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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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` NDA APPROVAL
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`NDA 22-301
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`Salix Pharmaceuticals, Inc.
`Attention: Benjamin M. Burgin, RAC
`Senior Manager, Regulatory Affairs
`1700 Perimeter Park Drive
`Morrisville, NC 27560
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`Dear Mr. Burgin:
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`Please refer to your new drug application (NDA) dated December 21, 2007, received December
`31, 2007, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act
`for Apriso (mesalamine) extended-release capsules 0.375g.
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`We acknowledge receipt of your submissions dated January 21, 2008, March 7, 2008, April 24,
`2008, April 25, 2008, May 7, 2008, May 13, 2008, June 13, 2008, July 25, 2008, August 1, 2008,
`August 14, 2008, August 22, 2008, September 16, 2008, October 1, 2008, October 3, 2008,
`October 15, 2008, October 16, 2008, October 17, 2008, and October 28, 2008.
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`This new drug application provides for the use of Apriso (mesalamine) extended-release capules
`0.375g for the maintenance of remission of ulcerative colitis in adults.
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`We have completed our review of this 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, please submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling. Upon
`receipt, we will transmit that version to the National Library of Medicine for public
`dissemination. For administrative purposes, please designate this submission, “SPL for approved
`NDA 22-301.”
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`

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`NDA 22-301
`Page 2
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` CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels that are identical to the enclosed carton and
`immediate container labels 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 titled
`Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product
`Applications and Related Submissions Using the eCTD Specifications (October 2005).
`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 22-301.” Approval of this
`submission by FDA is not required before the labeling is used.
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`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.
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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,
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`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to 5 years because the necessary
`studies are impossible or highly impracticable. This is because there are too few children with
`ulcerative colitis in that age range to study.
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`We are deferring submission of your pediatric study for ages 5 to 17 years for this application
`because this product is ready for approval for use in adults and the pediatric study has not been
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`completed.
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`Your deferred pediatric study required by section 505B(a) of the Federal Food, Drug, and
`Cosmetic Act is a required postmarketing study. The status of this postmarketing study must be
`reported annually according to 21 CFR 314.81 and section 505B(a)(3)(B) of the Federal Food,
`Drug, and Cosmetic Act. This required study is listed below.
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`1. Deferred pediatric study under PREA for the maintenance of remission of ulcerative colitis
`in pediatric patients ages 5 to 17 years to evaluate safety, effectiveness, and
`pharmacokinetics with Apriso (mesalamine granules) in at least two dosing regimens.
`Protocol Submission:
`June 1, 2009
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`Study Start:
`January 1, 2010
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`Final Report Submission:
`June 1, 2013
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`Submit final study reports to this NDA. For administrative purposes, all submissions related to
`this required pediatric postmarketing study must be clearly designated “Required Pediatric
`Assessment.”
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`NDA 22-301
`Page 3
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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, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert(s)
`to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert(s), at the time of initial dissemination or publication, accompanied by a Form
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`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 Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see www.fda.gov/cder/ddmac.
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`Please submit one market package of the drug product when it is available.
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`LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and to the following address:
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`MedWatch
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`Food and Drug Administration
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`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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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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`

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`NDA 22-301
`Page 4
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`If you have any questions, call Cristi Stark, Regulatory Project Manager, at (301) 796-1007.
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`Sincerely,
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` {See appended electronic signature page}
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`Donna Griebel, MD
`Director
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`Division of Gastroenterology 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.
`---------------------------------------------------------------------------------------------------------------------
`/s/
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`---------------------
`Donna Griebel
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`10/31/2008 02:57:51 PM
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