October 15, 2007 Corrected Approval Letter
Our STN: BL 125247/0
OMRIX Biopharmaceuticals, Ltd.
Attn: Robert L. Zeid, TLI Development
113 SE 5th St.
Oak Island, NC 28465
Dear Mr. Zeid:
This letter corrects our previous approval letter of August 27, 2007, regarding the licensure of Thrombin, Topical (Human) [EVITHROM®]. Our approval letter should have included language related to the reporting of infections disease transmission and adverse events. This language has been added on page 2, paragraphs 8, 9, and 10.
Your Biologics License Application for Thrombin, Topical (Human) was approved effective August 27, 2007. OMRIX Biopharmaceuticals was authorized to introduce or deliver for introduction into interstate commerce, Thrombin, Topical (Human) under U.S. License No. 1603. Thrombin, Topical (Human) is indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical. Thrombin, Topical (Human) may be used in conjunction with an Absorbable Gelatin Sponge, USP.
Under this license, you are authorized to manufacture Thrombin, Topical (Human) prepared at your facility, MDA Blood Services, Sheba Hospital, Ramat-Gan, POB 88, Kiryat Ono 55000, ISRAEL, REGISTRATION NUMBER 3003183625. You may label your product with the proprietary name EVITHROM® and will market it in 2 ml, 5 ml, and 20 ml dose vials.
The dating period for EVITHROM® shall be 2 years from the date of manufacture when stored frozen at -18oC and 30 days at 2-8oC when stored unopened.
Please submit final container samples of the product and each kit component in final containers together with protocols showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research (CBER).
You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in the manufacturing, testing, packaging or labeling of EVITHROM®, or in the manufacturing facilities.
In addition, pursuant to 21 CFR 600.80(c)(2)(Periodic Adverse Experience Reports), the Agency is requiring that manufacturers report on a monthly basis any infectious disease transmission associated or possibly associated with any licensed biological product that is not reportable under 21 CFR 600.80 (c)(1)(Fifteen-day Alert Reports). The timing of this monthly periodic reporting requirement was selected, among other reasons, to permit the acquisition of patient information, including clinical evaluation, sufficient to help in the timely assessment of a causal connection between the biological product and possible or documented infectious disease transmission. This new reporting requirement was also based on the observation of inconsistent practices by some manufacturers in submitting reports of possible infectious diseases.
Please note that this monthly reporting requirement applies only to infectious disease transmission. Other periodic reports should continue to be submitted on the quarterly or annual basis that is appropriate to each licensed biological product for all other adverse experiences not reportable under 21 CFR 600.80(c)(1). You should submit these monthly reports to The Center for Biologics Evaluation and Research, Division of Epidemiology, HFM-210, 1401 Rockville Pike, Rockville, MD, 20852-1448. Please contact the Division of Epidemiology (301-827-3974) if you have any questions about these periodic adverse event reporting requirements.
You must submit adverse experience reports under the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and you must submit distribution reports under 21 CFR 600.81. You should submit postmarketing adverse experience reports and distribution reports to the Center for Biologics Evaluation and Research, HFM-210, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Prominently identify all adverse experience reports as described in 21 CFR 600.80.
You must submit reports of biological product deviations under 21 CFR 600.14. You promptly should identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.
Please submit all final printed labeling at the time of use and include implementation information on FDA Form 356h and FDA Form 2567 as appropriate. Please provide a PDF-format electronic copy as well as original paper copies (ten for circulars and five for other labels). In addition, you may wish to submit two draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Two copies of final printed advertising and promotional labeling should be submitted at the time of initial dissemination, accompanied by a FDA Form 2253.
All promotional claims must be consistent with and not contrary to approved labeling. You should not make a comparative promotional claim or claim of superiority over other products unless you have submitted data to support such claims to us and have had them approved.
--- signature ---
Jay S. Epstein, M.D.
Office of Blood Research and Review
Center for Biologics Evaluation and Research