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Vaccines, Blood & Biologics

Summary of FDA Internal Meeting, January 11, 2013 - SOLX® System

DEPARTMENT OF HEALTH & HUMAN SERVICES                                                     Public Health Service

                                                                                                                            Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448

Our Reference:   Ref. # BN110059
                              CRMTS # 8746


TODAY’S DATE: January 11, 2013            PAGES: 6

TO:                 Lynn Jensen
Hemerus Medical, LLC
Fax number: (651) 635-0090
Email address:

FROM:           Sonday L. Kelly, MS, RAC
Regulatory Project Manager
Division of Blood Applications
Office of Blood Research and Review
Phone number: (301) 827-6162
Fax number: (301) 827-2857

SUBJECT:     Summary of FDA Internal Meeting

PRODUCT:   LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive; SOLX® System

Although we continue to reserve Thursday, January 17, 2013, 11:30 a.m. to 1 p.m., for a face to face meeting with you regarding this product, if you find that our attached responses and advice are sufficiently clear and complete to obviate the need for further discussion, please inform us in writing as soon as possible so that we may clear the meeting time.  These responses would then become the official FDA responses to your questions.

Alternatively, if you have questions regarding specific responses or advice, please inform us so that the appropriate members of the review team can provide clarification during the reserved meeting time.  Note that if there are any major changes to your development plan, the purpose of the meeting, or the questions based on our pre-meeting (preliminary) responses, we may not be prepared to discuss and/or to reach agreement on such changes at the meeting although we will try to do so if possible.

Questions from Hemerus Medical, LLC:


Hemerus Medical, LLC Question 1:
The clarifications and data presented above, including platelet counts, spleen weights and tissue histopathology, support the conclusion of the 14-Day Repeat Dose Toxicity Study stating the test article showed no biologically relevant effects when administered by intravenous injection to mice daily for 14 consecutive days.

Based on the foregoing, the clarifications submitted above are intended to adequately address FDA concerns.  Does FDA agree with this assessment and resolution?    

FDA Response to Question 1:
The assessment is acceptable.

Based on the similarity of the historical platelet count data and the recent platelet count data submitted, we find your response adequate to address the potential safety concerns associated with the platelet aggregation observed during the original repeat-dose toxicity study conducted with the SOLX® bag extract.  

The statistical analysis of the absolute and relative spleen weight data and explanation of the histopathology results that you provided are also considered adequate to address our previous safety concerns.  No further information is requested at the present time.

Hemerus Medical, LLC Question 2:
The container material tested and reported with Certificate 06-5803-N2 is comprised of identical materials to the SOLX® System containers.  Testing conducted under Certificate 06-5803-N2 and recent testing conducted under Report 10-1868-G1 both support material safety of the SOLX® System plastic containers. 

Based on the foregoing, the clarifications submitted above are intended to adequately address FDA concerns.  Does FDA agree with this assessment and resolution?      

FDA Response to Question 2:
The nonclinical testing results that qualified the safety of the original leukoreduction blood bag container also provide bridging data that support the qualification of the SOLX® blood bag container because you have assured FDA that the materials which comprise both the original bag and entire SOLX® system, including the circuits, are the same.  Therefore, the results generated from the extractables and leachables study conducted with the original blood bag, in addition to the past clinical experience with your original leukoreduction system are adequate to qualify the PVC used in the new circuits, and the filtration unit which constitute the new SOLX® system.  No additional information is required at this time.

 Container Labels

Hemerus Medical, LLC Question 3:
Please provide feedback for the container labels attached as Appendix 1 to this information packet.   

FDA Response to Question 3:
The container labels still do not follow ISBT consensus standard 2.0.  Please review the ISBT standards and revise the labels.  Please refer to the ICCBA website for standards:  Please see the attached example of a base label from the ICCBBA 2.0 standard.  Please note the location of the product and drug information.

Hemerus Medical, LLC Question 4:
Please verify that ISBT “over-labels” designed to cover the four quadrants of the base label are not required to be approved with this NDA submission.      

FDA Response to Question 4:
Your labels include the required information but it is not in the correct place.  Additionally, the “Rx Only” statement should be part of the upper left quadrant.  Please see example above for font size and location of language.

Additionally, the information on your new products description from ICCBA is not consistent with nomenclature.  We will contact ICCBA to correct the language.

Facility Inspection

Hemerus Medical, LLC Question 5:
Please confirm that the facility inspection review will proceed upon resubmission of
NDA BN110059.        

FDA Response to Question 5:
Your facility inspection review was closed on September 28, 2012, by the FDA Office of Compliance and Biologics Quality (OCBQ).  You are required to complete the corrective actions as committed, but no further corrective action reports are required by OCBQ.

Because the inspection has already taken place and the Division of Case Management (DCM) has closed out the inspection, there are no more inspection issues.

Hemerus Medical, LLC Question 6:
Who is the specific contact person at FDA for inquiries relating to the facility inspection and what is the preferred method of communication? Is there a mechanism, procedure or process that would allow for review of JMSS corrective action prior to resubmission?           

FDA Response to Question 6:
JMS facility inspection is now closed and no further communication regarding facility inspection is required.

Because there are no inspection issues to be resolved, there should be no need to contact the FDA regarding this inspection.  However, if you need to contact the FDA regarding inspections, please contact DCM.

Hemerus Medical, LLC Question 7:
Will FDA require another on-site facility inspection of JMSS as part of the NDA approval or will the evidence of completed CAPA suffice? 

FDA Response to Question 7:
Based on the facility inspection review, another on-site facility inspection of JMS-   Singapore is not required as part of this NDA approval.

If you have not received a letter from DCM, we cannot respond to the timing of your next inspection.  Please note that corrective actions will be reviewed and assessed during the next scheduled inspection of the facility.

Additional FDA Questions/Comments: 

  1. Regarding Reanalyzed Residual WBC Data: We disagree with the ----------(b)(4)-------- gating strategy in your Revised Reporting of Residual WBC in the Study and therefore the reanalysis of data is unacceptable.
    1. As stated by Bashir and Cardigan (Vox Sanguinis, 2003:85, 190-198):  “The decision whether to include extra-regional events in the residual WBC count depends on the nature of the events and their clinical significance.”  The clinical significance of the extra-regional events is unclear.  Not including these events in white blood cell (WBC) gate may undervalue possible adverse events caused by WBC fragments, such as secondary immunization.
    1. Using the (b)(4) controls to set the WBC gate has been the standardized practice in your DHMC clinical laboratory and how previous data was generated.  In order to achieve rWBC counting consistency, it is unacceptable to change the gating strategy for a particular set of data, retrospectively. 
  1. Regarding submission options, we recommend the following options:
    1. You could separate the 8 hour hold indication from ---------------(b)(4)------------. The 8 hour hold indication can be approved when all issues in the CR letter (issued on August 31, 2012) are satisfactorily addressed.
    1. -----------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------:
      1. --------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------.
      2. -----------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------

We recommend that you send your study protocol to FDA for review and concurrence before initiating the study.

Page Last Updated: 05/24/2013
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