The Purple Book: Understanding Biosimilars and Interchangeability from the FDA

The Purple Book isn’t a novel you read on the couch-it’s the U.S. Food and Drug Administration’s official, searchable database that tells you exactly which biological drugs are approved, which ones are biosimilars, and which ones can be swapped at the pharmacy like generics. If you’re a pharmacist, a prescriber, or even a patient trying to understand why your insulin prescription changed, this is the resource that makes sense of it all.

What Exactly Is the Purple Book?

The Purple Book is the FDA’s public record of all licensed biological products in the United States. It includes the original brand-name biologics, their biosimilar versions, and the rare subset called interchangeable biosimilars. Before 2020, this information was split across two separate lists-one for drugs regulated by CDER (like antibodies and hormones) and another for CBER products (like vaccines and cell therapies). Now, it’s all in one place, updated in real time, and searchable by product name, manufacturer, or status.

It’s not just a list. Each entry has key details: the date the product was approved under section 351(a) of the Public Health Service Act, whether it’s protected by exclusivity, and crucially-whether it’s been designated as biosimilar or interchangeable. The database uses color-coded cards: if two products share the same color, they’re linked as reference and biosimilar. You can also see icons showing how the drug is delivered-autoinjector, pre-filled syringe, vial-so pharmacists know what’s physically available.

Biosimilar vs. Interchangeable: The Critical Difference

Not all biosimilars are created equal. A biosimilar is a biological product that’s highly similar to an FDA-approved reference product. There might be tiny, harmless differences in inactive ingredients, but no meaningful difference in safety, purity, or potency. Think of it like two different brands of aspirin-same active ingredient, same effect, just different packaging or fillers.

An interchangeable biosimilar goes further. To earn that label, the manufacturer must prove that switching back and forth between the biosimilar and the original product won’t increase risk or reduce effectiveness. That means clinical studies where patients were switched multiple times between the two-sometimes every other dose-and still had the same outcomes. The FDA doesn’t say interchangeable biosimilars are better. They just say you can swap them without needing a new prescription each time.

This matters because only interchangeable products can be automatically substituted by a pharmacist, just like a generic pill. A regular biosimilar? You still need the doctor to write the brand name or specify "dispense as written."

How the FDA Determines Interchangeability

Getting an interchangeable designation isn’t just about proving similarity-it’s about proving switchability. The FDA requires data from clinical studies that show no increased risk when patients alternate between the reference product and the biosimilar. For example, if a patient uses Humira for rheumatoid arthritis and switches to an interchangeable biosimilar, then switches back, their immune response, side effects, and disease control must stay stable. No drop-off. No surprises.

These studies are more complex than the ones needed for basic biosimilarity. They often involve multiple switches over months, with careful monitoring. Pfizer’s analysis in 2024 confirmed that this is the key hurdle: most biosimilars pass the similarity test, but only a few have the switch data to earn interchangeability.

The FDA is clear: interchangeability doesn’t mean safer or more effective. It just means predictable when switching. And that’s a big deal for patients who might need to change treatments due to cost or availability.

State Laws Still Control What Pharmacists Can Do

Here’s where things get messy. Even if the FDA says a biosimilar is interchangeable, your pharmacist might not be allowed to swap it without telling your doctor. That’s because state laws control pharmacy practice, not federal approval.

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 might have to notify the doctor, document the swap, or inform the patient. A few states require prescriber permission every time. Others don’t allow substitution at all unless the prescription says "dispense as written." This creates a patchwork. A patient in Texas might get an interchangeable biosimilar automatically. A patient in California might need a new prescription. A patient in New York might be told the pharmacy can’t substitute at all-even if the FDA says it’s allowed.

The FDA’s Purple Book doesn’t track state rules. It only tells you what’s federally approved. So if you’re a pharmacist or a patient, you need to know your state’s laws too.

