CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203168Orig1s000
`
`MICROBIOLOGY REVIEW(S)
`
`
`
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`
`
`
`

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`Product Quality Microbiology Review
`17 January 2013
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`
`NDA 203-168/N-000
`
`
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`
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`
`
`NDA:
`
`Drug Product Name
`Proprietary:
`
`Non-proprietary:
`
`Prolensa™ 0.07%
`bromfenac ophthalmic solution
`
`1
`
`
`Review Number:
`
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`6 June 2012
`7 June 2012
`22 June 2012
`16 November 2012
`19 November 2012
`N/A
`19 December 2012
`19 December 2012
`N/A
`
`Assigned to Reviewer
`28 June 2012
`N/A
`N/A
`
`
`Submission History (for amendments only): Not applicable
`
`
`Applicant/Sponsor
`Name:
`
`
`Address:
`
`
`
`
`
`
`Representative:
`Telephone:
`
`
`ISTA Pharmaceuticals
`50 Technology
`Irvine, CA 92618
`
`Paul Nowacki
`949-789-3109
`
`Stephen E. Langille, Ph.D.
`
`Recommended for approval
`
`
`Name of Reviewer:
`
`Conclusion:
`
`
`
`
`Reference ID: 3248347
`
`

`

`NDA 203-168/N-000
`
`Microbiology Review #1
`
`Product Quality Microbiology Data Sheet
`
`A.
`
`1.
`
`2.
`
`4.
`
`5.
`
`6.
`
`TYPE OF SUBMISSION:
`
`Original submission- priority review
`
`SUBMISSION PROVIDES FOR:— information for a
`sterile topical ophthalmic drug
`product.
`
`MANUFACTURING SITE:
`
`Bausch and Lomb Pharmaceuticals,
`Inc
`
`8500 Hidden River Parkway
`Tampa, FL 33637
`Registration Number 1052807
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`
`0 Sterile solution in an LDPE
`- round bottle
`. Topical Ophthalmic
`0.07%
`
`METHOD(S) 0F STERILIZATION: -
`
`PHARMACOLOGICAL CATEGORY: Ophthalmic analgesic
`
`B.
`
`SUPPORTING/RELATED DOCUMENTS: None
`
`C.
`
`REMARKS: The submission was provided in eC'ID format. The following
`information requests were sent to the applicant on 1 November 2012 and 6
`November 2012.
`
`I. Providea 'us ' cation or
`
`
`
`2. Providea co; 0]
`
`Reference ID: 3248347
`
`Page 2 of17
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`

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`NDA 203—168/N—000
`
`Microbiology Review #1
`
`D) (4)
`
`3. Provide the raw data (plate counts)for the preservative fictiveness test
`results provided in tables J3-1, J3-2, and J3-3 located in the "Preservative
`Eflectiveness Tests and Methods " document located in section 3. 2.P. 3.5 ofthe
`application.
`
`4. Provide thefollowing information regarding endotoxin testingfor ProlensaTM
`
`a. The endotoxin limitfor the drugproduct (an endotoxin limit of
`suggested)
`b. The test method to be usedfor endotoxin testing
`c. Calculation ofthe maximum valid dilution
`d. The results ofit1hibition/erthancement testing
`e.
`Inclusion ofthe endotoxin limit and test method in the list ofdrugproduct
`specifications.
`
`«M0 is
`
`Responses to the information requests were provided on 16 November 2012 and
`19 December 2012 and have been incorporated into the body of this review.
`
`filename: N203 l68r1 .doc
`
`Reference ID: 3248347
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`Page 3 of 17
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`

