FDA Orange Book: How to Find the RLD and Reference Standard
The FDA Orange Book is the US government's list of approved drug products with their therapeutic equivalence ratings. If you are planning a bioequivalence (BE) study or a US generic filing, you use it to pin down two products: the Reference Listed Drug (RLD) your application relies on, and the Reference Standard (RS) your in vivo BE study must use. This guide shows how to find both, how to read the codes next to them, and what to do when the product you need is no longer sold.
Written By: Nitin Goswami, Senior Medical Content Writer | Reviewed By: Shilpi Banerjee, Registered Pharmacist (M.Pharm) | Last updated: 21 October 2026
In this guide
- What is the FDA Orange Book?
- RLD, Reference Standard and comparator: what is the difference?
- How to find the RLD and RS: step by step
- How to read therapeutic equivalence (TE) codes
- What if the RLD is discontinued?
- Orange Book vs Purple Book
- Common mistakes when choosing the reference product
- From Orange Book to your study: sourcing the exact product
- Quick answers
What is the FDA Orange Book?
Its official title is Approved Drug Products with Therapeutic Equivalence Evaluations. FDA describes it as the list of drug products approved on the basis of safety and effectiveness, together with therapeutic equivalence evaluations and the related patent and exclusivity information.
You can use it in three forms:
- Online search (electronic Orange Book) by proprietary name, active ingredient, application number, applicant, dosage form, route or patent number.
- The annual edition and its cumulative supplement, published as PDFs.
- Downloadable data files (products, patents and exclusivity), which FDA updates monthly.
Biologics are listed elsewhere
Biological products licensed under section 351 of the Public Health Service Act are listed in FDA's Purple Book. This includes "transition" products that were approved as NDAs and were deemed to be biologics licences on 23 March 2020.
Who uses it
- Formulation and regulatory teams at generic companies choosing the product to compare against.
- BA/BE CROs confirming which reference product goes into a study.
- Sourcing and supply teams who must buy that exact US product.
RLD, Reference Standard and comparator: what is the difference?
These three terms are often used as if they mean the same thing. They do not, and buying the wrong one can cost a study weeks. For a fuller background on RLDs, see our explainer on what an RLD is in pharma.
| Term | What it is | Who decides | Where you see it |
|---|---|---|---|
| Reference Listed Drug (RLD) | The approved drug product an ANDA applicant relies on when seeking approval. | FDA lists it | "RLD" in the RLD column |
| Reference Standard (RS) | The product FDA selects that an ANDA applicant must use in its in vivo BE study. Usually the RLD, but it can be a different product. | FDA selects it | "RS" in the RS column |
| Comparator | The product a test or investigational drug is compared with in a clinical study, as set out in the protocol. | Study sponsor, in line with the regulator | Not an Orange Book field |
Until 2017 the electronic Orange Book showed one marker for both. On 25 January 2017 FDA split them, so search results now show the RLD and the RS in separate columns.
How to find the RLD and RS: step by step
Search the product
Open the Orange Book search and enter the proprietary name, active ingredient or application number (at least 3 characters).
Read one row at a time
Each row is one product at one strength. The fields that matter are the application type (N for an NDA innovator product, A for an ANDA generic), application number, product number, strength, dosage form and route, TE code, RLD, RS and marketing category (RX, OTC or DISCN).
Match the exact product
Filter to the same dosage form, route and strength as your product. Immediate-release and extended-release versions of the same molecule are different products.
Find the RLD
The row marked RLD in the RLD column is the product your ANDA refers to.
Find the RS
The row marked RS in the RS column is the product your in vivo BE study must use. If RLD and RS sit on different rows, the RS row is the one to buy for the study.
Check the marketing status
DISCN means the product is in the discontinued list. Read the next section before you plan around it.
Check patents and exclusivity
Open the application's patent and exclusivity details. They affect when a generic can be filed or approved, so regulatory teams usually review them at this stage.
Record the details for sourcing
Note the proprietary name, active ingredient, strength, dosage form, application holder, application number and product number. A supplier needs all of these to buy the exact US product.
Not sure which product FDA expects?
FDA's guidance on referencing approved drug products in ANDA submissions explains how RLD and RS are chosen, and applicants can ask FDA through controlled correspondence when the choice is unclear.
