CENTER FOR DRUG EVALUATION AND RESEARCH
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`APPRCHHU.RACKAGEIKNC
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`APPLICATION NUMBER
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`21-372
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`Approval Letter(s)
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`I
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`”no$( DEPARTMENTOFHEALTH & HUMAN SERVICES
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`PUb‘iC“83““Service
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`Food and Drug Administration
`Rockville, MD '20857
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`NDA 21-372
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`Helsinn Healthcare S.A.
`c/o August Consulting
`Attention: Craig Lehmarm, Pharrn. D.
`515 Capital of Texas Highway, Suite 150
`Austin, TX 78746
`
`Dear Dr Lehmann:
`
`Please refer to your new drug application (NDA) dated September 26, 2002, received
`September 27, 2002, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`AloxiTM (palonosetron hydrochloride injection).
`
`We acknowledge receipt of your submissions dated October 11 and November 21, 2002 and
`January 24, April 9, April 24, May 15, June 6, June 9, June 13, June 16, June 18, June 20, June 25,
`July 1 ,July 17, and July 22, 2003.
`
`This new drug application provides for the use of AloxiTM (palonosetron hydrochloride injection) for:
`1)
`the prevention of acute nausea and vomiting associated with initial and repeat courses of
`moderately and highly emetogenic cancer chemotherapy, and
`the prevention of delayed nausea and vomiting associated with initial and repeat courses of
`moderately emetogenic cancer chemotherapy.
`
`2)
`
`It is approved, effective on the date of this
`We completed our review of this application, as amended.
`letter, {or use as recommended in the agreed-upon labeling text.
`
`Please note that, based on the primary stability data submitted, we are granting a 24-month expiration
`period for this product. When additional stability data are available, an extension of the expiration
`period may be requested by submission of a prior approval supplemental new drug application.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for-the package insert)
`and submitted labeling (carton label submitted June 25, 2003 and immediate container label submitted
`July I, 2003). 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 an electronic version of the FPL according to the guidance for industry titled Providing
`Regulatory Submissions in Electronic Formal - NDA. Alternatively, you may submit 20 paper copies
`of the FPI. as soon as it is available but no morelthan 30 days after it is printed. Individually mount 15
`of the copies on heavy—weight paper or similar material. For administrativepurposes, designate this
`submission“FPL for approved NDA 21-372.” Approval of this submission by FDA is not required
`before the labeling is used.
`
`

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`NDA 21-372
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`Page 2
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`FDA's Pediatric Rule [at 21 CFR 314.55/21 CFR 601.27] was challenged in court. On October 17,
`2002, the court ruled that FDA did not have the authority to issue the Pediatric Rule and has barred
`FDA from enforcing it. Although the government decided not to pursue an appeal in the courts, it will
`work with Congress in an effort to enact legislation requiringphannaceutical manufacturers to conduct
`appropriate pediatric clinical trials. In addition, third party interveners have decided to appeal the
`court's decision suiking down the rule. Therefore, we encourage you to submit a pediatric plan that
`describes development of your product in the pediatric p0pulation where it may be used. Please be
`aware that whether or not this pediatric plan and subsequent submission of pediatric data will be
`required depends upon passage of legislation or the success of the third party appeal.
`In any event, we
`hope you will decide to submit a pediatric plan and conduct the appropriate pediatric studies to provide
`important information on the safe and effective use of this drug in the relevant pediatric populations.
`
`The pediatric exclusivity provisions of FDAMA as reauthorized by the Best Pharmaceuticals for
`Children Act are not affected by the court's ruling. Pediatric studies conducted under the terms of
`section 505A of the Federal Food, Drug, and Cosmetic Act may result in additional marketing
`exclusivity for certain products. You should refer to the Guidance for Industry on Qualifying for
`Pediatric Exclusivity (available on our web site at www. fda gov/cder/pediatric) for details. We
`acknowledge your June 26, 2003 "Proposed Pediatric Study Request" submitted under 1N
`We are reviewing your submission and will respond to your proposalin a separate letter. FDA
`generally does not consider studies submitted to an NDA beforeissuance of a Written Request as
`responsive to the Written Request. Applicants should obtain a Written Request before submitting
`pediatric studies to an NDA.
`-
`
`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
`this division 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, MD 20857
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`Please submit one market package of the drug product when it is available.
`
`We have not completed validation of the regulatory methods. However, we expect your continued
`cooperation to resolve any problems that may be identified.
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR
`314.80 and 314.81). In addition, we request that you initiate a 15-day report [21 CPR 314.80(c)] for
`each of the following:
`0 All spontaneous reports of constipation requiring hospitalization or emergency room visit
`0 All spontaneous reports of possible complications of constipation such as obstruction,
`perforation, intestinal ulceration, toxic megacolon, ileus, or impaction resulting in
`hospitalization or emergency room visit
`0 All spontaneous reports of any cardiovascular adverse event
`
`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse event
`reports that are received directly by the FDA. New molecular entities and important new biologics
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`

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`NDA 21-372
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`Page 3
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`qualify for inclusion for three years after approval. Your firm is eligible to receive copies of reports for
`this product. To participate in the program, please see the enrollment instructions and program
`description details at www. fda.gov/medwateh/report/mmphtm.
`
`Ifyou have any questions,call Brian Strongin, R.Ph., M.B.A., Regulatory Project Manager at (301)
`827-7473.
`'
`'
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`Sincerely,
`
`{See appended electronic signature page}
`
`Julie Beitz, M.D.'
`
`Deputy Director
`Office of Drug Evaluation 1]]
`Center for Drug Evaluation and Research
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`Enclosure
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`

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`--------------------------h---------.----.---------------------------.-.-----------.—-----------------------n-—-_
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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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`/5/
`
`Julie Beitz‘
`7/24/03 02:35:52 PM
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`