Orange Book 
Questions and Answers 
Guidance for Industry
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
July 2022 
Generic Drugs   
Orange Book 
Questions and Answers 
 
Guidance for Industry
 
 
 
 
 
 
 
 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
July 2022 
Generic Drugs 
 
    Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 1 
III.  QUESTIONS AND ANSWERS ....................................................................................... 3 
A.  General Inquiries About the Content and Format of the Orange Book ................................... 3 
B.  Petitioned ANDAs .......................................................................................................................... 7 
C.  The Movement of Drug Products Between the Active and Discontinued Sections of the 
Orange Book ................................................................................................................................... 7 
D.  Patent Listings .............................................................................................................................. 10 
1. Listing Patents ............................................................................................................................... 10 
2.  Patent Listing Disputes ................................................................................................................. 13  Contains Nonbinding Recommendations 
Orange Book 
Questions and Answers 
Guidance for Industry1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION  
 
This guidance is intended to assist interested parties (including prospective drug product 
applicants, drug product applicants, and approved application holders) in utilizing the Approved 
Drug Products With Therapeutic Equivalence Evaluations publication (the Orange Book).2  This 
guidance provides answers to commonly asked questions that we have received from interested 
parties regarding the Orange Book.3 
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract. This document is intended 
only to provide clarity to the public regarding existing requirements under the law. FDA 
guidance documents, including this guidance, should be viewed only as recommendations, unless 
specific regulatory or statutory requirements are cited. The use of the word should in FDA 
guidance means that something is suggested or recommended, but not required. 
 
 
II.  BACKGROUND 
 
The Orange Book identifies (1) drug products approved by FDA under the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) and (2) patent and exclusivity information related to approved 
drug products.  In particular, the main criteria for the inclusion of a drug product in the Orange 
Book are that the drug product is the subject of an approved application and that FDA has not 
 
1 This guidance has been prepared by the Office of Generic Drugs in the Center for Drug Evaluation and Research at 
the Food and Drug Administration.  
2 The Orange Book is available at https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm.  
3 This guidance generally does not include topics addressed in the Orange Book Preface, the Frequently Asked 
Questions on The Orange Book, and the Frequently Asked Questions on Patents and Exclusivity web pages, which 
are available at https://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079068.htm, 
https://www.fda.gov/Drugs/InformationOnDrugs/ucm114166.htm, and 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079031.htm, respectively.  
  1  Contains Nonbinding Recommendations 
determined the drug product to have been withdrawn from sale for safety or effectiveness 
reasons.4  
 
The Orange Book is composed of four main parts:  
 
(1) The Prescription Drug Product List, which is a list of approved marketed prescription 
drug products with therapeutic equivalence evaluations (which along with the OTC Drug 
Product List is referred to as the Active Section);  
 
(2) The OTC Drug Product List, which is a list of marketed over-the-counter (OTC) drug 
products that have been approved in new drug applications (NDAs) or abbreviated new 
drug applications (ANDAs) (which along with the Prescription Drug Product List is 
referred to as the Active Section);  
 
(3) The Drug Products with Approval under Section 505 of the FD&C Act Administered by 
the Center for Biologics Evaluation and Research List; and  
 
(4) The Discontinued Drug Product List, which is a cumulative list of approved drug 
products that have never been marketed, are for exportation (e.g., only marketed outside 
the United States), are for military use, are not commercially distributed by a United 
States federal or state government entity, have been discontinued from marketing and 
FDA has not determined that they were withdrawn from sale for reasons of safety or 
effectiveness, or have had their approvals withdrawn for reasons other than safety or 
effectiveness subsequent to being discontinued from marketing (commonly referred to as 
the Discontinued Section). 
 
The Orange Book contains additional information, including three appendices and two addenda 
related to patents and exclusivity.  The Orange Book website also has a number of additional 
resources that can assist stakeholders with using the Orange Book and related questions.5 
 
In addition, the Orange Book contains therapeutic equivalence6 evaluations for approved 
multisource prescription drug products, which are reflected for drug products in the Active 
Section.7  These evaluations have been prepared to serve as public information and advice to 
state health agencies, prescribers, and pharmacists to promote public education on drug product 
selection and to foster containment of health care costs.8  
 
