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Vaccines, Blood & Biologics

Information Request Letter, April 16, 2012 - SOLX® System

DEPARTMENT OF HEALTH & HUMAN SERVICES                                                     Public Health Service

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


Our STN:  BN110059/0
Hemerus Medical, LLC
Attention:  Ms. Lynn Jensen
April 16, 2012
Sent by email:
Dear Ms. Jensen:
Please refer to your October 28, 2011, New Drug Application (NDA) submitted under Section 505(b) of the Federal Food, Drug, and Cosmetic Act for HEMERUS LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive.
We determined that the following information, related to manufacturing and product quality, is necessary to continue our review:
Validation/revalidation of the (b)(4) sterilizer:
  1. Please provide the design approach utilized for your autoclave (i.e. overkill).
  1. Please clarify the sterilization process you are using (i.e. -----------------------------------------------------(b)(4)--------------------------------------------------).
  1. Please clarify if all your loads in operation will be at the maximum load.  If not, provide a justification on why the minimum load was not validated.
  1. Please provide a summary of all deviations and their associated resolutions for your sterilization validations.
  1. Your submission states that there are ---(b)(4)--- sterilization conditions: ------(b)(4)---------------------------------------.  Please clarify if there is a validation for ---(b)(4)----- sterilization conditions.
  1. You stated that all thermal sensors are calibrated every ---(b)(4)-----.  Please explain why the sensors were not calibrated before and after each validation run.
  1. Please clarify if there were any sensors in the drain.
  1. One empty chamber cycle was performed in Study LAB/VR/039/06.  It appears that thermal sensors were placed in the bag for the empty chamber.  Please clarify how sensors were placed in bags if the chamber was empty.
  1. For the PQ, please clarify where the thermal sensors were placed in the system (i.e. in the anticoagulant solution) and a rationale for the placement.
  1. The validation states that in-bag sensors will be placed inside -------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------.
    • Please provide a side-by-side comparison of ---(b)(4)-- and ---(b)(4)---- (dimensions, materials, etc).  Please also provide a diagram of each bag.
    • Please clarify if (b)(4) solution is the Additive Solution A.  If so, please explain why the sensor was only placed in Additive Solution A and why the Citrate Phosphate Dextrose Solution (CPD) and Additive Solution B were not selected for placement of the sensor.
  1. In Study LAB/VR/039/06 several thermal sensors did not reach (b)(4) when sterilization dwell time started.  Please justify why this deviation is acceptable.
  1. Please clarify if the F0 value is based on the cumulative sterilization cycle (chamber heat up to chamber cool down) or the exposure time ----(b)(4)----------------.
  1. In Study LAB/VR/039/06 ---(b)(4)-------------- was used as a biological indicator (BI), which is typically used for --------(b)(4)--------------------------------.  In Study VP/031/LAB/09 ---(b)(4)-------- was used as a biological indicator.  ----(b)(4)----------------------------------- is usually used as a biological indicator for ----(b)(4)-------.
    • Please explain your BI organism selection.
    • Please explain why the BI organism was changed between the two studies.
  1. In Study VP/031/LAB/09 ----(b)(4)------- was used as a biological indicator.  Please explain why the bioburden test method and biological indicator sterility test method was not revalidated with ----(b)(4)---------.
  1. Please explain how you decided the locations to place the BIs within the system in the studies.
  1. Please provide the certificate of analysis for the BIs in Study LAB/VR/039/06 and their D115 values.
  1. Please provide the D115 values for all of the BIs used in Study VP/031/LAB/09.
  1. In Appendix V of Study LAB/VR/039/06 a drawing with the BI sample arrangement was provided. Please explain the acronyms (i.e. -(b)(4)-, etc).  It is not clear where Solution B is placed in the arrangement.  A photo of the arrangement or a larger drawing may be helpful.
  1. Please explain if there were any changes to the autoclave or load configuration between the initial validation and the revalidation.
  1. In Module 4 it states that a “new bag arrangement during sterilization” occurred.  Please elaborate on this change and if this new bag arrangement was included in any of the sterilization studies.
  1. In Study LAB/VR/039/06 one of the top 3 cold spots was location (b)(4).  However in Study VP/031/LAB/09 location (b)(4) was one of the top 3 hot spots.  Please explain this change.
  1. In several of your runs kinked tubes were found.  Please clarify if you evaluated if the kink affected sterilization process such as causing water to become pooled at the kinked tubing areas.  Please explain if this caused any water to become trapped in the kinked tubing areas or if the kinks inhibited -(b)(4)- from penetrating the complete system.
  1. It was noted that several positive controls in the BI sterility test results were negative in Study LAB/VR/039/06.  Additionally, several positive controls in the bacteriostasis and fugistasis results were negative in Study VP/031/LAB/09.  Please explain why this is acceptable.
Container closure:
  1. Please clarify if any container closure integrity testing has been performed on the complete system (LEUKOSEP® HWB-600-XL Leukocyte Reduction Filtration System for Whole Blood with CPD Anticoagulant and SOLX® Additive).  If so, please provide the study or the location of this study in the submission or DMF.  Additionally, provide a reference to any standards you use for this testing.
  1. Please explain what package testing has been completed to ensure sterility for the lifetime of the product.  Please provide a reference to any standards you use to perform the testing.
  1. Please provide the transportation SOP that will be used for routine manufacturing.
  1. Please clarify if your transportation validations address the worse case shipping conditions to demonstrate the product would not be compromised.
  1. Per Study TR/077/PED/2008, moisture was found in the inner box.
    • Please clarify if you have assessed how the moisture impacts your product.
    • Please clarify if your package inserts instructs the customer how to handle if the packaging or product is damp.
  1. Module 4 stated that “packaging modifications” were made.  Please clarify if the transportation testing ((b)(4) Report 0706135 Rev C and TP/077/PED/2008/JMS) was completed before or after packaging modifications were made.  
    • If it was completed prior to the packaging modifications, please clarify if transportation testing was evaluated after the packaging modifications.  
    • If transportation testing was not evaluated after the packaging modification, please provide a justification for not completing one.
Please submit your response to this information request as an amendment to this file by
April 30, 2012, referencing the date of this request.  
If we determine that your response to this information request constitutes a major amendment, we will notify you in writing. If you anticipate you will not be able to respond by this date, please contact the Agency immediately so a new response date can be identified.
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

Page Last Updated: 05/24/2013
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