CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICATION NUMBER:
`
`20-965
`
`CHEMISTRY REVIEW(S)
`
`

`

`DIVISION OF DERMATOLOGIC AND DENTAL DRUG PDDDUCTS
`urn-54o
`Review of Chemistry, Manufacturing, and Controls
`
`JUN I 6 1999
`
`EQA_K= 20-965
`
`§§£M+_BEEIEH_£= 1
`
`BE!IEK.DAIE= 10-JUN-1998
`
`§H§M1§§IQHLIIEE
`ORIGINAL
`AMENDMENT/BL
`
`DQEEMEHI_QAIE QEEELDBIE
`01-JUL-1998
`03-JUL-1998
`16—APR-1999
`19-APR—1999
`
`A§§I§E§Q_QAIE
`09-JUL-1998
`07-MAY—1999
`
`DRE
`
`A
`
`:
`
`DUSA Pharmaceuticals,
`400 Columbus Avenue
`
`Inc.
`
`—
`
`Valhalla, NY
`
`10595
`
`DR
`
`N
`
`Agent:
`
`Inc.
`Guidelines,
`10320 USA Today Way
`Miramar, FL 33025
`
`Wisteria:
`HgnpxgpxigjjijQEAfl:
`W:
`Chemicalrzxne/
`W:
`
`LEVULAN®
`aminolevulinic acid hydrochloride
`ALA! 5-ALAI S'ALA HClI 3'
`amino acid salt
`1
`s
`
`A S '
`
`'
`
`'
`
`'
`
`'
`
`DESI
`
`e
`
`u :
`
`N/A
`
`PHARMAQQLQQIQAL QATEQQRXZIHQIQLE;93: Topical treatment of actinic
`
`"’
`’
`'
`A‘ "
`"'
`keratoses in conjunction with a’
`'
`blue light illuminating device.
`
`7
`
`77W
`
`QQ§§§§_§QBM:
`§IB§E§I§§=
`
`BQQIE_QE_ADMIEI§IBAIIQH=
`Q;SPEN§EQ:
`
`CHEMI
`
`NAME
`
`RU
`
`Solid for topical solution
`20%
`
`Topical
`X
`Rx
`
`
`
`OTC
`
`0
`
`NH;
`
`Cl
`
`0
`
`OH
`
`Chemical Name:
`M01. Formula:
`Mol. Weight:
`CAS No.
`-
`Melting Pt.:
`pH (aq.):
`PK.=
`Solubilities:
`
`'
`
`S-aminolevulinic acid hydrochloride
`CghN09HCl
`167.59
`’
`[5451-09-2]
`151—156°C (decomp.)
`1.77 (1:5 aqueous solution)
`3.816
`freely soluble in water; slightly soluble in methanol,
`ethanol; practically insoluble in chloroform, hexane,
`mineral oil.
`'
`
`§QEEQBILH§_29§HMEHI§=
`
`mac: Type H.“mm... by
`
`-amino-1evu1inic
`letter dated 29-JUN-1998; for the manufacture of
`acid hydrochloride. This DMF has been reviewed in conjunction with
`this NBA and found to be adequate.
`The sponsor provided all pertinent
`
`

