CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`203496Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`Depamnrcmoarurendnumn sweat»
`Food and Drug Administration
`
`"
`
`'
`
`.
`
`PATENT INFORMATION iS'UBMIT-TED WITH THE FILING .
`
`‘ dewfiommrmm" ‘
`Expiration Delano/smote .
`See 0M6 statemenlon Page 8.
`'
`‘
`
`OF AN :NDA, AMENDMENT; ORSUPPLEMENT
`
`For Each Patent-That Claims-a Drug substance
`(Activelngredlent); Drug ,Product-{annuletlon and Composition)
`and/or-Method of Use
`
`0.125mg, 0.25mg, 1.0mg, 25mg
`
`Extended Release Tablet
`Thispatentdeclaration form is required to be submitted tothe Food and Drug Administration(FDA) with an NDAapplication,
`amendment, or supplement as required by 21CFR 3M.53 at the address proVided In 21 CFR 314.53(d)(4).’~
`Within thirty (30) days alter approval of an NBA orsupplement,or within thirty (30) day's 'ol issuance of-a new patent. a new patent
`declaration must be submitted ‘pursusntto‘ 21. CPR 314.53(c)(2)(ii) with all of the required. Informationbase‘d on the approved NDA or
`supplement.The information submittedin the declaration form submitted upon or-etter approval will battle only information relied
`upon by FDAtorlistlng a patent In the Orange Bock.
`For handwritten or typewriterversions (only) ofthis report:- If additional space is required forany narrative answer (is, one that
`doesnot require a 'Yes" or'No“. response). please attach anadditionalpage referencing thequestion number.
`FDA will notlistpatent information Ifyousubmitan Incompletepatent declaration or thepatentdeclaration indicates the
`patent Isnoteligibleforlisting.
`ForeachpetentsubmlttedforthependlngND/I.antendnrent,orsupplernentrelarenoedabove.youmusteub'nrltellthe
`Information described below. Ifyou are not submittlng any patents for this pending NDA.amendment, «supplement.
`complete above section and sectioned and 6;
`
`business within the United States)
`
`United Therapeutics Corporation
`
`receive notice ofpetent certification undersection 505(1))(3)
`and «mm ofthe Federal Food.Drug. and Cosmetic Act
`and 21‘CF-R 314.52 and 314.95 (if patent ovmeror-NDA
`applicant/holderdoesnotresideorhaveapiaceoi
`
`'-" W"
`available
`dbunce@urtithercom
`
`PSC GHPMS GUI) “3-1990
`
`EF
`
`

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`Doesthepreteritmthedrug ed‘ heethathis; aottvdihpredie'ntinthe-dntgprodueti
`described in ihe pending NDA.‘etne‘hdm‘ent.or- supplement?
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`desaibedindteNDA7miypeofnestdate tequhdisdesuibedeim CFR314.53(b)
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`32.4 .Spootty the-'poiyrhorohic We) deimod'by the patent tor which you have meted results described in 2.3.
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`drug product to sum the mm.)
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`inthepending NDA.amendinent,-oreuppiement?
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`patentnevei? (Mdnmlanuindoniyifmepaieniis a pmdud-by-ptooeu potent)
`,3. Drug Producucmpoemmmen)
`'
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`3.1 Mthntda‘fitedm'g pMuaasdefinedin 1 CF 3 4.3,in impending NDA‘amendment.
`
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`
`Use: (Submit MIcatIonormomodofu'se‘irifennafionns'idenflfled spedficeflybt'lhe’pmposedlabefing‘.)
`
`4.2. if the answer» 4.2-1; .
`'Yes.’ identifywiih‘speci-
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`ence .to the pmpoud '
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`product.
`
`ForthispendingNDAmmendlnenLorwppmni'mannoreleventpetenumdieimme'~95qu! w a Whirl); ’
`dummfioamimoroompodflonwrmemodhiofm.mmmmwmhmewflmmmmbm D Yes
`addudmminflingemcouiameoneuybeemmd«aweonnotfiwmdbymmoimepmennagedinme
`mnufeeium,maubdmmpm
`
`

