`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`203565Orig1s000
`
`MICROBIOLOGY REVIEW(S)
`
`
`
`
`
`
`
`
`

`

`
`
`Product Quality Microbiology Review
`
`4/24/2013
`
`
`
`NDA: 203565
`
`Drug Product Name
`Proprietary: Injectafer
`Non-proprietary: Iron Carboxymaltose
`
`
`Review Number: 2
`
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`1/30/2013
`1/30/2013
`2/28/2013
`
`
`
`
`
`
`Submission History (for 2nd Reviews or higher)
`Submit Date(s)
`Microbiology Review #
`9/30/2011
`1
`3/26/2013
`1
`
`Assigned to Reviewer
`3/08/2013
`
`
`Review Date(s)
`5/08/2013
`5/08/2013
`
`
`Applicant/Sponsor
`Name: Luitpold Pharmaceuticals Inc.
`Address: P.O. Box 9001, One Luitpold Dr., Shirley, NY 11967
`Representative: Marsh Simon
`Telephone: 610 650 4200
`
`
`Name of Reviewer: Steven P. Donald, M.S.
`
`Conclusion: Recommended for Approval
`
`
`
`
`Reference ID: 3301349
`
`

`

`Product Quality Microbiology Data Sheet
`1.
`TYPE OF SUBMISSION: Resubmission
`
`2.
`
`
`
`
`Microbiology Review #2
`
`
`SUBMISSION PROVIDES FOR: Amendment and complete response
`submission to complete response dated 7/23/2012
`
`MANUFACTURING SITE:
`
`
`
`
`NDA 203565
`
`
`
`
`A.
`
`3.
`
`
`4.
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY: Injection, IV, 50 mg Iron/ml in glass vials
`
`METHOD(S) OF STERILIZATION:
`
`
`
`PHARMACOLOGICAL CATEGORY: Treatment for iron deficiency
`
`
`5.
`
`6.
`
`SUPPORTING/RELATED DOCUMENTS: N203565r1.doc, dated 5/08/2012;
` and DMF review
`_Dec5_A1.doc, dated 4/24/2013.
`
`B.
`DMF
`
`
`
`C. REMARKS: An alternate manufacturing site,
`
`is proposed. The applicant’s letter of December 5, 2012 indicates a manufacturing site
`change. Section 3.2.P.3 in the subject submission lists only the
` location
`as the manufacturing site for the subject drug product, but at the top of the page it
`states: “In addition to those facilities previously identified within this NDA, the
`following facilities may be used for the indicated services associated with the
`manufacture of Injectafer at the alternate
`. manufacturing facility”.
`The subject submission provides only data for the 15 ml vial containing 750 mg iron.
`References to the
` vial are stated to have been removed from the batch records
`and other configurations of the drug product are not mentioned. It appears that at this
`time, this alternate facility will manufacture only the 750 mg configuration and
`manufacturing at the previously reviewed facility will remain unchanged. The
`Product Quality Microbiology review, dated 5/08/2012, which covered manufacturing
`at the
` facility, recommended the submission for approval. After the
`initial review of the 1/30/2013 submission, an information request was sent to the
`sponsor on 4/2/2013. A response dated 4/12/2013 was provided for review and is
`included herein.
`
`
`
`filename: N203565r2.doc
`
`
`
`
`
`Reference ID: 3301349
`
`
`
`Page 2 of 17
`
`
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`NDA 203565
`
`Microbiology Review #2
`
`Executive Summary
`
`I.
`
`Recommendations
`
`A.
`
`Recommendation on Approvability - Recommended for
`Approval
`
`B.
`
`Recommendations on Phase 4 Commitments and/or
`
`Agreements, if Approvable — N/A
`
`II.
`
`Summary of Microbiology Assessments
`
`A.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology — Injectafer will be
`(we)
`
`B.
`
`C.
`
`Brief Description of Microbiology Deficiencies —
`No product quality microbiology deficiencies were identified
`based upon the information provided.
`
`Assessment of Risk Due to Microbiology Deficiencies —
`N/A
`
`D.
`
`Contains Potential Precedent Decision(s)— D Yes X No
`
`III.
`
`Administrative
`
`A.
`
`Reviewer's Signature
`
`B.
`
`Endorsement Block
`
`C.
`
`CC Block
`
`N/A
`
`Steven P. Donald, M.S.
`
`Microbiology Reviewer
`
`Stephen Langille, Ph.D.
`Senior Microbiology Reviewer
`
`14 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`Reference ID: 3301349
`
`Page 3 of 17
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`STEVEN P DONALD
`04/30/2013
`
`STEPHEN E LANGILLE
`04/30/2013
`
`Reference ID: 3301349
`
`

