`RESEARCH
`
`APPLICATION NUMBER:
`21-920
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`CHEMISTRY REVIEW(S)
`
`•
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 1 of 12
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`YREVIEW
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`NDA 21-920
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`Naproxen Sodium Capsules
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`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
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 2 of 12
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`Table of Contents
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`Table of Contents ..................................................................................................... 2
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`Chemistry Review Data Sheet ................................................................................. 4
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`The Executive Summary ......................................................................................... 8
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`I. Recommendations ............................................................................... · ................................ 8
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`A. Recommendation and Conclusion on Approvability ................................................ 8
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`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements,
`and/or Risk Management Steps, if Approvable ........................................................ 8
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`II. Summary of Chemistry Assessments ............................................................................... 8
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`A. Description of the Drug Product(s) and Drug Substance(s) .................................... 8
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`B. Description of How the Drug Product is Intended to be Used ................................. 8
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`C. Basis for Approvability or Not-Approval Recommendation ................................... 9
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`III. Administrative .................................................................................................................... 9
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`A. Reviewer's Signature ................................................................................................... 9
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`B. Endorsement Block ...................................................................................................... 9
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`C. CC Block ....................................................................................................................... 9
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`Chemistry Assessment .......................................................................................... 10
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`I. DRUG SUBSTANCE ........................................................................................................ 10
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`1. Description & Characterization
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`....................... .-.................................................... 10
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`a. Description ........................................................................................................................................................ 10
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`b. Characterization I Proof of Structure ............................................................................................................ 10
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`2. Manufacturer
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`.......................................................................................................... 10
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`3. Synthesis I Method of Manufacture
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`...................................................................... 10
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`4. Process Controls
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`...................................................................................................... 10
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 3 of 12
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`CHEMISTRY REVIEW .
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`5. Reference Standard
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`..........................................................................•..................... 11
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`6. Regulatory Specifications I Analytical Methods
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`................................................. 11
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`7. Container/Closure System for Drug Substance Storage
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`..................................... 12
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`8. Drug Substance Stability
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`....................................................................................... 12
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`II. DRUG PRODUCT ........................................................................................................... 12
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`1. Components/Composition
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`.................................................•.................................... 12
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`2. Specifications & Methods for Drug Product Ingredients
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`................................... 13
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`a. Active Ingredient(s) .......................................................................................................................................... 13
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`b. Inactive Ingredients ......................................................................................................................................... 13
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`3. Manufacturer(s)
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`..................................................................................................... 13
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`4. Methods of Manufacturing and Packaging
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`.......................................................... 14
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`a. Production Operations ..................................................................................................................................... 14
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`b. In-Process Controls & Tests ............................................................................................................................ 14
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`c. Reprocessing Operations ................................................................................................................................. 15
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`5. Regulatory Specifications a~d Methods for Drug Product
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`................................ 15
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`a. Sampling Procedures ....................................................................................................................................... 15
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`b. Regulatory Specifications and Methods ......................................................................................................... 15
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`6. Container/Closure System
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`..................................................................................... 26
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`7. Microbiology
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`........................................................................................................... 27
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`8. Drug Product Stability
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`.......................................................................................... 27
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`III.INVESTIGATIONAL FORMULATIONS ................................................................... 29
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`IV. ENVIRONMENTAL ASSESSMENT ............................................................................ 29
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`V. METHODS VALIDATION ............................................................................................ 30
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`VI. LABELING ...................................................................................................................... 30
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`VII. ESTABLISHMENT INSPECTION ......................................................................... 30
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`VIII.
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`DRAFT DEFICIENCY LETTER ................................................................ 31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 4 of 12
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`CHEMISTRY REVIEW
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`Chemistry Review Data Sheet
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`Chemistry Review Data Sheet
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`1. NDA #: 21-920
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`2. REVIEW#: I
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`3. REVIEW DATE: 12-JAN-2006
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`4. REVIEWER: Rao Puttagunta, Ph.D.
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`5. PREVIOUS DOCUMENTS: N/A
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`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
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`· 7. NAME & ADDRESS OF APPLICANT:
`
`Name:
`Address:
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`Banner Pharmacaps Inc.