4 See 21 CFR 314.161. 
5 Available at the Orange Book homepage at https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm.  
6 Approved drug products are therapeutic equivalents if they are pharmaceutical equivalents for which 
bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile 
when administered to patients under the conditions specified in the labeling (21 CFR 314.3(b)). 
7 We note that those products with approved applications that are single-source (i.e., there is only one approved 
product available for that active ingredient, dosage form, route of administration, and strength) are also included in 
the Orange Book, but no therapeutic equivalence code is included with such products. 
8 Therapeutic equivalence evaluations in the Orange Book are not official FDA actions affecting the legal status of 
products under the FD&C Act.  See, e.g., 45 FR 72582 at 72597 (October 31, 1980). 
  2  Contains Nonbinding Recommendations 
 
The coding system for therapeutic equivalence evaluations is designed (1) to allow users to 
determine quickly whether the Agency has determined that a particular approved drug product 
(e.g., a particular strength, dosage form, and route of administration of an approved drug) is 
therapeutically equivalent to other pharmaceutically equivalent9 drug products and (2) to provide 
additional information to users on the basis of FDAs evaluations; the first item (i.e., therapeutic 
equivalence) is reflected in the first letter of the therapeutic equivalence code, and the second 
item (i.e., additional information) is reflected in the second letter of the code. 
 
As noted in the Introduction, this guidance provides answers to questions that have been received 
by the FDA staff that publishes and manages the Orange Book.  The questions and answers in 
this guidance cover the following topics:  
 
  General inquiries about the content and format of the Orange Book 
 
  Petitioned ANDAs 
 
  The movement of drug products between the Active and Discontinued Sections of the 
Orange Book 
 
  Patent listings 
 
 
III.  QUESTIONS AND ANSWERS 
 
A.  General Inquiries About the Content and Format of the Orange Book 
 
Q1.  Which applications are not listed in the Orange Book? 
 
A1.  The Orange Book does not include: (1) approved drug products that were discontinued 
either before the first edition in October 1980 or discontinued between 1980 and 1987, 
prior to the identification of discontinued products; (2) drug products that have a tentative 
approval;10 (3) drug products marketed before 1962 for which a Drug Efficacy Study 
 
9 Pharmaceutical equivalents are drug products in identical dosage forms and route(s) of administration that contain 
identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the same therapeutic moiety, 
or, in the case of modified-release dosage forms that require a reservoir or overage or such forms as prefilled 
syringes where the residual volume may vary, that deliver identical amounts of the active drug ingredient over the 
identical dosing period; do not necessarily contain the same inactive ingredients; and meet the identical compendial 
or other applicable standard of identity, strength, quality, and purity, including potency and, where applicable, 
content uniformity, disintegration times, and/or dissolution rates (21 CFR 314.3(b)).  They may differ in 
characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (including colors, 
flavors, preservatives), expiration date/time, and, within certain limits, labeling (Orange Book Preface at vii).   
10 Tentative approval is notification that an NDA or ANDA otherwise meets the requirements for approval under the 
FD&C Act, but cannot be approved because there is a 7-year period of orphan exclusivity for a listed drug under 
section 527 of the FD&C Act and  316.31 of this chapter, or that a 505(b)(2) application or ANDA otherwise meets 
the requirements for approval under the FD&C Act, but cannot be approved until the conditions in 
 
  3  Contains Nonbinding Recommendations 
Implementation review has not been completed; (4) biological products licensed by FDA 
under the Public Health Service Act (42 U.S.C. 262);11, 12 (5) marketed drug products that 
are not the subject of an approved NDA or ANDA (e.g., under OTC monograph); and (6) 
drug products compounded by a pharmacy pursuant to section 503A of the FD&C Act 
and drug products compounded by an outsourcing facility pursuant to section 503B of the 
FD&C Act.  Approved drug products are removed from the Orange Book when, for 
example, an approval is withdrawn under section 505(e)(1) through (5) or 505(j)(6) of the 
FD&C Act,13 when FDA has determined that the drug product was withdrawn from sale 
for reasons of safety or effectiveness,14 or when the status of an approval is converted 
from final approval to tentative approval.  In addition, certain products such as authorized 
generic drug products15 and re-labeled drug products16 are not separately identified in the 
Orange Book.       
 
