The Purple Book: Understanding Biosimilars and Interchangeability from the FDA

The Purple Book isn’t a book you can hold in your hands-it’s a living, searchable database run by the FDA that tells you exactly which biological medicines are approved, which ones are biosimilars, and which ones can be swapped out like generics. If you’re a pharmacist, doctor, or just someone trying to understand why a biologic prescription might be filled with a different name but the same effect, this is your go-to resource.

What the Purple Book Actually Does

The FDA launched the Purple Book in 2012 after Congress passed the Biologics Price Competition and Innovation Act (BPCIA). Back then, it was split into two parts-one for drugs regulated by CDER and another for biologics handled by CBER. That made it messy. In 2020, they fixed it. Now, it’s one clean, searchable database that includes every FDA-approved biological product, whether it’s a reference medicine, a biosimilar, or an interchangeable product.

Think of it like a family tree for biologics. At the top is the original reference product-say, Humira or Enbrel. Below it, you’ll see all the biosimilars that have been proven to work the same way. And if one of those biosimilars has the extra stamp of “interchangeable,” it’s listed right under the reference with a matching color code. That visual system helps you spot connections fast.

The database doesn’t just list names. Each product card shows the approval date, whether it’s protected by exclusivity, and whether it’s been cleared for substitution. You’ll also see icons for delivery methods-autoinjectors, pre-filled syringes, vials-so you know what form it comes in. This isn’t just for regulators. Pharmacists use it daily to make sure they’re dispensing correctly.

Biosimilar vs. Interchangeable: The Key Difference

Not all biosimilars are created equal. A biosimilar is a biological product that’s highly similar to its reference medicine. The FDA requires proof that there are no clinically meaningful differences in safety, purity, or potency. That’s a high bar. But being a biosimilar doesn’t mean you can automatically swap it in at the pharmacy.

An interchangeable product goes further. It has to prove that switching back and forth between the biosimilar and the original reference product doesn’t increase risk or reduce effectiveness. That means clinical studies where patients get the reference drug, then switch to the biosimilar, then switch back-and repeat. The results have to show no drop in outcomes, no new side effects, no loss of control over the disease.

Here’s the catch: every interchangeable product is a biosimilar, but not every biosimilar is interchangeable. The FDA doesn’t say one is better or safer than the other. It just says interchangeable products have passed an extra layer of testing for repeated switching.

Why Interchangeability Matters at the Pharmacy

Pharmacists can’t just swap a biologic for a biosimilar unless it’s labeled interchangeable-and even then, state laws get in the way.

As of 2023, 47 states and Puerto Rico allow pharmacists to substitute an interchangeable biosimilar without asking the doctor first. But some states require the pharmacist to notify the prescriber, inform the patient, or fill out paperwork. A few states still require the prescriber to specifically write “dispense as written” on the prescription to block substitution.

This patchwork of rules creates confusion. A patient in Texas might get an interchangeable biosimilar automatically. The same patient in New York might get the brand-name drug unless their doctor says otherwise. The FDA’s Purple Book tells you what’s federally approved-but it doesn’t tell you what your state allows.

That’s why pharmacists check the Purple Book before making any substitution. They don’t rely on brand names or packaging. They look at the official designation: 351(a) for the reference, 351(k) biosimilar, and 351(k) interchangeable. That’s the legal language that matters.

What’s in the Purple Book Right Now

As of late 2023, seven biologics had received the interchangeable designation from the FDA. Two of them are insulin products-critical for people with diabetes who need affordable, reliable treatment. Three are used for autoimmune conditions like rheumatoid arthritis and Crohn’s disease. Two are for eye conditions affecting vision in older adults.

These aren’t theoretical. They’re being used. And more are coming. Companies are actively submitting applications for interchangeability, especially for high-cost drugs where savings could be huge. The FDA is also updating its guidance on labeling to make sure the names and information on the packaging don’t mislead patients or providers.

The Purple Book is updated regularly. New products appear. Exclusivity periods end. Designations change. You can search by brand name, generic name, or manufacturer. The results can be long, but the filters help. You can sort by approval date, product type, or interchangeability status.

What the Purple Book Doesn’t Tell You

It won’t tell you how much a drug costs. It won’t tell you if your insurance covers it. It won’t tell you whether a pharmacy has it in stock. And it won’t override state laws.

It also doesn’t list “unbranded biologics.” The FDA considers those equivalent to brand-name products, but they’re not interchangeable biosimilars. That’s a legal gray area. The Purple Book sticks to what’s officially approved under the BPCIA.

Some people think interchangeable means “better.” It doesn’t. It just means it’s been tested for switching. A non-interchangeable biosimilar works just as well in most cases. The difference is in the pharmacy, not the patient.

How to Use the Purple Book

Go to the FDA’s website and search for “Purple Book.” You’ll land on the searchable database. Start with the reference product you’re familiar with-say, Enbrel. Click on it. Below, you’ll see all biosimilars approved to match it. If any have a green checkmark or a special label saying “interchangeable,” that’s your signal.

Click on those biosimilars. You’ll see their approval dates, the studies they passed, and whether they’re approved for the same conditions as the original. Look for the 351(k) designation. That’s the legal marker.

Pharmacists use this daily. Doctors use it when they’re unsure about substitution. Patients can use it to ask informed questions: “Is this the same as what I was prescribed? Can it be swapped?”

The Bigger Picture

The Purple Book is part of a larger effort to make biologics more affordable without sacrificing safety. Biologics used to cost tens of thousands a year. Biosimilars have cut those prices by 15% to 35% in many cases. Interchangeable products could drive that even lower by allowing automatic substitution.

But progress depends on clarity. If pharmacists don’t know which products can be swapped, or if state laws make it too complicated, patients won’t benefit. The Purple Book is the foundation. It’s the official record. What happens next-how it’s used, how states adapt, how insurers respond-is up to the system.

For now, it’s the most accurate, up-to-date source for knowing what’s approved, what’s interchangeable, and what you can expect when your biologic prescription is filled.