CENTER FOR DRUG EVALUATION AND .
`RESEARCH
`
`” APPLICA TION NUMBER:
`
`21-688
`
`CHEMISTRY REVIEWg S!
`
`

`

`NDA 21-688 '
`
`SENSIPAR (cinacalcet hydrochloride) 30, 60, 900mg Tablets
`
`CHEMISTRY DIVISION DIRECTOR REVIEW
`
`Applicant:
`
`Amgen, Inc.
`Address: One Amgen Center Dr.
`Thousand Oaks, CA
`
`Representative:
`Pamela Danagher, Manager Regulatory Affairs
`(805) 447-1000
`
`Indication:
`
`Treatment of secondary hyperparathyroidism in pts with chronic kidney
`disease not undergoing dialysis and for treatment of primary
`hyperparathyroidism whenparathyroidectomy is not a treatment option
`
`Presentations:
`
`30, 60, 90 mg tablets in HDPE bottles of 30. ._._..———-———-————~
`
`.
`. Physician sample HDPE bottles of 7
`count are also qualified. Bottles contain filler and a desiccant.
`
`BER Status:
`
`Acceptable 26~FEB-2004
`
`Consults:
`
`DMETS— SENSIPARlS acceptable 08-NOV-2003
`Statistics— none
`
`Biopharm— dissolution tests, acceptance criteria OK
`EA — no conSult - waiver requested - granted
`
`The SENSIPAR NDA was submitted OS-SEP-2003. CMC IR letters were issued 13—
`NOV-2003, 23-dec-2003, AND 26-jan—2004 (EMail) and was responded to in the
`amendments dated 03-DEC-2003 and lZ-JAN-2004, and 03-FEB-2004. The NDA was
`designated Priority.
`
`The drug substance is manufactured by:
`
`
`
`Structural characteriZation of the drug substance, and chirality determination was
`satisfactoryW
`m} was agreed at a pre-NDA
`
`

`

`
`
`M ‘
`J
`
`V Conclusion
`
`Drug substance information is acceptable.
`
`The drug product is a film coated immediate release tablet in strengths'of 30, 60, 90
`mg.
`
`submitted stability data
`_~—————--————f"-—~—f—_—'-—--
`support the proposed 24 month expiry. The stability protocol and commitment are
`acceptable. Labeling is acceptable.
`
`All associated DMFs are acceptable.
`
`Overall Conclusion
`
`Fr0m a CMC perspective the application an approval action is recommended.
`
`Eric P Duffy, PhD
`Director, DNDC II/ONDC
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/8/
`
`Eric Duffy
`3/8/04 11:51:05 AM
`CHEMIST
`
`

`

`
`
`NDA 21-688
`
`SENSIPARTM (cinacalcet hydrochioride) Tablets
`
`Amgen Inc.
`
`Shulin Ding, Ph.D.
`
`Division of Metabolic and‘Endocrine Drug Products
`
`

`

`
`
`Table of Contents
`
`Table of Contents
`
`......2
`
`Chemistry Review DataSheet3
`
`The Executive Summary7
`
`I. Recommendations .....................................................
`
`...................................... 7
`
`A. Recommendation and Conclusion on Approvability .............................................'.......................... 7 '
`B." Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements, and/or Risk
`Management Steps, if Approvable ................................................................................................... 7
`
`H. Summary of Chemistry Assessments ......................................................................................... 7
`
`A. Description ofthe Drug Product(s) and Drug Substance(s) ............................................................. 7
`
`B. Description of How the Drug Product is Intended to be Used.......................................................... 8
`C. Basis for Approvability or Not—Approval Recommendation ............................................................ 9
`
`III. Administrative........................................................................................................................... 9
`
`A. Reviewer’s Signature....: ................................................................................................................... 9
`B. Endorsement Block ........................................................................................................................... 9
`
`C. CC Block .......................................................................................................................................... 9
`
`Chemistry Assessment10
`
`_
`
`,1. Review Of Common Technical Document-Quality (Ctd-Q) Module 3.2: Body Of Data ....... 10
`
`S DRUG SUBSTANCE (Name, Manufacturer] ............................................................................... 10
`
`P DRUG PRODUCT [Name, Dosage form] .................................................................................... 51
`
`A APPENDICES ..................................................................................................'............. ‘. .............. 94
`
`R REGIONAL INFORMATION ...........................
`
`...................................................... 94
`
`H. Review 'OfCommon Technical Document-Quality (Ctd-Q) Module 1 ..................................95
`r A. Labeling & Package Insert ............................................................................................................ 95
`
`B. Environmental Assessment Or Claim Of Categorical Exclusion ................................................... 96
`
`HI.
`
`List Of Deficiencies To Be Communicated ....................................................................... 96
`
`