 
 
 
 314.107(b)(1)(iii), (b)(3), or (c) are met; because there is a period of exclusivity for the listed drug under 
 314.108; because there is a period of exclusivity for the listed drug under section 505A of the FD&C Act; because 
there is a period of exclusivity for the listed drug under section 505E of the FD&C Act; or because a court order 
pursuant to 35 U.S.C. 271(e)(4)(A) orders that the NDA or ANDA may be approved no earlier than the date 
specified.  A drug product that is granted tentative approval is not an approved drug and will not be approved until 
FDA issues an approval letter after any necessary additional review of the NDA or ANDA (21 CFR 314.3(b)).  
11 See the Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity 
or Interchangeability Evaluations available at 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplicat
ions/TherapeuticBiologicApplications/Biosimilars/ucm411418.htm.   
12 The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) required that, on March 23, 2020, an 
approved application for a biological product under section 505 of the FD&C Act be deemed to be a license for the 
biological product (i.e., an approved biologics license application (BLA)) under section 351 of the Public Health 
Service Act (PHS Act) (see section 7002(e)(4)(A) of the BPCI Act; see also section 7002(e)(4)(B)).  As a result, on 
March 23, 2020, subject to a limited exception described in section 7002(e)(4)(B) of the BPCI Act, FDA removed 
from the Orange Book the listings for biological products that had been approved in applications under section 
505 of the FD&C Act because these products are no longer listed drugs.  
13 See section 505(e) and 505(j)(6) of the FD&C Act. 
14 21 CFR 314.161. 
15 An authorized generic drug is a listed drug, as defined in 21 CFR 314.3(b), that has been approved under section 
505(c) of the FD&C Act and is marketed, sold, or distributed directly or indirectly to the retail class of trade with 
labeling, packaging (other than repackaging as the listed drug in blister packs, unit doses, or similar packaging for 
use in institutions), product code, labeler code, trade name, or trademark that differs from that of the listed drug (21 
CFR 314.3(b)).  Because an authorized generic drug (which may or may not have a proprietary name) is marketed 
under the brand name drug products NDA, the authorized generic drug is not separately listed in the Orange Book 
as it is already encompassed within the NDA listing under which it is marketed.  The relevant NDA will be listed in 
the Active Section of the Orange Book when an authorized generic is marketed.  FDA publishes a list of reported 
authorized generics and updates that list quarterly, which is available at https://www.fda.gov/about-fda/center-drug-
evaluation-and-research-cder/fda-listing-authorized-generics. 
16 A labeler engages in manufacturing, repacking, relabeling, or private-label distribution of the drug product.  
Products listed in the Orange Book are identified by the names of the holders of approved applications, rather than 
by the names of the manufacturers themselves, whereas FDAs National Drug Code Directory 
(https://www.accessdata.fda.gov/scripts/cder/ndc/index.cfm) identifies the labelers of such drug products. 
  4  Contains Nonbinding Recommendations 
Q2.  Can I access the current data files for the Orange Book?  How are data provided? 
 
A2.  Yes.  The Orange Book Data Files contain current Orange Book data for approved drug 
products and unexpired patent and exclusivity data, which are updated as outlined in 
Question 4.  They are available in a compressed ZIP file under Additional Resources. 
 
Q3.  When is the Orange Book updated?  What information is included in the updates?  
 
A3.  The information in the Orange Book is updated in two wayson its website and in print 
publications that are also available as downloadable PDFs.  Website updates occur on a 
daily, semimonthly, monthly, and annual basis.  Print updates occur on a monthly and 
annual basis.  We are striving to have more regular updates to the Orange Book and have 
recently added semimonthly website updates to its schedule.  
 
  The daily website updates generally occur (on business days) in the afternoon, 
Eastern Standard Time, and consist of patent information and new generic drug 
approvals.   
 
  The semimonthly website updates generally occur twice each month on a Monday.  
They consist of new drug approvals, ownership changes, market status updates, and 
various types of changes to drug listing information (e.g., changes related to 
therapeutic equivalence codes, trade names, and reference listed drug (RLD)17 or 
reference standard designation, among others), which have occurred in the current 
month.18 
 
  The monthly data files updates, the monthly website updates, and the monthly print 
updates, entitled Cumulative Supplement (CS), generally occur at the end of the 
second week of each month and consist of all changes to the Orange Book which 
occurred in the prior month.19   
 
  The print annual edition of the Orange Book, which is posted on the website, 
generally occurs in January and consists of a full copy of the Orange Book, including 
the Orange Book Preface, drug product lists, addendum, and appendices.20   
 
Q4.   When are newly approved NDA drug products listed in the Orange Book? 
 
