The Purple Book: Biosimilars and Interchangeability Explained

The Purple Book is not a book you can hold in your hands. 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 figuring out what can be substituted, what can’t, and why.

What Exactly Is the Purple Book?

The Purple Book started in 2010 as part of the Biologics Price Competition and Innovation Act (BPCIA). Before this law, there was no clear path for approving follow-on versions of complex biological drugs like Humira, Enbrel, or insulin. Unlike small-molecule drugs, which are chemically synthesized and easy to copy, biologics are made from living cells - think proteins, antibodies, or vaccines. Copying them isn’t as simple as making a pill version.

That’s where biosimilars come in. These are highly similar versions of brand-name biologics. They’re not exact copies - no one can make an exact copy of a living cell product - but they’re close enough that there’s no meaningful difference in safety or effectiveness. The Purple Book lists all of these approved products in one place.

In 2020, the FDA merged two separate lists into one searchable database. Before that, you had to check one list for drugs regulated by CDER and another for biologics from CBER. Now, everything’s in one place. You can search by brand name, active ingredient, or approval status. The results show you the reference product, its biosimilars, and any that are interchangeable.

Biosimilars vs. Interchangeable: What’s the Difference?

Not all biosimilars are created equal. Every interchangeable product is a biosimilar, but not every biosimilar is interchangeable. That’s the key point.

A biosimilar has been proven to be highly similar to the reference product. It matches in structure, function, and clinical outcomes. The FDA requires extensive lab testing, animal studies, and clinical trials to prove there are no meaningful differences in safety or effectiveness.

An interchangeable product goes further. To earn that designation, the manufacturer must show that switching between the biosimilar and the original product - multiple times, even back and forth - doesn’t increase risk or reduce effectiveness. That means if a patient uses the reference drug for a month, switches to the biosimilar for a month, then switches back, their response stays consistent. No drop in performance. No new side effects.

This is why interchangeability matters. It’s not about being better. It’s about being predictable. The FDA says interchangeable biosimilars are just as safe and effective as the original - even when you switch.

How the Purple Book Shows This Information

The Purple Book uses color-coded cards to make this easy. Each reference product has its own card. Underneath it, you’ll see cards for its biosimilars and interchangeable versions - all in matching colors. You can click on any card to see details like:

• When it was approved under section 351(a) of the Public Health Service Act
• Whether it’s a reference product, biosimilar, or interchangeable
• Whether it’s protected by exclusivity (meaning no biosimilar can be approved yet)
• What delivery method it uses - autoinjector, pre-filled syringe, IV bag

For example, if you search for adalimumab (the active ingredient in Humira), you’ll see the original product at the top. Below it, you’ll find multiple biosimilars like Amjevita, Cyltezo, and Hyrimoz. One of them - Amjevita - is marked as interchangeable. That means, under the right state laws, a pharmacist can swap it in without asking the doctor.

Why Interchangeability Isn’t Enough on Its Own

Just because the FDA says a product is interchangeable doesn’t mean a pharmacist can automatically swap it. Each state has its own rules.

As of 2023, 47 states and Puerto Rico allow pharmacists to substitute an interchangeable biosimilar without contacting the prescriber. But some states still require the doctor to approve the switch. Others require the patient to be notified in writing. A few even require the pharmacist to document the substitution in a special log.

This patchwork of rules creates confusion. A patient in Texas might get an interchangeable insulin without a problem. The same patient in New York might get the original brand because their state requires prescriber consent. The Purple Book tells you what the FDA says - but it doesn’t override state law.

It’s also important to know that the FDA doesn’t call interchangeable products “better.” They’re not more effective. They’re not safer. They’re just predictable when switched. The goal is cost savings and access - not superiority.

What Products Are Approved as Interchangeable?

As of late 2023, only seven biosimilars have received the interchangeable designation from the FDA. That number is growing, but slowly. Here’s what’s approved:

• Two insulin products - used for diabetes
• Three drugs for inflammatory conditions - like rheumatoid arthritis and Crohn’s disease
• Two treatments for eye conditions - used in retinal diseases

Most of these are for chronic conditions where patients stay on the drug for years. That’s why switching studies are so important - you can’t risk unpredictable responses in someone on long-term treatment.

The FDA continues to review new applications. Companies are pushing hard for interchangeability because it opens the door to automatic substitution - which means faster market entry and broader use. But the bar is high. Each application requires additional clinical data on multiple switches, which costs millions and takes years.

What the Purple Book Doesn’t Tell You

The Purple Book doesn’t cover unbranded biologics. These are products that are chemically identical to the reference product but were approved before the biosimilar pathway existed. The FDA considers them equivalent, but they’re not labeled as interchangeable. You won’t find them in the same section.

It also doesn’t list pricing. You can’t tell from the Purple Book how much a biosimilar costs compared to the brand. That info comes from pharmacies, insurers, and drug pricing databases.

And it doesn’t tell you which products are actually being used in clinics. Just because a biosimilar is approved doesn’t mean doctors are prescribing it. Some still prefer the original brand due to habit, patient preference, or lack of awareness.

Who Uses the Purple Book?

Pharmacists are the biggest users. When a prescription comes in for a biologic, they check the Purple Book to see if a biosimilar or interchangeable version is available - and whether their state allows substitution.

Prescribers use it too. When a patient asks if they can switch to a cheaper option, the doctor can look it up. Insurance companies use it to build formularies. Patient advocacy groups use it to explain treatment options.

Even manufacturers use it. If a company wants to develop a biosimilar, they need to know what’s already approved - and what’s protected by exclusivity. The Purple Book shows you exactly when the patent clock starts ticking.

What’s Next for the Purple Book?

The FDA is working on clearer labeling rules for biosimilars and interchangeable products. Right now, product names can be confusing. Some have similar names to the reference drug. The FDA is pushing for names that make it easier to track side effects and avoid mix-ups.

More interchangeable products are expected in 2025 and beyond. With insulin, autoimmune drugs, and cancer treatments on the horizon, the number of interchangeable options will likely double in the next two years.

But the biggest change won’t be in the database. It’ll be in how people use it. As awareness grows, so will substitution. The goal isn’t just to save money - it’s to make life-changing treatments more accessible to everyone.