`

`a Declaration Certification
`
`“6.1 ' WWW deelms that this is an accuratefandoernpleteaubmisslen of‘p‘atent inlonn'atien'for-the ND'A,"
`amendment, «supplement pending under section”: ofth'e Federal Food,- Drug. and Cosmetic Act. This time-
`sensltive patent‘lnformatien is submitted punuant'te ,21 CFR 314.511 attestth'ati am familiar with 21 CFR 314.53 and
`this submission complies with the'raquirements ofthe maletlo‘rrd-verifyunderpenelty efpedury that the foregoing is
`true and comet.
`
`Warning: A willfully and knowingly-false statement is a criminal offense under-18 0.5.6. 1001.
`
`6.2 Authorized signature‘ol NDA Applicant/Holder or Patent Owner (Attorney, Agent, Representative or
`other Authorized Oificial) (Provide Information below)
`
`Date Signed
`
`19August2013
`dbunce@unither.comonenmmm“WWW...
`Date. 2013.08.19 15143103001”
`MOVE: 'Ohiy' an NBA appllcaniiholder may subunit this declantlon directly to the FDA. Apatent ovr'rm time is not the NDA applicant!
`holder is authorised to clan the declaration but may not 'eubrnlt It dlrectiy to FDA. 21 CFR 31‘.53(c)(4) and (ext).
`
`Diutaflynlgnedby Minimum
`
`Check applicable box and provide lnl'onnatlon below.
`
`'
`
`'
`
`E NDA Applicant/Holder
`
`E] NDA Ammonia/Holders Attorney. Agent (Representative) or other
`Authorized Olflcial
`
`Name
`
`Dean Bunce. Executive Vice President Regulatory Affairs and Compliance, United Therapeutics Corporation
`
`[3 Patent Owner‘s Attorney, Agent (Representative) or Other Authorized
`Official
`
`‘
`(919) 3l3-1298
`
`Research Triangle Park/NC
`
`t 9'3”“. :
`I
`Q ;
`(919)485-8350
`
`"a Mass (ilevailabie)
`dbunce@unither.com
`
`information unless it displays a currently valid OMB control number.
`
`The public reporting burden for this collection of information has been estimated to average 20 hours per response, including the time for reviewing
`instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send
`comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to:
`
`Department of Health and Human Services
`Food and Drug Administration
`Office of Chief lnfennation Officer
`1350 Piccard Drive, Room 400
`Rockville, MD 20850
`
`An agency may not conduct or sponsor. and a person is no! required to respond to, a collection of
`
`Form FDA-minim
`
`‘
`
`,,
`
`'
`
`P3913
`
`