`

`
`
`Chemistry Review Data Sheet
`
`Chemistry Review Data Sheet
`
`1. NDA 21—688
`
`2. REVIEW #: 1 '
`
`3. REVIEW DATE: February 25, 2004 ‘
`
`4. REVIEWER: Shulin Ding, Ph.D.
`
`5. PREVIOUS DOCUMENTS:
`
`Previous Documents
`
`N/‘A
`
`Document Date
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`Submission s Reviewed
`
`.,
`
`Document Date
`
`.
`
`'
`
`Aug. 14, 2003
`' Presubmission
`‘Sep. 5, 2003
`Original
`Oct. 8, 2003
`Amendment to originalI
`Dec. 3, 2003
`Amendment2
`Jan. 12,2004
`Amendment3
`Feb. 3,2004
`'
`Amendment
`'The 10/8/03 amendment provides for an additional testing site for raw material testing, and a correction to the address of "—
`Laboratorios.
`_
`..
`2’I'he l2/3/03 amendment provides for (1) responses to the CMC questions includedIn the Nov. 18, 2003, 74-day filing review letter, (2)
`three replacement tables (Table 5, Data Summary for Yield and Purity ofAMG 073 Amide, Section 3.2SJ.6; Table 1, Commercial Batch
`_ Formula for Cinacalcet HCl Tablets, Section 3.2.P32; and Table 4, Moisture Accuracy Summary, Section 3.2.P.5.3.6), and (3) removal of
`"W from Item 4 ofNDA Ill-688.
`’I‘he l/12/U4 amendment provides for responses to the CMC questions includedin the IR letter dated Dec. 23, 2003.
`4The 2/3/04 amendment provides for responses to the CMC questions e-mailed to Amgen on Jan. 26, 2004.
`
`.
`
`.
`
`7. NAME & ADDRESS OF APPLICANT:
`
`Name: Amgen Inc.
`
`Address: One Amgen Center Drive, Thousand Oaks, CA 91320-1799
`
`Representative:
`
`Pamela Danagher, Manager Regulatory Affairs
`
`Telephone:
`
`805-447-1000
`
`Page 3 of 96
`
`

`

`
`
`
`
`Chemistry Review Data Sheet
`
`8. DRUG PRODUCT NAME/CODE/TYPE:
`
`a) Proprietary Name: SensiparTM
`b) Non-Proprietary Name (USAN): Cinacalcet hydrochloride
`0) Code Name/# (ONDC only): AMG 073, AMG 073 HO, AMG 99073-01
`d) Chem. Type/Submission Priority (ONDC only):
`
`.
`
`0 Chem. Type:
`
`1
`
`0 Submission Priority: P
`
`- 9. LEGAL BASISlFOR SUBMISSION: 505 (b)(1) *
`
`10; PHARMACOL. CATEGORY: Bone/calcium-phosphorous metabolism
`
`11. DOSAGE FORM:
`
`Tablet
`
`12. STRENGTH/POTENCY:
`
`30 mg, 60 mg, and 90 mg per tablet
`
`13. ROUTE OF ADMINISTRATION: Oral
`
`l4. Rx/OTC DISPENSED: A RX '1
`
`OTC
`
`15 . SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM):
`SPOTS product — Form Completed .
`
`'
`
`X Not a SPOTS product
`
`Page 4 Of 96
`
`

