Complete Response Letter_2 - Isoplate Solution
DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
Our STN: BN090067
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, that we received June 14, 2010, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Isoplate Solution, Multi-Electrolyte Injection, magnesium chloride USP 30mg/100mL.
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; and April 4, 2012.
The November 7, 2011, submission constituted a complete response to our February 4, 2011, action letter.
We have completed our review of your application, as amended, and have determined that we cannot approve this application in its present form. We have described our reason for this action below and, where possible, our recommendations to address this issue.
Clearance of the 510(k) submission for modification of the Trima device (Terumo BCT) for the collection of hyperconcentrated platelets is required before this application may be approved as this will constitute the only approved use of this product. Please notify us in writing when the 510(k) is cleared.
When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.
- Describe in detail any significant changes or findings in the safety profile.
- When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data as follows:
- Present new safety data from the studies/clinical trials for the proposed indication using the same format as the original NDA submission.
- Present tabulations of the new safety data combined with the original NDA data.
- Include tables that compare frequencies of adverse events in the original NDA with the retabulated frequencies described in the bullet above.
- For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
- Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.
- Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.
- Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original NDA data.
- Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
- Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.
- Provide English translations of current approved foreign labeling not previously submitted.
Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under 21 CFR 314.65. You may also request an extension of time in which to resubmit the application. A resubmission must fully address all the deficiencies listed. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.
Under 21 CFR 314.102(d), you may request a meeting or telephone conference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the FDA’s “Guidance for Industry - Formal Meetings Between the FDA and Sponsors or Applicants,” May 2009 at
The drug product may not be legally marketed until you have been notified in writing that this application is approved.
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