CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICATION NUMBER:
`
`20-114/S006
`
`ADMINISTRATIVE DOCUMENTS
`
`°°°°°1
`
`Exhibit 1053
`
`IPR2017-00807
`
`Exhibit 1053
`IPR2017-00807
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`,_Novonbot 1. 2010, covers the fotmuJ.at1on._coupoa1:1on. andlor method
`of use of Antclin (aulascina BC1) Nani Spray. 137 neg. This product
`in currontly approyod undnr Suction 505 of tho Federal Food. Drug and
`Cosmetic Act
`(RDA 20-114).
`
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`' R. Hensworth. Ph.D.
`'
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`_t_o_g:. Regulatory Affairs
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`Curt¢r—Wa.11tco. Inc.
`Cranbury. New Jersey
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`,Pedi3ttjic Page Printout
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`‘Page 1 of]
`
`PEDIATRIC PAGE
`(Contplcte for all original application and all officacy supplements)
`
`" NDA tlumber:
`
`020114
`
`Trade Name:
`
`ASTELIN NASAL SPRAY
`
`Supplement Number? 006
`Supplement Type:
`SE5
`Regulatory Action:
`OP :1’
`Action Date:
`1 1/15/99
`
`AZELASTlNE HYDROCHLORIDE
`
`Generic Name:
`H
`_
`‘Dosage Form:
`COMIS Indication: ALLERGIC RHlNlTlS
`
`"—~:
`
`-—
`
`Seasonal Allergic Rhirlfisin children 5 years aod older, and \l/asémotor Rhinitis in children 12 years and older. 7
`Igdjggtiggfi
`Adequate for SOME pecliatric'aTge, groups
`A
`7
`Label Adequacy:
`Forumulatlon Needed: NO NEW FORMULATION is needed
`
`_”
`
`Comments (if any):
`
`Approval based on revised labeling.
`
`t..san_re_r_&ar;us
`
`IJJIBLBEBDL
`
`5 years
`
`"
`
`0‘ Adult
`
`Slam:
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`Data
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`This pagewas last editeqey/15/00
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`DEPARTMENT OF HEALTI-{AND HUMAN SERVICES
`’"~i"UBUC HEALTH SERVICE
`FOOD AND QBUG ADMINISTRATION
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`PTO. Box 1001/Half Acre Road
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`Cranbury, NJ 08512
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`-Contact: George R. Hem
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`supplement. Ifpayment is sent by 0.8 mailercourier; please include a copy ofthis completed loan with payment
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`DEBARMEIST CERTIFICATION
`
`to
`Carter-Wallace, Inc. for its Wallace Laboratories, Division has made: diligent
`ensurethat no person ‘biarredunder Section 306 (a) or 306 (b) of the Federal, Food, Drug .
`
`and Cosmetic Act has provided or will provide any services in connection with this
`
`application. A11l?mp1cycc§‘Br Carter-Wallace, Inc. connectedwith this application will
`be required to certify to Carter-Wallace, Inc. that he ‘or she has not been-debarred. A ,/~’=
`
`persons not employed by Carter—Wallace, Inc. who provide services iii connection with
`
`f this application will be required to certify to Carter-Wallace, Inc. in connection with this,_
`_application that no person employed by them has been debarred under Section 306 (a) or
`
`"306 (b) of the Federal, Food, Drug and Cosmetic Act and that no_debarred person will in
`
`the future be employed by them. gelying in part on these certifications, Carter-Wallace,
`
`Inc. certifies.that1't‘did not and will not use in any capacity the services of any person
`
`i debarred under Section 306 (a) or 306 (b), ofthe Federal, Food, Drug and Cosmetic Act in
`
`connection with this application.
`
`F
`
`__
`
`CARTER-WAL
`
`INC.
`
`
`
`
`
`e R Hernsworth, Ph.D.
`Regulgory Affairs
`
`__
`
`By:
`
`_
`
`i r
`
`APPEARS THIS WAY
`on 0RlGlNAL_
`
`ceflif
`
`p
`
`"
`
`000005
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`N
`
`_
`
`Date; November 10, 1999
`
`000005
`
`