A4.   Newly approved NDA drug products will generally appear in the Active Section of the 
Orange Book in the month following their approval, and will remain there unless the 
 
17 The reference listed drug is the listed drug identified by FDA as the drug product upon which an applicant relies 
in seeking approval of its ANDA (21 CFR 314.3(b)) 
18 This schedule is current as of the publication of this guidance, but subject to change in the future. 
19 Since these publications are titled by month (i.e., March CS) the changes may be limited to those that occurred 
in that specific month only. 
20 The annual print publication (and corresponding website update) of the Orange Book memorializes the state of 
drug products from the prior year. 
  5  Contains Nonbinding Recommendations 
NDA holder notifies FDA that the drug product will not be available for sale within 180 
days of approval.21  If the NDA holder notifies FDA that it does not intend to market 
upon approval, the NDA drug product will, in the month following such approval, appear 
in the Discontinued Section.  See Question 4 above for additional information on updates 
to the Orange Book. 
 
Q5.      Do the daily updates to the Orange Book occur at a specific time of day? 
 
A5.      Daily updates to the Orange Book website are generally posted (on business days) in the 
afternoon, Eastern Standard Time.  For example, approval actions taken on ANDAs made 
in the morning will generally be reflected in that afternoons update.  Similarly, patent 
information from newly submitted Forms FDA 3542 received early in the day will 
generally be reflected in that afternoons update (if received later in the morning or in the 
afternoon, this information will generally be reflected in the daily updates for the next 
business day). 
 
Q6.   Are the marketing reports required under section 506I of the FD&C Act available 
to the public?22 
 
A6.  No.  Consistent with section 506I(f) of the FD&C Act, FDA does not publish copies of 
marketing reports submitted to the Agency, but updates the Orange Book, as appropriate, 
as the reports are reviewed and processed. 
 
Q7.  Is it possible to obtain previous editions of the Orange Book or an Orange Book 
Data File from FDA? 
 
A7.  Requests for previous editions of the Orange Book or an Orange Book Data File23  
should be made under the Freedom of Information Act.  Requests should be submitted 
either online via https://www.accessdata.fda.gov/scripts/foi/FOIRequest/index.cfm or in 
writing to FDAs Freedom of Information Staff at the following address: 
   
  Food and Drug Administration 
Division of Freedom of Information 
Office of the Executive Secretariat, OC 
5630 Fishers Ln., Rm. 1035 
 
21 See section 506I(b) of the FD&C Act.  If an NDA holder intends to market the drug product within 180 days of 
approval, no such notification should be submitted to the Agency.  
22 The FDA Reauthorization Act of 2017, Public Law 115-52 (Aug. 18, 2017) (FDARA) added section 506I to the 
FD&C Act, which imposes certain reporting requirements on NDA and ANDA holders regarding the marketing 
status of approved drug products.  Specifically, the three required marketing status notifications set forth in section 
506I of the FD&C Act are the following: notifications of the withdrawal of approved drugs from sale, notifications 
of approved drugs not being available for sale, and one-time reports on the marketing status of approved drugs. 
23 Available at the Orange Book homepage at  https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm.  
  6  Contains Nonbinding Recommendations 
Rockville, MD 20857.24  
 
 
B.  Petitioned ANDAs 
 
Q8.  A petitioned ANDA25 drug product is listed in the Orange Book without a 
therapeutic equivalence code.  What is its RLD?  Should a therapeutic equivalence 
code be assigned to that ANDA? 
 
A8.  For a petitioned ANDA, the RLD should be the listed drug referenced in the approved 
suitability petition.26  The first petitioned ANDA approved will not be pharmaceutically 
equivalent to the RLD and thus no therapeutic equivalence code would be assigned to it.  
However, after the first petitioned ANDA is approved, FDA generally will assign 
therapeutic equivalence codes to all ANDAs that contain the same petitioned differences 
from the RLD (i.e., in dosage form, route of administration, strength, or active ingredient 
(in a drug product with more than one active ingredient)) as the first petitioned ANDA to 
reflect whether these petitioned ANDAs are therapeutically equivalent to one another. 
 
C.  The Movement of Drug Products Between the Active and Discontinued 
Sections of the Orange Book 
 
Q9.  Are only those drug products for which approval of the application has been 
withdrawn (i.e., the approval of the drug product application has been withdrawn 
by FDA) considered withdrawn from sale by FDA? 
 
