CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`APPLICA TI0N NUMBER:
`
`NDA 22—249
`
`MICROBIOLOGY REVIEW(S)
`
`
`RESEARCH
`
`APPLICA TI0N NUMBER:
`
`NDA 22—249
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`Product Quality Microbiology Review
`
`06 FEB 2008
`
`NBA:
`
`22-249—BC
`
`Drug Product Name .
`Proprietary:
`Non-proprietary:
`Drug Product Priority Classification:
`
`Treanda® (proposed)
`Bendamustine hydrochloride
`1P
`
`Review Number:
`
`2
`
`Dates of Submission(s) Covered by this Review
`
`Letter
`07—JAN—2008
`
`Stamp
`08-JAN-2008
`
`Review Request
`08-JAN—2008
`
`Assigned to Reviewer
`08-JAN—2008
`
`Submission History (for amendments only)
`
`Submission Date(s)
`
`Microbiology Review #
`
`Review Date(s)
`
`.
`
`19-SEP-2007
`
`15-NOV—2007
`
`1
`
`1
`
`17—DEC-2007
`
`17—DEC-2007
`
`Applicant/Sponsor
`Name:
`Address:
`
`Cephalon, Inc.
`41 Moores Road
`
`‘
`
`Frazer, PA 19355
`
`Representative:
`
`Telephone:
`E-mail:
`
`Carol S. Marchione
`Senior Director & Group Leader
`Regulatory Affairs
`610-73 8-623 7
`cmarchiochephaloncom
`
`Name of Reviewer:
`
`Anastasia G. Lolas
`
`Conclusion:
`
`Recommended for approval
`
`
`
`Microbiology Review #2
`NDA 22-249
`
`
`Product Quality Microbiology Data Sheet
`
`A.
`
`1.
`
`2.
`
`3.
`
`TYPE OF SUBMISSION: Amendment to a new drug application
`
`SUBMISSION PROVIDES FOR: Responses to microbiology questions
`identified in Microbiology Review #1
`
`MANUFACTURING SITE:
`
`Pharmachemie B.V.
`
`Swensweg 5
`2003 RN Haarlem
`The Netherlands
`
`4.
`
`‘
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`> Lyophilized powder in a 20 mL single-use glass vial
`> Intravenous infiision
`
`> 100 mg
`
`METHOD(S) OF STERILIZATION:
`
`
`
`PHARMACOLOGICAL CATEGORY: Antineoplastic agent for
`treatment of patients with chronic lymphocytic lymphoma (CLL)
`
`5.
`
`6.
`
`SUPPORTING/RELATED DOCUMENTS:
`> Microbiology Review #1 dated l7-DEC-2007
`
`REMARKS: This amendment is an electronic submission and is in response to 6
`microbiology questions and 2 comments communicated to the applicant on 17-
`DEC-2007 (see DFS).
`
`B.
`
`C.
`
`file name: N022249R2.doc
`
`R P
`
`age 2 of 9
`
`
`
`Microbiology Review #2
`NDA 22-249 I
`a“
`
`Executive Summary
`
`1.
`
`Recommendations
`
`A.
`
`B.
`
`Recommendation on Approvability — NDA 22-249 is
`recommended for approval based on product quality microbiology
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable — N/A
`
`11.
`
`Summary of Microbiology Assessments
`
`A.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology — The drug product is
`
`/ _
`
`f
`
`K
`
`B.
`
`C.
`
`Brief Description of Microbiology Deficiencies — None
`
`Assessment of Risk Due to Microbiology Deficiencies — N/A
`
`III.
`
`Administrative
`
`A.
`
`Reviewer's Signature
`Anastasia G. Lolas
`
`B.
`
`Endorsement Block
`
`Stephen E. Langille, Ph.D.
`
`C.
`-
`
`‘
`
`CC Block
`N/A
`
`M P
`
`age 3 of 9
`
`
`
`
`
`
`
`
`
`
`
` .,
`
`:Delib'eratiV-ePTOCQSS
`
`I
`
`
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Anastasia Lolas
`2/6/2008 03:46:29 PM
`MICROBIOLOGIST
`
`Stephen Langille
`2/6/2008 03:48:49 PM
`MICROBIOLOGIST
`
`
`
`Product Quality Microbiology Review
`
`17 DEC 2007
`
`NBA:
`
`'
`
`'
`
`22—249
`
`Drug Product Name
`Proprietary:
`Non-proprietary:
`Drug Product Priority Classification:
`
`Treanda® (proposed)
`Bendamustine hydrochloride
`1P
`
`Review Number:
`
`1
`
`Dates of Submission(s) Covered by this Review
`
`
`
` Letter Stamp Review Request Assigned to Reviewer
`
`
`
`
`
`19-SEP—2007
`
`20—SEP-2007
`
`01-OCT-2007
`
`01 -OCT-2007
`
`
`
`
`
`
`
`16-NOV-200715-NOV-2007 N/A N/A -
`
`
`
`Submission History (for amendments only) — N/A
`
`Applicant/Sponsor
`Name:
`Address:
`V
`
`Representative:
`
`Telephone:
`E-mail:
`
`Cephalon, Inc._
`41 Moores Road
`Frazer, PA 19355
`
`Carol S. Marchione
`Senior Director and Group Leader
`Regulatory Affairs
`610-73 8-6237
`cmarchio@cephalon.com
`
`Name of Reviewer:
`
`Anastasia G. Lolas
`
`Conclusion:
`
`Approvable pending the resolution of product
`quality microbiology deficiencies (see Section 3 of
`review)
`
`
`
`Microbiology Review #1
`NDA 22-249
`
`
`Product Quality Microbiology Data Sheet
`
`A.
