FDA Orange Book: How Approved Generic Drugs Are Listed and Why It Matters

The FDA Orange Book is the single most important document for anyone who needs to know which generic drugs can legally replace brand-name medicines in the U.S. It’s not just a list-it’s the rulebook that tells pharmacists, doctors, insurers, and drug companies exactly which generics are safe to swap in place of expensive brand-name pills. If you’ve ever picked up a generic prescription and wondered why it was allowed to replace the name-brand version, the answer is in the Orange Book.

What the FDA Orange Book Actually Is

The official name is Approved Drug Products with Therapeutic Equivalence Evaluations. It’s been around since 1984, created as part of the Hatch-Waxman Act to make it easier for generic drugs to enter the market without re-proving safety and effectiveness from scratch. The FDA doesn’t test every generic drug itself. Instead, it relies on a shortcut: if a generic proves it behaves the same way in the body as the original brand-name drug, it gets approved.

That’s where therapeutic equivalence comes in. The Orange Book assigns every approved drug a code-usually an “A” or “B”-that tells you whether it’s interchangeable. An “A” code means the generic is considered bioequivalent and can be substituted without any concern. A “B” code means there’s uncertainty, and the pharmacist might need to check with the prescriber before swapping.

As of late 2023, the Orange Book listed over 16,000 approved drug products. Roughly 90% of all prescriptions filled in the U.S. are for generics, and nearly all of those substitutions are guided by this one document.

How Generic Drugs Get Listed

Generic drugs don’t go through the same long, expensive approval process as brand-name drugs. Instead, they use what’s called an Abbreviated New Drug Application, or ANDA. To get approved, the generic maker must prove two things: their drug has the same active ingredient, strength, dosage form, and route of administration as the original-and it’s absorbed into the body at the same rate and to the same extent.

The original brand-name drug is called the Reference Listed Drug, or RLD. In the Orange Book, every generic is linked to its RLD. If you search for a drug like Lipitor (atorvastatin), you’ll see the brand listed as the RLD, followed by dozens of generics-all marked as “No” in the RLD column. Each one has been approved because it matches the RLD’s performance.

The FDA doesn’t test these generics directly. It reviews data submitted by the manufacturer-usually from clinical bioequivalence studies-and approves if the evidence meets the standard. Once approved, the drug appears in the Orange Book the following month. The process is fast: in 2023, the average review time for an ANDA was just 10 months, down from over three years in 2010.

Therapeutic Equivalence Codes: What the Letters Mean

The TE code is the most critical piece of information in the Orange Book for pharmacists. It’s not just a label-it’s a legal signal.

• A codes mean the drug is therapeutically equivalent. These are the ones pharmacists can swap automatically, unless the prescriber writes “dispense as written.”
• B codes mean the drug is not considered equivalent. This could be due to inconsistent absorption, different inactive ingredients, or formulation issues. These generics can’t be substituted without a doctor’s permission.
• BN means the drug has no generic competitors. It’s a single-source product, often because patents or exclusivity are still in effect.
• AB1, AB2, etc., indicate multiple generics that are equivalent to the same RLD. The number just helps distinguish between them.

For example, if you look up metformin, you’ll see dozens of A-coded generics. But if you search for a complex inhaler like Advair, you might see fewer A codes-because matching the delivery system is harder. The Orange Book doesn’t always reflect real-world interchangeability for these products, which is why some pharmacists say they still need to use clinical judgment.

Authorized Generics: The Hidden Option

There’s another kind of generic you won’t find in the Orange Book: the authorized generic. These are brand-name drugs made by the original company but sold under a different label-often at a lower price. For example, the maker of Viagra might sell a generic version of sildenafil under its own name, with no brand logo.

Authorized generics aren’t approved through ANDAs. They’re marketed under the original NDA, so they’re not listed in the Orange Book. Instead, the FDA keeps a separate, quarterly updated list on its website. This list includes the brand name, the manufacturer, and when the authorized generic entered the market.

Why does this matter? Because authorized generics are often the first generics to hit the market after patent expiry-and they’re identical to the brand. Many patients don’t realize they’re getting the exact same pill, just cheaper.

Patents and Exclusivity: The Hidden Barriers

The Orange Book isn’t just about equivalence-it’s also where drug companies list their patents. This is where things get complicated.

When a brand-name company applies for FDA approval, it must list any patents that cover the drug’s chemical structure, formulation, or specific medical uses. These patents are published in the Orange Book. If a generic company files an ANDA and challenges one of those patents, the brand company can sue, triggering a 30-month legal hold on the generic’s approval.

Between 2005 and 2022, the number of patents listed in the Orange Book nearly doubled-from 8,000 to over 14,000. Critics call this “patent evergreening”-where companies file multiple narrow patents to delay competition. Supporters say it protects real innovation.

The FDA doesn’t decide which patents are valid. It just lists what’s submitted. That’s led to legal battles. In 2022, a federal court questioned whether the FDA had the authority to reject certain patents that seemed designed only to block generics. The system is under pressure to change.

How to Use the Electronic Orange Book

The FDA’s Electronic Orange Book is free and easy to use. Here’s how to find what you need:

1. Go to the search page and choose “Active Ingredients” or “Proprietary Name.”
2. Enter the drug name-like “losartan” or “Synthroid.”
3. Look at the results under “Dosage Form; Route.”
4. Find the RLD (marked “Yes”) and then see all the generics below it (marked “No”).
5. Check the TE code next to each generic.

For combination drugs (like those with two or three active ingredients), you’ll need to search each ingredient separately. Some products, like inhalers or eye drops, are harder to match, and the TE codes may not capture all the nuances.

Pharmacists and pharmacy benefit managers use automated systems that pull data directly from the Orange Book API. That API, launched in 2022, now handles over 2 million queries a month. But 41% of pharmacy systems still need human review because the data isn’t always clear-cut.

Why This Matters to You

If you’re a patient, the Orange Book is why your $200 brand-name pill became a $10 generic. It’s why your insurance company pushes you toward generics. It’s why your pharmacist can legally swap your medication without calling your doctor.

If you’re a prescriber, you need to understand TE codes. If you write a prescription for a drug with a “B” code, you’re telling the pharmacist: don’t substitute. If you don’t know the difference, you might accidentally block a cheaper option.

If you’re a generic drug maker, your entire business depends on accurate Orange Book listings. A misclassified TE code can delay market entry by a year or more. A patent that’s listed incorrectly can trigger lawsuits and block competitors.

The system isn’t perfect. Pharmacists report confusion with complex products. Patients sometimes get different generics from month to month and wonder why the pill looks different. And not all states have the same substitution laws.

But the Orange Book works. It’s the reason the U.S. spends less on prescription drugs than any other developed country, while still approving hundreds of new generics every year. The FDA is working on a “Digital Orange Book” by 2025 that will update in real time and make the data easier to use. Until then, it remains the backbone of America’s generic drug system.

What’s Next for the Orange Book

The FDA is under pressure to clean up outdated or misleading patent listings. In January 2023, it issued new guidance to prevent companies from listing patents that don’t actually cover the drug’s approved use. Commissioner Robert Califf said this was about “removing inappropriate barriers to generic competition.”

At the same time, the agency is testing more detailed equivalence ratings for complex drugs-like inhalers, injectables, and topical creams-where traditional bioequivalence studies don’t always capture real-world performance.

The goal is simple: make sure patients get the right drug, at the right price, without unnecessary delays. The Orange Book won’t disappear. But it’s evolving to keep up with modern medicine.