A9.   No.  A drug product considered withdrawn from sale is not limited to the withdrawal of 
approval of a drug product application.  The Agency has previously indicated that 
withdrawal from sale is not limited to a permanent withdrawal of a product but can 
include drug products for which any decision to discontinue marketing27 has been 
made.  In particular, FDA previously explained its interpretation that a drug is considered 
 
24 Recommendations on submitting a Freedom of Information Act request are provided on FDAs How to Make a 
FOIA Request web page, available at 
https://www.fda.gov/RegulatoryInformation/FOI/HowtoMakeaFOIARequest/default.htm.  
25 A petitioned ANDA is a type of ANDA for a proposed drug product that differs from the RLD in its dosage form, 
route of administration, strength, or active ingredient (in a product with more than one active ingredient) and for 
which FDA has determined, in response to a suitability petition submitted under section 505(j)(2)(C) of the FD&C 
Act, that clinical studies are not necessary to establish the safety and effectiveness of that proposed drug product.  
See also the proposed rule entitled Abbreviated New Drug Applications and 505(b)(2) Applications, published 
February 6, 2015 (80 FR 6802 at 6806).  For more on petitioned ANDAs, see the guidances for industry Referencing 
Approved Drug Products in ANDA Submissions (October 2020) and Determining Whether to Submit an ANDA or a 
505(b)(2) Application (May 2019).  We update guidances periodically.  For the most recent version of a guidance, 
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
26 21 CFR 314.94(a)(3)(i).  
27 See the final rule Abbreviated New Drug Application Regulations, published April 28, 1992 (57 FR 17950 at 
17956). 
  7  Contains Nonbinding Recommendations 
to have been withdrawn from sale for purposes of section 505(j)(5) and 505(j)(6)(C) of 
the FD&C Act if: 
 
the applicant has ceased its own distribution of the drug, whether or not it has 
ordered recall of previously distributed lots of the drug.  A routine, temporary 
interruption in the supply of a drug product would not be considered a 
withdrawal from sale, however, unless triggered by safety or effectiveness 
concerns.28  
 
  Likewise, FDA has considered a drug product to have been withdrawn from sale if the 
NDA or ANDA holder has notified FDA that the drug product is not being marketed.  
 
  Those drug products in the Discontinued Section for which a determination has been 
made that the products were not withdrawn for safety or effectiveness reasons and the 
determination has been published in a Notice in the Federal Register have been annotated 
with a footnote following the product strength: **Federal Register determination that 
product was not discontinued or withdrawn for safety or efficacy reasons**.  However, 
this notation may not appear for all such determinations published in Notices in the 
Federal Register.  For example, the Orange Book does not reflect determinations 
published in Notices in the Federal Register before 1995.  
 
Q10.  How should an NDA or ANDA holder notify FDA, under section 506I of the FD&C 
Act, that a drug product is or will be withdrawn from sale? 
 
A10.  The NDA or ANDA holder should submit a notification of withdrawal from sale in a 
letter to the applicable NDA or ANDA file29 through the electronic submissions 
gateway.30 The notification should prominently identify the submission as an 
ADMINISTRATIVE CHANGE / NOT AVAILABLE FOR SALE.31 
 
 
28 See the proposed rule Abbreviated New Drug Application Regulations, published July 10, 1989 (54 FR 28872 
at 28907).  For more information on recommendations related to accurate reporting of marketing status, see the 
guidance for industry Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and Cosmetic 
Act; Content and Format (August 2020).  
29 This guidance includes recommendations for the submission of documentation directly to an NDA or ANDA file, 
even if such documentation is intended for the Division of Orange Book Publication and Regulatory Assessment.  
Submissions to the application files are triaged and distributed, including to the Division of Orange Book 
Publication and Regulatory Assessment, as appropriate.  Submissions directly to the Division of Orange Book 
Publication and Regulatory Assessment are not recommended unless specifically directed (see, for example, 
Question 18).  
30 The electronic submissions gateway is available at 
https://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway/.  Questions related to electronic submissions 
should be emailed to the CDER Electronic Submission (ESUB) Team at esub@fda.hhs.gov. 
31 See guidance for industry Marketing Status Notifications Under Section 506I of the Federal Food, Drug, and 
Cosmetic Act; Content and Format (August 2020).   
  8  Contains Nonbinding Recommendations 
  NDA and ANDA holders are required to provide a written notification to FDA 180 days 
prior to withdrawing an approved drug product from sale.32  If it is not practicable to 
submit the notification 180 days before withdrawing the drug product from sale, that 
submission should be made as soon as practicable, but not later than the date of 
withdrawal from sale.33,34 
 
Q11.  How and when should an NDA or ANDA holder request that an application be 
moved from the Discontinued Section of the Orange Book to the Active Section? 
 