`

`INFORMATIONIAN!)llNSTRLlCTIONSiFORiFORM (35423.»
`narEiirltNeoaM'AnON SUBMITTEDTWITHariiEi-Itattme
`can-m ma. AMEND‘MENT‘ORSUPPLEMENT.-
`
`1c) Answer this question if applicable. If patent owner and NDA
`applicant/holder reside in the United States, leave space
`blank.
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section if the patent claims the drug
`substance that is the subject of the pending NDA, amendment, or
`supplement.
`
`2.4) Name the polymorphic form of the drug identified by the
`patent.
`
`2.5) A patent for a metabolite of the approved active ingredient
`may not be submitted. If the patent claims an approved
`method of using the approved drug product to administer the
`metabolite, the patent may be submitted as a method of use
`patent depending on the responses to section 4 of this form.
`
`2.7) Answer this question only if the patent is a product-by-
`process patent.
`
`3. Drug Product (Composition/Formulation)
`
`Complete all items in this section if the patent claims the drug
`product that is the subject of the pending NDA, amendment, or
`supplement.
`
`3.3) An answer to this question is required only if the referenced
`patent is a product-by-proccss patent.
`
`4. Method of Use
`
`Complete all items in this section if the patent claims a method of
`we of the drug product that is the subject of the pending NDA,
`amendment, or supplement (pending method of use).
`
`4.2) For each pending method of use claimed by the patent,
`identify by number the claim(s) in the patent that claim the
`pending use of the drug. An applicant may list together
`multiple patent claim numbers and information for each
`pending method of use, if applicable. However, each
`pending method of use must be separately listed within this
`section of the form.
`
`4.2a) Specify the part of the proposed drug labeling that is
`claimed by the patent.
`
`5. No Relevant Patents
`
`Complete this section only if applicable.
`
`6. Declaration Certification
`
`Complete all items in this section.
`
`6.2) Authorized signature. Check one of the four boxes that best
`
`Form 3542 should be used after NDA or supplement approval.
`This form is to be submitted within 30 days afler approval of an
`application. This form should also be used to submit patent
`information relating to an approved supplement under 21 CFR
`314.S3(d) to change the formulation, add a new indication or
`other condition of use, change the strength, or to make any other
`patented change regarding the drug, drug product, or any
`method of use.
`
`describes the authorized signature.
`
`General Information
`
`' To submit patent information to the agency the appropriate
`patent declaration form must be used. Two forms are available
`for patent submissions. The approval status of your New Drug
`Application will determine which form you should use.
`
`Form 3542a should be used when submitting patent information
`with original NDA submissions, NDA amendments and NDA
`supplements prior to approval.
`
`Form 3542 is also to be used for patents issued after drug
`approval. Patents issued afier drug approval are required to be
`submitted within 30 days of patent issuance for the patent to be
`considered "timely filed."
`
`Only information from form 3542 will be used for Orange Book
`publication purposes.
`
`Forms should be submitted as described in 21 CFR 314.53.
`Sending an additional copy of form 3542 to the Orange Book
`Staff will expedite patent publication in the Orange Book. The
`Orange Book Staff address (as of April 2007) is: Orange Book
`Staff, Office of Generic Drugs OGD/l-[FD-610, 7500 Standish
`Place, Rockville, MD 20855.
`
`' The receipt date is the date that the patent information is date
`stamped in the central document room. Patents are considered
`listed on the date received.
`
`’ Additional copies of these forms may be downloaded from the
`lntemet at:
`http://www.fda.gov/opacom/morechoices/fdaforms/
`fdajbrmsfitml.
`
`First Section
`
`Complete all items in this section.
`
`1. General Section
`
`Complete all items in this section with reference to the patent
`itself.
`
`1c)
`
`include patent expiration date, including any Hatch-Waxman
`patent extension already
`granted. Do not include any
`applicable pediatric exclusivity. The agency will include
`pediatric exclusivities where applicable upon publication.
`
`ld) Include full address of patent owner. If patent owner resides
`outside the US. indicate the country in the zip code block.
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 203496
`
`SUPPL #
`
`HFD # 110
`
`Trade Name Orenitram
`
`Generic Name Treprostinil diethanolamine
`
`Applicant Name United Therapeutics Corporation
`
`
`
`Approval Date, If Known
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
` YES X
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`c) Did it require the review of clinical data other than to support a safety claim or change in
`labeling related to safety? (If it required review only of bioavailability or bioequivalence
`data, answer "no.")
`
` YES X
`
`NO
`
`If your answer is "no" because you believe the study is a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`
`
`Reference ID: 3426073
`
`Page 1
`
`

`

`d) Did the applicant request exclusivity?
`
`YES X
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`3 years.
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES
`
`NO X
`
` If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`
`
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`YES
`
`NO X
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form of the active moiety, e.g., this particular ester or salt (including salts with hydrogen or
`coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate) has
`not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`
`
`
`
`YES X
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`Reference ID: 3426073
`
`Page 2
`
`

`

`
`NDA#
`
`22387
`
`NDA#
`
`21272
`
`NDA#
`
`2. Combination product.
`
`Tyvaso
`
`Remodulin
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing any one of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA, is considered not previously
`approved.)
`
`YES
`
`NO X
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the NDA
`#(s).
`
`NDA#
`NDA#
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval of the application
`and conducted or sponsored by the applicant." This section should be completed only if the answer
`to PART II, Question 1 or 2 was "yes."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`
`Reference ID: 3426073
`
`Page 3
`
`

