`
`APPROVED
`DRUG
`PRODUCTS
`
`WITH
`
`THERAPEUTIC
`EQUIVALENCE
`EVALUATIONS
`
`34" EDITION
`
`THE PRODUCTSIN THIS LIST HAVE BEEN APPROVED UNDER
`SECTION 505 OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT.
`
`U.S. DEPARTMENT OF HEALTH AND HUMANSERVICES
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`OFFICE OF MEDICAL PRODUCTS AND TOBACCO
`OFFICE OF GENERIC DRUGS
`
`2014
`
`EXHIBIT 1024
`0001
`
`
`
`APPROVED DRUG PRODUCTS
`with
`THERAPEUTIC EQUIVALENCE EVALUATIONS
`
`The productsin this list have been approved under section 505 of the
`Federal Food, Drug, and Cosmetic Act. This volumeis current through
`December31, 2013.
`
`34" EDITION
`
`ge RVI CES
`
`.
`
`>
`3
`
`WEALTH8
`
`°
`
`v
`
`>,
`
`Yay a
`
`Ys
`
`?
`
`C
`
`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...........:.:eceeeeete tees eee ee eee eee aeeteeeetateteeeeeeneadV
`
`INTRODUCTION.............cccccsccccessseeceeecsseeeeeecsssaeeeeeesaeeesesseneesessseeeeseessneeeeessceeeeeessneeeenssneeees vi
`1
`Content and EXCIUSION............ ccc cece ee eeeeneeeee ener eee eeec nena a aeee sere ennecnnaaaaaaeeeeeeeneesnasaeaeeeeeeeeneeas vi
`1.1
`Therapeutic Equivalence-Related Terms...............::::cssccssceeeeceeeeceeeceeecaeeeeeeeeeeeneeeensneneeness vi
`1.2
`Statistical Criteria for Bioequivalence.................cccceeseeeeecneeeeeeeeeeeeseesceneeeeeeeeeeeeessensnnnneees viii
`1.3
`Reference Listed Drug.............ccccccssssssssssseceeeceeesssessneeeseeeeceescsessncaeaeeeseeeeesessseaeseseseeeeeaeesseasx
`1.4
`General Policies and Legal Status «00.0.0... ... ccc ceccceeeeeeeeneeeeeeeeeeee sees aeeeeeeeeaeeeseeesaeeeeeeeeaaes xi
`1.5
`Practitioner/User RESpOnsibilitieS ...........cccccccccccccccceeceeeeeseeeseesseeseseeseseeseeeeseseesaeeeseeesanenaness xi
`1.6
`Therapeutic Equivalence Evaluations Codes...neni xiii
`1.7
`Description of Special Situations .......... cc ccccccceeeceeeeceeeseeeceeseeseeeaseeaseeasscesseessseasseeseees xX
`1.8
`Therapeutic Equivalence Code Changefor a Drug Enitity................:::ccccccseeesssssssssseeees xxii
`1.9
`1.10 Change of the Therapeutic Equivalence Evaluation for a Single Product...................: xxiii
`1.11
` DiISCONTINUCd SECTION... eee neerie ee eee cae ae eeee seer enetcaaaaaeeeeeeeeeeessssaeaeeseneneas xxiii
`1.12 Changes to the Orange Book...0.........ccccceeeceee rete eeeeeeeeeeeeeeeeeteaaeeeeeeaaaaeeeeeseaaeeeseeeneeeeeneee xxiii
`1.13 Availability of the Eqition...................ccccccccceeeceeeeceeeceeecneeeeeeeeneeseeeeeeeeeeeeeneeeeeenennenenennnenegs XxiV
`
`2
`2.1
`2.2
`2.3
`
`HOWTO USE THE DRUG PRODUCTSLISTS..0.....cccccccccecesessseceeeeeeeeeeeessennneeeeeeeeeeeeeeas 2-1
`Key Sections for Using the Drug ProductLists ................ccccceceeceeeeeeeeeeeeceeeeeeeesssees2-1
`Drug ProductIllustration ........... 0... cece eee eee eee eee eee rene eee ete ee eneeeeeea nae2-3
`Therapeutic Equivalence EvaluationsIllustration ...............cc.ccccceceeeeeeeeeesesseesseeeaes 2-4
`
`DRUG PRODUCTLISTS
`Prescription Drug ProductList ............. 0... cee eee tienes ena een anata eaaa 3-1
`OTC Drug ProductList ...............cccceccecece cece eee eceeeeeeeeaseeeaeaeeeeeeseaeeseeeeeeentasestaseetaneneanes 4-1
`Drug Products with Approval under Section 505 of the Act Administered
`by the Center for Biologics Evaluation and Research List..................:eeceeeeeeeeeeeeeeeeees 5-1
`Discontinued Drug ProductList ............ 0... cece eee eee eee nee ee nee ee sane eee eaten ea eneees 6-1
`Orphan Products Designations and Approvals List
`...................cccccceeeeeeeeeeseeeeeeeeeeeneeeaeaes 7-1
`Drug Products Which Must Demonstrate in vivo Bioavailability
`Only if Product Fails to Achieve Adequate Dissolution ............... 0.0. ccceeee cece eee eens eee teen eeeeeees 8-1
`
`APPENDICES
`A. Product Name Index .........:cinnn eeneie tenes A-1
`B. Product Name Index Listed by Applicant.....................cccc ec eceee eee ee ee eee ee eeeeeeeees B-1
`C. Uniform Terms ..........ccceee renee eae ee eeaneaeeeeneaeaes C-1
`
`PATENT AND EXCLUSIVITY INFORMATION ADDENDUDM ..............::ccceeeee tees ee eee eeeneeeeees AD1
`A. Patent and Exclusivity Lists ...........0. 0... ee eee eee eee e rene eee anaee eed ADA1
`B. Patent and Exclusivity Terms............. 0... cece eee e eee eee eee eee eee eee e eee eeeneneeae 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.