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`NDA 203-168/N-000
`
`Executive Summary
`
`
`I.
`
`Recommendations
`
`
`
`
`Microbiology Review #1
`
`
`Recommendation on Approvability -
`NDA 203-168/N-000 is recommended for approval from the
`standpoint of product quality microbiology.
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable -
`Not applicable
`
`
`
`Summary of Microbiology Assessments
`
`II.
`
`A.
`
`
`
`B.
`
`A.
`
`
`
`
`B.
`
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology -
`The drug product will be
`Bausch and Lomb Tampa, FL facility.
`
` at the
`
`Brief Description of Microbiology Deficiencies -
`No product quality microbiology deficiencies were identified
`based upon the information provided.
`
`Assessment of Risk Due to Microbiology Deficiencies -
`Not applicable.
`
`
`C.
`
`
`III. Administrative
`
`A.
`
`
`
`B.
`
`
`
`C.
`
`Reviewer's Signature _____________________________
`
`
`
` Stephen E. Langille, Ph.D.
`
`
`
` Senior Microbiology Reviewer
`
`Endorsement Block _____________________________
`
`
`
` Bryan Riley, Ph.D.
`
` Senior Microbiology Reviewer
`
`
`
`
`
`CC Block
`N/A
`
`
`
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`Reference ID: 3248347
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`Page 4 of 17
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`
`
`(b) (4)
`
`13 Pages have been Withheld in Full as b4 (CCI/TS) immediately
`following this page.
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`STEPHEN E LANGILLE
`01/22/2013
`
`BRYAN S RILEY
`01/22/2013
`I concur.
`
`Reference ID: 3248347
`
`

`

` PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`NDA Number: 203168
`Applicant: Ista Pharmaceuticals Inc.
`Letter Date: 6 June 2012
`Drug Name: Prolensa™ NDA Type: Original NDA
`Stamp Date: 7 June 2012
`
`
`1
`
`Comments
`Sections P.3.3 and
`P.3.5
`
`Section P.3.5
`
`Section P.3.5
`
`Sections P.2.4 and
`P.3.5
`
`Section P.5.1
`
`AET validation was
`provided (P.5.3).
`Sterility test validation
`not provided.
`No such studies were
`requested.
`
`
`
`The following are necessary to initiate a review of the NDA application:
`Content Parameter
`Yes No
`
`Is the product quality microbiology information described
`in the NDA and organized in a manner to allow substantive
`review to begin? Is it legible, indexed, and/or paginated
`adequately?
`2 Has the applicant submitted an overall description of the
`manufacturing processes and microbiological controls used
`in the manufacture of the drug product?
`3 Has the applicant submitted protocols and results of
`validation studies concerning microbiological control
`processes used in the manufacture of the drug product?
`4 Are any study reports or published articles in a foreign
`language? If yes, has the translated version been included
`in the submission for review?
`5 Has the applicant submitted preservative effectiveness
`studies (if applicable) and container-closure integrity
`studies?
`6 Has the applicant submitted microbiological specifications
`for the drug product and a description of the test methods?
`7 Has the applicant submitted the results of analytical method
`verification studies?
`
`X
`
`X
`
`X
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`
`
`X
`
`X
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`
`
`
`
`X
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`
`
`8 Has the applicant submitted all special/critical studies/data
`requested during pre-submission meetings and/or
`discussions?
`Is this NDA fileable? If not, then describe why.
`
`9
`
`
`
`X
`
`
`
`
`
`Additional Comments: The following information request should be conveyed to the applicant:
`“Provide the results of bacteriostasis/fungistasis testing conducted to verify the USP sterility test
`for Prolensa™.”
`
`Reviewing Microbiologist
`Stephen E. Langille, Ph.D.
`Senior Microbiology Reviewer
`NDMS/OPS/CDER
`
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`29 June 2012
`
`
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`Reference ID: 3153138
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`

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`Microbiology Secondary Reviewer
`John Metcalfe, Ph.D.
`Senior Microbiology Reviewer
`NDMS/OPS/CDER
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`
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`29 June 2012
`
`Reference ID: 3153138
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`STEPHEN E LANGILLE
`07/02/2012
`
`JOHN W METCALFE
`07/02/2012
`I concur.
`
`Reference ID: 3153138
`
`