Our STN: BN070012/145
Vaccines, Blood & Biologics
Fresenius Kabi Deutschland GmbH
Attention: Aparna Dagar, Ph.D.
APP Pharmaceuticals, LLC
1501 East Woodfield Road
Suite 300 East
Schaumburg, IL 60173
Dear Dr. Dagar:
Please refer to your Supplemental New Drug Application (sNDA) dated April 8, 2011, received May 10, 2011, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Voluven® 500 mL freeflex® flexible plastic intravenous solution container, 6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodium Chloride Injection.
We acknowledge receipt of your amendments dated April 8, 2011; June 9, 2011; July 8, 2011;
July 20, 2011; December 13, 2011; March 21, 2012; April 3, 2012; and April 24, 2012.
The March 21, 2012, submission constituted a complete response to our March 7, 2012, action letter.
This Prior Approval supplemental new drug application provides for Postmarketing Studies subject to reporting requirements of 21 CFR 314.81:
To perform a multiple-dose randomized controlled trial (RCT) to be conducted in children in the age group of 2 to 12 years. Fresenius Kabi will submit a final Clinical Study Protocol of this Phase 3 study entitled “Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven®) vs 5% HAS in volume substitution therapy during open-heart surgery in 2 to 12 years old pediatric patients” within 12 months of the Approval Letter and will submit the final Clinical Study Report to FDA within 36 months of the Approval Letter.
We have reviewed your submission and conclude that the above postmarkerting requirement #2 is fulfilled.
We have completed our review of this supplemental application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling [21 CFR 314.50(1)] in structured product labeling (SPL) format using the FDA automated drug registration and listing system (eLIST), as described at: http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content of labeling must be identical to the enclosed labeling, with the addition of any labeling changes in pending “Changes Being Effected” (CBE) supplements, as well as annual reportable changes not included in the enclosed labeling.
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.
The SPL will be accessible from publicly available labeling repositories.
Also, within 14 days, amend all pending supplemental applications for this NDA, including CBE supplements for which FDA has not yet issues and action letter, with the content of labeling
[21 CFR 314. 50(1)(1)(I)] in MS Word format, that includes the changes approved in this supplemental applications, as well as annual reportable changes and annotate each change. To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy should provide appropriate annotations, including supplement number(s) and annual report date(s).
We note that you have fulfilled the pediatric study requirements for all relevant pediatric age groups for this application.
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)].
You may request advisory comments on proposed introductory advertising and promotional labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory comments, (2) the proposed materials in draft or mock-up with annotated references, and (3) the Package insert(s) to:
Food and Drug Administration
Center for Biologics Evaluation and Research
Advertising and Promotional Labeling Branch
1401 Rockville Pike
Rockville, MD 20852-1448
You must submit final promotional material and package insert(s), accompanied by a Form FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81 (b)(3)(i)]. Form 2253 is available at http://www.fda.gov/opacom/morechoices/fdaforms/cder.html; instructions are provided on page 2 of the form.
We remind you that you must comply with reporting requirements for an approved NDA
(21 CFR 314.80 and 314.81).
If you have any questions, please contact the Regulatory Project Manager, Iliana Valencia, at
Basil Golding, M.D.
Division of Hematology
Office of Blood Research and Review
Center for Biologics
Evaluation and Research