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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 50-805
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`CollaGenex Pharmaceuticals, Inc.
`Attention: Christopher Powala
`Vice President, Drug Development and Regulatory Affairs
`41 University Drive
`Newton, PA 18940
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`Dear Mr. Powala:
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`Please refer to your new drug application (NDA) dated July 29, 2005, received August 1, 2005,
`submitted pursuant to section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act for Oracea™
`(doxycycline, USP) Capsules, 40 mg.
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`We acknowledge receipt of your submissions dated September 8, and October 26, 2005; January 5,
`February 10, March 17 and 24, April 7, 17, and 19, May 11, 15, 16, 22 (two), 25 (electronic mail), and
`26 (electronic mail), 2006.
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`This new drug application provides for the use of Oracea™ (doxycycline, USP) Capsules, 40 mg, for
`the treatment of inflammatory lesions (papules and pustules) of rosacea in adult patients.
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`We completed our review of this application, as amended. This application is approved, effective on
`the date of this letter, for use as recommended in the agreed-upon labeling text.
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`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package insert,
`text for the patient package insert, immediate container and container 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.
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`Please submit an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Format - NDA. 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. Individually mount 15
`of the copies on heavy-weight paper or similar material. For administrative purposes, designate this
`submission "FPL for approved supplement NDA 50-805.” Approval of this submission by FDA is not
`required before the labeling is used.
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`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.
`We are waiving the pediatric study requirement for ages 0 to 18 years for this application.
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`NDA 50-805
`Page 2
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`In addition, we remind you of your postmarketing study commitments in your letter dated May 26,
`2006. These commitments are listed below.
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`1. Submission of carcinogenicity study protocol and dose finding data: June 2007 Carcinogenicity
`study start date: August 2007 Submission of final carcinogenicity study report: February 2010.
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`Study protocol submission: June 2007
`Study start date: August 2007
`Final report Submission: February 2010
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`2. Conduct a properly designed human sperm motility and morphology study to evaluate the
`effects of long-term use of ORACEA™ (doxycycline, USP) 40mg on human sperm in male
`patients with rosacea. Study report submission within 2 years from date of approval.
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`Study protocol submission: September 2006
`Study start date: February 2007
`Final report Submission: June 2008
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`3. A post-approval Medication Error Monitoring Program for the proprietary name, Oracea™.
`This program should consist of:
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`15-Day reporting of all Medication Errors;
`Root Cause Analysis; and
`Trigger requiring a proprietary name change.
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`CollaGenex Pharmaceuticals agrees to a Medication Error Monitoring Program for the
`proprietary name, Oracea™, consisting of the above three components. Specifically, the
`sponsor will report as if it were a "15 day report" all medication errors, regardless of patient
`outcome. The sponsor will conduct a root cause analysis for each reported medication error and
`submit the analysis as a "follow-up" to the 15 day report.
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`Collagenex will promptly (within 30 days of receipt of the approval letter) submit a detailed
`plan that addresses circumstances that would trigger a name change and also include any other
`risk management actions and the time frame for implementation of such action.
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`In the event that a serious adverse event results from a medication error, CollaGenex will
`promptly meet with the Division to discuss ways to prevent future errors, including changing
`the propriety name, OraceaTM.
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`Submit clinical protocols 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 Commitment Protocol”, “Postmarketing Study Commitment Final Report”, or
`“Postmarketing Study Commitment Correspondence.”
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`NDA 50-805
`Page 3
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`In addition, submit three copies of the introductory promotional materials that you propose to use for
`this product. Submit all proposed materials in draft or mock-up form, not final print. Send one copy to
`the Division of Dermatology and Dental Products and two copies of both the promotional materials
`and the package insert directly to:
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`Food and Drug Administration
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Please submit one market package of the drug product when it is available.
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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, call Shalini Jain, Regulatory Project Manager, at (301) 796-0692.
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`Sincerely,
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`{See appended electronic signature page}
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`Stanka Kukich, M.D.
`Acting Division Director
`Division of Dermatology & Dental Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`Enclosure
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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.
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` /s/
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`Stanka Kukich
`5/26/2006 05:34:39 PM
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