A11.  Prior to requesting that an application be moved from the Discontinued Section to the 
Active Section, the application holder should determine whether the submission of a 
supplement under 21 CFR 314.70 or 314.97 is required prior to or at the time of 
introduction of the drug product into the marketplace. 
 
If a prior approval supplement under 21 CFR 314.70(b) is required: 
 
  The application holder should notify FDA 1 to 2 months prior to the anticipated 
approval of the supplement that the application holder is seeking market entry or 
re-entry via submission to the application file identified as an 
ADMINISTRATIVE CHANGE / NOTIFICATION OF COMMERCIAL 
MARKETING. 
 
  The product will generally be moved from the Discontinued Section to the Active 
Section upon approval of the supplement in a subsequent monthly cumulative 
supplement. 
 
If a Changes Being Effected supplement under 21 CFR 314.70(c) is required: 
 
  The application holder should determine the anticipated launch date, which is 
generally the date the drug product is put into the marketplace for distribution. 
 
  The application holder should notify FDA that the application holder is seeking 
market entry or re-entry approximately 1 to 2 months before the anticipated 
launch date via submission to the application file identified as an 
ADMINISTRATIVE CHANGE / NOTIFICATION OF COMMERCIAL 
MARKETING. 
 
  The product will generally be moved from the Discontinued Section to the Active 
Section upon the anticipated launch date in a subsequent monthly cumulative 
supplement. 
 
 
32 Section 506I(a) of the FD&C Act.  
33 Ibid.  
34 This notification addresses only the requirement in section 506I(a) of the FD&C Act; additional notifications may 
be required when a drug product is withdrawn from sale, for example, under section 506C(a) of the FD&C Act. 
  9  Contains Nonbinding Recommendations 
Q12.  When will a move of a drug product to or from the Discontinued Section be 
reflected in the Orange Book? 
 
A12.  A move to or from the Discontinued Section will generally be reflected in a future 
Orange Book monthly cumulative supplement update.  See Question 4 above for 
additional information on updates to the Orange Book.35 
 
D.  Patent Listings 
 
1.    Listing Patents 
 
Q13.   How does an NDA holder ensure that Form FDA 3542 (Patent Information 
Submitted Upon and After Approval of an NDA or Supplement)36 is timely filed?  
 
A13.  An NDA holder must submit information for each patent for which a claim of patent 
infringement could reasonably be asserted if a person not licensed by the owner of the 
patent engaged in the manufacture, use, or sale of the drug, and that claims the drug for 
which the applicant submitted the application and is a drug substance (active ingredient) 
patent or a drug product (formulation or composition) patent, or claims a method of using 
such drug for which approval has been granted in the application.37  The NDA holder 
must submit this patent information to the NDA on a Form FDA 3542.38  FDA publishes 
this patent information in the Orange Book.  This patent information must be submitted 
not later than 30 days after the date of approval of the NDA.39  If such a patent is issued 
after the date of approval of the application, the NDA holder must submit a Form FDA 
3542 not later than 30 days after the date of issuance of the patent.40  
 
With respect to any errors or omissions that FDA identifies in a Form FDA 3542, section 
314.53(c)(2)(ii) provides:  
 
If the applicant submits the required patent information within the 30 days, but 
we notify an applicant that a declaration form is incomplete or shows that the 
patent is not eligible for listing, the applicant must submit an acceptable 
declaration form within 15 days of FDA notification to be considered timely 
filed. 
 
35 We note that there may be user fee implications associated with moves to and from the Discontinued Section.  See 
FDAs latest guidance on assessing user fees under PDUFA. 
36 The Form FDA 3542 is available at 
https://www.fda.gov/downloads/aboutfda/reportsmanualsforms/forms/ucm048345.pdf.  
37 See section 505(b)(1)(A)(viii), 505(b)(1)(B), and 505(c)(2) of the FD&C Act; see also 21 CFR 314.53(b)(1).  
Patent information that is not the type of patent information required by subsection (b)(1)(A)(viii) shall not be 
submitted under this paragraph.  Section 505(c)(2) of the FD&C Act. 
38 21 CFR 314.53(c)(2)(ii). 
39 See section 505(c)(2) of the FD&C Act and 21 CFR 314.53(c)(1), 21 CFR 314.53(c)(2)(ii). 
40 See section 505(c)(2) of the FD&C Act and 21 CFR 314.53(c)(1), 21 CFR 314.53(c)(2)(ii) and 21 CFR 
314.53(d)(3). 
  10  Contains Nonbinding Recommendations 
 
