CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`202788Orig1s000
`
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`
`
`
`

`

`Product Quality Microbiology Review
`
`7 SEPTEMBER 2011
`
`
`
`NDA: 202788
`
`Drug Product Name
`Proprietary: N/A
`Non-proprietary: Fentanyl Sublingual Spray
`
`
`Review Number: 1
`
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`4 March 2011
`4 March 2011
`18 April 2011
`5 August 2011
`5 August 2011
`N/A
`
`Assigned to Reviewer
`21 April 2011
`N/A
`
`
`
`Submission History (for amendments only): N/A
`
`Applicant/Sponsor
`Name: Insys Therapeutics, Inc.
`Address: 10220 S. 51st Street, Suite 2, Phoenix, AZ 85044
`Representative: Lauren H. Wind, MPH, Senior Consultant (The
`Weinberg Group Inc.)
`Telephone: 202-730-4101
`
`
`Name of Reviewer: Bryan S. Riley, Ph.D.
`
`Conclusion: Recommended for Approval
`
`
`Reference ID: 3011338
`
`

`

`NDA 202788 (Fentanyl Sublingual Spray)
`
`Microbiology Review #1
`
`Product Quality Microbiology Data Sheet
`
`A.
`
`1.
`
`2.
`
`5.
`
`6.
`
`TYPE OF SUBMISSION: 505(b)(2) NDA
`
`SUBMISSION PROVIDES FOR: A sublingual drug product
`
`MANUFACTURING SITE:
`
`"’“"
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`M“) solution in a glass vial with rubber
`stopper, in a Single-dose sublingual spray apparatus, 100, 200, 400, 600,
`and 800 mcg/dose.
`
`METHOD(S) OF STERILIZATION: N/A
`
`PHARMACOLOGICAL CATEGORY: Opioid analgesic
`
`SUPPORTING/RELATED DOCUMENTS: N/A
`
`REMARKS: This was an eCTD submission. The following IR was sent to the
`applicant on 1 August 2011 — “Provide descn'ptions of the test methods used for
`microbial limits. Also provide a summary of the microbiological method
`suitability testing with the drug product.” The response to the [R was provided in
`an amendment dated 5 August 201 l. The amendment was reviewed in section P5
`of this review.
`
`filename: N202788R1.doc
`
`Reference ID: 301 1338
`
`Page 2 of 7
`
`

`

`
`
`
`Microbiology Review #1
`
`
`NDA 202788 (Fentanyl Sublingual Spray)
`
`Executive Summary
`
`
`Recommendations
`
`A.
`
`I.
`
`II.
`
`
`Recommendation on Approvability – This submission is
`recommended for approval on the basis of product quality
`microbiology.
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable – N/A
`
`
`Summary of Microbiology Assessments
`
`
`B.
`
`A.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology –
`
`
`
`Brief Description of Microbiology Deficiencies – N/A
`
`Assessment of Risk Due to Microbiology Deficiencies – N/A
`
`
`B.
`
`C.
`
`III. Administrative
`
`
`A.
`
`
`B.
`
`
`C.
`
`Reviewer's Signature _____________________________
`Bryan S. Riley, Ph.D.
`Senior Review Microbiologist, OPS/NDMS
`
`
`
`Endorsement Block ______________________________
`Stephen E. Langille, Ph.D.
`Senior Review Microbiologist, OPS/NDMS
`
`CC Block
`N/A
`
`
`
`
`
`Reference ID: 3011338
`
`
`
`Page 3 of 7
`
`
`
`(b) (4)
`
`4 Page(s) has 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/
`----------------------------------------------------
`
`BRYAN S RILEY
`09/07/2011
`
`STEPHEN E LANGILLE
`09/07/2011
`
`Reference ID: 3011338
`
`

`

`PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`NDA Number: 202788
`Applicant: Insys Therapeutics,
`Letter Date: 4 March 2011
`Inc.
`NDA Type: 505(b)(2)
`
`Stamp Date: 4 March 2011
`
`
`
`
`
`
`
` X
`
`
`
` X
`
`
`
` X
`
`
`
` X
`
`
`
` X
`
`
`
`
`
`
`
`1
`
`Comments
`The submission is in
`the eCTD format.
`
`
`
`
`
`
`
`The drug product is a
` sublingual
`spray in a unit-dose
`container.
`studies are not
`required.
`
`
`
`
`
`
`
`
`
`
`Drug Name: Fentanyl
`Sublingual Spray
`
`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?
`
`
`
`
`
` X
`
`
`
`
`
`
`
` X
`
`
`
`
`
` X
`
`X
`
`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?
`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
`
`Additional Comments: N/A
`
`
`
`
`Bryan S. Riley, Ph.D.
`
`Senior Review Microbiologist
`
`Stephen E. Langille, Ph.D.
`Senior Review Microbiologist
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`3 May 2011
`Date
`
`Date
`
`Reference ID: 2941763
`
`(b) (4)
`
`(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/
`----------------------------------------------------
`
`BRYAN S RILEY
`05/04/2011
`
`STEPHEN E LANGILLE
`05/04/2011
`
`Reference ID: 2941763
`
`