`CENTER FOR DRUG EVALUATION AND RESEARCH
`
`Approval Package for:
`
`
`APPLICATION NUMBER:
`
`203565Orig1s000
`
`
`INJECTAFER
`ferric carboxymaltose injection
`Luitpold Pharmaceuticals, Inc.
`January 17, 2013
`Injectafer (ferric carboxymaltose injection) as an
`iron replacement product indicated for the
`treatment of iron deficiency anemia in adult
`patients:
` who have intolerance to oral iron or have
`had unsatisfactory response to oral iron;
` who have non‐dialysis dependent chronic
`kidney disease.
`
`
`Trade Name:
`
`Generic Name:
`
`Sponsor:
`
`Approval Date:
`
`Indications:
`
`
`
`

`

`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`203565Orig1s000
`
`CONTENTS
`
`Reviews / Information Included in this NDA Review.
`
`
`X
`X
`X
`
`X
`X
`
`X
`X
`X
`
`X
`X
`X
`X
`X
`
`X
`X
`
`
`
`
`Approval Letter
`Other Action Letters
`Labeling
`REMS
`Summary Review
`Officer/Employee List
`Office Director Memo
`Cross Discipline Team Leader Review
`Medical Review(s)
`Chemistry Review(s)
`Environmental Assessment
`Pharmacology Review(s)
`Statistical Review(s)
`Microbiology Review(s)
`Clinical Pharmacology/Biopharmaceutics Review(s)
`Other Reviews
`Risk Assessment and Risk Mitigation Review(s)
`Proprietary Name Review(s)
`Administrative/Correspondence Document(s)
`
`
`

`

`
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`203565Orig1s000
`APPROVAL LETTER
`
`
`
`
`
`
`
`

`

`
`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`
`NDA 203565
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`NDA APPROVAL
`
`
`Luitpold Pharmaceuticals, Inc.
`Attention: Marsha E. Simon
`Sr. Manager, Regulatory Affairs
`800 Adams Avenue, Suite 100
`Norristown, PA 19403
`
`Dear Ms. Simon:
`
`Please refer to your New Drug Application (NDA) dated September 30, 2011, received
`October 3, 2011, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act
`(FDCA) for INJECTAFER (ferric carboxymaltose injection).
`
`We acknowledge receipt of your amendments dated November 15; December 5 and 13, 2011;
`January 6 and 11; February 8; March 26; April 13, 23, 24, and 27; May 16; June 6 and 25; July
`18; September 13; October 29; and December 5, 2012; January 30; February 5; March 13 and
`20; April 2 and 12; May 6 and 31; June 13; and July 2, 16 (2), 17, 19, 22 (2) and 24, 2013.
`
`The January 30, 2013, submission constituted a complete response to our July 23, 2012, action
`letter.
`
`This new drug application provides for the use of INJECTAFER (ferric carboxymaltose
`injection) as an iron replacement product indicated for the treatment of iron deficiency anemia in
`adult patients:
` who have intolerance to oral iron or have had unsatisfactory response to oral iron;
` who have non-dialysis dependent chronic kidney disease.
`
`Reference ID: 3347006
`
`

`

`NDA 203565
`Page 2
`
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert, text for the
`patient package insert). Information on submitting SPL files using eLIST may be found in the
`guidance for industry SPL Standard for Content of Labeling Technical Qs and As, available at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
`
`The SPL will be accessible via publicly available labeling repositories.
`
`CARTON AND IMMEDIATE-CONTAINER LABELS
`
`We acknowledge your July 22, 2013, submission containing final printed carton and container
`labels.
`
`CARTON AND IMMEDIATE-CONTAINER LABELS
`
`Submit final printed carton and immediate-container labels that are identical to the carton and
`immediate-container labels submitted on July 22, 2013, as soon as they are available, but no
`more than 30 days after they are printed. Please submit these labels electronically according to
`the guidance for industry Providing Regulatory Submissions in Electronic Format – Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(June 2008). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
`submission “Final Printed Carton and Container Labels for approved NDA 203565.”
`Approval of this submission by FDA is not required before the labeling is used.
`
`Marketing the product(s) with FPL that is not identical to the approved labeling text may render
`the product misbranded and an unapproved new drug.
`
`
`ADVISORY COMMITTEE
`
`Your application for INJECTAFER (ferric carboxymaltose injection) was not referred to an FDA
`advisory committee because this drug is not the first in its class, the safety profile is similar to
`that of other drugs approved for this indication, and the application did not raise significant
`safety or efficacy issues that were unexpected for a drug/biologic of this class.
`
`
`Reference ID: 3347006
`
`

