CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`RESEARCH
`
`APPLICA TI0N NUMBER:
`
`
`
`APPLICATION NUMBER:
`22-228
`
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`
`
`22-228
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`RESEARCH
`
`APPLICA TI0N NUMBER:
`
`
`
`APPLICATION NUMBER:
`22-228
`
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`
`
`22-228
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`Product Quality Microbiology Review
`
`17 JUNE 2009
`
`
`22-288/N-000
`
`
`NDA:
`
`Drug Product Name
`Proprietary:
`Bepreve™
`Non-proprietary:
`Bepotastine besilate
`
`ophthalmic solution.
`Drug Product Priority Classification: S.
`
`
`Review Number:
`
`Dates of Submission(s) Covered by this Review
`Letter
`Stamp
`Review Request
`12 NOV 2008
`12 NOV 2008
`17 NOV 2008
`03 JUN 2009
`03 JUN 2009
`N/A
`
`1.
`
`Assigned to
`Reviewer
`20 NOV 2008
`N/A
`
`ISTA Pharmaceuticals®, Inc.
`15295 Alton Parkway
`Irvine, CA 92618
`Paul Nowacki
`949-789-3109
`
`John W. Metcalfe, Ph.D.
`
`Recommend approval.
`
`
`Applicant/Sponsor
`Name:
`Address:
`
`Representative:
`Telephone:
`
`
`Name of Reviewer:
`
`Conclusion:
`
`
`
`
`NDA 22-288/N-000
`
`
`
`Product Quality Microbiology Data Sheet
`
`A.
`1.
`TYPE OF SUBMISSION: Original NDA.
`
`2.
`
`Microbiology Review #1
`
`
`SUBMISSION PROVIDES FOR: A new drug product.
`
`MANUFACTURING SITE:
`
`
`
`
`
`
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`(cid:190) Solution in LDPE dropper bottle.
`(cid:190) Topical ophthalmic.
`(cid:190) 1.5%.
`
`METHOD(S) OF STERILIZATION: Sterile filtration followed by
`.
`
`PHARMACOLOGICAL CATEGORY: The drug product is indicated
`for the treatment of ocular itching associated with allergic conjunctivitis.
`
`
`SUPPORTING/RELATED DOCUMENTS: None.
`
`REMARKS:
`The NDA is submitted electronically in the CTD format.
`
`As of 13 January 2009 there is no ONDQA Initial Quality Assessment in DFS.
`
`An information request was forwarded by this reviewer to the OND project
`manager for dissemination to the applicant on 15 May 2009. Following is the
`information request:
`
`
`A sterility assurance review of NDA 22-288 is on-going. Please address the
`following comments:
`
` Section 4.2 of Process Validation Plan: 1.5% Bepotastine Besilate
`Ophthalmic Solution (Module 3.2.P.3.3) states the following:
`
`
`“A bulk solution hold study will be performed to demonstrate
`that the bulk solution can be held for a predetermined length of
`time (e.g. multiple days) and will meet chemistry and bioburden
`specifications. The hold time for the sterile filtered bulk solution
`will also be validated.”
`
`
`
`
`
`Page 2 of 17
`
`
`
` (cid:190)
`
`3.
`
`
`4.
`
`
`5.
`
`
`6.
`
`B.
`
`C.
`
`
`
`
`
`(b) (4)
`
`(b) (4)
`
`
`
`NDA 22-288/N-000
`
`
`
`
`Provide the holding times and supporting data/rationale for the bulk solution
`prior to filtration and the sterile solution prior to filling.
`
`Microbiology Review #1
`
`
`
`The applicant amended the NDA on 03 June 2009 with responses to this
`information request. The applicant responses are summarized and reviewed in
`appropriate sections of this review.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`File Name: N022288R1.doc
`
`
`
`
`
`
`Page 3 of 17
`
`
`
`(b) (4)
`
`
`
`NDA 22-288/N-000
`
`Executive Summary
`
`
`
`
`
`Microbiology Review #1
`
`
`Recommendations
`
`A.
