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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:
  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.
  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.
  ------------------------------------------------------------------------------------------------------------------------------------------------(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
 

    
 
