CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICATION NUMBER:
`21-920
`
`CHEMISTRY REVIEW(S)
`
`•
`
`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 1 of 12
`
`

`

`YREVIEW
`
`NDA 21-920
`
`Naproxen Sodium Capsules
`
`Banner Pharmacaps Inc.
`
`Rao Puttagunta, Ph.D.
`Branch III/Pre-Marketing Assessment Division II
`Office of New Drug Quality Assessment
`Center for Drug Evaluation and Research
`
`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 2 of 12
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`

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`Table of Contents
`
`Table of Contents ..................................................................................................... 2
`
`Chemistry Review Data Sheet ................................................................................. 4
`
`The Executive Summary ......................................................................................... 8
`
`I. Recommendations ............................................................................... · ................................ 8
`
`A. Recommendation and Conclusion on Approvability ................................................ 8
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements,
`and/or Risk Management Steps, if Approvable ........................................................ 8
`
`II. Summary of Chemistry Assessments ............................................................................... 8
`
`A. Description of the Drug Product(s) and Drug Substance(s) .................................... 8
`
`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 Assessment .......................................................................................... 10
`
`I. DRUG SUBSTANCE ........................................................................................................ 10
`
`1. Description & Characterization
`
`....................... .-.................................................... 10
`
`a. Description ........................................................................................................................................................ 10
`
`b. Characterization I Proof of Structure ............................................................................................................ 10
`
`2. Manufacturer
`
`.......................................................................................................... 10
`
`3. Synthesis I Method of Manufacture
`
`...................................................................... 10
`
`4. Process Controls
`
`...................................................................................................... 10
`
`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 3 of 12
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`CHEMISTRY REVIEW .
`
`5. Reference Standard
`
`..........................................................................•..................... 11
`
`6. Regulatory Specifications I Analytical Methods
`
`................................................. 11
`
`7. Container/Closure System for Drug Substance Storage
`
`..................................... 12
`
`8. Drug Substance Stability
`
`....................................................................................... 12
`
`II. DRUG PRODUCT ........................................................................................................... 12
`
`1. Components/Composition
`
`.................................................•.................................... 12
`
`2. Specifications & Methods for Drug Product Ingredients
`
`................................... 13
`
`a. Active Ingredient(s) .......................................................................................................................................... 13
`
`b. Inactive Ingredients ......................................................................................................................................... 13
`
`3. Manufacturer(s)
`
`..................................................................................................... 13
`
`4. Methods of Manufacturing and Packaging
`
`.......................................................... 14
`
`a. Production Operations ..................................................................................................................................... 14
`
`b. In-Process Controls & Tests ............................................................................................................................ 14
`
`c. Reprocessing Operations ................................................................................................................................. 15
`
`5. Regulatory Specifications a~d Methods for Drug Product
`
`................................ 15
`
`a. Sampling Procedures ....................................................................................................................................... 15
`
`b. Regulatory Specifications and Methods ......................................................................................................... 15
`
`6. Container/Closure System
`
`..................................................................................... 26
`
`7. Microbiology
`
`........................................................................................................... 27
`
`8. Drug Product Stability
`
`.......................................................................................... 27
`
`III.INVESTIGATIONAL FORMULATIONS ................................................................... 29
`
`IV. ENVIRONMENTAL ASSESSMENT ............................................................................ 29
`
`V. METHODS VALIDATION ............................................................................................ 30
`
`VI. LABELING ...................................................................................................................... 30
`
`VII. ESTABLISHMENT INSPECTION ......................................................................... 30
`
`VIII.
`
`DRAFT DEFICIENCY LETTER ................................................................ 31
`
`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 4 of 12
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`CHEMISTRY REVIEW
`
`Chemistry Review Data Sheet
`
`Chemistry Review Data Sheet
`
`1. NDA #: 21-920
`
`2. REVIEW#: I
`
`3. REVIEW DATE: 12-JAN-2006
`
`4. REVIEWER: Rao Puttagunta, Ph.D.
`
`5. PREVIOUS DOCUMENTS: N/A
`
`6. SUBMISSION(S) BEING REVIEWED:
`
`Submission(s) Reviewed
`Original
`Amendment (BC)
`Amendment (BC)
`Amendment (BC)
`Amendment (BC)
`
`Document Date
`15-APR-2005
`29-JUL-2005
`14-0CT-2005
`04-JAN-2006
`05-JAN-2006
`
`· 7. NAME & ADDRESS OF APPLICANT:
`
`Name:
`Address:
`
`Banner Pharmacaps Inc.
