`RESEARCH
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`APPLICATION NUMBER:
`022501Orig1s000
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`OTHER ACTION LETTERS
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`COMPLETE RESPONSE
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`NDA 022501
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`Warner Chilcott Company, LLC
`Attention: Ileana Brown
`Director, Regulatory Affairs
`100 Enterprise Drive
`Rockaway, NJ 07866
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`Dear Ms. Brown:
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`Please refer to your new drug application (NDA) dated and received March 26, 2009, submitted
`under section 505(b) of the Federal Food, Drug, and Cosmetic Act for norethindrone acetate and
`ethinyl estradiol tablets/ethinyl estradiol tablets/ferrous fumarate tablets.
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`We acknowledge receipt of your amendments dated April 9 and 22, July 22 and 23, September 1
`and 21, October 16 and 20, November 10, 11, 20, and 30, December 3, 17, and 23, 2009, and
`January 19, 20, and 21, 2010.
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`We have completed the review of your application, as amended, and have determined that we
`cannot approve this application in its present form. We have described below our reasons for
`this action and, where possible, our recommendations to address these issues.
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`PRODUCT QUALITY
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`During inspections of a drug substance manufacturing facility and a control testing laboratory
`used to support this application, our field investigators conveyed deficiencies to the
`representatives of the respective facilities. These deficiencies have not been resolved.
`Satisfactory resolution of these deficiencies is required before this application can be approved.
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`LABELING
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`Labeling remains unresolved. We will continue labeling discussions based on your submission of
`January 21, 2010.
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`SAFETY UPDATE
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`When you respond to the above deficiencies, include a safety update as described at
`21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and
`clinical studies/trials of the drug under consideration regardless of indication, dosage form, or
`dose level.
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`NDA 022501
`Page 2
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`1. Describe in detail any significant changes or findings in the safety profile.
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`2. When assembling the sections describing discontinuations due to adverse events, serious
`adverse events, and common adverse events, incorporate new safety data as follows:
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`• Present new safety data from the studies/clinical trials for the proposed indication
`using the same format as the original NDA submission.
`• Present tabulations of the new safety data combined with the original NDA data.
`•
`Include tables that compare frequencies of adverse events in the original NDA with
`the retabulated frequencies described in the bullet above.
`• For indications other than the proposed indication, provide separate tables for the
`frequencies of adverse events occurring in clinical trials.
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`3. Present a retabulation of the reasons for premature trial discontinuation by incorporating
`the drop-outs from the newly completed trials. Describe any new trends or patterns
`identified.
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`4. Provide case report forms and narrative summaries for each patient who died during a
`clinical trial or who did not complete a trial because of an adverse event. In addition,
`provide narrative summaries for serious adverse events.
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`5. Describe any information that suggests a substantial change in the incidence of common,
`but less serious, adverse events between the new data and the original NDA data.
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`6. Provide updated exposure information for the clinical studies/trials (e.g., number of
`subjects, person time).
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`7. Provide a summary of worldwide experience on the safety of this drug. Include an
`updated estimate of use for drug marketed in other countries.
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`8. Provide English translations of current approved foreign labeling not previously
`submitted.
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`OTHER
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`Within one year after the date of this letter, you are required to resubmit or take one of the other
`actions available under 21 CFR 314.110. If you do not take one of these actions, we will
`consider your lack of response a request to withdraw the application under 21 CFR 314.65. A
`resubmission must fully address all the deficiencies listed. A partial response to this letter will
`not be processed as a resubmission and will not start a new review cycle.
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`Under 21 CFR 314.102(d), you may request a meeting or telephone conference with us to
`discuss what steps you need to take before the application may be approved. If you wish to have
`such a meeting, submit your meeting request as described in the FDA’s Guidance for Industry -
`Formal Meetings Between the FDA and Sponsors or Applicants, May 2009 at
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`NDA 022501
`Page 3
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`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM153222.pdf.
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`The drug product may not be legally marketed until you have been notified in writing that this
`application is approved.
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`If you have any questions, call Karl Stiller, Regulatory Project Manager, at (301) 796-1993.
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`Sincerely,
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`{See appended electronic signature page}
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`Scott Monroe, M.D.
`Director
`Division of Reproductive and Urologic Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`Application
`Type/Number
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`NDA-22501
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`Submission
`Type/Number
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`ORIG-1
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`Submitter Name
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`Product Name
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`--------------------
`WARNER
`CHILCOTT CO INC
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`SCOTT E MONROE
`01/26/2010
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`(b) (4)
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