The Purple Book: Understanding Biosimilars and Interchangeability from the FDA

The Purple Book isn’t a novel you read for fun-it’s the FDA’s official, searchable database that tells pharmacists, doctors, and patients exactly which biological drugs are biosimilars, which are interchangeable, and how they connect to the original brand-name products. Think of it as the rulebook for biologics in the U.S. healthcare system. Unlike generic pills, biological drugs are made from living cells, making them far more complex. That’s why the FDA created a special system to track them-and the Purple Book is where all that information lives.

What Exactly Is the Purple Book?

The Purple Book is a digital compendium maintained by the U.S. Food and Drug Administration. It lists every FDA-approved biological product, including the original reference drugs and their biosimilar and interchangeable versions. Before 2020, this information was split across two separate lists-one for drugs regulated by CDER (like insulin and monoclonal antibodies) and another for CBER products (like vaccines and blood products). Now, it’s all in one place. That makes it easier for pharmacists to check if a drug they’re about to dispense is a biosimilar or interchangeable, and which reference product it matches.

Each product card in the Purple Book shows the brand name, generic name, and the date it was licensed. It also flags whether the product is a 351(a) reference product, a 351(k) biosimilar, or a 351(k) interchangeable. The colors match up: if a biosimilar shares the same color card as the reference product, it means they’re linked. You’ll also see icons for delivery methods-autoinjectors, prefilled syringes, vials-so you know how the drug is administered.

Biosimilars vs. Interchangeable Products: The Key Difference

Not all biosimilars are created equal. A biosimilar is a biological product that’s highly similar to its reference drug, with no clinically meaningful differences in safety, purity, or potency. That means it works the same way in the body. But here’s the catch: just because a product is a biosimilar doesn’t mean a pharmacist can swap it in automatically.

An interchangeable product goes one step further. To earn that label, the manufacturer must prove that switching between the biosimilar and the original reference drug-multiple times, back and forth-won’t increase risk or reduce effectiveness. That’s not just about one dose. It’s about repeated switching, like changing brands every month. The FDA requires clinical studies showing that patients who alternate between the two get the same results as those who stick with the original.

So, all interchangeable products are biosimilars. But only a few biosimilars are interchangeable. As of late 2023, only seven products had received the interchangeable designation from the FDA. These include two insulin products, three for inflammatory conditions like rheumatoid arthritis, and two for eye diseases. The rest are biosimilars without interchangeability.

Why Interchangeability Matters for Pharmacists

This distinction has real-world consequences. If a doctor prescribes Humira, and a biosimilar version is available but not interchangeable, the pharmacist must dispense exactly what’s written on the prescription. No substitutions allowed.

But if the biosimilar is labeled as interchangeable, the pharmacist can swap it in-just like they would with a generic pill. However, even then, it’s not automatic. State laws control what happens at the pharmacy counter. As of 2023, 47 states and Puerto Rico allow pharmacists to substitute an interchangeable biosimilar without contacting the prescriber. But in those states, they still have to notify the patient and keep records. In the other three states, the pharmacist must get the doctor’s permission first.

This patchwork of rules creates confusion. A pharmacist in Texas might swap a biosimilar without a call to the doctor. One in New York might need a signature. The Purple Book tells you what’s federally approved-but you still need to check your state’s pharmacy board rules to know what you can actually dispense.

How the FDA Determines Interchangeability

Getting the interchangeable label isn’t easy. The FDA doesn’t just look at lab data or one clinical trial. They demand switching studies-where patients are moved back and forth between the reference product and the biosimilar over weeks or months. The goal? Prove that switching doesn’t cause more side effects, flare-ups, or loss of effectiveness.

For example, if a patient with Crohn’s disease is on a reference biologic and switches to an interchangeable biosimilar, then switches back, their disease activity should stay stable. No spikes. No drop in response. The FDA’s guidance says the risk must be no greater than if they never switched at all.

Importantly, the FDA stresses that interchangeable doesn’t mean better. It doesn’t mean safer. It just means the switching process is predictable and safe. A non-interchangeable biosimilar works just as well as the reference drug-its only limitation is that it can’t be swapped without a doctor’s okay.

What’s Not in the Purple Book

The Purple Book doesn’t list every biologic on the market. It only includes products approved under the Biologics Price Competition and Innovation Act (BPCIA) of 2010. That means older biologics, approved before 2010, aren’t included unless they’ve been re-evaluated under the new pathway.

It also doesn’t include "unbranded biologics." These are products that are equivalent to a brand-name drug but were approved under older rules. The FDA considers them equivalent, but they’re not classified as biosimilars or interchangeable under the BPCIA. So if you’re looking for a substitute, make sure you’re checking the right category.

And while the Purple Book tells you what’s approved, it doesn’t tell you what insurance will cover. That’s a separate battle. Even if a biosimilar is interchangeable, a payer might still require prior authorization or prefer the brand-name drug. The Purple Book gives you the facts. It doesn’t fix your pharmacy benefit manager’s formulary.

How to Use the Purple Book

The database is free and searchable on the FDA’s website. You can search by brand name, generic name, or manufacturer. If you type in "Enbrel," you’ll see the original product and any biosimilars linked to it. Click on a biosimilar, and you’ll see its approval date, interchangeability status, and whether it’s approved for the same uses as the reference drug.

For pharmacists, this is a daily tool. When a prescription comes in for a biologic, they pull up the Purple Book to check if a biosimilar is available and whether they can substitute it. For doctors, it helps when discussing cost-saving options with patients. For patients, it’s a way to verify that the drug they’re getting is legitimate and approved.

The FDA has also made it user-friendly. The search results are grouped under the reference product. You don’t have to scroll through dozens of unrelated drugs. Everything is organized. And the color-coded cards make it easy to spot matches at a glance.

The Future of Biosimilars and the Purple Book

More biosimilars are coming. Companies are actively submitting applications for interchangeability, especially for high-cost drugs like Humira, Enbrel, and Remicade. The first interchangeable insulin products hit the market in 2021, and since then, the number has grown. Experts expect at least a dozen more interchangeable biosimilars to be approved by 2026.

But progress isn’t just about approvals. It’s about adoption. Even with federal backing, pharmacy substitution still depends on state laws and payer policies. Until those barriers break down, the full cost-saving potential of biosimilars won’t be realized.

The Purple Book is evolving too. The FDA has released draft guidance on labeling for biosimilars and interchangeable products, aiming to make prescribing and dispensing clearer. They’re also working on better tools to help providers understand which products are interchangeable across states.

For now, the Purple Book remains the most reliable source for up-to-date, official information on biological products in the U.S. It’s not perfect, but it’s the only place you can go to find out, with certainty, whether a drug is interchangeable-and what that actually means for your care.