FDA Listing for Biosimilars: How They Are Evaluated and Approved

The FDA doesn’t rate biosimilars like you’d rate a movie or a restaurant. There’s no star system, no green checkmarks, no ‘highly recommended’ labels. Instead, the FDA uses a rigorous, science-driven process to determine if a biosimilar is truly similar enough to its reference biologic to be approved for use in patients. This isn’t about opinions-it’s about hard data, complex chemistry, and years of testing.

What Makes a Biosimilar Different From a Generic

People often confuse biosimilars with generics. They’re not the same. Generics are exact copies of small-molecule drugs-like aspirin or metformin-made from simple chemical formulas. You can recreate them perfectly in a lab because their structure is straightforward.

Biosimilars, on the other hand, are copies of biologic drugs. These are made from living cells-yeast, bacteria, or mammalian cells-and are far more complex. A single biologic drug can have hundreds of tiny variations in its structure, like sugar chains attached at specific spots or slight twists in its protein shape. These differences don’t change how the drug works, but they matter a lot when you’re trying to copy it.

That’s why a biosimilar isn’t called a ‘generic.’ It’s called a ‘biosimilar’ because it’s highly similar, but not identical. The FDA requires proof that any differences are minor and don’t affect safety or effectiveness.

The FDA’s Step-by-Step Approval Process

Getting a biosimilar approved isn’t a shortcut. It’s a detailed, multi-layered process that starts in a lab and ends in a clinic.

Analytical studies come first. Developers must use advanced tools-mass spectrometers, chromatography systems, capillary electrophoresis-to compare every possible characteristic of their product to the reference drug. They look at molecular weight, charge variants, glycosylation patterns, and more. The FDA expects 95-99% similarity across 200-300 critical quality attributes. If the data doesn’t meet this bar, the application gets rejected before it even moves to the next phase.

Then come non-clinical studies. These include animal tests to check for toxicity. The FDA may waive these if the analytical data is strong enough. That’s a big shift from 2015, when animal studies were almost always required.

Next, human studies. Usually, this means a pharmacokinetic (PK) study-how the body absorbs, moves, and clears the drug-and a pharmacodynamic (PD) study-how the drug affects the body. These are done in healthy volunteers or patients, with 50-100 people per group. The design is often a crossover: you get the biosimilar, then the reference drug, or vice versa, to eliminate individual variation.

Immunogenicity is non-negotiable. All biosimilars must be tested for immune reactions. Even tiny differences can trigger antibodies that make the drug less effective-or worse, cause side effects. Studies track immune responses for 24 to 52 weeks.

And now, the big change: fewer clinical trials. Before 2024, most biosimilars needed full clinical trials comparing safety and effectiveness in patients. Now, if the analytical data is rock-solid, the FDA may allow approval without those large, expensive studies. This has cut development time and costs by up to 60% for simpler proteins, according to Sandoz’s chief scientist in late 2024.

The Purple Book: The Official FDA List

Once approved, a biosimilar shows up in the FDA’s Purple Book. Think of it as the official directory of all biologics and their biosimilars. It’s updated daily now, since early 2025, and it’s searchable online.

Each entry includes:

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

As of October 2025, the Purple Book lists 43 approved biosimilars and 387 reference biologics. Only 17 of those biosimilars are labeled interchangeable-that’s the highest standard. To earn that label, a biosimilar must prove it can be switched with the reference product multiple times without increasing risk. That’s harder than just being similar. Only a few have cleared this bar so far.

Interchangeable vs. Non-Interchangeable: What It Means for You

If a biosimilar is interchangeable, a pharmacist can swap it for the brand-name drug without asking the doctor. In most states, that’s allowed by law.

If it’s not interchangeable, the prescriber must specifically write the biosimilar’s name on the prescription. Many doctors still default to the original biologic out of habit or uncertainty.

The difference isn’t about safety. Both types are equally safe. The interchangeable label is about substitution rules and pharmacy practice, not clinical performance. Only 17 out of 43 approved biosimilars have it-because the data requirements are tougher. Developers need to show that switching back and forth between the biosimilar and the reference product doesn’t change outcomes. That means extra clinical data, sometimes multiple switches in a single study.

Why It Takes So Long to Get to Market

Even after approval, many biosimilars sit on the shelf. Why? Patent lawsuits.

Biologic makers often file multiple patents on minor variations of their drugs-method of delivery, storage conditions, dosing schedules. These create what’s called a ‘patent thicket.’ A biosimilar company can get FDA approval, but still can’t launch until the courts decide who owns what.

Between 2015 and 2025, the FDA approved 43 biosimilars. Only 29 actually reached pharmacies. The average delay between approval and launch? 11.3 months.

Developers also face high costs. The analytical phase alone can cost $120-180 million. It takes 10-12 months just to collect and analyze the data. That’s why only a handful of companies can afford to play this game.

Real-World Safety: No Red Flags After 9 Years

Some patients worry: if a biosimilar isn’t identical, is it safe?

The data says yes. Since Zarxio-the first FDA-approved biosimilar-hit the market in 2015, there have been no new safety signals tied to biosimilars. The FDA’s Sentinel Initiative, which tracks adverse events in millions of patients, shows biosimilar adverse event rates are statistically identical to reference products: 0.8 per 10,000 patients versus 0.7 for the originals.

Cancer Support Community, a major patient advocacy group, reviewed all 43 approved biosimilars in 2025 and found no cases where a biosimilar caused harm that the original didn’t.

Market Growth and Future Challenges

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. But it’s still behind projections.

Oncology biosimilars-like those for rituximab and trastuzumab-are leading the way. They capture 65-75% of the market within 18 months of launch. Why? Patients and oncologists are more focused on cost and access.

In autoimmune diseases like rheumatoid arthritis, adoption is slower. Adalimumab biosimilars, approved in 2023, only reached 28% market share by mid-2025. Payers and doctors are hesitant. Some insurers still require prior authorization. Some physicians still prefer the original.

The FDA’s 2025 roadmap aims to fix this. New guidance for complex biosimilars-like antibody-drug conjugates-is coming in late 2026. AI tools will soon help analyze analytical data faster. And a formal interchangeability framework for combination products is due by 2027.

The goal? 30% market share by 2030. That could mean $250 billion in savings over the next five years.

What’s Next?

The biggest hurdle now isn’t science-it’s perception. Patients need to trust that a biosimilar is just as safe. Pharmacists need to feel confident substituting. Doctors need to know switching won’t hurt outcomes.

The science is solid. The data is clear. The FDA’s process is among the strictest in the world. And with every new approval, the evidence grows stronger.

The question isn’t whether biosimilars work. It’s whether the system will let them reach the patients who need them.