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 prescriber, or even a patient trying to understand why your insulin changed, this is the resource that holds the answers. Unlike the Orange Book for small-molecule drugs, the Purple Book deals with complex biological products-drugs made from living cells, like insulin, rheumatoid arthritis treatments, and cancer therapies. And because these drugs aren’t simple chemical copies, the rules around substitution are more complicated. That’s where biosimilars and interchangeability come in.

What the Purple Book Actually Contains

The Purple Book lists every FDA-licensed biological product, including the original reference products and their biosimilar or interchangeable versions. It’s not just a list-it’s a structured database with color-coded product cards. Each card shows the brand name, the generic name, the date it was approved, and whether it’s a reference product (351(a)), a biosimilar (351(k)), or an interchangeable biosimilar (also 351(k), but with extra designation). The color matching is key: if two products have the same color card, one is biosimilar or interchangeable with the other. This makes it easy to spot which drugs are linked.

It also includes details like whether the product had exclusivity protection when it launched, what delivery systems it uses (like autoinjectors or pre-filled syringes), and whether it’s regulated by CDER (drugs) or CBER (biologics like vaccines and cell therapies). Since 2020, the FDA merged two separate lists into one searchable platform, fixing years of confusion. Before that, you had to check two different databases. Now, you type in a drug name-say, Humira-and instantly see all the biosimilars approved to match it, along with which ones can be swapped without a doctor’s permission.

Biosimilar vs. Interchangeable: The Key Difference

All interchangeable products are biosimilars, but not all biosimilars are interchangeable. That’s the most important thing to remember.

A biosimilar is a biological product that’s highly similar to its reference drug. The FDA requires extensive testing to prove there are no clinically meaningful differences in safety, purity, or potency. That means it works the same way in the body. But being similar isn’t enough to allow automatic substitution at the pharmacy.

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. This isn’t just one study-it’s multiple switching studies where patients alternate between the two drugs over time. The FDA wants to see that the outcome stays the same whether you start with the brand, switch to the biosimilar, switch back, or keep switching. If the results are consistent, the FDA grants the interchangeable designation.

Here’s the catch: the FDA doesn’t say interchangeable biosimilars are better or safer. They just say they’re predictable when swapped. A non-interchangeable biosimilar works just as well in practice, but you can’t automatically substitute it unless your state law and prescriber allow it.

Why Interchangeability Matters for Pharmacists

Pharmacists are on the front lines of drug substitution. If a doctor prescribes Humira, and there’s an interchangeable biosimilar available, the pharmacist can legally swap it without calling the doctor-if state law permits it. But here’s where it gets messy: federal law says the FDA can approve interchangeability, but state law controls whether substitution actually happens.

As of 2023, 47 states and Puerto Rico allow pharmacists to substitute interchangeable biosimilars without prescriber approval. But even in those states, rules vary. Some require the pharmacist to notify the prescriber. Others require patient consent or documentation. A few states still require the prescriber to specifically write “dispense as written” on the prescription to block substitution.

This patchwork creates real-world confusion. A patient in California might get an interchangeable biosimilar automatically. The same patient in New York might get the brand-name drug unless the doctor explicitly allows substitution. The Purple Book tells you what’s federally approved-but it doesn’t tell you what your state allows. That’s why pharmacists need to know both the federal designation and their state’s pharmacy laws.

What’s in the Purple Book Right Now?

As of late 2023, only seven biosimilars had earned the interchangeable designation from the FDA. That’s out of dozens of approved biosimilars. The interchangeable ones include:

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

These are high-cost drugs where substitution could save billions. But the approval process is slow. Manufacturers have to run extra studies, and the FDA reviews them carefully. The number of interchangeable products is expected to grow, but it’s not happening overnight.

It’s also worth noting: the Purple Book doesn’t list “unbranded biologics.” Some companies market biosimilars without brand names, calling them “equivalent.” But the FDA doesn’t consider those interchangeable unless they’ve gone through the full 351(k)(4) approval process. Just calling something “equivalent” doesn’t make it interchangeable under federal law.

How to Use the Purple Book Like a Pro

Using the Purple Book isn’t hard, but you need to know what you’re looking for. Here’s how:

1. Go to the FDA’s Purple Book page (fda.gov/purplebook).
2. Use the search bar to type in the brand name or generic name of a biological drug.
3. Look at the results. Each product card shows its designation: 351(a), 351(k) Biosimilar, or 351(k) Interchangeable.
4. Match the color of the product cards. If two cards are the same color, one is biosimilar or interchangeable with the other.
5. Check the “Interchangeable” column-yes or no. If it says yes, that product can be substituted where state law allows.
6. Click on the product to see its full approval history, including the date it was licensed and whether it had exclusivity.

Don’t rely on memory or outdated sources. The Purple Book is updated weekly. A product that wasn’t interchangeable last month might be today. Always check before dispensing.

What the FDA Isn’t Telling You

The FDA is clear: interchangeability doesn’t mean the drug is better. It just means switching won’t hurt. But in the real world, some prescribers still prefer the brand. Some patients worry about switching, even if it’s safe. And insurers often push for the cheapest option, which may not always be the interchangeable one.

Also, the Purple Book doesn’t include pricing. You can’t tell from the database which biosimilar is cheaper. That’s up to pharmacy benefit managers and insurers. The FDA’s job is to confirm safety and equivalence-not to set prices or control access.

Finally, the Purple Book doesn’t explain state laws. You need to check your state pharmacy board’s website separately. Some states have detailed guidance on substitution protocols, others don’t. That’s the hidden layer of complexity.

What’s Next for Biosimilars?

More biosimilars are coming. More will seek interchangeability. The FDA has issued draft guidance on labeling to make sure prescribers and pharmacists understand what each product can and can’t do. Companies are investing heavily in switching studies because the payoff is huge: if your biosimilar is interchangeable, it can be substituted automatically, just like a generic pill.

But the real barrier isn’t science-it’s perception. Many doctors and patients still think biosimilars are “less than.” The Purple Book helps by giving transparent, science-based data. But changing minds takes time. Education, clear labeling, and real-world outcomes will matter more than any database.

The Purple Book isn’t perfect. It doesn’t solve every problem. But it’s the most reliable source we have to understand what’s approved, what’s interchangeable, and what’s allowed. For anyone working with biological drugs, it’s not optional-it’s essential.