• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

  • Print
  • Share
  • E-mail

Midcycle Review Memo, March 21, 2013 - SOLX System

FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
 


MEMORANDUM

INTERNAL Memorandum

Date:              March 21 , 2013

From:             Xuan Chi, M.D., Ph.D.
Lead reviewer
Laboratory of Cellular Hematology
DH/OBRR/CBER/FDA
(301)-827-2008

Through:      Jaroslav Vostal, M.D., Ph.D.
Chief, Laboratory of Cellular Hematology
Division of Hematology/OBRR/CBER/FDA
(301)-827-9655

To:                  Sonday Kelly, M.S.
Regulatory Project Manager
CBER/OBRR/DBA
(301)-827-6122

Subject:         Review of Hemerus’ response to FDA CR letter.
Submission #: NDA BN110059
Product:         The LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive also called “SOLX® System”.

Revised Indications for Use:

The LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive also called “SOLX® System” is intended for the manufacture of:
• CPD/AS-7 Red Blood Cells (RBC), Leukocytes Reduced prepared at ambient temperature and, placed at 1 to 6° C within 8 hours of collection. CPD/AS-7 Red Blood Cells, Leukocytes Reduced may be stored at 1 to 6° C for up to 42 days after collection.
• Fresh Frozen Plasma (FFP), Leukocytes Reduced prepared and placed in a freezer at -18° C or colder within 8 hours of collection. Fresh Frozen Plasma (FFP), Leukocytes Reduced may be stored at -18° C or colder for up to one year after collection.

Introduction:  
1. HEMERUS Medical, LLC submitted an original NDA for the HEMERUS LEUKOSEP HWB-600-XL Leukocyte Reduction Filtration System for the Whole Blood with CPD anticoagulant and SOLX additive solutions (also called SOLX System). It is designed with an integrated donor needle, blood diversion bag with integrated blood sampling port, whole
blood collection bag, LEUKOSEP® leukoreduction filter, red blood cell storage bag,
plasma storage bag and SOLX® additive solution bags. SOLX additive solution is a new red blood cell additive solution.
2. A CR letter was issued on August 31, 2012.
3. Hemerus submitted Amendment A15 on February 26, 2013, intended to address all concerns outlined in the FDA complete response letter.

Review Summary:

  1. Original FDA (CR) comment: Please provide a summary of chemical stability studies in support of a---(b)(4)--- shelf life claim. Real time stability testing of only one lot has been completed. Please submit stability updates for lot ----(b)(4)----- and lot ----(b)(4)------ to the Agency in periodic reports and at the end of ---(b)(4)--- storage study. If any data fall out of the stability specification, you should change the shelf life claim accordingly. You can request a shorter shelf life if it is supported by available data to prevent a delay in approval. When

the ---(b)(4)---- storage study data become available you can then request an extension of the shelf life.
Summary of the Applicant’s response on February 26, 2013: Hemerus has successfully demonstrated 2-year, real-time stability on three lots of SOLX® System product; therefore, Hemerus has modified the SOLX® System shelf-life claim to 24 months from date of manufacture.
FDA follow-up comments on March 21, 2013: This response is acceptable.

  1. Original FDA (CR) comment: Regarding extraction studies on SOLX® circuits:

The responses you provided in Amendment 14 to BN110059 for FDA questions # 16, 21 b
 and 24 a are not adequate to address the risk associated with the decreased platelet counts
 observed in mice administered leachate from the circuits and storage bags that comprise
the SOLX® system. Specifically, your response speculates that the lower platelet count
 in test animals results from in vitro, spontaneous platelet aggregation. This explanation is not sufficient and this issue remains a safety concern that must be addressed prior to approval.

Summary of the Applicant’s response on February 26, 2013:  Hemerus concluded that the decreased platelet counts were the result of inherent procedural variation while drawing blood samples from mice (i.e. slow flow through the needle or insufficient mixing with anticoagulant leading to platelet clumping and/or sample clotting). Platelets that are “clumped” or clotted are not counted by the instrument leading to invalid, low results. Hemerus also did spleen weight analysis and histopathological analysis of all major organs, and showed there were no significant differences between test and control groups studied. Hemerus concluded that the test article of the 14-Day Repeat Dose Toxicity Study showed no biologically relevant effects when administered by intravenous injection to mice daily for 14 consecutive days.
FDA follow-up comments on March 21, 2013: This response is acceptable.

  1. ------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------.  

         The current IFU statement is:
The LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole   Blood with CPD Anticoagulant and SOLX® Additive also called “SOLX® System” is intended for the manufacture of:
• CPD/AS-7 Red Blood Cells (RBC), Leukocytes Reduced prepared at ambient temperature and, placed at 1 to 6° C within 8 hours of collection. CPD/AS-7 Red Blood Cells, Leukocytes Reduced may be stored at 1 to 6° C for up to 42 days after collection.
• Fresh Frozen Plasma (FFP), Leukocytes Reduced prepared and placed in a freezer at -18° C or colder within 8 hours of collection. Fresh Frozen Plasma (FFP), Leukocytes Reduced may be stored at -18° C or colder for up to one year after collection.

 FDA comments on March 21, 2013: the current IFU statement is acceptable.

Letter-ready comments:
None