`

`
`Chemistry Review Data Sheet
`
`16. CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR
`FORMULA, MOLECULAR WEIGHT:
`
`Established (INN, USAN) Name:
`Chemical Name:
`CAS Registry Number:
`Molecular Formula:
`Molecular weight:
`
`'
`
`Cinacalcet Hydrochloride
`N-[l-(R)—(-)—(1-naphthyl)ethyl]-3-[3--(trifluoromethyl)phenyl]-l-
`aminopropane hydrochloride
`364782-34-3
`C22H22F3N'HC1
`393.87 g/mole (HCl salt)
`
`357.41 g/mole (free base)
`
`mam
`
`022H22F3N- H0!
`(393. 87)
`
`17. RELATED/SUPPORTING DOCUMENTS:
`
`A. DMFs:
`
`DMF #
`
`TYPE
`
`HOLDER
`
`ITEM REFERENCED
`
`CODE'
`
`STATUS
`
`nnadrv ll green
`
`Adequate
`
`DATE
`
`REVIEW
`COMMENTS
`COMPLETED
`1/l6/04fiReviewed by Sheldonkosky
`Chem Rev# 1
`
`‘
`
`Adequate
`
`l/l6/04
`
`9/22/00
`
`Reviewed by Sheldon Markofsky
`Chem Rev # 1
`Reviewed by Dale Koble
`Chem Rev # l
`
`Adequate
`
`9/12/00
`5/09/96
`
`Reviewed by Sharon Kelley, Chem Rev # 1
`Reviewed by Mike Adams, Chem Rev # 12
`
`Reviewed by Donald N. Klein
`Chem Rev # IS
`Reviewed by Sara C. Pope
`Chem Rev # 23
`
`Adequate
`
`Not
`Applicable
`
`Not applicable
`
`"
`
`Adequate
`
`12/6/00
`
`Reviewed by Moo-Jhong Rhee
`Chem Rev # l
`
`
`
`
`
`
`
`Reviewed by Lorenzo Rocca
`
`Chem Rev # 3
`
`
`
`Action codes formDuMF Tibia? h
`l — DMF Reviewed.
`Other codes indicate why the DMF was not reviewed, as follows:
`2 —’l‘ype l DMF
`3 — Reviewed previously and no revision since last review
`4 — Sufficient information in application
`5 — Authority to reference not granted
`6 - DMF not available
`7 — Other (explain under "Comments")
`
`5/30/2003
`
`Adequate
`
`Page 5 of 96
`
`

`

`
`
`Chemistry Review Data Sheet
`
`B. Other Documents:
`
`DOCUMENT
`
`APPLICATION NUMBER
`
`DESCRIPTION
`
`-18. STATUS:
`
`.
`
`,
`
`-
`
`.
`ONDC:
`CONSULTS/CMC
`
`'
`
`
`
`
`
`
`
`
`
`
`__—_
`MIME—_—
`Gemma Kui‘ ers, PhD.
`
`
`
`
`_—__
`_m_—_
`_-—11-8—03
`_-_———
`
`-_-_——
`*Amgen requests a categorical exclUsion per 21 CFR 25.3l(a) since the Expected Environment or Introductory
`Concentration (EEC or BIC) is projected to be less than 1 pm per billion (ppb). '.
`
`l9. ORDER OF REVIEW (OGD Only): N/A
`
`APPEARS THIS WAY .
`on ORIGINAL
`
`Page 6 of 96
`
`

`

`
`Chemistry Assessment Section ‘
`
`'_ The Chemistry Review for NDA 21-688
`
`The Executive Summafl '
`
`I.
`
`' Recommendations
`
`A,
`
`Recommendation and Conclusion on Approvability
`
`NDA 21-688 is recommended for approval fi’om the standpoint of chemistry, manufacture and
`controls, pending a satisfactory cGMP status of the manufacturing/testing sites.
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements,
`' and/or Risk Management Steps, if Approvable
`
`None
`
`11,
`
`Summary of Chemistry Assessments
`
`A. Description of the Drug Product(s) and Drug Substance(s)
`1) Drug Product
`.
`_
`.
`t
`
`The proposed drug product, SiensiparTM is a-—-—\___ light green, film-coated, oval-
`shaped tablet for oral administration, and intended for the treatment of primary and secondary
`hyperparathyroidism.
`
`Sensiparm. tablets contain 30 mg, 60 mg and 90 mg of cinacalcet free base equivalent (33 mg, 66
`mg, and 99 mg as the hydrochloride salt, respectively). The active ingredient is the free base
`whereas the drug substance is the hydrochloride salt. The tablets also contain the following
`inactive ingredients: pre-gelatinized starch, microcrystalline cellulose, povidone, crospovidone,
`colloidal silicon dioxide, and magnesium stearate. The tablets are coated with color (Opadry® 11
`green) and clear film-coat (Opadry® clear),'carnauba wax, and printed with Opaoode® black ink.
`
`
`
`M
`
`
`
`Long term’stability data‘(three batches, for each strength) are provided for the 30 mg and the 90 mg
`tablets. The batches were manufactured at the designated commercial manufacturing site, and
`their scale ranged from pilot to commercial scale. All stability results met the specifications with
`no significant trend observed for chemical assay and drug dissolution (see Chemistry Assessment
`for details). ‘
`A
`‘
`'
`
`Based on the data submitted,
`the recommended expiry period for the drug product is 24 months for the bottle configuration ~_
`
`- when stored at controlled room temperature, 25°C
`
` w
`
`: (excursions permitted 15-30°C).
`
`The clinical studies were conducted using ~ (Phase 1 and early Phase 2), and bioequivalent
`tablets (Phase 2’ and Phase 3). With the exception of a N ’ the proposed to-be-
`
`Page 7 of 96
`
`

