DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`Rockville MD 20857
`
`NDA 21-344
`
`AstraZeneca Pharmaceuticals
`Attention: Anthony Rogers
`Vice President, Regulatory Affairs
`1800 Concord Pike
`P.O. Box 8355
`Wilmington, DE 19803-8355
`
`Dear Mr. Rogers:
`
`Please refer to your new drug application (NDA) dated March 28, 2001, received March 28, 2001,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for FASLODEX
`(fulvestrant) Injection.
`
`We acknowledge receipt of your submissions dated January 18; April 9; May 25; June 5; July 19 and
`20; August 9, 28 and 31; September 13 and 28; October 11, 12, 18 (2), 24 and 29; November 9 and 13
`(2); December 10, 11, 14 and 31, 2001; January 22, 30 and 31; February 1 and 11; and April 16
`and 22, 2002.
`
`This new drug application provides for the use of FASLODEX (fulvestrant) Injection for the
`treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with
`disease progression following antiestrogen therapy.
`
`We have completed the review of this application, as amended, and have concluded that adequate
`information has been presented to demonstrate that the drug product is safe and effective for use as
`recommended in the agreed upon enclosed labeling text. Accordingly, the application is approved
`effective on the date of this letter.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert,
`immediate container and carton labels). Marketing the product with FPL that is not identical to the
`approved labeling text may render the product misbranded and an unapproved new drug.
`
`Please submit the copies of final printed labeling (FPL) electronically according to the guidance for
`industry titled Providing Regulatory Submissions in Electronic Format - NDA (January 1999).
`Alternatively, you may submit 20 paper copies of the FPL as soon as it is available but no more than 30
`days after it is printed. Please individually mount ten of the copies on heavy-weight paper or similar
`material. For administrative purposes, this submission should be designated "FPL for approved NDA
`21-344." Approval of this submission by FDA is not required before the labeling is used.
`
`

`

`NDA 21-344
`Page 2
`
`We remind you of your postmarketing study commitments in your facsimile dated April 25, 2002.
`These commitments are listed below.
`
`1. To perform a study of the effect of ketoconazole treatment on the pharmacokinetics of
`fulvestrant following intravenous dosing of fulvestrant.
`
`In order to be interpretable, the commitment is to perform a study with a sufficient number of
`subjects and measurements. A sufficient number is one that results in a confidence interval of
`the ratio (ketoconazole + fulvestrant: fulvestrant alone) of the log-transformed AUC0-t for the
`treatments of 0.40 or less.
`
`Protocol Submission:
`Study Start:
`Final Report Submission:
`
`Within 2 months of the date of this letter.
`Within 4 months of the date of this letter.
`Within 10 months of the date of this letter.
`
`2. To update survival data on the randomized studies #20 and #21 and to submit a study report
`when 75% of the patients have died.
`
`3. To submit reports of all medication errors, both potential and actual, that occur within the
`United States with Faslodex for two years following the date of approval. Potential errors
`should be reported and summarized quarterly. All actual errors should be submitted within 15
`days regardless of patient outcome. Yearly reports of potential and actual errors occurring with
`FASLODEX should be submitted for two years following the date of approval. Within one
`month of approval, AstraZeneca Pharmaceuticals will meet with FDA to clarify the meaning of
`the terms potential medication error and actual medication error.
`
`Submit the clinical protocol for the ketoconazole interaction study to your IND for this product.
`Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to
`this NDA. In addition, under 21 CFR 314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a
`status summary of each commitment in your annual report to this NDA. The status summary should
`include expected summary completion and final report submission dates, any changes in plans since
`the last annual report, and, for clinical studies, number of patients entered into each study. All
`submissions, including supplements, relating to these postmarketing study commitments must be
`prominently labeled "Postmarketing Study Protocol", "Postmarketing Study Final Report", or
`"Postmarketing Study Correspondence."
`
`Validation of the regulatory methods has not been completed. At the present time, it is the policy of
`the Center not to withhold approval because the methods are being validated. Nevertheless, we expect
`your continued cooperation to resolve any problems that may be identified.
`
`Be advised that, as of April 1, 1999, all applications for new active ingredients, new dosage forms, new
`indications, new routes of administration, and new dosing regimens are required to contain an
`assessment of the safety and effectiveness of the product in pediatric patients unless this requirement is
`waived or deferred (63 FR 66632). We are waiving the pediatric study requirement for this action on
`this application.
`In addition, please submit three copies of the introductory promotional materials that you propose to
`
`

`

`NDA 21-344
`Page 3
`
`use for this product. All proposed materials should be submitted in draft or mock-up form, not final
`print. Please send one copy to the Division of Oncology Drug Products and two copies of both the
`promotional materials and the package insert directly to:
`
`Division of Drug Marketing, Advertising, and Communications, HFD-42
`Food and Drug Administration
`5600 Fishers Lane
`Rockville, Maryland 20857
`
`We remind you that you must comply with the requirements for an approved NDA set forth under
`21 CFR 314.80 and 314.81.
`
`If you have any questions, call Amy Baird, Consumer Safety Officer, at (301) 594-5771.
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Robert Temple, M.D.
`Director
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`Enclosure
`
`

`

`---------------------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`---------------------------------------------------------------------------------------------------------------------
` /s/
`---------------------
`Robert Temple
`4/25/02 02:20:43 PM
`
`