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 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 why your insulin prescription changed, this is the document that holds the answers.

What Exactly Is the Purple Book?

The Purple Book is the U.S. Food and Drug Administration’s living database of all licensed biological products. It includes reference biologics-the original, brand-name drugs-and their biosimilar and interchangeable copies. Before 2020, this information was split across two separate lists, making it confusing to navigate. Now, it’s one clean, searchable tool updated in real time.

Think of it like a phone book for biologics. Instead of listing names and numbers, it lists drug names, approval dates, whether a product is biosimilar or interchangeable, and what it’s approved to replace. It doesn’t just list products-it shows relationships. If you search for Humira, you’ll see every biosimilar that’s been approved to copy it, grouped right under its name. The color-coded product cards make it easy: matching colors mean they’re linked to the same reference product.

Biosimilars vs. Interchangeable Biosimilars: The Key Difference

All interchangeable products are biosimilars. But not all biosimilars are interchangeable. That’s the single most important thing to understand.

A biosimilar is a biological product that’s highly similar to an already-approved reference drug. The FDA requires proof that there are no clinically meaningful differences in safety, purity, or potency. That means it works the same way, with the same side effects, and produces the same results. But here’s the catch: a biosimilar doesn’t automatically get the green light for substitution at the pharmacy counter.

An interchangeable biosimilar goes further. To earn that label, the manufacturer must prove that switching back and forth between the biosimilar and the original drug doesn’t increase risk or reduce effectiveness. That means if a patient takes the reference drug for six months, then switches to the biosimilar for six months, then switches back-their health outcomes stay the same. These are called switching studies, and they’re more complex than the standard biosimilar trials.

The FDA is clear: interchangeability doesn’t mean the drug is better. It just means you can swap it without a doctor’s permission-assuming your state allows it.

How the FDA Determines Interchangeability

Getting an interchangeable designation isn’t just about showing similarity. It’s about proving predictability.

For a biosimilar to be labeled interchangeable, the company must submit data from clinical studies that show:

• Switching between the reference product and the biosimilar doesn’t lead to increased safety risks.
• There’s no drop in effectiveness when patients alternate between the two.
• The immune response remains stable across multiple switches.

This isn’t theoretical. For example, the first two interchangeable insulin products-Basaglar and Semglee-were approved after studies showed patients could switch between them and Lantus without changes in blood sugar control or adverse events. The same standard applies to drugs for rheumatoid arthritis, Crohn’s disease, and eye conditions.

As of late 2023, only seven biosimilars had earned the interchangeable label. That’s out of over 30 approved biosimilars. The bar is high because the FDA wants to be certain that pharmacists can substitute these drugs without compromising care.

State Laws Control What Happens at the Pharmacy

Just because the FDA says a drug is interchangeable doesn’t mean a pharmacist can automatically swap it.

Each state sets its own rules. As of 2023, 47 states and Puerto Rico allow pharmacists to substitute an interchangeable biosimilar for the prescribed reference product without contacting the doctor. But that doesn’t mean they always do.

In some states, pharmacists must:

• Notify the prescribing doctor when a substitution is made.
• Document the change in the patient’s record.
• Inform the patient that a substitution occurred.

Other states require the prescriber to specifically write “dispense as written” or “no substitution” on the prescription. And a few states still don’t allow substitution at all.

This patchwork of laws creates real-world confusion. A patient in New York might get their interchangeable biosimilar without a hitch. The same patient in California might need a new prescription just to get the same drug. The Purple Book tells you what’s federally approved-but it doesn’t tell you what your local pharmacy can do.

What the Purple Book Doesn’t Tell You

The Purple Book is precise, but it’s not complete. It doesn’t include pricing. It doesn’t tell you which biosimilars are covered by your insurance. And it doesn’t explain how to navigate the confusing labels on the packaging.

Also, don’t confuse “interchangeable” with “unbranded.” An unbranded biologic is a version of a reference product without a brand name, but it’s not necessarily a biosimilar. The FDA treats unbranded biologics as equivalent, but they don’t go through the 351(k) approval pathway. That means they’re not covered by the same interchangeability rules.

And while the Purple Book shows which products are approved, it doesn’t track how often they’re actually used. Many doctors still prescribe the original brand, even when a cheaper, interchangeable option is available-partly because of habit, partly because of misinformation.

Why the Purple Book Matters

Biologics are some of the most expensive drugs on the market. Humira, for example, cost patients and insurers over $20 billion a year before biosimilars arrived. The Purple Book is the tool that makes savings possible.

For pharmacists, it’s a quick reference to know which drugs they can swap without breaking the law. For doctors, it helps them understand what alternatives are available. For patients, it’s proof that cheaper options are safe and regulated.

It’s also a signal to manufacturers: if you want your drug to be used widely, get that interchangeable designation. The market is shifting. Companies like Pfizer, Amgen, and Sandoz are pouring resources into switching studies because they know the real win isn’t just getting approved-it’s being able to replace the brand-name drug at the pharmacy counter.

How to Use the Purple Book

Go to the FDA’s website and search for “Purple Book.” You’ll land on the searchable database. Here’s how to use it:

1. Type in the brand name of a biologic-like Enbrel or Remicade.
2. Look for the product card with the same color as the reference product. Those are the biosimilars.
3. Check the designation: 351(a) = reference product, 351(k) Biosimilar, 351(k) Interchangeable.
4. Click on the product card to see details: manufacturer, approval date, product form (autoinjector, vial, etc.), and whether it’s interchangeable.
5. Use the filters to narrow results by therapeutic area or approval year.

The database is updated weekly. If a new interchangeable biosimilar gets approved, it shows up within days. That’s faster than most drug guides.

What’s Next for Biosimilars?

The number of interchangeable biosimilars is growing. More are in the pipeline-especially for diabetes, autoimmune diseases, and cancer treatments. The FDA has signaled it will continue to refine its guidance, particularly around labeling, to make sure patients and providers aren’t misled.

But progress depends on more than science. It depends on education. Many clinicians still think biosimilars are “second-rate.” The Purple Book helps correct that by showing exactly what data the FDA used to approve them.

As more biosimilars get interchangeable status, and as more states update their laws to allow substitution, we’ll see real cost savings. The goal isn’t just to lower prices-it’s to make sure patients get the right treatment, without barriers.

What to Do Next

If you’re a patient: Ask your pharmacist if your biologic has an interchangeable biosimilar option. Check the Purple Book yourself to confirm the status.

If you’re a provider: Use the Purple Book to stay current on available alternatives. Don’t assume your patient’s drug hasn’t changed-new biosimilars arrive every few months.

If you’re a pharmacist: Bookmark the Purple Book. Keep a printed cheat sheet of your state’s substitution laws. And always document substitutions clearly.

The Purple Book isn’t just a government document. It’s the key to making complex, expensive drugs more accessible. The science is solid. The approvals are real. Now, it’s up to the system to catch up.