The Purple Book: Understanding Biosimilars and Interchangeability from the FDA

The Purple Book isn’t a book you buy at a bookstore. It’s a live, searchable database run by the U.S. Food and Drug Administration (FDA) that tells you exactly which biological drugs are approved, which ones are biosimilars, and which ones can be swapped out like generics. If you’re a pharmacist, a prescriber, or even a patient trying to understand why your insulin or arthritis drug changed without a new prescription, the Purple Book is the official source you need to trust.

What Exactly Is the Purple Book?

The Purple Book is the FDA’s official list of all licensed biological products in the U.S. That includes the original brand-name biologics, the biosimilars that copy them, and the rare few that are approved as interchangeable. Before 2020, this information was split into two separate lists-one for drugs managed by the Center for Drug Evaluation and Research (CDER), and another for biologics like vaccines and cell therapies handled by the Center for Biologics Evaluation and Research (CBER). Now, it’s one clean, searchable database that updates in real time.

Think of it like a digital index card system for complex medicines. Each product card shows the brand name, the generic name, the date it was approved, and crucially, whether it’s a reference product (the original), a biosimilar, or an interchangeable biosimilar. The cards are color-coded: matching colors mean products are linked by biosimilarity or interchangeability. If you see two cards with the same color, one is likely the original and the other is its copy.

Biosimilars vs. Interchangeable Biosimilars: The Key Difference

Not all biosimilars are created equal. All interchangeable biosimilars are biosimilars-but only a small number ever reach the interchangeable status. Here’s why that matters.

A biosimilar is a biological product that’s highly similar to an FDA-approved reference product. There might be tiny differences in inactive ingredients, but no clinically meaningful differences in safety, purity, or how well it works. That’s the standard for approval. The FDA requires extensive lab tests, animal studies, and human clinical trials to prove this.

An interchangeable biosimilar goes further. To earn that label, the manufacturer must prove that switching back and forth between the biosimilar and the original drug doesn’t increase risk or reduce effectiveness. That means if a patient takes the reference product for six months, then switches to the biosimilar for three months, then switches back-there should be no drop in results or spike in side effects. This is called a “switching study,” and it’s not required for regular biosimilars.

As of November 2023, only seven biosimilars in the U.S. had received this interchangeability designation. They include two insulin products, three for inflammatory diseases like rheumatoid arthritis, and two for eye conditions. That’s out of dozens of approved biosimilars. The FDA makes it clear: interchangeability doesn’t mean the drug is better. It just means it can be substituted without a doctor’s new order.

Why Does Interchangeability Matter to Pharmacists?

This is where things get real for people behind the pharmacy counter. In most states, pharmacists can substitute a generic drug for a brand-name pill without asking the doctor. But for biologics, the rules are different.

Even if the FDA says a biosimilar is interchangeable, the pharmacist still has to follow state law. As of 2023, 47 states and Puerto Rico allow pharmacists to swap an interchangeable biosimilar for the original without contacting the prescriber. But in those states, there are often extra steps: they must notify the doctor, document the switch, and sometimes inform the patient.

In the other three states, substitution is either banned or requires the prescriber to specifically allow it on the prescription. That means a patient in New York might get a biosimilar automatically, while a patient in California might need a new script-even if both are using the exact same FDA-approved product.

This patchwork system creates confusion. A pharmacist in Texas might stock three interchangeable insulin biosimilars, but if the patient moves to Florida, the rules change. The Purple Book doesn’t tell you what your state allows-it only tells you what the FDA approved. You still need to check your state pharmacy board’s rules.

How to Use the Purple Book Like a Pro

The Purple Book isn’t built for casual browsing. It’s a tool for professionals. Here’s how to use it effectively:

1. Go to the FDA’s Purple Book page on fda.gov.
2. Use the search bar to look up a brand name, like "Humira" or "Enbrel."
3. Click on the reference product card. You’ll see all the biosimilars and interchangeable products linked to it under the same color group.
4. Look for the "351(k) Interchangeable" tag next to any product. That’s your green light for substitution-at least at the federal level.
5. Check the "Date Licensed" to see how long the product has been on the market. Older products have more real-world data.

Pro tip: Don’t rely on the product name alone. Two biosimilars might have similar names but be linked to different reference products. Always match the product card color and the FDA designation.

What the Purple Book Doesn’t Tell You

The Purple Book is powerful, but it’s not a complete guide. It won’t tell you:

• What your insurance will cover
• Which biosimilar your pharmacy stocks
• How much a patient will pay out of pocket
• Whether a prescriber is willing to switch a patient

It also doesn’t label "unbranded biologics" as interchangeable-even though the FDA considers them equivalent. These are products without a brand name, often made by the same company as the original, and they’re not always listed the same way.

And while the FDA updates the Purple Book regularly, there’s always a lag. A product might be approved last week but won’t show up until the next database refresh. Always check the "Last Updated" date at the top of the page.

Why This Matters for Patients

Biologics are expensive. Humira, for example, costs over $7,000 a month without insurance. Biosimilars can cut that cost by 30% to 50%. Interchangeable biosimilars can drop it even further because pharmacies can swap them without extra paperwork.

But patients don’t always know they’re getting a copy. If your doctor prescribes "adalimumab," you might get a biosimilar without being told. That’s legal and safe-but it’s still a big change. The Purple Book helps you verify that the drug you’re getting is approved and backed by science.

Patients with chronic conditions-like Crohn’s disease, psoriasis, or diabetes-often stay on biologics for years. Knowing whether their medication is interchangeable gives them confidence that switching won’t break their treatment. The FDA’s data shows no drop in effectiveness after multiple switches. That’s not just theory. It’s proven in real patients.

The Future of Biosimilars in the U.S.

The number of biosimilars approved each year is rising. In 2024, more companies are applying for interchangeability status than ever before. Insulin, monoclonal antibodies, and even some cancer drugs are in the pipeline.

But progress is slow. The U.S. lags behind Europe and Canada in biosimilar adoption. Why? High legal costs, patent battles, and payer restrictions all play a role. The Purple Book is meant to cut through that noise. It’s a transparent tool that puts the facts in one place.

As more biosimilars hit the market, the Purple Book will become even more essential. It’s not just a reference-it’s the foundation for safer, cheaper, and more predictable care. For pharmacists, it’s the rulebook. For doctors, it’s the evidence base. For patients, it’s the reassurance they’re getting a drug that works.