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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 022501/S-009
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Allergan Pharmaceuticals International, LTD c/o Allergan Sales, LLC
`Attention: Jennifer Poon, PharmD
`Senior Manager, Global Regulatory Affairs
`Harborside Financial Plaza 5
`185 Hudson Street, Suite 1900
`Jersey City, NJ 07311
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`Dear Dr. Poon:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received August 11,
`2017, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Lo Loestrin® Fe (ethinyl estradiol, ethinyl estradiol/norethindrone acetate, and ferrous
`fumarate).
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`We also refer to our safety labeling change notification letter dated, April 26, 2017, notifying
`you, under Section 505(o)(4) of the FDCA, of new safety information that you had incorporated
`into labeling and submitted as a prior approval supplement. On August 9, 2017, a supplement
`approval letter was sent approving the labeling text. Upon review of the approved labeling text,
`you had identified that the new safety information was inadvertently included in an inappropriate
`section of the patient labeling which includes the following (deletions are denoted with
`a strikethrough):
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`
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`What are the most serious risks of taking Lo Loestrin Fe?
`Like pregnancy, birth control pills increase the risk of serious blood clots,
`especially in women who have other risk factors, such as smoking, obesity, or age
`greater than 35. It is possible to die from a problem caused by a blood clot, such
`as a heart attack or a stroke.
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`Some examples of serious blood clots are blood clots in the:
`• Legs (deep vein thrombosis)
`• Lungs (pulmonary embolus)
`• Eyes (loss of eyesight)
`• Heart (heart attack)
`• Brain (stroke)
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`Reference ID: 4165064
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`NDA 022501/S-009
`Page 2
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`A few women who take birth control pills may get:
`• High blood pressure
`• Gallbladder problems
`• Rare cancerous or noncancerous liver tumors
`• Take any Hepatitis C drug combination containing
`ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may
`increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the
`blood.
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`
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`Therefore, this “Changes Being Effected” supplemental new drug application provides for
`revisions to the labeling that include the removal of this text.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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`CONTENT OF LABELING
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`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)with the addition of any labeling changes in pending “Changes Being
`Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed
`labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As”
`at http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/
`UCM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`Reference ID: 4165064
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`NDA 022501/S-009
`Page 3
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`REQUIRED PEDIATRIC ASSESSMENTS
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`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.
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`Because none of these criteria apply to your application, you are exempt from this requirement.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available
`at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
`s/UCM443702.pdf ).
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`Reference ID: 4165064
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`NDA 022501/S-009
`Page 4
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`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available
`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found
`at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf.
`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.
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`All promotional materials that include representations about your drug product must be promptly
`revised to be consistent with the labeling changes approved in this supplement, including any
`new safety information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials
`should include prominent disclosure of the important new safety information that appears in the
`revised package labeling. Within 7 days of receipt of this letter, submit your statement of intent
`to comply with 21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or
`electronically in eCTD format. For more information about submitting promotional materials in
`eCTD format, see the draft guidance for industry (available
`at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
`s/UCM443702.pdf ).
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
`
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`If you have any questions, please call Meredith Hillig, M.S., Safety Regulatory Project
`Manager, at (301) 796-1218.
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`Sincerely,
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`{See appended electronic signature page}
`
`Christine P. Nguyen, M.D.
`Acting Director
`Division of Bone, Reproductive and Urologic Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`ENCLOSURE:
`Content of Labeling
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`
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`Reference ID: 4165064
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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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`CHRISTINE P NGUYEN
`10/10/2017
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`Reference ID: 4165064
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