`

`NDA 203565
`Page 3
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new
`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
`administration are required to contain an assessment of the safety and effectiveness of the
`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
`deferred, or inapplicable.
`
`We are waiving the pediatric study requirement for ages 0 to 1 years because necessary studies
`are impossible or highly impracticable due to the infrequency of the condition in this age group.
`
`We are deferring submission of your pediatric studies for ages 1 to 17 years for this application
`because this product is ready for approval for use in adults and the pediatric studies have not
`been completed.
`
`Your deferred pediatric studies required by section 505B(a) of the FDCA are required
`postmarketing studies. The status of these postmarketing studies must be reported annually
`according to 21 CFR 314.81 and section 505B(a)(3)(B) of the FDCA. These required studies are
`listed below.
`
`2064-1
`
`Identify an optimal dose of INJECTAFER (ferric carboxymaltose injection) for the
`pediatric patient population. Conduct one or more pharmacokinetic (PK) and
`pharmacodynamic (PD) trials in pediatric patients aged 1 to <17 years with iron
`deficiency anemia sufficient to justify and to characterize the dose to be tested in a
`confirmatory clinical trial of safety and efficacy. Identify the most relevant PD
`endpoints to measure.
`
`Final Protocol Submission: 07/2014
`Trial Completion:
`
`07/2016
`Final Report Submission:
`07/2017
`
`
`
`
`
`2064-2 Determine the safety and efficacy of INJECTAFER (ferric carboxymaltose injection)
`in pediatric patients aged 1 to <17 years with iron deficiency anemia by conducting a
`randomized, active-controlled clinical trial.
`
`
`
`
`
`Final Protocol Submission: 01/2017
`Trial Completion:
`
`01/2020
`Final Report Submission:
`01/2021
`
`
`
`Submit the protocols to your IND 063243, with a cross-reference letter to this NDA.
`
`Reports of these required pediatric postmarketing studies must be submitted as a new drug
`application (NDA) or as a supplement to your approved NDA with the proposed labeling
`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`
`Reference ID: 3347006
`
`

`

`NDA 203565
`Page 4
`
`
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
`the submission.
`
`PROMOTIONAL MATERIALS
`
`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
`
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
`
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more
`information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
`
`METHODS VALIDATION
`
`We have not completed validation of the regulatory methods. However, we expect your
`continued cooperation to resolve any problems that may be identified.
`
`EXPIRATION DATING
`
`An expiration dating period of 24 months is granted for the drug product, when stored at 25°C
`(77°F) excursions permitted between 15°C to 30°C (59°F to 86°F).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
`
`Reference ID: 3347006
`
`

`

`NDA 203565
`Page 5
`
`
`If you have any questions, call Amy Baird, Regulatory Project Manager, at (301) 796-4969.
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Edvardas Kaminskas, M.D.
`Deputy Director
`Division of Hematology Products
`Office of Hematology and Oncology Products
`Center for Drug Evaluation and Research
`
`
`
`
`Enclosure(s):
`Content of Labeling
`
`
`
`Reference ID: 3347006
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`EDVARDAS KAMINSKAS
`07/25/2013
`
`Reference ID: 3347006
`
`