DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Food and Drug Administration
`Rockville, MD 20857
`
`NDA 21-462
`
`Eli Lilly & Company
`Attention: John F. Worzalla
`Regulatory Research Scientist, U.S. Regulatory Affairs
`Lilly Corporate Center
`Indianapolis, IN 46285
`
`Dear Mr. Worzalla:
`
`Please refer to your new drug application (NDA) dated September 29, 2003, received September
`30, 2003, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for
`Alimta® (pemetrexed, LY231514).
`
`We acknowledge receipt of your submissions dated October 24, November 22, December 6,
`2002; January 10, 28, February 13, March 24, 27, April 3, May 9, 12, 29, June 18, 26, 30, July
`29, 30, August 8, 15, 21, 28, September 2, 3, 4, 9, 12, 15, 16, 19, 22, 29, October 6, 7, 20,
`November 4, 5, 6, 14, 18, 24, 26, December 1, 4, 5, 10, 11, 12, 15, 16, 29, 2003, and January 12,
`2004.
`
`This new drug application provides for the use of Alimta® (pemetrexed, LY231514) in the
`treatment of patients with malignant pleural mesothelioma whose disease is either unresectable
`or who are otherwise not candidates for curative surgery.
`
`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the agreed-upon attached labeling text.
`
`The final printed labeling (FPL) must be identical to the enclosed labeling (text for the package
`insert and the patient package insert). 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.
`
`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 NDA 21-462."
`Approval of this submission by FDA is not required before the labeling is used.
`
`Sandoz Inc.
`Exhibit 1038-0001
`
`Teva – Fresenius
`Exhibit 1038-00001
`
`

`
`NDA 21-462
`Page 2
`
`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 Oncology Drug Products 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
`
`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).
`
`The Med-Watch-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 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/medwatch/report/mmp.htm.
`
`If you have any questions, call Patty Garvey, Regulatory Project Manager, at (301) 594-5766.
`
`Sincerely,
`{See appended electronic signature page}
`
`Robert Temple, M.D.
`Director
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`Enclosure: labeling
`
`Sandoz Inc.
`Exhibit 1038-0002
`
`Teva – Fresenius
`Exhibit 1038-00002
`
`

`
`Thisis a representation ofan electronic record that was signed electronically and
`this pageisthe mani~station ofthe electronic signature.
`
`Robert Temple
`2/4/04 07:52:20 PM
`
`Sandoz Inc.
`Exhibit 1038-0003
`
`Teva – Fresenius
`Exhibit 1038-00003