`

`«
`~
`
`-
`
`" ’\ DEPARTMENT or-' HEALTH AND HUMAN senvrces
`Public Health Service
`Food and Drug
`
`~
`
`Form Approved: OMB No. 0910-0396
`7 Expiration Date: 3131102
`
`CERTIFICATION: FINANCIAL INTERESTS AND g
`ARRANGEMENTS OF CLINICAL INVESTIGATORS
`’
`TO BE COMPLETED BYAPPUCANT
`
`—
`
`With respect to aIl’oovered clinical studies (or specific clinical studies listed below (it _appropriate)) submitted
`in support of this application. lcertify to one of the statements below as appropriate.'I understand that this
`certification is made in compliance with 21 CFR part 54 and that for the purposes of thirstatement, a clinical
`investigator includes the spouse and each dependent child of the investigator as defined in 21 CFR 54.2(d).
`
`’ ”
`
`~ —Pl¢a.r¢ mark the applicable checkbox.
`
`__
`
`R
`
`I have not entered into any financial
`DU (1) As the sponsor of the submitted studies, -I certify that
`arrangement with the listed clinical investigators (enter names of clinical investigators below or attach
`list of names to this form) whereby the value of compensation to the investigator couldbe affected by
`the outcome of the study as defined in 21 CFR 54.2(a).
`I also certify that each listed clinical
`investigator required to disclose to the sponsor whether the investigator had a proprietary interest in
`this product or a significant equity in the sponsor as defined in_21_CFFt 54.2(b) did not disclose any
`such interests. I further certify that no listed investigator was the recipient of significant payments of
`other sorts as defined in 21 CFR 54.2(f).
`
`
`
`'
`
`4?
`
`applicant, I certify that based on information obtained from the sponsor or trom participating clinical
`investigators. the listed clinical investigators (attach list of names to this lonn) did not participate in
`any financfal arrangement with the sponsor of a covered study whereby the value of compensation to
`the investigator for conducting the study could be affected by the outcome of the study (as defined in
`2'rCF1’-I 542(3)): had no proprietary interest in this product or significant equity interest in the sponsor
`of the covered study (as defined in 21 CFR 54.2(b)): and was not the recipienml significant payments
`pfother sorts (as defined in 21 CFR 5426)).
`"
`"
`I
`
`[:1 (3) As the applicant who is submitting a study or studies sponsored by a firm or party other than the
`applicant. lcertify that I have acted with due diligence to obtain from the listed clinical investigators
`{attach list of names) or from the sponsor the Information required under 54.4 andit was not possible
`Jodo so. The reason why this information could not be obtained is attached.
`2
`
`NAME
`
`Jay R. Brennan
`FIFIM/ORGANIZATION
`
`I V.P. Finance & Business Development
`
`
`
`Inc.
`
`Dcpanlncnt of Health and Human Services
`Food and Drug Admininnsion
`S600 Fishes Linc. Room MC-03
`Rockville. MD 11857
`
`ouunyau-ago-an-Ia-e-utrsourculolrdll-I6‘ 5
`
`
`
`Wallace Laboratoriest,.Division of Carter-—Irlallace,
`
`IF
`>
`'
`Paperwork Reduction Act Statement
`Anagency rruynorconductorsponsonund apcrsonisnotrcquiredlorcsporrdlomcollcctiouof
`Information unless it displays a currently valid OMB control number. Public reporting burden for this
`collection of’ inlormatior.
`is estimated to average I hour per response. including time for reviewing
`instruction... searching existing data aourccs. pthuirr; and maintaining the necessary dun. and
`completing and reviewing the collection of informaxiun. Send comments regarding this burden
`cstinmeornnyothcraspectofthisoollcctiouoliafotlnatiolrtolheaddrmlolherigiiz
`
`FORM FDA 3454 (3199)
`
`000006
`
`000006
`
`