`

`'
`NDA 20—965
`DUSA Pharmaceuticals
`
`"
`
`LEVULAN® KERASTICK’ for Topical Solution, 20%
`
`chemistry, manufacturing and control data pertaining to the drug
`substance in the DMF.
`
`DMF(
`signed by
`made from?
`
`LzzfiflillL'
`
`better dated June 14, 1996,
`or the manufacture of tubular containers
`
`k
`
`iType III,K
`our?
`12—APR-1996, Signed by?
`Low Density Polyethylene resin.
`
`'
`
`zauthorized by letter dated
`or the manufacture of'
`
`]
`
`)Type I, Guidelines Analytical Laboratories, Inc., authorized
`DMFi
`by letter dated 29-JUN-1998, signed by Sam Swetland; for the
`facilities, personnel and procedures used by this contract lab and
`agent.
`
`BELAIED_DQ§HMEHI§=
`Patents:
`INDi
`
`Sfor 5—ALA solution, 10%; active in RFD-540.
`
`The following patents are claimed for the drug or method of use of the
`drug:
`
`
`U.S. Patent No. 5,079,262, expiration date 28-JUL-2009, owned by
`Queens University at Kingston and assigned exclusively to DUSA
`Pharmaceuticals,
`Inc. for method of use of LEVULAN for topical
`treatment of actinic keratoses.
`
`U.S. Patent No. 5,211,938, expiration date 18-MAY-2010, owned by
`Queens University at Kingston and assigned exclusively to DUSA
`Pharmaceuticals,
`Inc. for method of use of LEVULAN for topical
`treatment of actinic keratoses.
`
`U.S. Patent No. 5,422,093, expiration date 28-JUL—2009, owned by
`Queens University at Kingston and assigned exclusively to DUSA
`Pharmaceuticals,
`Inc. for method of use of LEVULAN for topical
`treatment of actinic keratoses.
`
`g
`
`Appendices:
`1.
`Manufacturing process flowchart, 7 pages.
`2.
`hpplicator tip schematic drawing,
`3.
`icro io ogy consultation reviews, 11 pages.
`4.
`Draft package insert incorporated changes, 17 pages.
`5.
`Draft carton and applicator labels, 9 pages.
`6.
`Stability program summary table, 2 pages.
`7.
`Investigational formulation and clinical trial summary tables,
`pages;
`
`1 page.
`
`5
`
`moo
`
`.
`.
`
`Report from Joint Pre-approval inspection, 15 pages.
`Establishment Inspection Report, 2 pages.
`
`QQEfiHLI§=
`
`The proposed trade name "LEVULAN KERASTICK" was submitted to the
`Labeling and Nomenclature Committee (LNC) on 04-JUN-1999 through
`Chairman Dan Boring, Ph.D.
`(BED-530).
`
`

`

`l
`
`NDA 20-965
`DUSA Pharmaceuticals
`LEVULAN® KERASTICK“ for Topical Solution,
`
`20%
`
`QQEQLHEIQE§_£_B§£QMMEEDBIIQH§=
`
`NOT APPROVABLE
`
`Based on the review of the chemistry, manufacturing and controls
`information presented in the NDA, and the inspections of the
`manufacturing facilities, a recommendation of "Not Approvable" is
`made.
`
` f_ . Hathawayr h.D.
`Review Chemist
`
`cc: Orig. NDA 20-965 (with all appendices)
`HFD-S40/DivisionFile (with all appendices)
`
`cc: With Appendices 1 and 2 only:
`HFD-S40/Chem/JSHathaWay
`'
`
`RFD—540/ChemTeader/WHDeCamwb/l
`HFD-S40LinDir/Jwilkinq
`,
`,
`1 PH] ______
`
`,
`
`ff
`
`HFD-830/DivDir/CWChen
`HFD—S40/Med0ff—r—IMOkun
`HEB-54 0 / Pharmfizg/Largigd
`HFD-540/Prongr/OCintron
`HFD—BOS/Micro/PCooney
`HFD-BOS/Micro/BRiley
`HFD-/BioPharm/DBashaw_
`
`»
`
`m.--
`
`filgngmg:
`
`D:\WPFILES\NDAS\ORIGNDAS\NDA20965\N20965R.000
`
`@511?!31§.: i
`
`‘ V ._
`
`’ mugs nus WAY
`cu: ORIGINAL
`
`