`4125 Premier Drive
`High Point, NC 27265
`
`Representative: Shelly K. Meachum
`Director, Regulatory Affairs
`336-812-8700 x 3312
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`Telephone:
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`8. DRUG PRODUCT NAME/CODE/TYPE:
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`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
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`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
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`9. LEGAL BASIS FOR SUBMISSION: 505 (b)(2)
`RLD: Aleve® (naproxen sodium) Tablets , 220 mg, Bayer Healthcare, NDA 20-204
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`10. PHARMACOL. CATEGORY: Analgesic, Anti-inflammatory and Anti-pyretic
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`11. DOSAGE FORM:
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`Capsule, Liquid Filled
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`12. STRENGTH/POTENCY: 220 mg (naproxen sodium)/capsule
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`13. ROUTE OF ADMINISTRATION: Oral
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`14. Rx/OTC DISPENSED:
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`Rx
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`X OTC
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`15. SPOTS (SPECIAL PRODUCTS ON-LINE TRACKING SYSTEM):
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`_ _ SPOTS product- Form Completed
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`X Not a SPOTS product
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`16. CHEMICAL NAME, STRUCTURAL FORMULA, MOLECULAR •
`FORMULA, MOLECULAR WEIGHT:
`
`ON a
`
`0
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`(-)-6-methoxy-a-methyl-2-naphthaleneacetic acid, sodium salt, C 14H 13Na03, Mol. Wt. 252.24
`
`Appears This Way
`On Original
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`Page 5 of 31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 6 of 12
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`RiEVlEW'',,,,' '
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`Chemistry Review Data Sheet
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`17. RELATED/SUPPORTING DOCUMENTS:
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`A.DMFs:
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`DMF# TYPE
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`HOLDER
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`11940
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`II
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`14194
`
`IV
`- --- -
`(-· .--,
`
`Albemarle
`Corp.
`Banner
`Pharmacaps
`
`ITEM
`REFERENCED
`
`Naproxen Sodium
`
`Gel Mass
`
`I
`
`I
`
`(
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`3
`
`3
`
`4
`
`4
`
`4
`
`4
`
`I
`
`f
`
`'-'
`
`I
`I
`
`4
`
`I
`I
`
`4
`
`I 4
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`CODE 1 STATUS2
`
`DATE
`REVIEW
`COMPLETED
`---
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`---
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`---
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`---
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`---
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`---
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`---
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`---
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`---
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`COMMENTS
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`---
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`---
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`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
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`' Adequate
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`Adequate
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`N/A
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`N/A
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`N/A
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`N/A
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`N/A
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`N/A
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`N/A
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`DMFs continued:
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`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")
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`Page 6 of 3I
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 7 of 12
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`CHEMISTRY REVIEW
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`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)
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`B. Other Documents: N/ A
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`DOCUMENT
`IND
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`APPLICATION NUMBER
`71,161
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`DESCRIPTION
`Naproxen sodium capsules, 220 mg
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`18. STATUS:
`
`CONSULTS/ CMC
`RELATED
`REVIEWS
`Biometrics
`EES
`Pharm/Tox
`Biopharm
`LNC
`Methods Validation
`OPDRA
`EA
`Microbiology
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`RECOMMENDATION
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`DATE
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`REVIEWER
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`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
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`Page 7 of31
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 8 of 12
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`CHEMISTRY REVIEW
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`Chemistry Assessment Section
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`The Chemistry Review for NDA 21-920
`
`The Executive Summary
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`I. Recommendations
`
`A. Recommendation and Conclusion on Approvability
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`From the chemistry standpoint this NDA is recommended for approval.
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`B. Recommendation on Phase 4 (Post-Marketing) Commitments, Agreements, and/or
`Risk Management Steps, if Approvable
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`NIA
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`II. Summary of Chemistry Assessments
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`A. Description of the Drug Product(s) and Drug Substance(s)
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`1. Drug Substance
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`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.
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`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.
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`The drug product is packaged in -
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`· bottles with a child-resistant cap.
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`B. Description of How the Drug Product is Intended to be Used
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`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.
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 9 of 12
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`>:'CHEMISTRY REVIEW
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`Chemistry Assessment Section
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`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.
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`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.
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`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.
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`I
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`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.
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`·
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`The proposed dissolution acceptance criterion of Q = ----. m 45 minutes is acceptable.
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`The NDA 21-920 is recommended for approval based on the submitted CMC
`information.
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`· III. Administrative
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`A. Reviewer's Signature
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`N/A
`B. Endorsement Block
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`N/A
`
`C. CC Block
`
`N/A
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`Appears This Way
`On Original
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`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
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`_ _ Draft Labeling
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`- -
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`Deliberative Process
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`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.
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`/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
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`Petitioner Catalent Pharma Solutions
`Ex. 1028, Pg. 12 of 12
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