`

`WITHHOLD \
`
`PP» «=6
`
`000007
`
`000007
`
`

`

`v E
`
`‘
`
`lf P.-KRTMENT OF HEALTH 81 HUMAN SERVICES
`
`
`
`William E. Berger, M.D.
`2673?. Crown Valley Parkway
`Suite 361
`
`Mission Viejo, CA 92691
`
`—Dgar.Dr. Berger:
`
`Food and Drug Administration
`Rockville MD 20857
`
`MAY 30
`
`1000
`
`Between March 28 - 29,2000, Mr. Randall N. Johnson, representing theil-‘bod and Drug
`Administration (FDA) inspected your conduct as the investigator of record of a clinical study
`(protocol #346) of thefinvestigational drug Astelin® (a_zelastine hydrochloride) Nasal Spray that
`you conducted for Wallace Laboratories. This inspection is part of FDA’s Bioresearch
`.
`0
`Monitoring Program. This program includes inspections to deterrnine the validity of clinical
`drug studies that may provide the basis for drug marketing approval and to assure that the rights
`Ed welfare of the human subjects who participated in those studies have been protected.
`
`/——>,
`
`/.
`
`— From our evaluation of the inspection report prepared by Mr. Johnson and your oral responses to
`the inspectional observations, we conclude that you did not adhere to all pertinent Federal
`, regulations and/or good clinical investigational practices governing the conduct of clinical
`investigations and the protection of human subjects. In particular, we note your lack of
`documentation for the final disposition of unused study drugvat the close of the study.
`
`Please ensure that corrective actions will be taken to prevent similar problems in your current
`and future studies.
`‘
`I
`
`We appreciate the cooperation shown Investigator Johnson during the inspection. Should you
`have any questions ‘or concerns regarding this letter or the inspection, please contact me by letter
`' at the address given_below.
`
`.
`
`W
`
`‘
`
`Sincerely,
`
`.
`
`/ ..
`David A. Lepay, M.D., Ph.D.
`Director
`
`I
`
`Division of Scientific Investigations
`Office of Medical Policy (HFD-45)
`Center for Dmg Evaluation and Research
`7520 Standish" Place, Suite 103
`
`Rockville, MD20855
`
`000008
`
`000008
`
`

`

`.1 l\ .1.
`
`
`
`
`
` /é /QEPARTMEVTorHEALTH 81 HUMAN sanvicss _ . T ’}"{r~\>Ud.
`
`
`
`—
`'37
`
`
`
`Food and Drug Administration
`Rockville MD 20857
`
`T,
`
`_
`
`V
`
`Q.‘ N... ‘7 pg-_
`
`9,:
`
`A
`‘ JonathanMatz,M.D.
`Atlantic Asthma&Allergy
`7939 Honeygo Blvd,v#2l9
`Baltimore, Maryland 21236
`
`.
`
`3 ;;_,-
`" T-._'.\
`;—i
`
`.
`
`Dear Dr. Matz:
`
`_ In
`
`JUN.
`
`9
`
`205:0
`
`. Between March 20 and 28, 2000, Ms. Barbara A. Burke, representing the Food and Drug
`Administration (FDA) inspected your conduct as the investigator of record of a clinical study
`(protocol #375) of the investigational drug Astelin®l (azelastine hydrochloride) Nasal Spray that
`you_cgnducted for Wallace Laboratories. This inspection is part of FDA’s Bioresearch
`Monitoring Program. This program includes inspections to determine the‘valid_ity of clinical
`drug studies that may provide the basis for drug marketing approval and tovassure that the rights
`and welfare of the human subjects who participated in those studies have been protected.
`
`At the close of the inspection, Ms. Burke presented her inspectional observations
`(Form FDA 483) and discussed these observations with you- From our evaluation of the
`inspection report, your oral responses to the inspectional observations and your unsigned letter
`dated April 10, 2000, we conclude that you did not adhere to all pertinent federal regulations
`and/or good clinicalinvestigational practices governing the conduct of clinical investigations and
`the protection of human subjects. In particular, we note that you failed to: (1) maintairfadequate
`Drug Dispensing Records; (2) exclude one subject (#35) due to use of a prohibited medication;
`(3) adequately and accurately report thejdates of adverse events for five subjects (#21, 24, 28,
`M313. and 322);‘and (4) document the concomitant medications for two subjects (#5 and 26).
`
`-~
`
`Please. ensure that corrective actions will be taken to prevent problems in your current
`_and future studies.
`We appreciate the cooperationshown Investigator Burke during the inspection. Should you have
`‘any questions ‘or concerns regarding tliisjetter or the inspection, please contact me by letter at the
`address given below.
`'
`—
`‘
`*
`‘
`*
`”
`
`S
`———
`
`,_
`
`5
`
`0
`
`A
`
`Sincerelyoyours,
`
`,
`/3/5
`,
`r
`%~DavidA.Lepay,M.D.,Ph.D.
`
`Director
`
`Division of Scientific Investigations
`'
`Office of Medical Policy (HZFD-45)
`Center for Drug Evaluation and Research
`7520 Standish Place, Suite 103
`‘
`Rockville,
`20855
`
`000009
`
`»—e»
`
`_
`
`000009
`
`