`

`DIVISION OF DERMATOLOGIC AND DENTAL DRUG PRODUCTS DEC
`urn-540
`Review of Chemistry, Manufacturing, and Controls
`
`2 1999
`
`NDA #: 20—965
`
`CHEM. REVIEW #: 2
`
`REVIEW DATE: 02-DEC-1999
`
`SUBMISSION/TYPE DOCUMENT DATE CDER DATE ASSIGNED DATE
`ORIGINAL
`Ol-JUL-l998
`03-JUL-l998
`Review #1
`AMENDMENT/BL
`l6-APR-l999
`l9-APR-l999 Review #1
`AMENDMENT/NC
`28-JUL-1999
`29-IUL-l999
`08-AUG-1999
`AMENDMENT/AZ
`Ol-OCT-l999
`04-OCT-1999
`l4-OCT-l999
`AMENDMENT/BC
`ll-OCT-l999
`15-OCT-l999
`22-OCT-1999
`AMENDMENT/BL
`11-Nov-1999
`12-Nov-1999 22-Nov-1999
`
`NAME & ADDRESS OF APPLICANT: DUSA Pharmaceuticals, Inc.
`400 Columbus Avenue
`
`Agent:
`
`.
`DRUG PRODUCT NAME
`
`Valhalla, NY 10595
`
`Guidelines, Inc.
`10320 USA Today Way
`Miramar, FL 33025
`
`.
`#MW—iw—E—mnwe ,7 7
`Nonproprietgy/USAN:
`Code Names/#‘s:
`Chemical Tm]
`Therapeutic Class:
`
`,
`
`7 Wm LEVULAN®
`aminolevulinic acid hydrochloride
`ALA, S-ALA, S—ALA HC], S-
`amino acid salt
`1 S
`
`ANDA Suitability Petition/DESI/Patent Status:
`
`N/A
`
`PHARMACOLOGICAL CATEGORY/INDICATION: Topical treatment of actinic
`keratoses in conjunction with a blue light
`illuminating device.
`
`DOSAGE FORM:
`STRENGTHS:
`ROUTE OF ADMINISTRATION:
`DISPENSED:
`
`J
`
`Solid for topical solution
`20%
`Topical
`_X_ RX __ OTC
`
`CHEMICAL NAME STRUCTURAL FORMULA MOLECULAR FORMULA
`
`MOL.WT:
`
`0
`
`oWk/NH;
`
`OH
`
`.
`
`or
`
`Chemical Name:
`Moi. Formula;
`Moi. Weight:
`LLNHVWILLCAS No.
`
`S-aminolevulinic acid hydrochloride
`C5H9N03.HC1
`167.59
`7454.51.09.21
`
`,
`
`,
`
`,
`
`,
`
`V _ 7
`
`7
`
`,7 ,7 L
`
`

`

`NDA 20-965
`
`DUSA Pharmaceuticals
`LEVULAN® KERAS'I'ICKTM for Topical Solution, 20%
`
`Melting Pt.:
`pH (aq.):
`pK.:
`
`151-156°C (decomp.)
`1.77 (1:5 aqueous solution)
`3.816
`
`SUPPORTING DOCUMENTS:
`
`)authorized by letter dated 29-JUN-
`:7"
`ll ype IL}
`DMH
`1998; for the manufacture of 5-amino-levulinic acid hydrochloride.
`
`REMARKS
`
`Amendments and correspondence covered in this review were received as follows:
`7/29/99: Comparison of USP and EP specifications for Purified Water
`10/4/99: Complete r¢sponse to 6/27/99 action letter
`10/15/99: Amendment of D
`1 1/ 12/99: Revision of package insert
`
`CONCLUSIONS & RECOMMENDATIONS:
`
`
`
`APPROVAL
`
`Bat—slid on the reviEW of meThenfisw, manufacturing and controls information presented in the
`NDA and the subsequent amendments listed above, a recommendation of "Approval " is made.
`
`
`
`J. S. Hathaway, Ph.D.
`Review Chemist
`
`cc:
`
`Orig. NDA 20-965
`HFD-540/DivisionFile
`
`HFD-S40/Chem/JSHathaway
`
`HFD-540/Chemreammr/wmecflrfw/W
`
`HFD-540/DivDir/IWi1kin
`
`'
`
`HFD-830/DivDir/CWChen
`
`HFD-540Med0ffr/M0kun
`
`HFD-S40/PhannTox/LReid
`HFD-S40/Prongr/0Cintron
`HFD-805/Micro/PCooney
`HFD~805lMicrolBRiley
`l-IFD-/BioPharm/DBashaw
`
`m! a! 44
`
`filename: C:\My Documents\MSWordDocs\NDAS\OrigNDAsWDA20965\N20965R.001.doc
`
`