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`
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`
`
`
`
`
`
`APPROVED
`
`DRUG
`
`PRODUCTS
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`WITH
`
`THERAPEUTIC
`
`
`EQUIVALENCE
`
`EVALUATIONS
`
`34th EDITION
`
`
`
`
`
`
`
`
`
`THE PRODUCTS IN THIS LIST HAVE BEEN APPROVED UNDER
`SECTION 505 OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT.
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`OFFICE OF MEDICAL PRODUCTS AND TOBACCO
`OFFICE OF GENERIC DRUGS
`
`
`
`2014
`
`
`0001
`
` EXHIBIT 1024
`
`

`

`
`
`APPROVED DRUG PRODUCTS
`
`with
`THERAPEUTIC EQUIVALENCE EVALUATIONS
`
`
`
`
`
`
`
`The products in this list have been approved under section 505 of the
`Federal Food, Drug, and Cosmetic Act. This volume is current through
`December 31, 2013.
`
`
`
`
`
`
`
`34th EDITION
`
`
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`OFFICE OF MEDICAL PRODUCTS AND TOBACCO
`
`OFFICE OF GENERIC DRUGS
`
`
`2014
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`0002
`
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`APPROVED DRUG PRODUCTS
`with
`Therapeutic Equivalence Evaluations
`
`CONTENTS
`
`PAGE
`
`
`PREFACE TO THIRTY FOURTH EDITION……………………………………..…................iv
`
`
`
`
`
`1
`INTRODUCTION...................................................................................................................vi
`
`
`
`1.1
`Content and Exclusion......................................................................................................vi
`
`
`
`1.2
`Therapeutic Equivalence-Related Terms .........................................................................vi
`
`
`
`1.3
`Statistical Criteria for Bioequivalence............................................................................. viii
`
`
`
`1.4
`Reference Listed Drug.......................................................................................................x
`
`
`
`1.5
`General Policies and Legal Status ................................................................................... xi
`
`
`
`1.6
`Practitioner/User Responsibilities..................................................................................... xi
`
`
`
`1.7
`Therapeutic Equivalence Evaluations Codes................................................................. xiii
`
`
`
`1.8
`Description of Special Situations ..................................................................................... xx
`
`
`
`1.9
`Therapeutic Equivalence Code Change for a Drug Entity ............................................. xxii
`
`
`
`1.10 Change of the Therapeutic Equivalence Evaluation for a Single Product .................... xxiii
`
`
`
`1.11 Discontinued Section .................................................................................................... xxiii
`
`
`
`1.12 Changes to the Orange Book ....................................................................................... xxiii
`
`
`
`1.13 Availability of the Edition ............................................................................................... xxiv
`
`
`
` 2 HOW TO USE THE DRUG PRODUCTS LISTS ..............................................................2-1
`
`2.1
`Key Sections for Using the Drug Product Lists …………………….….………………......2-1
`
`2.2
`Drug Product Illustration ……………………………………………..….…………….……..2-3
`
`2.3
`Therapeutic Equivalence Evaluations Illustration ………………….….…………..………2-4
`
`
`
`
`
`
`DRUG PRODUCT LISTS
`
`Prescription Drug Product List ……………………………………….…………….………………...3-1
`
`OTC Drug Product List ……………………………………………….…………….…………………4-1
`
`Drug Products with Approval under Section 505 of the Act Administered
`
`by the Center for Biologics Evaluation and Research List ...……….…….………………...5-1
`
`Discontinued Drug Product List .…………………………………………….…….………………....6-1
`
`Orphan Products Designations and Approvals List …………….………….…….………………..7-1
`
`Drug Products Which Must Demonstrate in vivo Bioavailability
`
`Only if Product Fails to Achieve Adequate Dissolution …………………..………………………..8-1
`
`
`
`APPENDICES
`A. Product Name Index ……….…...………………………….………..……………………A-1
`B. Product Name Index Listed by Applicant ………………….……..……………………..B-1
`
`C. Uniform Terms …………………………………………….………..…………...………...C-1
`
`
`
`PATENT AND EXCLUSIVITY INFORMATION ADDENDUM ……….……..………………..........AD1
`
`A. Patent and Exclusivity Lists …………………………….…..……..……………..……ADA1
`B. Patent and Exclusivity Terms ...……………………….….………...…………………ADB1
`
`
`
`
`
`0003
`
`

