilars, only 29 have launched as of 2025. The average time from approval to market is 11.3 months.

Market Growth and Where It’s Headed

The U.S. biosimilar market grew from $1.2 billion in 2018 to $12.7 billion in 2024. That’s 18% of the total biologics market. The FDA expects it to hit 30% by 2030, saving patients and insurers $250 billion cumulatively.

Oncology biosimilars-like those for rituximab and trastuzumab-are leading adoption. In some cases, they’ve captured 65-75% of the market within 18 months. But in autoimmune diseases like rheumatoid arthritis, uptake is slower. Adalimumab biosimilars, launched in 2023, only reached 28% market share by mid-2025.

Payers and doctors are still cautious. Many prefer to stick with the original brand, even when the biosimilar is cheaper and proven safe.

Recent Changes Making It Easier

The FDA has made major updates to speed things up without lowering standards:

• In September 2024, they removed the requirement for comparative efficacy studies in many cases-saving developers $50-100 million per product.
• In June 2025, they allowed indication extrapolation based on analytical data alone, meaning one study can support multiple uses of the drug.
• The Purple Book is now a searchable, API-accessible database with daily updates.

Looking ahead, the FDA plans to release guidance for biosimilars of complex products like antibody-drug conjugates by Q3 2026. They’re also testing AI tools to analyze analytical data faster. By 2027, they aim to have a formal framework for interchangeability of combination products.

What This Means for Patients

You don’t need to understand the science to benefit from it. The bottom line? Biosimilars approved by the FDA are safe. They work just like the original biologics. And they cost 15-30% less.

If your doctor prescribes a biosimilar, you’re not getting a lesser drug. You’re getting a scientifically proven alternative that helps lower costs across the system. If your pharmacist switches you to an interchangeable biosimilar, you can trust that it’s been held to the highest standard.

And if you’re prescribed a non-interchangeable biosimilar, you’ll still get the same safety and effectiveness-just with a prescription that specifically names the biosimilar.