DEPARTMENT OF HEALTH & HUMAN SERVICESPublic Health ServiceFood and Drug AdministrationRockville MD 20857NDA 20-896 April 30, 1998Hoffman-La Roche Inc.340 Kingsland StreetNutley, NJ 07110-1199Attention: Cynthia Dinella, Pharm. D. Group Director, Regulatory AffairsDear Dr. Dinella:Please refer to your new drug application dated October 28, 1997, received October 30, 1997,submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Xeloda(capecitabine) tablets, 150 mg and 500 mg.We acknowledge receipt of the following amendments:1997 November 11 and 13 December 231998 January 9, 27 (2), 28, and 29 February 4, 9, 12, 13, 20, 24 (2), 25, 27 (2), March 2, 4, 5, 9, 10, 11, 12, 13, 16, 17, 18, 26, and 27 April 2, 9, 15 (2), 16 (2), 21, 23, and 27.The User Fee goal date for this application is April 30, 1998.This new drug application provides for the treatment of patients with metastatic breast cancerresistant to both paclitaxel and an anthracycline-containing chemotherapy regimen or resistant topaclitaxel and for whom further anthracycline therapy may be contraindicated, e.g., patients whohave received cumulative doses of 400 mg/m2 of doxorubicin or doxorubicin equivalents.Resistance is defined as progressive disease while on treatment, with or without an initialresponse, or relapse within 6 months of an anthracycline-containing adjuvant regimen.We have completed the review of this application, including the submitted draft labeling,according to the regulations for accelerated approval and have concluded that adequateinformation has been presented to approve Xeloda (capecitabine) tablets, 150 mg and 500 mg. foruse as recommended in the enclosed marked-up draft labeling. Accordingly, the application isapproved under 21 CFR 314.520. Approval is effective on the date of this letter.The final printed labeling (FPL) must be identical to the enclosed revised draft labeling. Marketing the product with FPL that is not identical to this draft labeling may render the productmisbranded and an unapproved new drug.Please submit 20 copies of the FPL as soon as it is available, in no case more than 30 days after it
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`NDA 20-896Page 2is printed. Please individually mount ten of the copies on heavy-weight paper or similar material. For administrative purposes, this submission should be designated "FINAL PRINTEDLABELING" for approved NDA 20-896. Approval of this submission by FDA is not requiredbefore the labeling is used.Should additional information relating to the safety and effectiveness of the drug becomeavailable, revision of that labeling may be required.We remind you of the Phase 4 commitments specified in your submission dated April 16, 1998.These commitments are listed below.(b)(4)CC----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Protocols, data, and final reports, should be submitted to your IND for this product and a copy ofthe cover letter sent to this NDA. In addition, we request under 21 CFR 314.81(b)(2)(vii) thatyou include in your annual report to this application, a status summary of each commitment. Thestatus summary should include the number of patients entered in each study, expected completionand submission dates, and any changes in plans since the last annual report. For administrativepurposes, all submissions, including labeling supplements, relating to these Phase 4 commitmentsmust be clearly designated "Phase 4 Commitments".Further, we acknowledge your April 9 and 14, 1998 commitments to address the following
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`NDA 20-896Page 3chemistry, manufacturing and controls concerns with due diligence:1. Three batches of each dosage strength Xeloda (capecitabine) Tablets manufactured using theimproved manufacturing process will be placed on stability, and the data will be included inthe annual report. 2. Within one year, R(b)(4)CC---------------------ined from commercially manufactured lots ofcapecitabine will be reviewed and compared to the current specifications to determine howthese specifications can be tightened. Revised specifications will be developed and submittedin a pre-approval supplement.We also remind you that, under 21 CFR 314.550, after the initial 120 day period following thisapproval, you must submit all promotional materials, including promotional labeling as well asadvertisements, at least 30 days prior to the intended time of initial dissemination of the labelingor initial publication of the advertisement.Validation of the regulatory methods has not been completed. At the present time, it is the policyof the Center not to withhold approval because the methods are being validated. Nevertheless,we expect your continued cooperation to resolve any problems that may be identified.Please submit one market package of the drug product when it is available.We remind you that you must comply with the requirements for an approved NDA set forth under21 CFR 314.80 and 314.81.If you have any questions, please contact Maureen Pelosi, Project Manager, at (301) 594-5768.Sincerely yours,Robert Temple, M.D.DirectorOffice of Drug Evaluation ICenter for Drug Evaluation and ResearchENCLOSURE
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`IMMUNOGEN 2213, pg. 3
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