`4125 Premier Drive
`High Point, NC 27265
`
`Representative: Shelly K. Meachum
`Director, Regulatory Affairs
`336-812-8700 x 3312
`
`Telephone:
`
`8. DRUG PRODUCT NAME/CODE/TYPE:
`
`a) Proprietary Name: N/A
`b) Non-Proprietary Name (USAN): Naproxen Sodium Capsules
`c) Code Name/# (ONDC only): N/A
`d) Chern. Type/Submission Priority (ONDC only):
`• Chern. Type: 3
`• Submission Priority: S
`
`Page 4 of31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 5 of 12
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`Chemistry Review Data Sheet
`
`9. LEGAL BASIS FOR SUBMISSION: 505 (b)(2)
`RLD: Aleve® (naproxen sodium) Tablets , 220 mg, Bayer Healthcare, NDA 20-204
`
`10. PHARMACOL. CATEGORY: Analgesic, Anti-inflammatory and Anti-pyretic
`
`11. DOSAGE FORM:
`
`Capsule, Liquid Filled
`
`12. STRENGTH/POTENCY: 220 mg (naproxen sodium)/capsule
`
`13. ROUTE OF ADMINISTRATION: Oral
`
`14. Rx/OTC DISPENSED:
`
`Rx
`
`X OTC
`
`15. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM):
`
`__ SPOTS product- Form Completed
`
`X Not a SPOTS product
`
`16. CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR •
`FORMULA, MOLECULAR WEIGHT:
`
`ON a
`
`0
`
`(-)-6-methoxy-a-methyl-2-naphthaleneacetic acid, sodium salt, C 14H 13Na03, Mol. Wt. 252.24
`
`Appears This Way
`On Original
`
`Page 5 of 31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 6 of 12
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`RiEVlEW'',,,,' '
`
`Chemistry Review Data Sheet
`
`17. RELATED/SUPPORTING DOCUMENTS:
`
`A.DMFs:
`
`DMF# TYPE
`
`HOLDER
`
`11940
`
`II
`
`14194
`
`IV
`- --- -
`(-· .--,
`
`Albemarle
`Corp.
`Banner
`Pharmacaps
`
`ITEM
`REFERENCED
`
`Naproxen Sodium
`
`Gel Mass
`
`I
`
`I
`
`(
`
`3
`
`3
`
`4
`
`4
`
`4
`
`4
`
`I
`
`f
`
`'-'
`
`I
`I
`
`4
`
`I
`I
`
`4
`
`I 4
`
`CODE 1 STATUS2
`
`DATE
`REVIEW
`COMPLETED
`---
`
`---
`
`---
`
`---
`
`---
`
`---
`
`---
`
`---
`
`---
`
`COMMENTS
`
`---
`
`---
`
`Complies with 21
`CFR § 177. 1520
`Complies with 21
`CFR §177.1520
`
`Complies with 21
`CFR §177.1210
`
`Complies with 21
`CFR §177.1520
`
`Complies with 21
`CFR § 177.1520
`Complies with 21
`CFR § 177.1520,
`178.2010 &
`178.3297
`Complies with 21
`CFR § 177.1520
`
`' Adequate
`
`Adequate
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`N/A
`
`DMFs continued:
`
`1 Action codes for DMF Table:
`
`I- DMF Reviewed.
`Other codes indicate why the DMF was not reviewed, as follows:
`2 -Type I 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")
`
`Page 6 of 3I
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 7 of 12
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`CHEMISTRY REVIEW
`
`Chemistry Review Data Sheet
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`2 Adequate, Inadequate, or N/ A (There is enough data in the application, therefore the
`DMF did not need to be reviewed)
`
`B. Other Documents: N/ A
`
`DOCUMENT
`IND
`
`APPLICATION NUMBER
`71,161
`
`DESCRIPTION
`Naproxen sodium capsules, 220 mg
`
`18. STATUS:
`
`CONSULTS/ CMC
`RELATED
`REVIEWS
`Biometrics
`EES
`Pharm/Tox
`Biopharm
`LNC
`Methods Validation
`OPDRA
`EA
`Microbiology
`
`RECOMMENDATION
`
`DATE
`
`REVIEWER
`
`6/28/05
`
`J. D Ambrogio
`
`N/A
`Acceptable
`N/A
`N/A
`N/A
`N/ A per new ONDC policy
`N/A
`Categorical Exclusion
`N/A
`
`Appears This Way
`On Original
`
`Page 7 of31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 8 of 12
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`CHEMISTRY REVIEW
`
`Chemistry Assessment Section
`
`The Chemistry Review for NDA 21-920
`
`The Executive Summary
`
`I. Recommendations
`
`A. Recommendation and Conclusion on Approvability
`
`From the chemistry standpoint this NDA is recommended for approval.