How to read therapeutic equivalence (TE) codes
The TE code shows how FDA rates a generic against the innovator prescription product. Codes starting with A mean FDA considers the products therapeutically equivalent. Codes starting with B mean it does not, at this time. The full definitions are in the Orange Book Preface.
| Code | Meaning (summary of the FDA Preface) |
|---|---|
| AB, AB1, AB2... | Bioequivalence requirements met. Numbered codes tie a product to a specific RLD; compare only products with the same code under the same heading. |
| AA | Conventional dosage forms with no known bioequivalence problems. |
| AN | Solutions and powders for aerosolisation. |
| AO | Injectable oil solutions; equivalent only when ingredient, concentration and type of oil all match. |
| AP | Injectable aqueous solutions and certain intravenous non-aqueous solutions. |
| AT | Topical products. |
| BC | Extended-release dosage forms without submitted bioequivalence data. |
| BD | Documented bioequivalence problems without adequate studies. |
| BE | Delayed-release oral dosage forms without in vivo bioequivalence studies. |
| BN | Aerosol-nebuliser products tied to a specific delivery system. |
| BP | Potential bioequivalence problems without adequate data. |
| BR | Suppositories or enemas for systemic absorption without in vivo evidence. |
| BS | Drug standard deficiencies. |
| BT | Topical products with bioequivalence issues. |
| BX | Insufficient data to decide; presumed not equivalent. |
| B* | Needs further FDA investigation before a position is taken. |
What if the RLD is discontinued?
The Discontinued Drug Product List holds approved products that are not in the active prescription or OTC lists, for example products never marketed, made only for export or military use, or withdrawn from sale. Products withdrawn for safety or effectiveness reasons are not included.
- A discontinued product can still be the RLD, unless FDA decides it was withdrawn for safety or effectiveness reasons.
- When the RLD is no longer marketed, FDA may select another approved product as the RS, generally a previously approved generic that is therapeutically equivalent to the RLD.
- In practice, follow the RS column. It tells you which product is actually available to buy for the BE study.
Orange Book vs Purple Book
| Orange Book | Purple Book | |
|---|---|---|
| Covers | Approved drug products, mainly small molecules (NDA and ANDA) | Biological products licensed under section 351(a) or 351(k) of the PHS Act |
| Equivalence shown as | TE codes (A / B) | Biosimilar and interchangeable status |
| Reference term | RLD and Reference Standard | Reference product |
| Also lists | Patents and exclusivity | Exclusivity periods and patent lists from reference product sponsors |
Source: Purple Book FAQs.
Common mistakes when choosing the reference product
- Matching only the active ingredient, without checking strength, dosage form and route.
- Buying the RLD for a BE study when FDA has named a different product as the RS.
- Missing a DISCN status, then finding the product cannot be bought in the quantity or expiry the study needs.
- Using the US RLD for a filing in another market. Each regulator has its own reference-product rules; the Orange Book governs US submissions.
- Accepting stock without proof of origin. A reference product should come with a traceable invoice, batch number, expiry and Certificate of Analysis.
From Orange Book to your study: sourcing the exact product
Finding the RS row is the desk work. The next step is buying that product in the US market, in the batch, quantity and expiry your study needs, and getting it to your site with its documents intact.
Ikris Pharma Network sources reference products from regulated markets including the USA, Europe, the UK, Japan, Australia, Canada and Switzerland. We can source specific batches and expiry dates, and supply them with a Certificate of Analysis, batch records, invoices and import/export documents. Our GDP-certified warehouse in Belgium and our GDP-compliant cold chain handle temperature-sensitive products. More on how this works for BA/BE studies is on our global RLD and innovator drug sourcing page and our clinical trial sourcing service.
Need the Reference Standard for your BE study?
Send us the proprietary name, active ingredient, strength, dosage form, application number, quantity, minimum expiry and delivery country. We reply within 24-48 hours.
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What is the difference between an RLD and a Reference Standard?
The RLD is the approved product a generic application relies on. The Reference Standard is the product FDA selects for the in vivo BE study. They are usually the same product, but not always.
Can a discontinued drug still be the RLD?
Yes, unless FDA determines it was withdrawn from sale for safety or effectiveness reasons. FDA may then name a different product as the Reference Standard.
How often is the Orange Book updated?
FDA updates the downloadable data files monthly. The annual edition is updated through cumulative supplements.
Does the Orange Book list biologics?
Biological products licensed under section 351 of the PHS Act are listed in FDA's Purple Book.
Is the US RLD accepted for BE studies filed in India or Europe?
That depends on the regulator where you file. The Orange Book RLD and RS apply to US ANDA submissions. For other markets, check that regulator's reference-product requirements before sourcing.
What details does a supplier need to source the RS?
The proprietary name, active ingredient, strength, dosage form, application holder, application and product number, the quantity, the minimum expiry and the delivery country.
Sources
- U.S. FDA - Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (search and data, current through October 2026)
- U.S. FDA - Orange Book Preface (definitions of RLD, RS, TE codes, discontinued list)
- U.S. FDA - Orange Book Data Files (field definitions; monthly updates)
- U.S. FDA - FDA introduces reference standard data updates to the Orange Book (25 January 2017)
- U.S. FDA - Guidance for Industry: Referencing Approved Drug Products in ANDA Submissions
- U.S. FDA - Purple Book FAQs
This article is general regulatory information for pharmaceutical professionals. Always confirm the current reference product with the regulator where you file.