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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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June 3, 2011 Approval Letter - Kedbumin

Our STN:  BL 125384/0

Kedrion, S.p.A
Attention:  Mr. Urs E. Aeberli
c/o: FFF Enterprises, Inc.
41093 County Center Drive
Temecula, CA  92591

Dear Mr. Aeberli:

We are issuing Department of Health and Human Services U.S. License No. 1851 to Kedrion S.p.A.,Via Provinciale Loc., Bolognana, Italy, under the provisions of section 351(a) of the Public Health Service Act controlling the manufacture and sale of biological products.  The license authorizes you to introduce or deliver for introduction into interstate commerce, those products for which your company has demonstrated compliance with establishment and product standards.

Under this license, you are authorized to manufacture the product Albumin (Human).  Albumin (Human) is indicated for:

  • Hypovolemic shock
  • Hypoalbuminemia
  • Prevention of central volume depletion after paracentesis due to cirrhotic ascites
  • Ovarian Hyperstimulation Syndrome (OHSS)
  • Adult Respiratory Distress Syndrome (ARDS)
  • Burns
  • Hemodialysis patients undergoing long term dialysis
  • Patients who cannot tolerate substantial volumes of salt solution
  • Priming solution for cardiopulmonary bypass 

Under this license, you are approved to manufacture Albumin (Human) at your facility in Via Provinciale Loc., Bolognana, Italy.  You may label your product with the proprietary name KEDBUMIN and will market it in 50 mL vials.

We did not refer your application to the Blood Products Advisory Committee because our review of information submitted in your BLA, including the clinical study design and trial results, did not raise concerns or controversial issues which would have benefited from an advisory committee discussion.

The dating period for KEDBUMIN shall be 36 months from the date of manufacture when stored at 0 – 30 °C and protected from light.  The date of manufacture shall be defined as the date of final sterile filtration of the formulated drug product. Following the final sterile filtration, no reprocessing/reworking is allowed without prior approval from the Agency. 

Please submit final container samples of the product 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 Biologic 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, including but not limited to, the manufacturing, testing, packaging or labeling of KEDBUMIN, or in the manufacturing facilities.

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, that 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 provide your final content of labeling in Structured Product Labeling (SPL) format and include the carton and container labels.  In addition, please submit three original paper copies for carton and container final printed labeling.  All final labeling should be submitted as Product Correspondence to this BLA at the time of use (prior to marketing) and include implementation information on FDA Form 356h [OPTION: and FDA Form 2567 as appropriate].

In addition, please submit the final content of labeling (21 CFR 601.14) in SPL format via the FDA automated drug registration and listing system, (eLIST), as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.  Information on submitting SPL files using eLIST may be found in the guidance for industry titled, “SPL Standard for Content of Labeling Technical Qs and As at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
UCM072392.pdf
.

You may 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. You must submit copies of your final advertisement and promotional labeling at the time of initial dissemination or publication, accompanied by Form FDA 2253 (21 CFR 601.12(f)(4)).

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 substantial evidence or substantial clinical experience to support such claims (21 CFR 202.1(e)(6)).

Please submit an amendment to all pending supplemental applications for this BLA that include revised labeling incorporating a revised content of labeling that includes [this/these] change(s).

ADVERSE EVENT REPORTING

You must submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and you must submit distribution reports as described in 21 CFR 600.81.  You should submit postmarketing adverse experience reports and distribution reports to the Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology HFM-210, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448.  Prominently identify all adverse experience reports as described in 21 CFR 600.80.  Per 21 CFR 600.2(f), please refer to http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm106001.htm for updated mailing address information.

PEDIATRIC REQUIREMENTS

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred, or inapplicable.

We are deferring submission of your pediatric study for ages 0-12 years for this application because this product is ready for approval for use in adults and the pediatric study has not been completed.

Your deferred pediatric study required under 505B(a) of the Federal Food, Drug, and Cosmetic Act is a required postmarketing study.  The status of this postmarketing study must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act.  This required study is listed below:

  • “A prospective, randomized, multicenter, controlled open label study to evaluate the safety of Kedbumin 25% compared to normal saline solution in the treatment of post-surgical hypovolemia associated with hypoalbuminemia in pediatric patients undergoing major elective surgery.”

This study will enroll a total of 100 subjects, 50 subjects in each treatment cohort, with approximately equal numbers of subjects in the following subpopulations: 1 day – 2 yr., 2 yr. – 6 yr., and 6 yr. – 12 yr.

Final Protocol Submission: May 20, 2011

Study Completion Date: September 30, 2013

Final Report Submission: December 31, 2013

Submit final study reports to this BLA.  For administrative purposes, all submissions related to this required pediatric postmarketing study must be clearly designated “Required Pediatric Assessment.”

Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70.  

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We request that you submit information concerning nonclinical and chemistry, manufacturing, and control postmarketing commitments and final reports to your BLA, STN BL 125384.

Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:

  • Postmarketing Study Correspondence
  • Postmarketing Study Commitment – Final Study Report
  • Supplement Contains Postmarketing Study Commitment – Final Study Report

For each postmarketing commitment not subject to the reporting requirements of 21 CFR 610.70, you may report the status to FDA as a “PMC Submission – Status Update.”  The status report for each commitment should include:

  • The original schedule for the commitment, and
  • The status of the commitment (i.e., pending, ongoing, delayed, terminated, or submitted).

When you have fulfilled your commitment, submit your final report as PMC Submission – Final Study Report or Supplement Contains Postmarketing Study Commitment – Final Study Report.

We will consider the submission of your annual report under section 506B and 21 CFR 601.70 to satisfy the periodic reporting requirement under section 505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and 21 CFR 601.70.  We remind you that to comply with 505(o), your annual report must also include a report on the status of any study or clinical trial otherwise undertaken to investigate a safety issue.  Failure to submit an annual report for studies or clinical trials required under 505(o) on the date required will be considered a violation of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.

Sincerely yours,   

 

Mary A. Malarkey
Director 
Office of Compliance and  Biologics Quality
Center for Biologics        
Evaluation and Research           

 

Jay S. Epstein, M.D.                
Director   
Office of Blood Research and Review
Center for Biologics  
Evaluation and Research