`
`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements, and/or
`Risk Management Steps, if Approvable
`
`NIA
`
`II. Summary of Chemistry Assessments
`
`A. Description of the Drug Product(s) and Drug Substance(s)
`
`1. Drug Substance
`
`Naproxen sodium is manufactured by Albemarle Corporation, Orangeburg, SC. The
`CMC information naproxen sodium was referenced to DMF 11940. The DMF ha:s been
`recently reviewed and found to be adequate.
`
`2. Drug Product:
`
`The Naproxen sodium capsules contain 220 mg of naproxen sodium (200 mg of
`naproxen) per capsule. These liquid filled dark green soft gelatin capsules contain
`naproxen sodium solubilized in a medium containing polyethylene glycol, propylene
`glycol, lactic acid, and povidone. The reference listed drug Aleve® tablets contain 220
`mg of naproxen sodium.
`
`The drug product is packaged in -
`
`· bottles with a child-resistant cap.
`
`B. Description of How the Drug Product is Intended to be Used
`
`The naproxen sodium capsules are orally administered for temporary relief of minor
`aches and pains due to: headache, backache, muscular aches, common cold, minor pain
`of arthritis, toothache, and menstrual cramps; and temporary reduction of fever. The
`naproxen sodium capsules are supplied in bottles of 15 and 200 counts. Each capsule
`contains naproxen sodium 220 mg (equivalent of naproxen 200 mg). The recommended
`dosing schedule is I capsule every 8 to 12 hours and the maximum daily dose is 3
`capsules.
`
`Page 8 of31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 9 of 12
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`>:'CHEMISTRY REVIEW
`
`Chemistry Assessment Section
`
`Recommended storage conditions: 20-25°C (68-77°F).
`
`The submitted drug product stability data include 18 months of stability data at
`25°C/60%RH and for 12 months af30°C/65%RH. The applicant proposed an expiration
`dating period of 24 months.
`
`C. Basis for Approvability or Not-Approval Recommendation
`
`The CMC information of the drug substance naproxen sodium was referenced to the
`DMF 11940. This DMF has been recently reviewed and found to be adequate. Since the
`drug substance is a compendia! item it is tested according to the USP specification and
`some additional tests such as residual solvents.
`
`All ingredients in the drug product are ofUSP/NF grade except for the sorbitol --. .
`solution. The composition of the drug product is not a safety concern.
`
`Appropriate in-process, release and stability acceptance criteria have been established
`for the drug product to ensure consistency in quality. The packaging materials were
`found adequate. The drug product specification was considered adequate.
`
`I
`
`The submitted drug product stability data for 18 months conform to the established
`acceptance criteria. The submitted stability data and the statistical analysis were
`considered adequate to support the proposed 24-nionth expiration dating period.
`
`·
`
`The proposed dissolution acceptance criterion of Q = ----. m 45 minutes is acceptable.
`
`The NDA 21-920 is recommended for approval based on the submitted CMC
`information.
`
`· III. Administrative
`
`A. Reviewer's Signature
`
`N/A
`B. Endorsement Block
`
`N/A
`
`C. CC Block
`
`N/A
`
`Appears This Way
`On Original
`
`Page 9 of31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 10 of 12
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`2L Page(s) Withheld
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`/
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`Trade Secret I Confidential
`
`__ Draft Labeling
`
`- -
`
`Deliberative Process
`
`Withheld Track Number: Chemistry-_.__,A_
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 11 of 12
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`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`/s/
`
`Rao Puttagunta
`2/16/2006 07:49:27 AM
`CHEMIST
`
`Moo-Jhong Rhee
`2/16/2006 09:09:46 AM
`CHEMIST
`Chief, Branch III
`
`Appears This 'Nay
`On Original
`
`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 12 of 12
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