April 25, 2024
Patent Listing in FDA’s Orange Book
For over 40 years, the U.S. Food and Drug Administration
patents beyond the active ingredient, including patents on
(FDA) has maintained a resource formally titled Approved
methods of using a drug, drug formulations, devices to
Drug Products with Therapeutic Equivalence Evaluations.
administer a drug, and methods of making a drug. A single
This frequently updated publication—now available as a
brand-name drug may thus be protected by multiple patents,
searchable online database—is more commonly called the
which may expire at different times.
“Orange Book” after the color of the print version’s cover.
Patent Listing in the Orange Book
The Orange Book
Only certain types of pharmaceutical patents are included in
The Orange Book lists all of the nonbiologic (a.k.a. “small-
the Orange Book. By statute, a company seeking FDA
molecule”) drugs approved by FDA to be marketed in the
approval of a new drug must include in their new drug
United States. (Biological products, which are drugs
application (NDA) any patent that either (1) “claims the
derived from living organisms—such as vaccines, blood
drug” and “is a drug substance (active ingredient) patent or
components, and monoclonal antibodies—are listed in a
a drug product (formulation or composition) patent”; or
separate FDA publication known as the “Purple Book.”)
(2) “claims a method of using such drug for which approval
Along with information about the approved drugs (e.g.,
is sought.” If the drug is later approved by FDA, the patent
dosages and forms), the Orange Book includes FDA’s
information in the NDA (along with any updates) is listed
therapeutic equivalence evaluations—that is, the approved
in the Orange Book with the drug.
products that are pharmaceutically equivalent and
bioequivalent to another approved product (e.g., a generic
FDA regulations provide that “[p]rocess patents, patents
form of a brand-name drug). Finally, the Orange Book
claiming packaging, patents claiming metabolites, and
includes information on patents and regulatory exclusivities
patents claiming intermediates” must not be included in an
that may protect a brand-name drug from generic
NDA. As a result, these types of patents should not be listed
competition.
in the Orange Book per FDA regulation.
The Orange Book serves as an important resource for health
Brand-name and generic drug manufacturers have disputed
care providers and the pharmaceutical industry. Health care
in court whether certain patents should be listed in the
providers may use the Orange Book to determine the
Orange Book. In Jazz Pharmaceuticals v. Avadel CNS
regulatory status of a product (e.g., whether a drug has been
Pharmaceuticals, the U.S. Court of Appeals for the Federal
approved by FDA or if an approval has been withdrawn).
Circuit held that a patent on a computerized risk evaluation
Pharmacists may use the Orange Book to determine
and mitigation strategy (REMS) system for a drug should
whether a therapeutically equivalent generic form of a drug
not have been listed in the Orange Book. Similarly, in In re
is available to substitute when they fill a prescription
Lantus Direct Purchaser Antitrust Litigation, the U.S.
written for a brand-name drug.
Court of Appeals for the First Circuit held that a patent on a
device for injecting a drug should not have been listed in
For drug manufacturers, the Orange Book’s information on
the Orange Book. A 2022 report from FDA and a 2023
a drug’s patents and regulatory exclusivities can be critical
report from the Government Accountability Office reveal
to whether and when generic competition occurs. (For more
varied stakeholder views on these issues, with some calling
information, see CRS Report R46679, The Role of Patents
for FDA to clarify the rules for listing REMS and device
and Regulatory Exclusivities in Drug Pricing.)
patents in the Orange Book.
Pharmaceutical Patents
The FDA’s “Ministerial” Role
Patents are a form of intellectual property that protect new
FDA does not actively police the patent information in
inventions. To obtain a patent, an inventor must file a patent
NDAs to make sure that the listed patents in fact claim the
application with the U.S. Patent and Trademark Office
drug or a method of using the drug. FDA maintains that it
(USPTO). USPTO reviews the application and grants a
lacks expertise in patent law and that its role with respect to
patent only if the claimed invention meets the statutory
Orange Book patents is only “ministerial.” In other words,
requirements. A patent’s term lasts for about 20 years.
FDA merely lists the patent information provided by drug
companies without independently verifying that the patent
Like any other invention, pharmaceutical-related
should be listed in the Orange Book. This approach has
innovations must be new, useful, nonobvious, and
raised concerns among some commentators that NDA filers
sufficiently described to be patented. For example, if a
may list inapplicable patents in the Orange Book to deter
person synthesizes a new chemical with potential use for
generic competition.
treating human disease, she may obtain a patent on that
chemical itself (an active-ingredient patent). Pharmaceutical
FDA does offer an administrative process through which
manufacturers often obtain many other types of drug
any person who “disputes the accuracy or relevance of
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Patent Listing in FDA’s Orange Book
patent information” in the Orange Book may notify FDA
market participants on notice that the FTC intends to
and seek correction of the patent information. But FDA will
scrutinize improper Orange Book listings to determine
not change the patent information in the Orange Book
whether these constitute unfair methods of competition in
unless the NDA holder agrees to amend or correct the
violation of Section 5 of the [FTC] Act.” FTC observed that
information in response to the patent listing dispute.
improperly listed patents “may disincentivize investments
in developing a competing product and increase the risk of
The Orange Book and Generic Entry
delayed generic and follow-on product entry, reducing
Prior to generic entry, the brand-name drug may be the only
patient access to more affordable prescription drugs and
available version of a product. Generic competition tends to
increasing costs to the healthcare system.”
bring down the price of a drug, in some cases sharply.
