Biosimilar Approval: How the FDA Reviews Biologic Alternatives in 2025

The U.S. Food and Drug Administration (FDA) doesn't treat biosimilars like generic pills. You can't just reverse-engineer a biologic drug the way you would a chemical tablet. Biologics are made from living cells - proteins, antibodies, complex molecules that behave differently in the body than simple chemicals. That’s why a biosimilar isn’t a copy. It’s a highly similar version, built to match the original in safety, purity, and potency. And as of October 2025, the FDA changed how it reviews them - making it faster, cheaper, and more science-driven than ever before.

Why Biosimilars Aren’t Generics

Generics are exact chemical copies of brand-name drugs. Take aspirin or metformin: their molecules are small, stable, and easy to reproduce. A generic pill has the same atoms in the same order. No guesswork. Biosimilars? They’re different. Think of them like a handmade replica of a Picasso painting. You can match the brushstrokes, colors, and composition, but you can’t recreate the exact same brush used by the artist. Biologics are made in living systems - cells grown in bioreactors. Tiny changes in temperature, nutrients, or cell lines affect the final product. Even minor differences can change how the drug works in the body.

That’s why the FDA requires far more than just chemical testing. Before 2025, getting a biosimilar approved meant running full-scale clinical trials comparing it directly to the original biologic - often taking 3 years and costing over $200 million. The goal was to prove it worked just as well. But with new analytical tools, the FDA now says: we don’t always need to test it on thousands of patients.

The 2025 FDA Guidance: What Changed

On October 29, 2025, the FDA released a draft guidance that overhauled its biosimilar review process. This wasn’t a minor tweak. It was the biggest update since the Biologics Price Competition and Innovation Act (BPCIA) passed in 2010. The key shift? Comparative efficacy studies are no longer routinely required.

Instead, the FDA now says: if you can show deep analytical similarity - using modern techniques like mass spectrometry, chromatography, and advanced bioassays - and prove your biosimilar behaves the same way in the body through pharmacokinetic (PK) and immunogenicity studies, that’s often enough. You don’t need to run a multi-year trial showing it treats rheumatoid arthritis or breast cancer just as well as the original.

The guidance sets three clear conditions where this streamlined path works:

1. The reference biologic and the biosimilar are made from the same type of clonal cell line and are highly purified.
2. The link between the molecule’s structure and its clinical effect is well understood (like with adalimumab or trastuzumab).
3. A human PK study - showing how fast the drug enters and leaves the bloodstream - is feasible and meaningful.

For complex molecules like antibody-drug conjugates, where the structure-function relationship isn’t fully mapped, the FDA still recommends full clinical studies. But for most monoclonal antibodies - the most common type of biologic - this new path cuts development time from 8-10 years to 5-7 years and reduces costs from $100-300 million to $50-150 million.

Interchangeability: The Big Controversy

One of the biggest debates in biosimilars is interchangeability. That’s when a pharmacist can swap a biosimilar for the brand-name drug without asking the doctor. In the U.S., this has been a major barrier. The FDA used to require switching studies - testing whether patients do fine when they alternate between the original and biosimilar over time. That added more cost and delay.

In October 2025, FDA Commissioner Marty Makary made a bold statement at the GRx+Biosims conference: “Every biosimilar should have the designation of interchangeable.” He called interchangeability “a legislative term, not a scientific term.”

That sparked controversy. Critics argue that removing the extra hurdle could confuse doctors and patients. Dr. Robert Popovian from PhRMA warned it might undermine trust. But the FDA has already acted: two denosumab biosimilars - Enoby and Xtrenbo - received interchangeability designations in October 2025, the first time multiple interchangeable biosimilars were approved for the same reference product.

Here’s the catch: federal law still requires a separate application for interchangeability. The FDA can’t just declare all biosimilars interchangeable by fiat. That’s a job for Congress. Until then, the agency continues to approve interchangeability on a case-by-case basis - but with much lower barriers.