`

`
`
`gmmsmv REVIEW
`
`Chemistry Assessment Section
`
`marketed formulation is identical to the product used in Phase 3 pivotal studies for secondary
`hyperparathyroidism. The “has been shown not to-impact the in—yitro dissolution and
`stability profiles of the finished drug product.
`
`
`
`I
`
`5:1
`
`2) Drug Substance
`
`Cinacalcet hydrochloride is the recommended International Nonproprietary Name (INN) and the
`United States Adopted Name (USAN) for the drug substance. Cinacalcet hydrochloride is a
`calcimimetic agent. It acts as an allosteric modulator of the calcium-sensing'receptor on the
`parathyroid cell surface.
`-
`‘
`
`
`Cinacalcet hydrochloride is a secondary amine with a pKa of -— It is a white to off-white, non-
`crystalline powder with a melting range ofN
`crystallineW temperature. It is slightly soluble in water,
`
`resulting in a
`‘ (25°C). It is also slightly soluble in
`..—’-- Cinacalcet hydrochloride is freely soluble in methanol, ethanol,m
`
`
`
`Mflm
`
`
`
`
`The molecule of Cinacalcet hydrochloride has one ‘chiral center, and Cinacalcet is the R-
`
`enantiomer. Pharmacological studies have shown that the R—enantiomer is much more potent than
`the L
`'
`.
`-
`'
`‘
`'
`
`B. Description of How the Drug Product is Intended to be Used
`
`Note: The following description is based on the revised draft label submitted by Amgen on Feb. 20, 2004s
`
`SENSIPARTM tablets are supplied in 30, 60, and 90 mg strengths. SENSIPARTM tablets should be
`taken whole and should not be divided. They should be taken with food or shortly after a meal.
`SENSIPART" dosage must be individualized. Below is dose recommendation for each group of
`patients:
`
`secondary Hwemarathyroidrlsm in Patients with Chronic Kidney Disease
`The recommended starting oral dose of SensiparTM is 30 mg once daily. Serum calcium and serum
`phosphorus should be measured within 1 week and iPTH should be measured 1 to 4 weeks after
`initiation or dose adjustment of Sensipar’“. SensiparWI should be titrated every 2 to 4 weeks
`through sequential doses of 60, 90, 120 and 180 mg once daily to achieve a range consistent with
`the NKF—K/DOQI recommended target for iPTH;
`
`Page 8 of 96
`
`

`

`
`CHEMISTRY REVIEW, —
`
`Chemistry Assessment Section
`
`CKD patients undergoing dialysis: 150-300 pg/mL
`W
`
`SensiparTM can be used alone or in combination with vitamin D sterols; phosphate binders '-
`W During dose titration, serum calcium
`
`levels should be monitored fiequenfly and if serum
`‘
`_
`fl
`.
`_
`m \
`
`Parathyroid Carcinoma
`The recommended starting oral dose of SensiparTMIS 30 mg twice daily.
`The dosage of Sensipar"'M should be titrated every 2 to 4 weeks through sequential doses of 30 mg .
`twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as
`necessary to normalize serum calcium levels.
`
`Special Populations
`Geriatric patients: Age does not alter the pharmacokinetics of Sensiparm; no dosage adjustment
`is required for geriatric patients.
`
`Patients with renal impairment: Renal impairment does not alter the pharmacokinetics of
`Sensipar’"; no dosage adjustment is necessary for renal impairment.
`
`Patients with hepatic impairment..—————_————-—_._,__——-————-———~-
`
`" '..-24-and42fold,
`respectively. In patients with moderate - severe hepatic impairment, PTH and serum calcium
`concentrations should be closely monitored throughout treatment with SensiparTM.
`
`C. Basis for Approvability or Not-Approval Recommendation
`
`NDA 21-688 is recommended for approval (pending Office of Compliance’s recommendation
`regarding cGMP status for the manufacturing site of drug substance) based on the following:
`
`Formulation comparability ofpivotal batches to the proposed to-be—marketed drug product
`' 0'
`0 Manufacturing process comparability ofpivotal batches to the proposed to-be-marketed drug
`product
`i O Validated stability-indicating assay method to support lot release and stability monitoring of
`drug product
`0 Adequate stability package to support the recommended expiry period for drug product
`i O Adequate specifications/controls for drug substance and drug product
`
`III.
`
`Administrative
`
`A. Reviewer’s Signature "
`
`B. Endorsement Block: in DFS
`
`C. CC Block: in DFS
`
`Shulin Ding, Ph.D.
`
`Page 9 of 96
`
`