`

`
`
`
`
`
`FOOD AND DRUG ADMINISTRATION
`
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`APPROVED DRUG PRODUCTS
`
`with
`
`Therapeutic Equivalence Evaluations
`
`
`
`PREFACE TO THIRTY FOURTH EDITION
`
`The publication, Approved Drug Products with Therapeutic Equivalence
`Evaluations (the List, commonly known as the Orange Book), identifies drug
`products approved on the basis of safety and effectiveness by the Food and
`Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the
`Act). Drugs on the market approved only on the basis of safety (covered by
`the ongoing Drug Efficacy Study Implementation [DESI] review [e.g., Donnatal®
`Tablets and Librax® Capsules] or pre-1938 drugs [e.g., Phenobarbital
`
`Tablets]) are not included in this publication. The main criterion for the
`inclusion of any product is that the product is the subject of an application
`with an effective approval that has not been withdrawn for safety or efficacy
`reasons. Inclusion of products on the List is independent of any current
`regulatory action through administrative or judicial means against a drug
`product. In addition, the List contains therapeutic equivalence evaluations
`for approved multisource prescription drug products. These evaluations have
`been prepared to serve as public information and advice to state health
`agencies, prescribers, and pharmacists to promote public education in the area
`of drug product selection and to foster containment of health care costs.
`Therapeutic equivalence evaluations in this publication are not official FDA
`actions affecting the legal status of products under the Act.
`
`Background of the Publication. To contain drug costs, virtually every
`state has adopted laws and/or regulations that encourage the substitution of
`drug products. These state laws generally require either that substitution be
`limited to drugs on a specific list (the positive formulary approach) or that
`it be permitted for all drugs except those prohibited by a particular list
`(the negative formulary approach). Because of the number of requests in the
`late 1970s for FDA assistance in preparing both positive and negative
`formularies, it became apparent that FDA could not serve the needs of each
`state on an individual basis. The Agency also recognized that providing a
`single list based on common criteria would be preferable to evaluating drug
`products on the basis of differing definitions and criteria in various state
`laws. As a result, on May 31, 1978, the Commissioner of the Food and Drug
`Administration sent a letter to officials of each state stating FDA's intent
`to provide a list of all prescription drug products that are approved by FDA
`for safety and effectiveness, along with therapeutic equivalence
`determinations for multisource prescription products.
`
`The List was distributed as a proposal in January l979. It included only
`currently marketed prescription drug products approved by FDA through new drug
`applications (NDAs) and abbreviated new drug applications (ANDAs) under the
`provisions of Section 505 of the Act.
`
`The therapeutic equivalence evaluations in the List reflect FDA's
`application of specific criteria to the multisource prescription drug products
`on the List approved under Section 505 of the Act. These evaluations are
`presented in the form of code letters that indicate the basis for the
`evaluation made. An explanation of the code appears in the Introduction.
`
`A complete discussion of the background and basis of FDA's therapeutic
`equivalence evaluation policy was published in the Federal Register on
`January 12, 1979 (44 FR 2932). The final rule, which includes FDA's responses
`to the public comments on the proposal, was published in the Federal Register
`iv
`
`
`0004
`
`

`

`
`on October 31, 1980 (45 FR 72582). The first publication, October 1980, of
`the final version of the List incorporated appropriate corrections and
`additions. Each subsequent edition has included the new approvals and made
`appropriate changes in data.
`
`On September 24, 1984, the President signed into law the Drug Price
`Competition and Patent Term Restoration Act (1984 Amendments). The 1984
`Amendments require that FDA, among other things, make publicly available a
`list of approved drug products with monthly supplements. The Approved Drug
`Products with Therapeutic Equivalence Evaluations publication and its monthly
`Cumulative Supplements satisfy this requirement. The Addendum to this
`publication identifies drugs that qualify under the 1984 Amendments for
`periods of exclusivity (during which ANDAs or applications described in
`Section 505(b)(2) of the Act for those drugs may not be submitted for a
`specified period of time and, if allowed to be submitted, would be tentatively
`approved) and provides patent information concerning the listed drugs which
`also may delay the approval of ANDAs or Section 505(b)(2) applications. The
`Addendum also provides additional information that may be helpful to those
`submitting a new drug application to the Agency.
`
`The Agency intends to use this publication to further its objective of
`obtaining input and comment on the publication itself and related Agency
`procedures. Therefore, if you have comments on how the publication can be
`improved, please send them to the Director, Division of Labeling and Program
`Support, HFD-610, Office of Generic Drugs, Center for Drug and Evaluation and
`Research, 7620 Standish Place, Rockville, MD 20855. Comments received are
`publicly available to the extent allowable under the Freedom of Information
`regulations.
`
`v
`
`
`0005
`
`