`

`Product Quality Microbiology Review
`
`8 May 2012
`
`
`
`
`
`
`203-565/N-000
`
`
`
`
`
`
`
`
`
`
`NDA:
`
`Drug Product Name
`Injectafer®
`Proprietary:
`
`Non-proprietary: Ferric Carboxymaltose
`
`1
`
`
`Review Number:
`
`Dates of Submission(s) Covered by this Review
`Submit
`Received
`Review Request
`30 September 2011
`3 October 2011
`17 October 2011
`26 March 2012
`26 March 2012
`N/A
`
`Assigned to Reviewer
`20 October 2011
`N/A
`
`
`
`Submission History (for amendments only): N/A
`
`
`Applicant/Sponsor
`Name:
`
`
`Address:
`
`
`
`
`
`
`
`
`
`
`Representative:
`Telephone:
`
`
`Luitpold Pharmaceuticals Inc.
`P.O. Box 9001
`One Luitpold Dr.
`Shirley, NY 11967
`
`Marsha E. Simon
`610-650-4200
`
`Stephen E. Langille, Ph.D.
`
`Recommended for approval
`
`
`Name of Reviewer:
`
`Conclusion:
`
`
`
`
`Reference ID: 3127645
`
`

`

`NDA 203-565/N-000
`
`
`
`
`
`
`Microbiology Review # 1
`
`
`Product Quality Microbiology Data Sheet
`1.
`TYPE OF SUBMISSION:
`
`Original NDA
`
`2.
`
`
`
`SUBMISSION PROVIDES FOR:
`
`
`
`
`
` aqueous intravenous
`
`
`
`
`
`
`injection.
`
`MANUFACTURING SITE:
`
`
`
`
`
`
` Luitpold Pharmaceuticals
`
`Inc.
`
` of an
`
`3.
`
`
`4.
`
`
`A.
`
`B.
`
`C.
`
`DOSAGE FORM, ROUTE OF ADMINISTRATION AND
`STRENGTH/POTENCY:
`
`• Sterile liquid
`• 50 mg iron/mL in glass
`vials
`Intravenous injection
`
`•
`
`METHOD(S) OF STERILIZATION:
`
`
`
`PHARMACOLOGICAL CATEGORY: Treatment of iron deficiency
`
`
`5.
`
`6.
`
`SUPPORTING/RELATED DOCUMENTS: Not applicable
`
`REMARKS: The application was submitted in eCTD format. An information
`request was conveyed to the applicant via e-mail on 19 March 2012. The
`applicant responded on 26 March 2012.
`
`
`
`filename: N203565r1.doc
`
`
`
`
`
`Reference ID: 3127645
`
`
`
`Page 2 of 12
`
`
`
`(b) (4)
`
`(b) (4)
`
`

`

`NDA 203-565/N—000
`
`Microbiology Review # 1
`
`Executive Summary
`
`I.
`
`Recommendations
`
`A.
`
`Recommendation on Approvability
`NDA 203-565 is recommended for approval from the standpoint of
`product quality microbiology.
`
`B.
`
`Recommendations on Phase 4 Commitments and/or
`
`Agreements, if Approvable -
`Not applicable
`
`H.
`
`Summary of Microbiology Assessments
`
`A.
`
`B.
`
`C.
`
`Brief Description of the Manufacturing Processes that relate to
`Product Quality Microbiology -
`Injectafer will be
`
`M0
`
`Brief Description of Microbiology Deficiencies —
`Ne deficiencies were identified based upon the information
`provided.
`
`Assessment of Risk Due to Microbiology Deficiencies —
`Not applicable
`
`III.
`
`Administrative
`
`A.
`
`Reviewer's Signature
`
`B.
`
`Endorsement Block
`
`Stephen E. Langille, PhD.
`
`John Metcalfe, Ph.D., Senior Microbiology Reviewer
`
`C.
`
`CC Block
`
`N/A
`
`9 Page(s) has been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`Reference ID: 31 27645
`
`Page 3 of 12
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`05/08/2012
`
`JOHN W METCALFE
`05/08/2012
`I concur.
`
`Reference ID: 3127645
`
`

`

` PRODUCT QUALITY MICROBIOLOGY FILING CHECKLIST
`NDA Number: 203-565
`Applicant: Luitpold Inc.
`Letter Date: 30 September 2011
`Drug Name: Injectafer®
`NDA Type: Standard
`Stamp Date: 3 October 2011
`
`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
`
`
`
`
`
` X
`
`
`1
`
`Comments
`
`
`
`
`
`
`
`
`
`The drug product is
`not preserved.
`Integrity testing is
`covered in section
`3.2.P.2.5
`
`
`
`
`
`
`
`
`
`
`
` 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?
`
`X
`
`X
`
`
`
`Is this NDA fileable? If not, then describe why.
`
`X
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3052513
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`9
`
`Additional Comments: The application was submitted in eCTD format. The drug product is
`
`
`No such studies were
`requested from the
`New Drug
`Microbiology Staff
`
`
`(b) (4)
`
`

`

`
`
`
`
`
`
`
`
`Date
`
`Date
`
`Reviewing Microbiologist
`Stephen E. Langille, Ph.D.
`
`Microbiology Secondary Reviewer/Team Leader
`John Metcalfe, Ph.D. Senior Microbiology Reviewer
`
`
`
`
`
`
`
`Reference ID: 3052513
`
`

`

`---------------------------------------------------------------------------------------------------------
`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
`12/01/2011
`
`JOHN W METCALFE
`12/01/2011
`I concur.
`
`Reference ID: 3052513
`
`