`

`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). If the answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`summary for that investigation.
`
`YES X
`
`NO
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approval of the application or supplement?
`YES X
`
`NO
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`
`(b) Did the applicant submit a list of published studies relevant to the safety and effectiveness
`of this drug product and a statement that the publicly available data would not independently
`support approval of the application?
`
`YES
`
`NO X
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`YES
`
`NO
`
` If yes, explain:
`
`
`
`
`
`(2) If the answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`
`Reference ID: 3426073
`
`Page 4
`
`

`

`demonstrate the safety and effectiveness of this drug product?
`
`YES
`
`NO X
`
` If yes, explain:
`
`
`
`(c)
`
`If the answers to (b)(1) and (b)(2) were both "no," identify the clinical investigations
`submitted in the application that are essential to the approval:
`
`Study #302
`
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results of another investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`product? (If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`
`
`YES
`
`YES
`
`
`
`NO X
`
`NO
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`Investigation #1
`
`YES
`
`NO X
`
`Reference ID: 3426073
`
`Page 5
`
`

`

`Investigation #2
`
`YES
`
`NO
`
`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new"):
`
`Study #302
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct of the investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`
`
`!!
`
`! NO
`! Explain:
`
`
`
`!!
`
`
`! NO
`! Explain:
`
`Investigation #1
`
`IND # 71537
`
`YES X
`
`
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`
`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`
`Reference ID: 3426073
`
`Page 6
`
`

`

`interest provided substantial support for the study?
`
`!!
`
`
`! NO
`! Explain:
`
`!!
`
`
`! NO
`! Explain:
`
`Investigation #1
`
`YES
`Explain:
`
`
`
`Investigation #2
`
`YES
`Explain:
`
`
`
`
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies sponsored or conducted by its predecessor in interest.)
`
`YES
`
`NO X
`
`If yes, explain:
`
`=================================================================
`
`Name of person completing form: Wayne Amchin
`Title: Senior Consumer Safety Officer, Division of Cardiovascular and Renal Products
`Date: 12-19-13
`
`
`Name of Office/Division Director signing form: Norman Stockbridge, M.D., Ph.D.
`Title: Director, Division of Cardiovascular and Renal Products
`
`Reference ID: 3426073
`
`Page 7
`
`

`

`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3426073
`
`Page 8
`
`APPEARS THIS WAY ON
`ORIGINAL
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`WAYNE S AMCHIN
`12/20/2013
`
`NORMAN L STOCKBRIDGE
`12/20/2013
`
`Reference ID: 3426073
`
`

`

`United Therapeutics Corp.
`
`1.3.3 Debarment‘ACertification
`NDA 203496
`
`DEBARMENT CERTlFICAT-ION
`
`NDA 203496
`
`(but)
`
`(treprostinil diethanolamine) Sustained Release Tablets
`
`United Therapeutics Corporation hereby certifies that it did not and will not use in any
`
`capacity the services of any person debarred under section 306 ofthe Federal Food, Drug, and
`
`Cosmetic Act in connection with this application.-
`
`{See Appended Electronic Signature Page}
`
`Dean Bunce
`
`EVP, Regulatory Affairs and Compliance
`
`Page 1
`
`

`

`Debarment Certification Orginal NDA
`
`ELECTRONIC SIGNATURES
`
`
`
`Dean Buncc
`
`Signedby ,
`
`'
`
`Meaninwtfignm -
`Regulatory Affairs Approval
`
`21-Dec-2011 19:25 GMTQOS'
`
`
`
`

