March 5, 2013 Approval Letter - Isoplate Solution in 500mL EXCEL containers; Multi-Electrolyte Injection
Our Reference: NDA BN090067/0
B. Braun Medical, Inc.
Attention: Ms. Rebecca Stolarick
901 Marcon Boulevard
Allentown, PA 18109
Dear Ms. Stolarick:
Please refer to your New Drug Application (NDA) dated June 14, 2010, received June 14, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, for Isoplate Solution in the 500mL EXCEL Container.
We acknowledge receipt of your amendments dated June 18, 2010; November 15, 2010; November 18, 2010; February 17, 2011; April 1, 2011; May 9, 2011; May 19, 2011; July 5, 2011; August 4, 2011; November 7, 2011; January 11, 2012; February 7, 2012; March 19, 2012; April 4, 2012; May 16, 2012; August 15, 2012; January 4, 2013; January 25, 2013; February 6, 2013; February 12, 2013; and February 15, 2013.
The January 4, 2013, submission constituted a complete response to our May 8, 2012 action letter.
This new drug application provides for the use of Isoplate™ Solution Platelet Additive Solution [PAS-F] as an isotonic solution to replace a portion of the plasma to store Platelet Pheresis, Leukocytes Reduced PAS products collected using a hyperconcentrated collection on Terumo BCT’s Trima Accel® System.
We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
CONTENT OF LABELING
The SPL will be accessible via publicly available labeling repositories.
CARTON AND IMMEDIATE-CONTAINER LABELS
We acknowledge your January 25, 2013, submission containing final printed carton and container labels.
REQUIRED PEDIATRIC ASSESSMENTS
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(s) in pediatric patients unless this requirement is waived, deferred, or inapplicable.
Because none of these criteria apply to your application, you are exempt from this requirement.
POSTMARKETING REQUIREMENTS UNDER 505(o):
Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act (FDCA) authorizes FDA to require holders of approved drug and biological product applications to conduct postmarketing studies and clinical trials for certain purposes, if FDA makes certain findings required by statute.
Therefore, based on appropriate scientific data, FDA has determined that you are required to conduct the following:
- Track Adverse Events
You have committed to conduct a controlled postmarketing study to track adverse events in the recipients of Trima Accel collected platelets stored in 65% Isoplate/ 35% plasma. Adverse events (e.g., transfusion reactions) will be captured through active surveillance of the test and the control products (platelets stored in plasma). Transfusion reactions will be classified and compared by type (e.g., TRALI, febrile non-hemolytic transfusion reaction, allergic reaction, etc.). Terumo BCT will conduct the postmarketing requirement at select institutions that are currently transfusing Trima Accel collected platelets in plasma and are planning to switch over to Trima Accel collected platelets stored in Isoplate.
A complete statistical plan including hypothesis testing will be submitted with the final protocol.
The timetable you submitted on February 15, 2013, states that you will conduct this study according to the following schedule:
Final Protocol Submission: Terumo BCT commits to begin the PMR study within 3 months of FDA approval of the final PMR protocol and statistical analysis plan.
Study Completion: Terumo BCT anticipates the study will take 6 years to complete (12,000 transfusions).
Final Report Submission: Terumo BCT anticipates submitting the final report within 6 months after study completion.
Submit the protocol(s) to your IND 13684, with a cross-reference letter to this NDA. Submit all final report(s) to your NDA. Prominently identify the submission with the following wording in bold capital letters at the top of the first page of the submission, as appropriate: “Required Postmarketing Protocol Under 505(o)”, “Required Postmarketing Final Report Under 505(o)”, “Required Postmarketing Correspondence Under 505(o).”
Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any study or clinical trial required under this section. This section also requires you to periodically report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a safety issue. Section 505B of the FDCA, as well as 21 CFR 314.81 (b)(2)(vii) requires you to report annually on the status of any postmarketing commitments or required studies or clinical trials.
FDA will consider the submission of your annual report under section 506B and 21 CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirements under section 505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and 21 CFR 314.81 (b)(2)(vii). 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 consider a violation of FDCA section 505(o)(3)(ii) and could result in enforcement action.
You may request advisory comments on proposed introductory advertising and promotional labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the proposed materials in draft or mock-up form with annotated references, and the package insert to:
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Compliance and Biologics Quality
Advertising and Promotional Labeling Branch
1401 Rockville Pike, Suite 200N, HFM-99
Rockville, MD 20852-1448
As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the package insert, at the time of initial dissemination or publication, accompanied by a Form FDA 2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For more information about submission of promotional materials to the Office of Prescription Drug Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
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, call Sonday L. Kelly, MS, RAC, Regulatory Project Manager at (301) 827-6162.
Jay S. Epstein, MD
Office of Blood Research and Review
Center for Biologics
Evaluation and Research
Content of Labeling
Carton and Container Labeling