`
`Recommendation on Approvability – NDA 22-288/N-000 is
`recommended for approval on the basis of issues pertaining to
`sterility assurance.
`
`
`B.
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable – Not applicable.
`
`
`Summary of Microbiology Assessments
`
`I.
`
`II.
`
`
`Brief Description of the Manufacturing Processes that relate to
`A.
`Product Quality Microbiology - Following compounding, the bulk drug
`solution is sterilized
`
`
`
`
`
`
`
`
`Brief Description of Microbiology Deficiencies – There are no
`microbiology deficiencies identified.
`
`Assessment of Risk Due to Microbiology Deficiencies – Not
`applicable.
`
`
`III. Administrative
`
`
`B.
`
`
`C.
`
`A.
`
`
`
`B.
`
`
`
`C.
`
`
`
`
`
`
`
`Reviewer's Signature _____________________________
`
`
`
`
`John W. Metcalfe, Ph.D.
`
`Endorsement Block_______________________________
`
`
`
`
`Stephen Langille, Ph.D.
`
`CC Block
`N/A
`
`
`
`Page 4 of 17
`
`
`
`(b) (4)
`
`13 Page(s) has been Withheld in Full following this page as B4 (CCI/TS)
`
`
`
`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`John Metcalfe
`6/17/2009 02:06:27 PM
`MICROBIOLOGIST
`
`Stephen Langille
`6/17/2009 02:07:15 PM
`MICROBIOLOGIST
`
`
`
`
`Deliverables by Mid-Cycle for Product Quality Microbiology
`
`(1)
`
`Team participation requested, submission received and assigned to Microbiology
`reviewer (by day 21).
`(2) Microbiology reviewer performs filing review and a preliminary review of draft
`labeling (by day 45).
`(3) Microbiology reviewer completes the filing checklist and identifies filing issues
`and/or other major deficiencies. Checklist is signed off in DFS by secondary
`reviewer/Team Leader (by day 45).
`(4) When potential fileability issues or serious deficiencies are identified, the
`Microbiology reviewer attends the filing meeting and presents the filing issues
`and/or deficiencies to be communicated to the applicant.
`First review completed prior to mid-cycle meeting with secondary reviewer’s
`concurrence. Information request sent soon after completion of the first review
`(by month 5).
`(6) Microbiology reviewer attends appropriate team meetings and the mid-cycle
`meeting and presents findings accordingly.
`Reviewer and secondary reviewer/Team Leader communicate frequently
`regarding the review status, submission data and deficiencies.
`
`(5)
`
`(7)
`
`
`
`Drug Name: Bepreve™
`Bepotastine besilate
`ophthalmic solution
`
`The following are necessary to initiate a review of the NDA application:
`Content Parameter
`Yes No
`
`
`Is the product quality microbiology information described
`X
`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?
`8 Has the applicant submitted all special/critical studies/data
`requested during pre-submission meetings and/or
`discussions?
`
`
`1
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`X
`
`X
`
`X
`
`X
`
`X
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`NDA Number: 22-288
`Letter Date: 12 NOV 2008
`Applicant:
`Ista Pharmaceuticals®, Inc.
`NDA Type: Standard
`
`Stamp Date: 12 NOV 2008
`
`Comments
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`I am unaware of any
`pre-submission special
`studies/data that were
`requested.
`
`
`X
`
`
`
`Is this NDA fileable? If not, then describe why.
`
`9
`
`Additional Comments: None.
`
`
`
`
`
`Reviewing Microbiologist
`
`Stephen Langille, Ph.D.
`
`
`
`
`
`Microbiology Secondary Reviewer/Team Leader
`
`
`
`
`
`
`John W. Metcalfe, Ph.D.
`
`
`
`
`
`09 DEC 2008
`Date
`
`Date
`
`
`
`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`John Metcalfe
`12/17/2008 07:44:01 AM
`MICROBIOLOGIST
`
`Stephen Langille
`12/18/2008 09:28:00 AM
`MICROBIOLOGIST
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