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`TYPE OF SUBMISSION: New drug application
`
`SUBMISSION PROVIDES FOR: New drug product
`
`MANUFACTURING SITE:
`
`Pharmachemie B.V.
`
`Swensweg 5
`2003 RN Haarlem
`The Netherlands
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`
`> Lyophilized powder in a 20 mL single-use glass via
`> Intravenous infiisiOn
`'
`
`> 100 mg»
`
`METHOD(S) OF STERILIZATION:
`
`
`
`PHARMACOLOGICAL CATEGORY: Antineoplastic agent for
`treatment of patients with chronic lymphocytic lymphoma (CLL)
`
`B.
`
`SUPPORTING/RELATED DOCUMENTS:
`
`> IND 67,554
`> OGD Microbiology Review #3 of DMF F" (dated 01-AUG-2006);
`
`was found adequate at
`
`C.
`
`REMARKS: This is an electronic submission in CTD format. This NDA has
`been selected as a pilot for the new GRMP process. The drug product has also
`obtained an orphan drug designation.
`
`A completed filing checklist was entered in DFS on 18-OCT-2007. ONDQA’s
`Initial Quality Assessment has identified product quality microbiology as a
`critical issue for final recommendation on this application.
`
`An information request was sent to the applicant on 08-NOV-2007 to provide the
`following (identified during the filing review):
`
`3
`
`/
`
`/ /
`
`An amendment was submitted on November 15,2007 and this information has
`been included in the relevant sections of the review.
`
`file name: N022249R1.doc
`
`
`Page 2 of 18
`
`
`
`NDA 22-249
`
`Microbiology Review #1
`
`R E
`
`xecutive Summary
`
`I.
`
`Recommendations
`
`A.
`
`B.
`
`Recommendation on Approvability — NDA 22-249 is approvable
`pending the resolution of product quality microbiology
`deficiencies (see Section 3)
`
`Recommendations on Phase 4 Commitments and/or
`Agreements, if Approvable — N/A
`
`11.
`
`Summary of Microbiology Assessments
`
`A.
`
`B.
`
`C.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology — The drug product is
`/
`/_’
`
`Brief Description of Microbiology Deficiencies — Additional
`
`information is needed regarding the
`studies
`
`and
`validation studies.
`
`Assessment of Risk Due to Microbiology Deficiencies —
`Additional information is needed to assess the adequacy of certain
`sterilization processes, and as a result the sterility assurance of the
`product.
`'
`
`'
`
`III.
`
`Administrative
`
`A.
`
`Reviewer's Signature
`Anastasia G. Lolas
`
`B.
`
`Endorsement Block
`
`Bryan S. Riley, Ph.D.
`
`C.
`
`CC Block
`N/A
`
`m.
`
`Page 3 of 18
`
`
`
` Trade'Secref/uCémfidential
`
`'
`
`I
`
`‘
`
`
`
`
`
`
`
` . _ I _1_ .‘ DraftLabelmg _»
`
`
`
`._
`
`_
`
`..
`
`
`
`
`
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Anastasia Lolas
`12/17/2007 10:10:04 AM
`MI CROB IOLOGI ST
`
`I revised it as we discussed.
`
`
`
`PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`
`NDA Number: 22-249
`Drug Name: TREANDA®
`
`Applicant: Cephalon, Inc.
`NDA Type: 1P
`
`Letter Date: l9—SEP—2007
`Stamp Date: 20-SEP-2007
`
`The following are necessary to initiate a review of the NDA application:
`
`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?
`_
`
`Has the applicant submitted an overall description of the
`manufacturing processes and microbiological controls used
`in the manufacture of the drug product?
`Has the applicant submitted protocols and results of
`validation studies concerning microbiological control
`processes used in the manufacture of the drug product?
`
`Results of studies are
`prov1ded m a table
`format (no protocols
`or study reports, no
`dates). Sufficient
`detail is lacking in
`some cases.
`
`All micro information
`is in English.
`
`.
`
`Studies nqtjubmitted
`for the
`—’
`
`.ests.
`
`Micro did not
`partlerpate in any pre-
`submrssron meetings.
`
`
`
`Are any study reports or published articles in a foreign
`language? If yes, has the translated version been included
`in the submission for review?
`
`Has the applicant submitted preservative effectiveness
`studies (if applicable) and container-closure integrity
`studies?
`
`Has the applicant submitted the results of analytical method
`verification Studies?
`
`Has the applicant submitted all special/critical studies/data
`requested during pre—submission meetings and/or
`discussions?
`.
`
`Additional Comments: Missing information (#7) can be requested from the applicant as sobn as
`possible. An information request will be prepared during the review period of this NDA to-
`
`request additional detail on certain studies. The vial and carton labels r
`
`
`.——————\ . The package insertW
`
`Anastasia G. Lolas, Reviewing Microbiologist
`
`Bryan S. Riley, Ph.D., Microbiology Secondary Reviewer
`
`10/18/07
`
`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/
`
`Anastasia Lolas
`10/18/2007 02:10:42 PM
`MICROBIOLOGIST
`
`Bryan Riley
`10/18/2007 02:11:50 PM
`MICROBIOLOGIST
`
`
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