Filing Letter - Isoplate Solution
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
Our Reference: NDA BN090067
B. Braun Medical, Inc.
Attention: Ms. Susan Olinger
901 Marcon Boulevard
Allentown, PA 18109
Dear Ms. Olinger:
Please refer to your new drug application (NDA) dated June 9, 2010, received June 14, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act, for Isoplate Solution in the 500 mL EXCELâ Container.
We also refer to your submission dated June 18, 2010.
We have completed our filing review and have determined that your application is sufficiently complete to permit a substantive review. Therefore, in accordance with 21 CFR 314.101(a), this application is considered filed 60 days after the date we received your application. The review classification for this application is Standard. Therefore, the user fee goal date is April 14, 2011.
We are reviewing your application according to the process described in the Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products. Therefore, we have established internal review timelines as described in the guidance, which includes the timeframes for FDA internal milestone meetings (e.g., filing, planning, midcycle, team and wrap-up meetings). Please be aware that the timelines described in the guidance are flexible and subject to change based on workload and other potential review issues (e.g., submission of amendments). We will inform you of any necessary information requests or status updates following the milestone meeting or at other times, as needed, during the process. If major deficiencies are not identified during the review, we plan to communicate proposed labeling and, if necessary, any postmarketing requirement/commitment requests by April 14, 2011.
Our filing review is only a preliminary evaluation of the application and is not indicative of deficiencies that may be identified during our review. Issues may be added, deleted, expanded upon, or modified as we review the application.
We request that you submit the following information:
- Drug Master File (DMF) letters of authorizations should reference the DMF number, the specific item being referenced, and the date of the submission for that item. Please provide revised DMF letters of authorizations for the ---(b)(4)---- Sodium Chloride, USP and Potassium Chloride, USP drug substances. FDA is unable to review the referenced DMFs in support of your NDA in the absence of an adequate letter of authorization.
- It is noted that B. Braun Medical, Inc. conducted the chemical, biological and physical functional testing on the Excel® plastic container in accordance with the USP requirements and additional B. Braun tests. The product’s proposed indication is for platelet storage in the following ratio: 65% Isoplate Solution and 35% plasma. It is stated in the label that Isoplate Solution will not be used for direct infusion. However, please note that Isoplate Solution will be directly infused into patients as a component of apheresis platelet products. This is of concern because there can be an accumulation of extractables/leachables beyond the acceptable range with multiple use (doses) of product. The levels of each extractable/leachable need to be assessed at the maximum daily dose of the combination product to ensure safety. Please see the comments below:
a. Please note the toxicological evaluation of leachables/extractables from the plastic should be based on animal studies that defined a toxic dose of an intravenous (IV) administered compound and on the anticipated clinical application of the product. Please identify each extractable/leachable and calculate their levels at the maximum clinical dose, to ensure that it is within an acceptable range.
b. Please submit electronically all preclinical (toxicological) studies that are cross referenced in order to complete the file.
Please respond to the above requests for additional information. While we anticipate that any response submitted in a timely manner will be reviewed during this review cycle, such review decisions will be made on a case-by-case basis at the time of receipt of the submission.
We reference the waiver granted on May 5, 2008 for the pediatric study requirements for this application.
If you have any questions, please call Iliana Valencia, Regulatory Project Manager, at (301) 827-6161.
Basil Golding, M.D.
Division of Hematology
Office of Blood Research and Review
Center for Biologics
Evaluation and Research