`

`1. INTRODUCTION
`
`
`
`
` 1.1 Content and Exclusion
`
`
`
`The List is composed of four parts: (1) approved prescription drug
`products with therapeutic equivalence evaluations; (2) approved
`over-the-counter (OTC) drug products for those drugs that may not be marketed
`without NDAs or ANDAs because they are not covered under existing OTC
`monographs; (3) drug products with approval under Section 505 of the Act
`administered by the Center for Biologics Evaluation and Research; and (4) a
`cumulative list of approved products that have never been marketed, are for
`exportation, are for military use, have been discontinued from marketing, or
`have had their approvals withdrawn for other than safety or efficacy reasons
`subsequent to being discontinued from marketing.1 This publication also
`includes indices of prescription and OTC drug products by trade or established
`name (if no trade name exists) and by applicant name (holder of the approved
`application). All established names for active ingredients generally conform
`to official compendial names or United States Adopted Names (USAN) as
`
`prescribed in (21 CFR 299.4(e)). The latter list includes applicants’ names
`as abbreviated in this publication; in addition, a list of uniform terms is
`provided.
`
`An Addendum contains drug patent and exclusivity information for the
`Prescription, OTC, Discontinued Drug Product Lists, and for the Drug Products
`with Approval under Section 505 of the Act Administered by the Center for
`Biologics Evaluation and Research. The publication may include additional
`information that the Agency deems appropriate to disseminate.
`
`Prior to the 6th Edition, the publication had excluded OTC drug products
`and drug products with approval under Section 505 of the Act administered by
`the Center for Biologics Evaluation and Research because the main purpose of
`the publication was to provide information to states regarding FDA's
`recommendation as to which generic prescription drug products were acceptable
`candidates for drug product selection. The 1984 Amendments required the
`Agency to begin publishing an up-to-date list of all marketed drug products,
`OTC as well as prescription, that have been approved for safety and efficacy
`and for which new drug applications are required.
`
`Under the 1984 Amendments, some drug products are given tentative
`approvals. The Agency will not include drug products with tentative approval
`in the List. Tentative approval lists are available at ANDA (Generic) Drug
`Approvals. When the tentative approval becomes a full approval through a
`subsequent action letter to the application holder, the Agency will list the
`drug product and the final approval date in the appropriate approved drug
`product list.
`
`Distributors or repackagers of products on the List are not identified.
`Because distributors or repackagers are not required to notify FDA when they
`shift their sources of supply from one approved manufacturer to another, it is
`not possible to maintain complete information linking product approval with
`the distributor or repackager handling the products.
`
`
`1.2 Therapeutic Equivalence-Related Terms
`
`
`Pharmaceutical Equivalents. Drug products are considered pharmaceutical
`equivalents if they contain the same active ingredient(s), are of the same
`
`1 Newly approved products are added to parts 1, 2, or 3, of the List, depending on the dispensing
`requirements (prescription or OTC) or approval authority, unless the Orange Book staff is
`otherwise notified before publication.
`
`
`
`
`
`vi
`
`
`0006
`
`