A few months later, FTC announced that it had used FDA’s
The process for generic drug approval by FDA is governed
administrative process to challenge more than 100 patents
by the Hatch-Waxman Act of 1984 (P.L. 98-417), as
as improperly listed in the Orange Book, including patents
amended. Under Hatch-Waxman, a drug company may
relating to drug-delivery devices such as asthma inhalers
seek FDA approval for a generic version of an approved
and epinephrine autoinjectors. FTC also sent notice letters
brand-name drug by filing an abbreviated new drug
to 10 drug companies informing them of FTC’s actions and
application (ANDA). An ANDA must make one of four
its view that these patents were improperly listed in the
certifications with respect to every patent listed in the
Orange Book. FTC’s letters noted that it retained the right
Orange Book:
to take further action, including an investigation under
Section 5 of the FTC Act.
• Paragraph I: Certifies that there are no patents listed for
that drug in the Orange Book.
In response to FTC’s actions, several drugmakers opted to
•
delist (i.e., remove) some or all of the patents challenged by
Paragraph II: Certifies that all the patents listed in the
FTC. Other drugmakers refused to delist the patents,
Orange Book for that drug are expired.
arguing that the patents were properly included in the
• Paragraph III: Certifies that the ANDA filer does not
Orange Book. In March 2024, FTC filed a brief in a patent
challenge the patent(s) listed in the Orange Book.
case involving a generic version of a Teva asthma inhaler,
•
urging the court to order Teva to remove the patents at issue
Paragraph IV: Certifies that the ANDA filer challenges
from the Orange Book (which were among those FTC had
the patent(s) listed in the Orange Book as invalid or not
challenged using FDA’s process).
infringed (i.e., inapplicable).
Issues for Congress
FDA may approve ANDAs with paragraph I or II
certifications immediately. If the generic applicant makes a
The types of patents required to be listed in the Orange
paragraph III certification, FDA may not approve the
Book and their effect on generic entry under the Hatch-
ANDA until the patents at issue have expired.
Waxman Act ultimately derive from statutes Congress
created and could amend, should it choose to do so.
If the generic applicant makes a paragraph IV certification
and the NDA filer timely sues in court for patent
One issue concerns responsibility for monitoring Orange
infringement, this triggers a 30-month stay. FDA cannot
Book patent listings. Due to FDA’s ministerial role with
approve the ANDA for 30 months, unless the court resolves
respect to Orange Book patents, disputes over Orange Book
the patent dispute earlier (so-called “patent linkage”).
patent listings are more often decided by courts in Hatch-
Waxman or antitrust litigation. Congress may consider
In considering whether and when to file an ANDA, generic
whether to impose more responsibilities on FDA, FTC, or
drug companies will assess the expiration date, scope, and
the courts, or whether to expand current procedures for
validity of patents listed in the Orange Book. They may
challenging Orange Book patents before FDA or in court.
weigh, for example, the costs and benefits of challenging a
patent under paragraph IV or instead waiting for a patent to
Another issue is whether additional clarity is needed on the
expire under paragraph III. The patent information in the
types of patents that may be listed in the Orange Book.
Orange Book can thus affect when generic competition
Congress updated the statute on the types of patents that
begins for a particular drug.
should be listed in 2021 (P.L. 116-290), and FDA has
issued and updated its regulations on these issues. Even so,
It is generally in the interest of NDA holders to list all
disputes continue over whether certain patent types (e.g.,
relevant patents in the Orange Book. While patent holders
REMS or drug-delivery devices) should be listed.
may still sue in court for infringement of drug patents that
are not listed in the Orange Book, the ANDA filer need not
A final issue Congress may consider is the relationship
certify as to unlisted patents and the 30-month stay would
between Orange Book patents and the 30-month stay.
not apply. FDA could therefore approve the ANDA on its
Congress could consider, for example, whether the 30-
own schedule, unless a court ruled otherwise.
month stay should apply only to certain patent types (e.g.,
active ingredient patents but not drug-delivery devices).
The FTC’s 2023 Policy Statement
In September 2023, the Federal Trade Commission (FTC)
Kevin J. Hickey, Legislative Attorney
issued a policy statement concerning some drug
manufacturers’
IF12644
alleged “improper listing of patents” in the
Orange Book. The intent of the statement was to “put
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Patent Listing in FDA’s Orange Book


Disclaimer
This document was prepared by the Congressional Research Service (CRS). CRS serves as nonpartisan shared staff to
congressional committees and Members of Congress. It operates solely at the behest of and under the direction of Congress.
Information in a CRS Report should not be relied upon for purposes other than public understanding of information that has
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