FDA Orange Book: How Approved Generic Drugs Are Listed

The FDA Orange Book is the official government list that tells pharmacists and doctors which generic drugs can safely replace brand-name medicines. It’s not just a directory-it’s the rulebook for how generics enter the market, compete on price, and get approved without repeating every clinical trial. If you’ve ever picked up a cheaper version of a prescription and wondered how the FDA knows it’s just as safe and effective, the Orange Book is why.

What Is the FDA Orange Book?

The official name is Approved Drug Products with Therapeutic Equivalence Evaluations. It’s been around since 1984, when Congress passed the Hatch-Waxman Act to balance two goals: letting drug companies protect their patents and letting generics enter the market faster. Today, it’s an online database updated every month by the FDA’s Center for Drug Evaluation and Research (CDER). As of late 2023, it lists over 16,000 approved drug products-both prescription and over-the-counter.

Here’s the key: 90% of all prescriptions filled in the U.S. are for generic drugs. But not all generics are created equal. The Orange Book is what tells you which ones are interchangeable and which ones aren’t. Without it, pharmacies couldn’t legally substitute a cheaper version for a brand-name drug in most cases.

How Generic Drugs Get Listed

Generic drug makers don’t file a full New Drug Application (NDA) like brand-name companies do. Instead, they use the Abbreviated New Drug Application, or ANDA. The word “abbreviated” doesn’t mean easy-it means they don’t have to repeat expensive clinical trials. But they must prove one thing: bioequivalence.

Bioequivalence means the generic drug delivers the same amount of active ingredient into the bloodstream at the same rate as the brand-name version. If it passes, the FDA approves it. But here’s the catch: the generic must be compared to a specific brand-name drug called the Reference Listed Drug (RLD). The RLD is the original product that the FDA has already approved as safe and effective.

In the Orange Book, every drug is marked with a column labeled “RLD.” If it says “Yes,” that’s the original brand. If it says “No,” it’s a generic version built off that RLD. You can’t list a generic without naming its RLD. That’s the backbone of the whole system.

Therapeutic Equivalence Codes: What the Letters Mean

Every approved generic gets a Therapeutic Equivalence (TE) code. These one- or two-letter codes tell you whether the drug is considered interchangeable with the brand. Here’s what they mean:

• A = Therapeutically equivalent. This is the gold standard. Pharmacists can substitute it without a doctor’s permission in most states.
• B = Not therapeutically equivalent. Something’s off-maybe the absorption rate is too different, or the formulation causes issues. Don’t swap these without consulting a doctor.
• BN = Single-source product. Only one manufacturer makes this drug, so no generics exist yet.
• AB = Therapeutically equivalent and approved as interchangeable. Often used for complex drugs like inhalers or injectables where equivalence is harder to prove.

These codes are critical. A pharmacy’s computer system checks the TE code before substituting a generic. If the code is “B,” the system blocks the swap. That’s not a glitch-it’s the law.

Patents and Exclusivity: The Hidden Rules

The Orange Book doesn’t just list drugs. It also lists patents. This is where things get complicated.

Brand-name companies must submit patent information to the FDA within 30 days of a patent being issued. These patents cover the active ingredient, how the drug is made, or how it’s used. Each patent gets a unique code, like “U-123.”

Why does this matter? Because if a generic company files an ANDA and challenges one of these patents, the brand company can sue. If they do, the FDA puts a 30-month hold on approving the generic-even if the patent is weak. This is called the “30-month stay.” It’s meant to protect innovation, but critics say it’s often used to delay competition.

As of 2022, there were over 14,000 patents listed in the Orange Book-up from about 8,000 in 2005. Some experts call this “patent evergreening”: extending monopoly power by filing multiple minor patents on the same drug. The FDA says it’s reviewing how patents are listed to stop abuse.

Authorized Generics: The Secret Weapon

There’s another kind of generic you won’t find in the Orange Book: authorized generics.

An authorized generic is the exact same drug as the brand-name version, just sold without the brand name. The same company that makes the brand also makes and sells this version-often at a lower price to compete with other generics. It’s the same pills, same packaging, same factory.

Because it’s made under the original NDA, not an ANDA, it doesn’t appear in the Orange Book. Instead, the FDA keeps a separate list called the List of Authorized Generic Drugs, updated quarterly. This list tells you which brand company makes the authorized generic, what the trade name is, and when it entered the market.

Authorized generics can be confusing. If you see a generic that looks identical to the brand, it might not be a true generic at all-it could be the brand’s own product.

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. Start with the Proprietary Name search if you know the brand name (like Lipitor or Advair).
2. Then use the Ingredient Search to find all drugs with the same active ingredient (like atorvastatin or fluticasone).
3. Filter by Dosage Form and Route (e.g., tablet, oral; inhaler, inhalation).
4. Look for the RLD column and TE codes. Only “A” and “AB” codes are interchangeable.

Pro tip: If you’re looking for a combination drug like Trelegy Ellipta (which has three ingredients), you have to search each ingredient separately. The system doesn’t let you search by all three at once.

What’s Not in the Orange Book

Not every drug gets a TE code. Over-the-counter (OTC) drugs are listed in a separate section-but they’re not evaluated for therapeutic equivalence. That’s because OTC products don’t need a prescription, and the FDA doesn’t regulate substitutions the same way.

Also, drugs with “tentative approval” don’t appear in the Orange Book. These are generics that passed all tests but are waiting for patent or exclusivity issues to clear. You’ll find them on Drugs@FDA, but not in the Orange Book.

Discontinued drugs? They show up in their own section. No RLD, no TE code-just a note that they’re no longer sold.

Real-World Problems and Confusion

Even with all this structure, people get it wrong. Pharmacists report that 62% of them have seen a situation where the Orange Book said a drug was interchangeable, but state law didn’t allow it. Or a patient got a generic that didn’t work the same way, even though the TE code said “A.”

Complex drugs like inhalers, eye drops, and topical creams are especially tricky. The FDA admits that bioequivalence for these products is harder to prove. Some TE codes for these drugs are still being reviewed.

Pharmacy software companies say 78% of their clients use Orange Book data-but 41% still need extra help interpreting the codes. That’s because the system isn’t perfect. It’s a tool, not a crystal ball.

The Bigger Picture: Why It Matters

The U.S. generic drug market is worth $67 billion a year. The Orange Book is the engine behind that. Without it, generics couldn’t compete. Prices would stay high. Patients would pay more.

Studies show that multi-source generics-those with multiple brands competing-cost 18% to 22% less than single-source drugs. That’s billions saved every year.

The FDA is working to improve it. In 2023, they released new guidance to stop companies from listing too many weak patents. They’re also building a new “Digital Orange Book” by 2025 that will update in real time, not monthly.

But the system still depends on honesty. If a brand company lies about a patent, or a generic maker misrepresents its product, the whole system breaks. That’s why the FDA’s role isn’t to test drugs-it’s to make sure the rules are followed.