`

`34TH EDITION - 2014 - APPROVED DRUG PRODUCT LIST
`ADA 39 of 215
`
`PRESCRIPTION AND OTC DRUG PRODUCT PATENT AND EXCLUSIVITY LIST
`
`See report footnote for information regarding report content
`
`APPL/PROD
`NO
`
`PATENT NO
`
`PATENT
`EXPIRATION
`DATE
`
`CYANOCOBALAMIN - NASCOBAL
`Jun 11, 2024
`N 021642 001 7229636
`Mar 12, 2024
`7404489
`Jun 01, 2024
`7879349
`CYCLOBENZAPRINE HYDROCHLORIDE - AMRIX
`N 021777 001 7387793
`Feb 26, 2025
`7544372
`Nov 14, 2023
`7790199
`Nov 14, 2023
`7820203
`Nov 14, 2023
`7829121
`Nov 14, 2023
`CYCLOBENZAPRINE HYDROCHLORIDE - AMRIX
`N 021777 002 7387793
`Feb 26, 2025
`7544372
`Nov 14, 2023
`7790199
`Nov 14, 2023
`7820203
`Nov 14, 2023
`7829121
`Nov 14, 2023
`CYCLOSPORINE - NEORAL
`N 050715 001 5985321
`CYCLOSPORINE - NEORAL
`N 050715 002 5985321
`CYCLOSPORINE - NEORAL
`N 050715 003 5985321
`CYCLOSPORINE - NEORAL
`N 050716 001 5985321
`CYCLOSPORINE - RESTASIS
`May 17, 2014
`N 050790 001 5474979
`Aug 27, 2024
`8629111
`CYSTEAMINE BITARTRATE - PROCYSBI
`N 203389 001 8026284
`Sep 22, 2027
`8129433
`Jan 26, 2027
`CYSTEAMINE BITARTRATE - PROCYSBI
`N 203389 002 8026284
`Sep 22, 2027
`8129433
`Jan 26, 2027
`CYSTEAMINE HYDROCHLORIDE - CYSTARAN
`N 200740 001
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`CYTARABINE - DEPOCYT
`Mar 03, 2015
`N 021041 001 5723147
`DABIGATRAN ETEXILATE MESYLATE - PRADAXA
`N 022512 001 6087380
`Feb 18, 2018
`7866474
`Aug 31, 2027
`7932273
`Sep 07, 2025
`DABIGATRAN ETEXILATE MESYLATE - PRADAXA
`N 022512 002 6087380
`Feb 18, 2018
`7866474
`Aug 31, 2027
`7932273
`Sep 07, 2025
`DABRAFENIB MESYLATE - TAFINLAR
`N 202806 001 7994185
`8415345
`DABRAFENIB MESYLATE - TAFINLAR
`N 202806 002 7994185
`8415345
`DALFAMPRIDINE - AMPYRA
`N 022250 001 5540938
`8007826
`8354437
`8440703
`
`Jan 20, 2030
`Jan 20, 2030
`
`Jan 20, 2030
`Jan 20, 2030
`
`Jul 30, 2018
`May 26, 2027
`Dec 22, 2026
`Apr 08, 2025
`
`PATENT
`DELIST
`REQUESTED
`
`EXCLUSIVITY
`CODE(S)
`
`EXCLUSIVITY
`
`EXPIRATION
`
`DATE
`
`
`NDF
`
`NDF
`
`NP
`ODE
`
`Apr 30, 2016
`
`Apr 30, 2016
`
`Oct 02, 2015
`Oct 02, 2019
`
`NCE
`
`Oct 19, 2015
`
`NCE
`
`Oct 19, 2015
`
`NCE
`ODE
`
`NCE
`ODE
`
`NCE
`ODE
`
`May 29, 2018
`May 29, 2020
`
`May 29, 2018
`May 29, 2020
`
`Jan 22, 2015
`Jan 22, 2017
`
`PATENT
`CODES
`
`DP U-817
`DP
`DP U-1152
`
`DP
`DP
`DP
`
`DP
`DP
`DP
`
`DP
`
`DP
`
`DP
`
`DP
`
`DP
`DP
`
`DP
`
`DP
`
`U-979
`
`U-1088
`
`U-979
`
`U-1088
`
`U-1399
`
`U-1399
`
`DP U-806
`
`DS DP U-1089
`DP
`DS DP
`
`DS DP U-1089
`DP
`DS DP
`
`DS DP U-1406
`DS DP U-1406
`
`DS DP U-1406
`DS DP U-1406
`
`U-1030
`U-1030
`U-1030
`U-1030
`
`0007
`
`