`

`_
`'
`
`_
`=
`
`‘
`
`
`
`, e40 ’
`‘
` <65 page(s) have been _ ~_
`removed because it _
`‘V
`?
`» Teontains trade secret f
`_
`and/or confidential
`information that18 not .
`disClOsable.
`
`*
`
`'
`
`

`

`
`
`This is a representationof an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`
`Shulin Ding
`2/25/04 02:39:03 PM
`CHEMIST
`
`Please concur. Action package to be sent tomorrow.
`
`Mamta Gautam—Basak
`
`2/25/04 02:59:55 PM
`CHEMIST
`Concur
`
`

`

`Page 1 of 3
`
`ESTABLISHMENT EVALUATION REQUEST
`
`SUMMARY REPORT
`
`Application
`
`: NDA 21688/000
`
`\Sponsor:
`
`AMGEN
`
`Org Code
`
`: 510
`
`Priority
`
`:'1P
`
`1840 DEHAVILLAND DR
`
`THOUSAND OAKS, CA
`
`913201789
`
`Stamp Date
`
`: 08-SEP-2003 ‘
`
`Brand Name :
`
`SENSIPAR(CINACALCET HCL)
`
`PDUFA Date
`
`: 08dMAR-2004
`
`'
`
`30/60/9OMG TABS
`
`Action Goal
`
`:
`
`_
`
`, Estab. Name:
`
`District Goal: 08-JAN—2004
`
`Generic Name:
`
`-CINACALCET HCL-
`
`Dosage Form:
`
`(TABLET)
`
`Strength
`
`:
`
`30, 60, AND 90 MG
`
`.FDA Contacts:
`
`D. HEDIN
`
`Project Manager
`
`(RFD-510)
`
`301-827—6392
`
`S. DING
`
`Review Chemist
`
`(RFD-510)
`
`301-827—6385
`
`M. GAUTAM BASAK
`
`Team Leader
`
`(HFD—SlO)
`
`301-827-9084
`
`Overall Recommehdation:
`
`ACCEPTABLE on 26-FEB-2004by S. ADAMS (HFD—322) 301—827-9051
`
`Establishment
`
`:
`
`'
`
`FEI
`
`m m
`
`I'DMF No:
`
`'
`
`.
`
`AADA:
`
`ResponsibilitieS:
`
`_e_;.———-——-—~——————______.____
`
`Profile
`
`:
`
`CTL
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`0C RECOMMENDATION‘
`
`Milestone Date:
`
`13-JAN-04
`
`Decision
`
`’
`
`Reason
`
`:
`
`:
`
`ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`
`

`

`Establishment
`
`:
`
`CFN : 2026154
`
`FEI
`
`: 2026154
`
`AMGEN INC
`
`ONE AMGEN CENTER DRIVE.
`
`THOUSAND OAKS, CA 91362
`
`DMF No:
`
`‘ AADAz’
`
`Responsibilities:
`
`FINISHED DOSAGE STABILITY TESTER -
`
`Profile
`
`:
`
`CTL
`
`,OAI Status: ,
`
`NONE
`
`Last Milestone:
`
`OC RECOMMENDATION
`
`'
`
`‘
`
`Milestone Date:'
`
`l9—DEC-O3
`
`Decision
`
`Reason »
`
`:
`
`’:
`
`ACCEPTABLE
`
`-
`
`DISTRICT RECOMMENDATION
`
`Establishment:
`
`: m FEI
`
`: ,M
`
`.fl
`
`C.._.—————-—
`
`DMF NO:
`
`.
`
`‘
`
`'
`
`‘
`
`AADA:
`
`Responsibilities:
`
`_._..——————————-—.———-———-
`
`