`

`ACTION PACKAGE CHECKLIST
`
`NDA # 203496
`
`NDA Supplement #
`BLA Supplement #
`
`_
`IfNDA. Eflicacy Supplement Type.
`
`Proprietary Name: Orenitram
`Established/Proper Name: treprostinil
`Dosage Form:
`Tablets
`
`RPM: WayneAmcmn
`
`Applicant: United Therapeutics Corporation
`Agent for Applicant (if applicable):
`
`NDAs and NDA Efficacy Supplements:
`
`505
`
`2 0 '
`
`' al NDAs and 505
`
`2 NDA su
`
`lements:
`
`NDA Application Type: X 505(b)(l) E] 505(b)(2)
`Eflicacy Supplement:
`l:] 505(b)(1)
`[:I 505(b)(2)
`
`Listed drug(s) relied upon for approval (include NDA #(s) and drug
`name(s)):
`
`(For additional information regarding 505(b)(2)s.
`please refer to
`ht_tp://inside fda.gov:9003/CDER/OfficeofNewDrugs/I
`mmediateOffice/RegulatogAffairsTeam/ucmOZ 7499.
`lltm
`
`Provide a brief explanation of how this product is difl'erent from the listed
`drug.
`
`I:] This application does not reply upon a listed drug.
`I:] This application relies on literature.
`I:] This application relies on a final OTC monograph.
`I:] This application relies on (explain)
`
`lication two months rior to EVERY actiona
`2 a
`For ALL
`review the information in the 50512)!” Assessment and submit the
`draft2 to CDER 0ND IO for clearance. Finalize the 505(b)(2)
`Assessment at the time of the approval action.
`
`On the day of approng check the Orange Book again for any new
`patents or pediatric exclusivity.
`
`D No changes
`
`I:I Updated Date of check:
`
`If pediatric exclusivity has been granted or the pediatric information in
`the labeling of the listed drug changed, determine Whether pediatric
`information needs to be added to or deleted from the labeling of this
`drug.
`
`0:0 Actions
`
`Proposed action
`0
`.
`0 User Fee Goal Date 15 2/16/2014
`
`0
`
`Previous actions (specifi type and datefor each action taken)
`
`X AP
`
`
`
`TA
`
`CR
`
`D
`D
`13' None CR oh 10/23/12, on
`on 3/22/13
`
`l The Application Information Section is (only) a checklist. The Contents ofAction Package Section (beginning on page 5) lists
`the documents to be included in the Action Package.
`2 For resubmissions. (b)(2) applications must be cleared before the action, but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER 0ND IO unless the Assessment has been substantively revised (e.g.. nrew listed drug, patent certification
`revised).
`
`Version 12/09/2013
`
`Reference ID: 3426395
`
`

`

`NDA/BLA #
`
`Page 2
`
`Ifaccelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`Application Characteristics 3
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions. see
`hfipzflwww fda.gov/downloads/Drugs/GuidanceComplianceRegylatoglnfonnation/Guida
`11ces/11c111069965.
`. Ifnot submitted. ex tlain
`
`
`
`I: Priority
`Review priority: X Standard
`Chemical classification (new NDAs only):
`
`3
`
`El Fast Track
`I:I Rolling Review
`X Orphan drug designation
`I:I Breakthrough Therapy designation
`
`D Rx—to-OTC full switch
`D Rx-to-OTC partial switch
`|:I Direct-to-OTC
`
`NDAs: Subpart H
`E] Accelerated approval (21 CFR 314.510)
`B Restricted distribution (21 CFR 314.520)
`Subpart I
`[3 Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`D Restricted distribution (21 CFR 601.42)
`Subpart H
`[3 Approval based on animal studies
`
`|:| Submitted in response to a PMR
`|:| Submitted in response to a PMC
`D Submitted in response to a Pediatric Written Request
`
`Comments :
`
`REMS: E] MedGuide
`|:] Communication Plan
`D ETASU
`lj MedGuide w/o REMS
`El REMS not required
`
`O
`0.. BLAs only: Ensure RMS—BIA Product Information Sheetfor TBP and RMS—BLA Facility
`Information Sheetfor TBP have been completed and forwarded to OPI/OBI/DRM (Vicky
`Carter
`
`I:] Yes. dates
`
`v BLAs only: Is the product subject to oflicral FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I: Yes D No
`
`°3° Public communications (approvals only)
`
`0 Oflice of Executive Programs (OEP) liaison has been notified of action
`
`X Yes
`
`I:] No
`
`0
`
`0
`
`Press Office notified of action (by OEP)
`
`Indicate what types (if any) of information dissemination are anticipated
`
`I: Yes D No
`X None
`
`E] HHS Press Release
`E] FDA Talk Paper
`D CDER Q&As
`I:I Other
`
`
`
`3 Answer all questions in all sections in relation to the pending application. i.e.. if the pending application is an NDA or BLA
`supplement. then the questions should be answered in relation to that supplement. not in relation to the original NDA or BLA. For
`example. if the application is a pending BLA supplement. then a new RMS—BLA Product Information Sheetfor TBP must be
`completed.
`
`Version 1 2/09/20]3
`
`Reference ID: 3426395
`
`

