The FDA Orange Book – “Approved Drug Products with Equivalence Evaluation”
| What it is | How it works | Where to find it |
|------------|--------------|------------------|
| The Orange Book is the FDA’s official registry of all drugs that have received New Drug (NDA) or Abbreviated New Drug Application (ANDA) approval. | For each product, the FDA records a therapeutic equivalence rating (often called an “equivalence evaluation”) that tells you whether a generic can be considered interchangeable with the brand‐name reference product. | On the FDA website: https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm |
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1. What is “Equivalence Evaluation”?
- Therapeutic Equivalence Rating
- C – Therapeutically equivalent (generics with a “C” rating are considered interchangeable).
- P – Not therapeutically equivalent but the generic may be interchangeable (the FDA notes that other factors—such as formulation differences—might affect interchangeability).
- E – Equivalence not evaluated (usually for products that haven’t been reviewed for equivalence, such as recently approved generics that are still under review).
- Why it matters
- Pharmacists use the rating to decide whether a generic can replace a brand drug in a patient’s medication regimen.
- Regulators and manufacturers use it to prove that a new generic meets the FDA’s standards for therapeutic equivalence.
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2. How the Rating Is Determined
1. Bioequivalence Studies – The generic manufacturer must demonstrate that the drug’s active ingredient behaves the same way in the body as the brand (e.g., same bioavailability).
2. In‑vitro Studies – For drugs with complex formulations (like sustained‑release tablets), the manufacturer may need to show that the release profile matches the reference product.
3. FDA Review – The FDA evaluates the data and assigns a rating.
- C if the evidence shows no clinically meaningful differences.
- P if there are minor differences that the FDA believes are clinically acceptable but not proven to be equivalent.
- E if the data are insufficient or not yet reviewed.
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3. How to Use the Orange Book to Find Equivalence Evaluations
1. Go to the Orange Book search page
- URL: https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
2. Choose a search method
- Brand Name – look up the reference product (e.g., “Amoxicillin”).
- Generic Name – find all generics for that active ingredient.
3. View the “Equivalence Evaluations” column
- The table will list all approved products, their approval dates, and their therapeutic equivalence rating.
4. Interpret the rating
- C = “Equivalent”
- P = “Not equivalent but may be interchangeable”
- E = “Equivalence not evaluated”
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4. Practical Example
| Brand Product | Generic Name | FDA Approval Date | Equivalence Rating |
|---------------|--------------|-------------------|--------------------|
| Tylenol 500 mg (acetaminophen) | Acetaminophen 500 mg (various brands) | 1975 | C |
| Zithromax 500 mg (azithromycin) | Azithromycin 500 mg (generic) | 2004 | C |
| Prozac 20 mg (fluoxetine) | Fluoxetine 20 mg (generic) | 2019 | P* |
* The “P” rating indicates that the generic is considered interchangeable in most therapeutic situations, but the FDA notes a small difference in formulation that could affect certain patients.
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5. When the Orange Book Might Not Show a Rating
- Recently Approved ANDAs – The rating may still be under review, so “E” will appear until the FDA publishes the final rating.
- Biosimilars – These are listed separately; equivalence evaluation for biologics is more complex and often uses a “biosimilarity” designation rather than a simple C/P/E rating.
- Non‑US Approvals – Drugs approved outside the U.S. but later submitted for U.S. approval will appear only after the FDA’s evaluation.
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6. Useful Tips for Practitioners
1. Double‑Check the Generic’s Label – Even a “C” rated generic should have the same dosage strength and form as the brand.
2. Monitor the Orange Book Updates – The FDA updates the database monthly; check for any changes in rating that might affect your formulary.
3. Use the “Therapeutic Equivalence” Search – If you’re looking for all generics that are “C” rated for a specific drug, filter the results accordingly.
4. Cross‑Reference with the FDA’s “Generic Drug Database” – For the most recent FDA approvals and pending applications.
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Quick How‑to: Finding the Equivalence Rating for a Drug
1. Open the Orange Book link.
2. In the search box, type the drug name (e.g., “lisinopril”) and hit