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Vaccines, Blood & Biologics

Information Request Letter, June 29, 2012 - SOLX® System

DEPARTMENT OF HEALTH & HUMAN SERVICES                                                     Public Health Service

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


Hemerus Medical, LLC
Attention: Ms. Lynn Jensen
June 29, 2012
Sent by email:
Dear Ms. Jensen:
We are reviewing your October 28, 2011 new drug application (NDA) for LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive.  We have determined that the following information is necessary to continue our review:
  1. In your initial validation of Sterilizer (b)(4) (Validation Report LAB/VP/039/06), you used  -------(b)(4)------------------------------- as your biological indicator with an unknown D-value. Since the D-value is unknown, the resistance cannot be evaluated and we cannot correlate how the validation correlates to the bioburden in the facility. Therefore, this initial validation is not valid.
  2. Additionally, after the initial validation you changed the bag arrangement and only performed one additional re-validation run using -------(b)(4)---------------------- as the biological indicators with a D121-value of ---(b)(4)-----. From the list of bacteria and fungus isolated at your facility, it appears that you have had spore forming organisms that have not been assessed for resistance. What you have assessed have not been adequately represented (i.e. spore formers, mold). Therefore we cannot assess the adequacy of your chosen biological indicators. To address these concerns, please provide the following additional information:
    1. Please provide additional studies to compare the resistance of representative organisms in your facility. To facilitate comparison to your chosen validation biological indicator, we recommend that your thermal studies also include the biological indicator. Please note, if your thermal resistance studies indicate a facilitate isolate more resistant then -------(b)(4)------ then additional validation runs with a new, more resistant biological indicators should be provided.
    2. Additional runs to demonstrate reproducibility need to be performed with the new bag arrangement using a sufficiently resistant biological indicator for us to be able to evaluate the effectiveness of your sterilization cycle.
  3. Please clarify if the container closure integrity testing on the system was performed after sterilization and -----(b)(4)---------.
  1. You performed a transportation simulation study (Report Number 0706135) and evaluated the results in Report TP/077/PED/2008. The general appearance and label peel testing did not meet the acceptance criteria. The outer boxes, inner boxes, labels, and dividers were damaged and moisture was found in the package. Per Report PC407240 and FR407240 you subsequently changed the packaging configuration and shipped cartons from Singapore to Hemerus. In PC407240 and FR407240, you only evaluated the foil and failed to evaluate the general appearance of the outer boxes, inner boxes, divers, tubs, and labels and failed to evaluate the label peel testing. Please address the following questions.
    1. Please provide the shipping conditions (i.e. time, temperature, etc), how many carton were shipped, and if the study represented the worse case shipping conditions (i.e. time, temperature, etc.).
    2. Please clarify how many runs were performed in this study.
    3. Please clarify if the packaging of the cartons in this study reflects routine manufacturing conditions.
    4. The transportation SOP you provided does not include how the inner box, outer box, and dividers are assembled in the carton. Please explain how the cartons are packaged and if this information is captured in a different SOP.
    5. Please provide the investigation report (root cause) for the failed acceptance criteria in Report TP/077/PED/2008, what changes were made to address these failures (corrective action), and how you ensure the effectiveness of the corrective action (i.e. SOP changes).
    6. Please provide the justification for changing the packaging configuration.
    7. Provide the shipping criteria during routine operation (i.e. time, temperature, etc).
  1. In Testing Report TP/248/PED/2010 (Design Verification Testing of --(b)(4)-- Real Time Aged SOLX Blood Bag System ------(b)(4)------ the label peel test failed (label peeled off without being destroy by careful mean) on the blood bag. You have indicated as a corrective action you have implemented a -------------(b)(4)-----. You stated that you repeated the test at zero years after implementing the corrective action.
    1. Please explain if you have repeated the label peel test at the shelf life of your product since implementing the corrective action.
    2. If not, please explain if you have evaluated the label peel test on accelerated aged product.
The review of this submission is on-going and issues may be added, expanded upon, or modified as we continue to review this submission. 
Please submit your response to this information request as an amendment to this file by
July 13, 2012 referencing the date of this request.  If you anticipate you will not be able to respond by this date, please contact me immediately so a new response date can be identified.
If we determine that your response to this information request constitutes a major amendment, we will notify you in writing. 
The action due date for this file is August 31, 2012.
If you have any questions, please contact me at (240) 507-8446.
Sonday L. Kelly, M.S.
Regulatory Project Manager

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