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 doctor, or even a patient trying to understand your treatment options, this tool is critical. It’s the official source for knowing what’s legally substitutable and what’s not.

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 everything from insulin and rheumatoid arthritis drugs to vaccines and cancer treatments. But it doesn’t just list names. It tells you whether a product is the original (called a reference product), a biosimilar, or an interchangeable biosimilar. This distinction matters because not all biosimilars can be automatically swapped at the pharmacy counter.

Before 2020, the FDA kept two separate lists-one for drugs under the Center for Drug Evaluation and Research (CDER) and another for those under the Center for Biologics Evaluation and Research (CBER). That made it confusing. Now, it’s one unified database. You can search by brand name, generic name, or manufacturer. The results show you the approval date, whether the product has exclusivity protection, and its regulatory status. Each product card is color-coded. Matching colors mean the products are linked-like a biosimilar tied to its original reference drug.

Biosimilars vs. Interchangeable Products: The Key Difference

All interchangeable products are biosimilars. But not all biosimilars are interchangeable. That’s the core confusion.

A biosimilar is a biological product that’s highly similar to an already-approved reference product. The FDA requires rigorous testing to prove there are no clinically meaningful differences in safety, purity, or potency. That means it works the same way in the body. But being similar isn’t enough to be swapped automatically.

An interchangeable product has to meet an extra standard. It must show that switching back and forth between the biosimilar and the original drug doesn’t increase risk or reduce effectiveness. Think of it like this: if you start on the brand drug, then switch to the biosimilar, then switch back-your body shouldn’t react differently. That’s what interchangeability means.

To prove this, companies run switching studies. These aren’t simple trials. They involve patients getting multiple switches between the reference and the biosimilar over time. The data must show no drop in effectiveness and no spike in side effects. The FDA doesn’t say interchangeable products are better-they’re just proven safe to swap.

Why Does Interchangeability Matter at the Pharmacy?

Here’s where it gets real for patients and pharmacists. If a doctor prescribes Humira, and there’s an interchangeable biosimilar on the market, your pharmacist can legally substitute it without calling the doctor-if your state allows it.

But here’s the catch: federal approval doesn’t override state law. As of 2023, 47 states and Puerto Rico let pharmacists substitute interchangeable biosimilars without prior approval from the prescriber. But some states require the pharmacist to notify the doctor, inform the patient, or keep detailed records. A few states still don’t allow substitution at all.

That means the same drug might be swapped in New York but not in California. Pharmacists have to check their state’s rules every time. It’s messy, but it’s the reality. The Purple Book tells you what the FDA says. Your state’s pharmacy board tells you what you can actually do.

What’s in the Purple Book Right Now?

As of late 2023, only seven biosimilars had received the interchangeable designation. That’s not a lot compared to the dozens of biosimilars approved overall. The majority of biosimilars are still labeled as non-interchangeable. That means even if they’re cheaper, pharmacists can’t swap them unless the prescriber specifically allows it.

The interchangeable products include:

• Two insulin products (used for diabetes)
• Three drugs for inflammatory conditions like rheumatoid arthritis and Crohn’s disease
• Two treatments for eye conditions like macular degeneration

The FDA keeps adding to the list. Companies are actively submitting applications for interchangeability. But the bar is high. The clinical data required takes years and millions of dollars to generate. That’s why only a handful have made it so far.

How to Use the Purple Book

The database is free and easy to use. Go to the FDA’s website and search for any biological drug. The results show you:

• The original product (351(a) licensed)
• All biosimilars linked to it (351(k) biosimilar)
• Any that are interchangeable (351(k) interchangeable)

Each entry includes icons for delivery methods-like autoinjectors or prefilled syringes. You can see when the product was approved and whether it’s still under exclusivity. If you’re comparing costs or planning a switch, this is the only source you need.

The FDA even has a video walkthrough showing how to filter results. Search for a drug like adalimumab, and you’ll see all the biosimilars grouped under the original Humira. Click on one, and you’ll see its interchangeability status right there. No guesswork.

What the Purple Book Doesn’t Tell You

The Purple Book doesn’t list prices. It doesn’t say which biosimilars are covered by insurance. It doesn’t explain how to handle prior authorizations. It also doesn’t mention “unbranded biologics”-a term the FDA uses for products that are equivalent to brand-name drugs but weren’t approved under the biosimilar pathway. These aren’t interchangeable biosimilars, even if they’re chemically the same.

And while it’s the most accurate source for regulatory status, it doesn’t replace clinical judgment. A doctor might still prefer the original drug for certain patients, even if a biosimilar is interchangeable. The Purple Book gives you the legal and scientific facts. You still need to apply them to individual cases.

What’s Next for Biosimilars?

More interchangeable products are coming. Insulin biosimilars are leading the charge because they’re widely used and have simpler structures. But complex drugs like monoclonal antibodies are harder to copy exactly. That’s why interchangeability is still rare.

The FDA is also updating its guidance on labeling. New rules will make it clearer how interchangeable biosimilars should be named and described on packaging. This is meant to reduce confusion among prescribers and pharmacists.

The big picture? Biosimilars are lowering costs. Interchangeable ones could make that happen faster by allowing automatic substitution. But the system is still evolving. Patients need to know their rights. Pharmacists need clear rules. And everyone needs the Purple Book as their starting point.

Common Questions About the Purple Book

Final Thoughts

The Purple Book is the backbone of transparency in the biological drug market. It answers the questions pharmacists and patients are asking: Can I swap this? Is it legal? Is it proven? It’s not perfect-it doesn’t cover cost or access-but it’s the only place where you can get the official, up-to-date facts on biosimilars and interchangeability.

As more biosimilars enter the market, and as states update their laws, the Purple Book will become even more essential. Whether you’re a patient, a provider, or a pharmacist, knowing how to use it means you’re not guessing-you’re deciding with confidence.