Under the terms of the regulation, to be considered timely filed as of the date of the 
original submission of patent information, the NDA holder must submit an acceptable 
Form FDA 3542 within 15 days of FDAs original notification.41  NDA holders should 
carefully read the instructions to Form FDA 3542 in correcting such deficiencies. 
Following the submission of a Form FDA 3542 that the Agency determines is acceptable, 
the patent information will be reflected in the Orange Book.   
 
Q14.  How does an NDA holder ensure that an amendment to the description of an 
approved method of use claimed by the patent is timely filed?  
 
A14.   An NDA holders amendment to the description of an approved method(s) of use (MOU) 
claimed by the patent will be considered timely filed if it is submitted within 30 days of 
(1) patent issuance, (2) approval of a corresponding change to the drug product labeling, 
or (3) a decision by the U.S. Patent and Trademark Office or a Federal court that is 
specific to the patent and alters the construction of a method-of-use claim(s) of the 
patent.42  Outside of these circumstances, and except as provided in the patent listing 
dispute regulations,43 an amendment to the description of the approved MOU claimed by 
the patent will not be considered timely filed.44 
 
Q15.  How can an NDA holder submit a reissued patent to the Orange Book for listing? 
 
A15.  An NDA holder is required to request that the original patent be removed from the 
Orange Book once a patent is reissued45 because, upon patent reissuance, the original 
patent is surrendered and ceases to have legal effect.46  Consistent with our regulations 
for any request to withdraw a patent from the Orange Book, the original patent will 
remain listed in the Orange Book until FDA determines that no first applicant is eligible 
for 180-day exclusivity based on a paragraph IV certification to that patent or after the 
180-day exclusivity period of a first applicant based on that patent has expired or has 
been extinguished or relinquished.47 
 
 
 
 
41 21 CFR 314.53(c)(2)(ii). 
42 21 CFR 314.94(a)(12)(vi) and 21 CFR 314.50(i)(4).  For a decision by the U.S. Patent and Trademark Office or a 
Federal court that is specific to the patent and alters the construction of a method-of-use claim(s) of the patent, the 
amendment must contain a copy of that decision.  21 CFR 314.94(a)(12)(vi) and 21 CFR 314.50(i)(4).         
43 See 21 CFR 314.53(f)(1). 
44 21 CFR 314.94(a)(12)(vi) and 21 CFR 314.50(i)(4).    
45 21 CFR 314.53(f)(2)(i). 
46 See the final rule Abbreviated New Drug Applications and 505(b)(2) Applications, published October 6, 2016 
(81 FR 69580 at 69601), referencing 37 CFR 1.178(a). 
47 21 CFR 314.53(f)(2)(i). 
  11  Contains Nonbinding Recommendations 
Q16.  How does FDA receive and process a request from an NDA holder for removal of a 
patent or patent information from the Orange Book?   
 
A16.  If an NDA holder determines that a patent or patent claim no longer meets the statutory 
requirements for listing, the NDA holder must promptly notify FDA to amend or 
withdraw the patent information and request that the patent information be removed from 
the Orange Book.48  Where any claim of a listed patent has been cancelled or invalidated 
pursuant to a final decision issued by the Patent Trial and Appeal Board (PTAB) of the 
United States Patent and Trademark Office or by a court, from which no appeal has been, 
or can be, taken, if the NDA holder determines that a patent or patent information no 
longer meets the statutory listing requirements, the NDA holder must notify FDA in 
writing within 14 days of the decision and request that such patent or patent information, 
as applicable, be amended or withdrawn in accordance with the decision and include 
information related to the patent cancellation or invalidation decision (including a copy of 
the decision).49  As described above, FDA will remove a patent or patent information 
from the Orange Book if there is no first applicant eligible for 180-day exclusivity based 
on a paragraph IV certification to that patent or after the expiration, extinguishment, or 
relinquishment of any 180-day exclusivity period for a first applicant.50 
 
An NDA holder may submit a withdrawal of a patent and request for removal of the 
patent from the Orange Book by letter to the NDA file.51  The letter must contain the 
NDA number, each product to which the request applies, and the patent number.52  A 
Form FDA 3542 is not required to be submitted for this request, but the NDA holder 
should clearly and prominently identify that it is seeking patent withdrawal and removal 
from the Orange Book under 21 CFR 314.53(f)(2)(iv). 
 