`

`Division Director’s Memorandum
`
`Thursday, September 14, 2000
`Date:
`20-] lA,-S_El-006
`T
`g
`NDA:
`Carter—Wallace Laboratories
`.
`0‘
`Sponsor:
`Froprietary Name: ~ Astelin (azelastine HCL) Nasal Spray
`
`D
`
` : Thisis a supplemental NDA for Astelin Nasal Spray, an antihistaniintr
`nasaispray previously approved for the treatment of seasonal allergic rhinitis in adults 0
`e— and children down to age 5. This application is for the vasomotor rhinitis indication for
`Astelin down inpatients ages 12 and above. Dr. Lee’s primary medical review and Dr.
`Chowdhury’s se_condar'y rev_iew offer very fine discussions of the data and I concur with
`their findings.
`7
`-
`”
`
`”
`
`CMC: No new issues, as there are no changes proposed to the marketed, approved
`product.
`
`Pharmacology/toxicology: No new issues, given the indication andpopulation sought.
`
`Labeling: The labeling needed some modification from that proposed by the sponsor,
`— particularly to achieve better clarity about the indication sought, the appropriate dose and
`_the related safety information. The sponsor has submitted appropriate labeling except for
`some necessary restructuring of the Dosage and Administration section. They have
`agreed to changes proposed by Dr.“Lee and this will be stated
`the approval letter.
`
`>j¢
`
`_
`
`» ' -’
`
`_(;_c_>_r__1<_:l_u_sio_r_1_§: This supplement will be approved.
`
`
`
`APPEARS THIS WAY
`ON ORIGINAL ~
`
`RJM Division Director Memo
`
`M NDA 2o—u'4 sswos
`000010
`
`09/14/00
`
`000010
`
`

`

`CATEGORICAL EXCLUSION FROM PREPARATION OF AN
`
`ENVIRONMENTAL ASSESSMENT
`
`—Wallace Laboratories states that the Astelin (azelastine HCI) Nasal Spray, 137 mcg
`Vasomotor Rhinitis Supplement qualifies for a categorical exclusion from the preparation
`of an environmental assessment. The applicable categorical exclusion is cited as 21 CFR
`25.31 (b). To the best of our knowledge therearev no extraordinary circumstances that
`exist with regards tothe Astelin Nasal Spray Vasomotor Rhinitis Supplement.
`
`_ APPEARSMTHIS WAY
`are sarsrrzai
`
`VIIIICXC
`
`00001 1
`
`———
`
`000011
`
`