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 Product Approval Information

Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448

November 25, 1997 Our Reference No.: 96-1433

Carl R. Illian, Ph.D.
Genetics Institute, Inc.
One Burtt Road
Andover, MA 01810-5901

Dear Dr. Illian:

Your biologics license application for Oprelvekin is approved effective this date. Genetics Institute, Inc., Andover, MA is hereby authorized to manufacture and ship for sale, barter, or exchange in interstate and foreign commerce Oprelvekin under Department of Health and Human Services Biologics License No. 1163.

Oprelvekin is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia.

In accordance with approved labeling, your product will bear the tradename Neumega, and will be marketed in single-use vials containing 5 mg of Oprelvekin.

You are not currently required to submit samples of future lots of Oprelvekin to the Center for Biologics Evaluation and Research (CBER) for release by the Director, CBER, under 21 CFR 610.2. FDA will continue to monitor compliance with 21 CFR 610.1 requiring assay and release of only those lots that meet release specifications.

The dating period for this product shall be 24 months from the date of manufacture when stored at 2-8°C. The date of manufacture shall be defined as the date of final sterile filtration of the formulated product. The purified, unformulated bulk Oprelvekin may be stored up to 36 months from the date of manufacture when stored at -80°C. Results of ongoing stability studies should be submitted throughout the dating period as they become available including the results of stability studies from the first three production lots.

We acknowledge your written commitments of October 30, 1997 and November 6, 1997, regarding manufacturing:

  1. To reevaluate the release specifications for Drug Substance and for Drug Product at the end of the next manufacturing campaign, in conjunction with the Quality Unit Annual Product Review, and to submit these revised specifications by the end of April 1999, for review and approval.
  2. To reevaluate the stability specifications for Drug Product and to submit by the end of September 1999, revised specifications for review and approval.
  3. To reevaluate the hold times for in process intermediates, based on revised Drug Substance specifications, and to submit the study report, along with appropriate revisions, for review and approval.
  4. To validate the use of the [-----------------] used for identity testing of recombinant human interleukin eleven (rhuIL-11) in release testing and to submit the validation report prior to the next Drug Substance manufacturing campaign.
  5. To repeat the photostability study on lyophilized Drug Product, on the final packaging configuration as well as the immediate container/closure, in accordance with the ICH Photostability Guidance, and to submit these data in the spring of 1998.
  6. To recalculate control limits for in-process yields based on the [-----] campaign and submit by the end of December 1998, revised control limits for review and approval.
  7. To complete the validation study extending the cycles of use for the QAE/S chromatography resins by developing a RP-HPLC assay to determine the relative level of host cell proteins in the in-process QAE/S product pool batches from lots 7A14G018 through 7A14G021, to compare these batches to earlier batches and to submit these data for FDA review as a BLA supplement prior to the start of the [-----] campaign.
  8. We acknowledge your written commitments of October 24, 1997, regarding clinical issues:

  9. To submit the final report for Study C9607-14 entitled "A Single Dose, Open-Label Pharmacokinetic Pilot Study of Recombinant Human Interleukin Eleven (rhuIL-11) in Subjects with Renal Failure and Normal Volunteers" and to submit proposed revisions to the package insert, if indicated, on the basis of the study findings, before April 1, 1998.
  10. To conduct a randomized, controlled clinical trial of Oprelvekin in pediatric patients receiving combination chemotherapy. As part of this commitment you will submit the results of the pilot study conducted by the Children’s Cancer Study Group (CCG) which will establish the optimal dose and schedule for the combination of ifosphamide, cisplatin, and topotecan and provide estimates of the platelet transfusion requirements and time to platelet recovery, and your proposal for the randomized controlled clinical trial in pediatric patients.

Any changes in the manufacture, packaging or labeling of the product or in the manufacturing facilities will require the submission of information to your biologics license application for our review and written approval consistent with 21 CFR 601.12.

We acknowledge your written correspondence of November 17, 1997, withdrawing the proposed Comparability Protocol submitted in section 4F of this license application. We understand that a revised comparability protocol will be submitted as a post-licensure manufacturing supplement which will be reviewed under a separate reference number.

It is requested that adverse experience reports be submitted in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and that distribution reports be submitted as described (21 CFR 600.81). All adverse experience reports should be prominently identified according to 21 CFR 600.80 and be submitted to the Center for Biologics Evaluation and Research, HFM-210, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448.

Please submit three copies of all final printed labeling at the time of use and include part II of the label transmittal form with completed implementation information. In addition, you may wish to submit draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2567 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Staff, HFM-202, 1401 Rockville Pike, Rockville, MD 20852-1448. Final printed advertising and promotional labeling should be submitted at the time of initial dissemination, accompanied by an FDA Form 2567. All promotional claims must be consistent with and not contrary to approved labeling. No comparative promotional claim or claim of superiority over other similar products should be made unless data to support such claims are submitted to and approved by the Center for Biologics Evaluation and Research.

Sincerely yours,

--- signature ---

Jay P. Siegel, M.D., FACP
Office of Therapeutics Research and Review
Center for Biologics Evaluation and Research

Last Updated: 1/14/2001

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Date created: September 25, 2003

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