`
`
`
`
`
`OMEArPEOM
`
`To contain drug costs, virtually every
`Background of the Publication.
`tate has adopted laws and/or regulations that encourage the substitution of
`rug products.
`These state laws generally require either that substitution be
`imited to drugs on a specific list (the positive formulary approach) or that
`t be permitted for all drugs except those prohibited by a particular list
`the negative formulary approach). Because of the number of requests in the
`ate 1970s for FDA assistance in preparing both positive and negative
`ormularies, it became apparent that FDA could not serve the needs of each
`tate 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.
`
`
`
`It included only
`in January 1979.
`The List was distributed as a proposal
`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
`
`
`
`The first publication, October 1980, of
`on October 31, 1980 (45 FR 72582).
`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.
`
`the President signed into law the Drug Price
`On September 24, 1984,
`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.
`
`0005
`
`
`
`1.
`
`INTRODUCTION
`
`1.1 Content and Exclusion
`
`
`
`(1) approved prescription drug
`The List is composed of four parts:
`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.’ 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.
`
`
`
`the publication had excluded OTC drug products
`Prior to the 6th Edition,
`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.
`
`
`
`
`
`some drug products are given tentative
`Under the 1984 Amendments,
`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
`
`’ 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
`
`
`
`PRESCRIPTION AND OTC DRUG PRODUCT PATENT AND EXCLUSIVITY LIST
`
`34TH EDITION - 2014 - APPROVED DRUG PRODUCT LIST
`
`ADA 39 of 215
`
`See report footnote for information regarding report content
`
`
`
`APPL/PROD
`NO
`
`PATENT NO
`
`CYANOCOBALAMIN - NASCOBAL
`
`PATENT
`EXPIRATION
`DATE
`
`N 021642
`
`001
`
`Jun 11, 2024
`7229636
`Mar 12, 2024
`7404489
`Jun 01, 2024
`7879349
`YCLOBENZAPRINE HYDROCHLORIDE - AMRIX
`
`N 021777
`
`OO1
`
`Feb 26, 2025
`7387793
`Nov 14, 2023
`7544372
`Nov 14, 2023
`7790199
`Nov 14, 2023
`7820203
`Nov 14, 2023
`7829121
`CYCLOBENZAPRINE HYDROCHLORIDE - AMRIX
`
`N 021777
`
`002
`
`7387793
`7544372
`7790199
`7820203
`7829121
`CYCLOSPORINE - NEORAL
`N 050715
`001
`5985321
`CYCLOSPORINE - NEORAL
`N 050715
`002
`9985321
`CYCLOSPORINE — NEORAL
`N 050715
`003
`9985321
`CYCLOSPORINE -— NEORAL
`N 050716
`001
`5985321
`CYCLOSPORINE - RESTASIS
`N 050790
`001
`5474979
`8629111
`CYSTEAMINEBITARTRATE-PROCYSBI
`N 203389
`001
`8026284
`8129433
`CYSTEAMINE BITARTRATE - PROCYSBI
`
`Feb 26, 2025
`Nov 14, 2023
`Nov 14, 2023
`Nov 14, 2023
`Nov 14, 2023
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`Sep 26, 2014
`
`May 17, 2014
`Aug 27, 2024
`
`Sep 22, 2027
`Jan 26, 2027
`
`
`
`002
`
`N 203389
`
`8026284
`8129433
`YSTEAMINE HYDROCHLORIDE -
`
`Sep 22, 2027
`Jan 26, 2027
`CYSTARAN
`
`N 200740
`
`001
`
`CYTARABINE - DEPOCYT
`Mar 03, 2015
`N 021041 O01
`5723147
`DABIGATRAN ETEXILATE MESYLATE -— PRADAXA
`N 022512
`001
`6087380
`Feb 18, 2018
`7866474
`Aug 31, 2027
`7932273
`Sep 07, 2025
`DABIGATRAN ETEXILATE MESYLATE - PRADAXA
`
`002
`
`N 022512
`
`6087380
`7866474
`7932273
`DABRAFENIB MESYLATE — TAFINLAR
`N 202806
`001
`7994185
`8415345
`DABRAFENIBMESYLATE-TAFINLAR
`N 202806
`002
`7994185
`8415345
`DALFAMPRIDINE - AMPYRA
`
`Feb 18, 2018
`Aug 31, 2027
`Sep 07, 2025
`
`Jan 20, 2030
`Jan 20, 2030
`
`Jan 20, 2030
`Jan 20, 2030
`
`Jul 30, 2018
`May 26, 2027
`Dec 22, 2026
`Apr 08, 2025
`
`N 022250
`
`001
`
`5540938
`8007826
`8354437
`8440703
`
`U-1030
`U-1030
`U-1030
`U-1030
`
`
`
`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
`
`
`
`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
`
`0007
`
`