How the FDA Actually Reviews a Biosimilar

The process starts with a Biologics License Application (BLA) under Section 351(k) of the Public Health Service Act. The FDA doesn’t just look at one piece of data. It demands a full picture:

• Analytical studies: Over 200 quality attributes are measured - protein structure, sugar chains, impurities, stability. Techniques like liquid chromatography and high-resolution mass spectrometry compare the biosimilar to the original at a molecular level.
• Nonclinical studies: Toxicity tests in animals, if needed. Often skipped if analytical data is strong.
• Pharmacokinetic (PK) studies: Shows how the body absorbs, distributes, and clears the drug. Must match the reference product within strict limits.
• Immunogenicity assessment: Does the biosimilar cause more or different immune reactions? Even small differences here can lead to side effects or reduced effectiveness.
• Clinical studies: Now only required if the above data isn’t sufficient. Often just one study, focused on PK or safety in a sensitive population.

After submission, the FDA has 30 days to review the application for completeness. If accepted, the clock starts on the review timeline. Under BsUFA III (Biosimilars User Fee Amendments), the FDA aims to complete reviews in 10 months for standard applications and 8 months for priority ones.

Who’s Winning and Who’s Struggling

As of late 2025, the FDA has approved 76 biosimilars. But only 28 companies have brought any to market. Most are big players: Sandoz (17 approved), Pfizer (12), Amgen (10). Smaller biotechs? Only 12 biosimilars came from companies with fewer than 100 employees. Why? The analytical tools needed - mass spectrometers, automated bioassay platforms - cost millions. Setting up a quality control system takes 12-18 months. That’s a wall for startups.

Still, the tide is turning. Emerging players like Viatris and Biocon are gaining ground. And the FDA’s new guidance is helping. The Biosimilars Council reports 87 technical consultations were provided to small developers in 2025 alone. The FDA’s Biosimilars Community Resource Center had over 12,700 visitors in October 2025.

Market share is still low in the U.S. - just 23% for products with biosimilar options. Compare that to Europe, where biosimilars hold 67% of the market. Why? In the U.S., physician hesitation, payer restrictions, and patent lawsuits have slowed adoption. The FTC found that 68% of approved biosimilars have been delayed by patent litigation.

Real-World Impact: Hospitals, Patients, Costs

The savings are real. A single biologic like adalimumab (Humira) can cost $50,000-$100,000 per patient per year. Biosimilars typically launch at 15-35% lower prices. Mayo Clinic reported a 37% drop in biologic spending after switching to biosimilars for cancer treatments - saving $18 million annually.

Patients are noticing too. A September 2025 Arthritis Foundation survey of 1,247 users showed 78% were satisfied with biosimilar effectiveness. But 41% had initial safety concerns. After talking to their doctors, 68% of those worries disappeared.

On Reddit’s r/pharmacy community, a November 2025 thread on switching to a biosimilar for rheumatoid arthritis had 87 responses. Sixty-three percent said their symptoms stayed the same. Twenty-two percent reported minor differences - mostly injection site reactions. No major safety issues.

But here’s the problem: state laws. Thirty-four states still require special rules before a pharmacist can substitute a biosimilar. Even if the FDA says it’s interchangeable, a pharmacist in Texas or Florida might still need a doctor’s OK. That creates confusion and delays.

What’s Next

The FDA’s draft guidance is open for public comment until January 27, 2026. Final rules are expected by June 2026. Industry analysts predict biosimilar approvals could jump from 8-10 per year to 15-20. By 2030, McKinsey forecasts biosimilars could capture 40-50% of the market - up from 23% - saving the U.S. healthcare system $150 billion annually.

But challenges remain. Patent thickets still block entry. Physician education is lagging. And the interchangeability debate isn’t over. Until Congress clarifies the law, the FDA walks a tightrope - pushing science forward while respecting legal boundaries.

The message is clear: biosimilars are here to stay. The FDA’s 2025 update removes the biggest roadblocks. The next step? Making sure patients, doctors, and pharmacists know how to use them - and that the savings actually reach the people who need them most.