CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`206276Orig1s000
`
`MICROBIOLOGY / VIROLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`

`

`Product Quality Microbiology Review
`
`31 December 2014
`
`NDA:
`
`206276
`
`Drug Product Name
`Proprietary:
`Non-proprietary:
`
`PAZEO
`Olopatadine Hydrochloride Ophthalmic Solution,
`0.77%
`
`Review Number:
`
`1
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`30 July 2014
`30 July 2014
`12 August 2014
`5 December 2014
`5 December 2014
`N/A
`17 December 2014
`17 December 2014
`N/A
`
`Assigned to Reviewer
`21 August 2014
`N/A
`N/A
`
`Submission History (for 2nd Reviews or higher): Not applicable
`Applicant/Sponsor
`Name:
`Address:
`
`Alcon
`601 South Freeway
`Fort Worth, TX 76134-2099
`Naj Sharif, Ph.D.
`817-568-6494
`
`Representative:
`Telephone:
`
`Name of Reviewer:
`
`Stephen E. Langille, Ph.D.
`
`Conclusion:
`
`Recommended for Approval
`
`Reference ID: 3682589
`
`

`

`NDA 206276
`
`Microbiology Review # 1
`
`Product Quality Microbiology Data Sheet
`
`A.
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
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`6.
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`TYPE OF SUBMISSION: Original Submission – Priority Review
`
`SUBMISSION PROVIDES FOR:
` processing information for
`two manufacturing sites and multiple contract manufacturing sterilization
`sites for container closure components.
`
`MANUFACTURING SITES:
`
`Alcon Research, Ltd.
`6201 South Freeway
`Fort Worth, Texas 76134
`Drug Establishment Registration No.
`1610287
`
`and
`
`sa Alcon-Couvreur nv
`Rijksweg 14
`B-2870 Puurs
`Belgium
`Drug Establishment Registration No.
`3002037047
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`
` Sterile Ophthalmic Solution
` Topical
`0.77%
`
`
`METHOD(S) OF STERILIZATION:
`
` processing
`
`PHARMACOLOGICAL CATEGORY: Treatment of itching associated
`with allergic conjunctivitis
`
`B.
`
`C.
`
`SUPPORTING/RELATED DOCUMENTS: Not applicable
`
`REMARKS: The application was provided in eCTD format.
`
`filename: N206276r1.doc
`
`Reference ID: 3682589
`
`Page 2 of 27
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`(b) (4)
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`(b) (4)
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`

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`NDA 206276
`
`Microbiology Review # 1
`
`Executive Summary
`
`I.
`
`Recommendations
`
`A.
`
`B.
`
`Recommendation on Approvability - Recommended for
`Approval
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable -
`Not applicable
`
`II.
`
`Summary of Microbiology Assessments
`
`A.
`
`B.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology -
`The drug product will be
`bottles. The HPMC solution will be
` olopatadine solution.
`
`filled into 4 ml LDPE dropper
`
`
`
`
`Brief Description of Microbiology Deficiencies -
`No deficiencies were identified based upon the information
`provided.
`
`C.
`
`Contains Potential Precedent Decision(s)-
`
`Yes
`
` No
`
`III.
`
`Product Quality Microbiology Risk Assessment
`
`A.
`Risk Factor
`
`CQA
`
`Ster.
`
`Initial Product Quality Microbiology Risk Assessment
`Additional Review
`Detect.
`Risk
`Severity
`Modifier
`Prob.
`Emphasis
`(D)
`Priority
`of
`for
`of
`based on Risk (in
`Number6
`Effect
`O(3, 4, 5)
`Occ.
`addition to normal
`(RPN)
`(S)
`(O)
`review process)
`Simulations and
`interventions conducted
`during media fills,
`Environmental
`monitoring
`
`5
`
`225
`
`10
`
`-1
`
`5
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`Reference ID: 3682589
`
`Page 3 of 27
`
`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`

`

`NDA 206276
`
`Microbiology Review # 1
`
`RPN <50 = Low Risk; RPN 50-120 = Moderate Risk; RPN >120 = High Risk
`
`Final Risk Assessment - The applicant has presented adequate
`B.
`information to mitigate risks outlined in the initial product quality microbiology
`risk assessment.
`
`IV.
`
`Administrative
`
`A.
`
`B.
`
`C.
`
`Reviewer's Signature _____________________________
`Stephen E. Langille, Ph.D.
`Senior Microbiology Reviewer
`
`Endorsement Block
`Bryan Riley, Ph.D. – Acting NDMS Team Leader
`
`CC Block
`N/A
`
`Reference ID: 3682589
`
`Page 4 of 27
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`23 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
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`(b) (4)
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`01/05/2015
`
`BRYAN S RILEY
`01/05/2015
`I concur.
`
`Reference ID: 3682589
`
`

`

`
`
`
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`PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`
`
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`
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`NDA Number: 206276
`
`
`
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`
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`Applicant: Alcon Research Ltd.
`
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`Letter Date: 30 July 2014
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`
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`Drug Name: Olopatadine
`
`
`Hydrochloride Ophthalmic Solution
`0.77%
`
`
`
`
`
`
`
`NDA Type: Original NDA
`
`
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`Stamp Date: 30 July 2014
`
`
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`es
`Y
`--_
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`The following are necessary to initiate a review of the NDA application:
`Content Parameter
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`Is the product quality microbiology information described in the
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`NDA and organized in a manner to allow substantive review to
`begin? Is it legible, indexed, and/or paginated adequately?
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`Has the applicant submitted an overall description of the
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`manufacturing processes and microbiological controls used in the
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`
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`manufacture of the drug product?
`
`
`
`X
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`
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`X -
`
`- Section P.2.5
`
`
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`
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`I SectionP.3.3
`
`
`Section P.2.5 and
`
`
`section P.5.
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`Section P.5
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`NDMS
`
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`The drug product is
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`Has the applicant submitted protocols and results of validation
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`studies concerning microbiological control processes used in the
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`manufacture of the drug product?
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` Are any study reports or published articles in a foreign language?
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`If yes, has the translated version been included in the submission
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`for review?
`
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`I I
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`
`X
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`><
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`X
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`N/A
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`N/A
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`7
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`Has the applicant submitted preservative effectiveness studies (if
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`applicable) and container-closure integrity studies?
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`Has the applicant submitted microbiological specifications for the
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`drug product and a description of the test methods?
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`Has the applicant submitted the results of analytical method
`verification studies?
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`Has the applicant submitted all special/critical studies/data
`requested during pre-submission meetings and/or discussions?
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`I t
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`f sterile, are extended post-constitution and/or post-dilution hold
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`imes in the draft labeling supported by microbiological data?
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`Is this NDA fileable? If not, then describe why.
`
`
`
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`.-requested from the
`
`
`I—
`
`
`
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`Additional Comments: None.
`
`
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`
`
`Stephen E. Langille, Ph.D.
`
`
`Senior Microbiology Reviewer
`
`
`
`John Metcalfe, PhD.
`
`
`
`
`
`Senior Microbiology Reviewer
`
`
`
`
`
`12 August 2014
`
`
`
`
`
`[2 August 2014
`
`
`
`Reference ID: 3608544
`
`
`
`Reference ID: 3705748
`Reference ID: 3705748
`
`

`

`
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`
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`
`
`
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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.
`
`
`
`
`
`
`
`STEPHEN E LANGILLE
`
`08/12/2014
`
`
`
`
`
`JOHN W METCALFE
`
`08/12/2014
`
`
`Iconcun
`
`
`
`Reference ID: 3608544
`
`
`
`Reference ID: 3705748
`Reference ID: 3705748
`
`