Q17.  An NDA holder has requested that a patent be removed from the Orange Book.  
The patent remains in the Orange Book with a delist request flag.  When will the 
patent be removed? 
 
A17.  A patent may remain listed for a certain period even if the NDA holder requests that it be 
removed because a first applicant may retain eligibility for 180-day exclusivity based on 
a paragraph IV certification to this patent.53  
 
Until the patent is removed from the Orange Book  after any associated 180-day 
exclusivity has expired or has been extinguished or relinquished  ANDA applicants 
must submit or maintain appropriate certifications to the patent notwithstanding the NDA 
 
48 21 CFR 314.53(f)(2)(i). 
49 Section 505(j)(7)(D) of the FD&C Act, as added by section 2(d) of the Orange Book Transparency Act of 2020. 
50 Section 505(j)(7)(D) of the FD&C Act and 21 CFR 314.53(f)(2)(i). 
51 21 CFR 314.53(f)(2)(iv). 
52 Ibid.  
53 21 CFR 314.53(f)(2)(i). 
  12  Contains Nonbinding Recommendations 
holders request to remove the patent.54  Applicants submitting a 505(b)(2) application 
are not required to certify to a patent when the delist request flag is set to Y in the Orange 
Book.55 
 
2.    Patent Listing Disputes 
 
Q18.    Can a patent listing be disputed?  
 
A18.    Yes.  Section 314.53(f)(1) outlines a process through which a person other than the NDA 
holder can dispute the accuracy or relevance of patent information published in the 
Orange Book, as well as the process for the relevant NDA holder to respond to such 
disputes.  If any person either disputes the accuracy or relevance of patent information 
submitted to the Agency and published by the Agency in the Orange Book or believes 
that an NDA holder has failed to submit required patent information, that person must 
first notify the Agency in a written or electronic communication titled 314.53(f) Patent 
Listing Dispute.56  The patent listing dispute may be sent to the Division of Orange 
Book Publication and Regulatory Assessment at orangebook@fda.hhs.gov.57 
 
The patent listing dispute must include a statement of dispute that describes the specific 
grounds for disagreement regarding the accuracy or relevance of patent information, 
which FDA will send to the applicable NDA holder.58  Section 314.53(f)(1) states: 
 
For a dispute regarding the accuracy or relevance of patent information regarding 
an approved method of using the drug product, this statement of dispute must be 
only a narrative description (no more than 250 words) of the persons 
interpretation of the scope of the patent.  This statement of dispute must only 
contain information for which the person consents to disclosure because FDA 
will send the text of the statement to the applicable NDA holder without review 
or redaction. 
 
  FDA will forward the dispute to the NDA holder as described in the regulation.  
 
 
 
 
 
 
 
54 21 CFR 314.94(a)(12)(viii)(B). 
55 21 CFR 314.50(i)(6)(ii)(A 505(b)(2) applicant is not required to provide or maintain a certification to a patent or 
patent information that remains listed only for purposes of a first applicants 180-day exclusivity for its ANDA). 
56 21 CFR 314.53(f)(1). 
57 Alternatively, the patent listing dispute may be submitted to the following address: Office of Generic Drugs, 
Central Document Room, 5901B Ammendale Road, Beltsville, MD 20705. 
58 21 CFR 314.53(f)(1).  
  13  Contains Nonbinding Recommendations 
Q19.  How does FDA provide notification to the public of whether a patent listing dispute 
has been submitted? 
 
A19.  For all patent listing disputes, FDA promptly posts information to a Patent Listing 
Dispute List website59 indicating whether (1) a patent listing dispute has been submitted 
to FDA and (2) the NDA holder has timely responded to the patent listing dispute.60  The 
Patent Listing Dispute List contains relevant drug product information and information 
on the disputed patent.  This list is cumulative in nature and is organized by the drug 
product established name and patent number(s).  
 
59 The Orange Book Patent Listing Dispute List website is available at 
https://www.fda.gov/Drugs/InformationOnDrugs/ucm559235.htm. 
60 See 21 CFR 314.53(f)(1)(iii). 
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