Which Products Are Interchangeable? (As of 2025)

As of late 2023, only seven biosimilars had earned the interchangeable designation from the FDA. By 2025, that number has grown slightly, but it’s still a small fraction of the total biosimilars on the market.

Here’s what’s approved so far:

• Two insulin products (used for diabetes)
• Three treatments for inflammatory diseases like rheumatoid arthritis and Crohn’s disease
• Two therapies for eye conditions (retinal diseases)

These are all high-cost biologics that previously had no competition. Now, interchangeable versions are slowly entering the market, often at 15-30% lower prices than the original. But because of state laws and slow adoption by insurers, many patients still get the brand name unless their provider pushes for the biosimilar.

The Purple Book lists each one clearly: you can search for "Humira," and you’ll see the original product card in one color, and the interchangeable biosimilars in the same color underneath. No guesswork.

Why the Purple Book Matters for Patients and Providers

For doctors, the Purple Book helps avoid confusion. You can check whether the biosimilar your patient is taking is interchangeable or just biosimilar. That affects how you write prescriptions and whether you need to follow up after a switch.

For pharmacists, it’s a daily tool. When a prescription comes in for a biologic, they pull up the Purple Book to see if a substitution is legally allowed. If the product is interchangeable, and state law permits it, they can swap it without calling the doctor.

For patients, it’s about transparency. If you’re paying out of pocket for a $20,000 biologic, knowing there’s a cheaper, FDA-approved interchangeable version could save you thousands. But you won’t know unless you-or your provider-look it up.

The FDA designed this tool to cut through the noise. No marketing hype. No vague claims. Just facts. And that’s rare in drug pricing.

What’s Next for Biosimilars?

More applications for interchangeability are coming. Companies are investing in the complex switching studies because the payoff is bigger: automatic substitution means faster market uptake. Insurers are starting to favor interchangeable biosimilars in formularies because they’re cheaper and legally substitutable.

The FDA is also updating guidance on labeling to make sure biosimilar packaging clearly states whether it’s interchangeable. No more confusion on the shelf.

But adoption still lags. Many prescribers don’t know how to use the Purple Book. Many patients don’t know their insulin can be swapped. And many pharmacies still default to the brand name because they’re unsure of the rules.

The Purple Book is the foundation. But real change happens when patients ask for it, when pharmacists use it, and when doctors trust it.

How to Use the Purple Book

It’s free. It’s online. And it’s easy:

1. Go to fda.gov/purplebook (no login needed).
2. Search by brand name (e.g., "Enbrel") or active ingredient.
3. Look for the color-coded cards. Matching colors = biosimilar or interchangeable.
4. Check the "Product Status" column. It will say "351(k) Interchangeable" if it’s substitutable.
5. Click on a product card to see details: manufacturer, date licensed, exclusivity status, delivery method.

You can also filter by product type: insulin, monoclonal antibodies, vaccines, etc. The database updates weekly, so it’s always current.

Common Misconceptions

• "Interchangeable means better." No. It means switchable. Safety and effectiveness are the same as the reference product.
• "All biosimilars can be swapped." Only the ones labeled "interchangeable" by the FDA-and only if your state allows it.
• "The Purple Book is for doctors only." Anyone can use it. Patients, pharmacists, even students.
• "Unbranded biologics are interchangeable." No. The FDA doesn’t use that term. If it’s not labeled "interchangeable," it’s not automatically substitutable.

Final Thoughts

The Purple Book is one of the most underused tools in modern medicine. It’s not flashy. It doesn’t have ads. It doesn’t try to sell you anything. It just tells you what’s approved, what’s interchangeable, and who made it.

For a system that spends billions on biologics every year, this level of transparency is rare. And it’s exactly what’s needed to bring down costs without compromising safety.

If you’re in healthcare, bookmark it. If you’re a patient, ask your pharmacist if your biologic has an interchangeable version. And if you’re a prescriber-start using it when you write prescriptions. The future of affordable biologics isn’t in marketing. It’s in this database.