`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`203341Orig1s000
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`

`

`Product Quality Microbiology Review
`
`11 June 2012
`
`
`
`NDA:
`
`Drug Product Name
`Proprietary:
`Non-proprietary:
`
`203-341/N-000
`
`Bosulif®
`bosutinib monohydrate
`
`1
`
`Assigned to Reviewer
`15 December 2012
`n/a
`n/a
`n/a
`
`
`Review Number:
`
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`17 November 2011
`17 November 2011
`12 December 2011
`06 March 2012
`06 March 2012
`n/a
`16 May 2012
`16 May 2012
`n/a
`31 May 2012
`31 May 2012
`n/a
`
`
`
`
`Submission History (for amendments only): N/A
`
`Applicant/Sponsor
`Name:
`
`Address:
`
`Representative:
`Telephone:
`
`Wyeth Pharmaceutical, Inc.
`(Wholly owned subsidiary of Pfizer, Inc.)
`500 Arcola Rd.
`Collegeville, PA 19426-3982
`Carl M. DeJuliis, Pharm. D.
`860-441-1693
`
`Robert J. Mello, Ph.D.
`
`The application is recommended for
`approval from microbiology product quality
`standpoint.
`
`
`Name of Reviewer:
`
`Conclusion:
`
`
`
`
`
`Reference ID: 3143967
`
`

`

`NDA 203341/N-000
`
`Microbiology Review #1
`
`Product Quality Microbiology Data Sheet
`
`TYPE OF SUBMISSION: New Drug Application
`
`SUBMISSION PROVIDES FOR: Marketing Authorization
`
`MANUFACTURING SITE:
`
`"’""
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY: Film coated tablets; oral administration; 100 mg and
`500 mg. Packaging is in 60ml HDPE bottles with a 28mm screw cap closure and
`an inner aluminum foil/
`(I'm. A single HDPE silica gel desiccant
`canister is included in each container.
`
`METHOD(S) OF STERILIZATION: N/A. The drug product is a non-sterile
`tablet.
`
`PHARMACOLOGICAL CATEGORY: Tyrosine kinase inhibitor for the
`treatment of chronic, accelerated, or blast phase Ph+ chronic myelogenous
`leukemia (CML) in patients with resistance or intolerance to prior therapy.
`
`B.
`
`C.
`
`SUPPORTING/RELATED DOCUMENTS: None
`
`REMARKS:
`
`An ONDQA chemistry filing review was performed and no microbiology issues
`were highlighted.
`The submission was provided in electronic eCTD format accessible through EDR.
`An information request was transmitted via the Division Project Manager to the
`applicant on 16 April 2012 requesting the removal of
`(mo
`and inclusion of MLT within
`
`the long term stability program at a minimum of the T=0 time point. The applicant
`responded in the 16 May 2012 and 31 May submissions. Their responses are
`reviewed within the body of this report.
`
`Filename: N203341N000R1.doc
`
`Reference ID: 3143967
`
`Page 2 of 9
`
`

`

`NDA 203341/N-000
`
`Microbiology Review #1
`
`Executive Summary
`
`1.
`
`Recommendations
`
`A.
`
`B.
`
`Recommendation on Approvability — Recommend Approval
`
`Recommendations on Phase 4 Commitments and/or Agreements, if
`Approvable — N/A
`
`Summary of Nlicrobiology Assessments
`
`A.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology —
`(m4)
`
`B.
`
`C.
`
`Brief Description of Microbiology Deficiencies — None
`
`Assessment of Risk Due to Microbiology Deficiencies — N/A
`
`Administrative
`
`A.
`
`Reviewer's Signature:
`
`B.
`
`Endorsement Block:
`
`C.
`
`CC Block
`
`N/A
`
`Robert J. Mello, Ph.D.
`
`Senior Microbiology Reviewer
`
`John W. Metcalfe, Ph.D.
`
`Senior Microbiology Reviewer
`
`6 Page(s) have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`Reference ID: 3143967
`
`Page 3 of 9
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ROBERT J MELLO
`06/12/2012
`
`JOHN W METCALFE
`06/12/2012
`I concur.
`
`Reference ID: 3143967
`
`

`

`Drug Name: BOSULIF®
`
`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?
`
`
`1
`
`X
`
`X
`
`
`
`
`
`-
`
`
`
`
`
`
`
`X
`
`X
`
`-
`
`X
`
`
`PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`Letter Date: 17 November 2011
`NDA Number: 203-341
`Applicant: Wyeth
`Pharmaceuticals, Inc.
`NDA Type: 505(b)(1)
`
`Stamp Date: 17 November 2011
`
`Comments
`Section 3.2.P.2.5, and
`Section 3.2.P.8 pages
`3-6
`
`Section 3.2.P.3.3,
`pages 1-3.
`
`No information
`submitted
`
`
`
`Not Applicable
`
`No microbial control
`specifications were
`submitted.
`No methods related to
`microbial control were
`submitted
`
`Not Applicable
`
`The Application is
`fileable but additional
`information will be
`required for a
`complete review of
`the submission.
`
`7 Has the applicant submitted the results of analytical method
`verification studies?
`
`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
`
`X
`
`-
`
`
`
`
`Additional Comments: see below.
`
`
`Robert J. Mello, Ph.D. Senior Review Microbiologist
`
`Stephen Langille, Ph.D. Senior Review Microbiologist
`
`
`
`
`
`
`
`Reference ID: 3061431
`
`
`
`
`
`
`
`
`
`Date
`
`Date
`
`

`

`NDA 203-341/N-000 Filing Memo
`
`
`
`
`DATE: 12/20/2011
`
`
`
`Product Quality Microbiology Assessment
`
`
`
`The drug product is an immediate release film coated tablet containing either 100mg or 500mg
`of bosutinib.
`
`There was no information on the environmental controls (air/surface/water) within the
`manufacturing environment. There were no specifications for microbial limits of the drug
`product, nor was there any justification for not having such a microbial limit specification. The
`following information should be requested from the Applicant:
`
`
`Please provide a release specification for microbial limits of the drug product or
`provide an acceptable justification, which would include appropriate supportive
`data, for not having such a microbial limit specification.
`
`
`
`
`[END]
`
`Reference ID: 3061431
`
`Page 2 of 2
`
`(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/
`----------------------------------------------------
`
`ROBERT J MELLO
`12/20/2011
`
`STEPHEN E LANGILLE
`12/20/2011
`
`Reference ID: 3061431
`
`