`

`ESTABLISHMENT_EVALUATION REQUEST
`
`SUMMARY REPORT
`
`Profile
`
`CTL
`
`0A1 Status:
`
`NONE
`
`aujs— 9 v4.
`
`Last Milestone:
`
`OC RECOMMENDATION
`
`Milestone Date:
`
`25-SEP-03
`
`Decision
`
`Reason
`
`ACCEPTABLE
`
`BASED ON PROFILE
`
`‘Establishment
`
`DMF Nb:
`
`AADA:
`
`Responsibilities:
`
`3Profile
`
`CTL
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`OC RECOMMENDATION
`
`Milestone Date:
`
`27-OCTr03
`
`’IDeoision
`
`Reason
`
`ACCEPTABLE
`DISTRICT RECOMMENDATION
`
`Establishment
`
`DMF NO:
`
`AADA:
`
`Responsibilities:
`
`Profile
`
`TCM
`
`OAI Status:
`
`NONE
`
`Last Milestone;
`
`OC RECOMMENDATION
`
`Milestone Date:
`
`lS-OCT-03
`
`Decision
`
`ACCEPTABLE
`
`

`

`Reason
`
`.‘.-\‘:
`
`.
`
`.. DISTRICT RECOMMENDATION
`
`Establishment»:
`
`~_flé_4_q_a;_______;_______;_‘___‘._;
`
`We
`
`DMF NO:
`
`AADA:
`
`Responsibilities :
`
`__,.__.——————————————-——_
`
`Profile
`
`:
`
`CTL
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`0C RECOMMENDATION.
`
`Milestone Date:
`
`‘29-SEP-03
`
`Decision
`
`Reason
`
`:
`
`:'
`
`‘ ACCEPTABLE
`
`BASED ON FILE REVIEW
`
`gEstablishment
`
`: W
`
`~DMF NO:
`
`V
`
`‘
`
`AADA:
`
`

`

`”VESTABLISHMENT EVALUATION REQUEST "
`
`SUMMARY REPORT
`
`Responsibilities:
`
`Profile
`
`' CTL
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`OC RECOMMENDATION
`
`Milestone Date:>
`
`Decision
`
`Reason
`
`25-SEP-03
`
`.ACCEPTABLE
`
`BASED ON RROFILE
`
`Establishment
`
`DMF No:
`
`'AADA:
`
`Responsibilities:
`
`Profile
`
`CSN
`
`OAI Status:
`
`NONE
`
`Last Milestone:
`
`0C RECOMMENDATION
`
`‘Milestone Date:
`
`Decision
`
`Reason
`
`26-FEB-04
`
`'ACCEPTABLE
`
`DISTRICT RECOMMENDATION
`
`

`

`MEMORANDUM
`
`’
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`PUBLIC HEALTH SERVICE
`FOOD AND DRUG ADMINISTRATION
`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`_
`
`. DATE:
`
`_
`A TO:
`FROM:
`
`,
`
`‘
`
`March 3, 2004
`
`-
`
`Randy Hedin, Project Manager (HFD-S10)
`Shulin‘ Ding,~Chemistry Reviewer (HFD—820 co-located with
`HFD~510) ‘
`
`SUBJECT:
`
`-
`
`NDA 21-688: Review of the Modified Container Label and
`Establishment Inspection Results
`
`Container Label Review
`
`Background
`
`Modified container label items are provided by the applicant for review as a response to the
`agency’s recommendation on the proposed container label. The recommendation was e-mailed
`to the applicant by the project manager on February 13, 2004. Specifically, the agency requested
`the applicant to follow the standard format (SensiparTM (cinacalcet HCl) Tablets) for the
`trademark printed on all labeling (carton, bottle and packaging insert). The agency also
`requested the applicant to further differentiate different strengths of tablets through color
`difference on the container label.
`‘
`-
`
`,
`
`Reviewer’s evaluation ‘
`
`The applicant has complied with the agency’s requests. The trademark of the modified container ,
`label conforms to the standard format, and color differentiation among different strengths has
`been enhanced through a significant adjustment in the shade of the proposed colors. The
`modified container label items submitted through a letter dated Feb. 26, 2004, are acceptable.
`
`Establishment Evaluation
`
`Establishment inspection was completed after the signing-off the primary chemistry review of
`the'NDA. The overall recommendation from the Office of Compliance is, therefore, not in the
`primary review. EER (Establishment Evaluation report) has been issued since then. Per
`Establishment Evaluation Summary Report dated February 27, 2004,. the overall
`recommendation form the Office of Compliance is acceptable.
`
`

`

`lI
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic Signature.
`
`/S/
`
`-
`Shulin Ding
`3/3/04 01:40:42 PM
`CHEMIST
`
`Mamta Gautam— Basak
`
`3/3/04 02: 01: 58 PM
`CHEMIST
`' Concur
`
`