`

`NDA/BLA #
`
`Page 3
`
`0’0
`0 Exclusivity
`
`Is approval of this application blocked by any type of exclusivity?
`
`O NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
`drug or biologic for the proposed indication(s)? Refer to 21 CFR
`316.3(b)(13)f0r the definition of "same drug "for an orphan drug (i.e.,
`active moietv). This definition is NOT the same as that usedfor NDA
`chemical classification.
`
`X No
`
`If. yes. NDA/BLA #
`date exclusivity expires:
`
`and
`
`0
`
`0
`
`0
`
`(b)(2) NDAs only: Is there remaining 5-year exclusivity that would bar
`efiective approval of a 505(b)(2) application)? (Note that, even ifercliish'ity
`remains, the application may be tentatively approved ifit is otherwise ready
`for approval.)
`
`E] No
`If yes. NDA #
`exclusivity expires:
`
`(b)(2) NDAs only: Is there remaining 3-year exclusivity that would bar
`eflecfive approval of a 505(b)(2) application? (Note that, even iferclusivitv
`remains, the application may be tentatively approved ifit is othenvise ready
`for approval.)
`
`I: No
`If yes. NDA #
`exclusivity expires:
`
`(b)(2) NDAs only: Is there remaining 6-month pediatric exclusivity that
`would bar efl'ective approval of a 505 (b)(2) application? (Note that, even if
`exclusivity remains, the application may be tentatively approved ifit is
`othenvise readyfor approval.)
`
`I: No
`If yes. NDA #
`exclusivity expires:
`
`0 NDAs only: Is this a single enantiomer that falls under the 10-year approval
`limitation of 505(u)? (Note that, even ifthe 10—year approval limitation
`period has not evpired. the application may be tentatively approved ifit is
`othenvise readyfor approval.)
`
`X No
`
`and date 10—
`If yes. NDA #
`year limitation expires:
`
`0°.
`0
`
`Patent Information (NDAs only)
`
`Patent Information:
`
`Verify that form FDA-3 542a was submitted for patents that claim the drug for
`which approval is sought.
`Ifthe drug is an old antibiotic. skip the Patent
`Certification questions.
`
`Patent Certification [505(b)(2) applications]:
`Verify that a certification was submitted for each patent for the listed drug(s) in
`the Orange Book and idutify the type of certification submitted for each patent.
`
`X Verified
`
`I:] Not applicable because drug is
`an old antibiotic.
`
`21 CFR 314.50(i)(1)(i)(A)
`D Verified
`
`21 CFR 314.50(i)(1)
`I: (ii)
`I: (ii)
`
`[505(b)(2) applications] If the application includes a paragraph III certification.
`it cannot be approved until the date that the patent to which the certification
`pertains expires (but may be tentatively approved if it is otherwise ready for
`approval).
`
`I: No paragraph III certification
`Date patent will expire
`
`[505(b)(2) applications] For each paragraph IV certification. verify that the
`applicant notified the NDA holder and patent owner(s) of its certification that the
`patent(s) is invalid, unenforceable. or will not be infringed (review
`documentation of notification by applicant and documentation of receipt of
`notice by patent owner and NDA holder). (Ifthe application does not include
`any paragraph IV certifications, mark "N/A " and skip to the next section below
`(Summary Reviews».
`
`I: N/A (no paragraph IV certification)
`El Verified
`
`
`
`
`
`Version: 12/09/2013
`
`Reference ID: 3426395
`
`

`

`NDA/BLA #
`Page 4
`
`
`
`[505(b)(2) applications] For each paragraph IV certification, based on the
`questions below, determine whether a 30-month stay of approval is in effect due
`to patent infringement litigation.
`
`Answer the following questions for each paragrap