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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: ljensen@hemerus.com

 

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:

 
  Please provide the design approach utilized for your autoclave (i.e. 
overkill).
  Please clarify the sterilization process you are using (i.e. 
  -----------------------------------------------------(b)(4)--------------------------------------------------).
  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.
  Please provide a summary of all deviations and their associated resolutions 
  for your sterilization validations.
  Your submission states that there are ---(b)(4)--- sterilization conditions: 
  ------(b)(4)---------------------------------------.  Please clarify if there 
  is a validation for ---(b)(4)----- sterilization conditions.
  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.
  Please clarify if there were any sensors in the drain.
  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.
  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.
  The validation states that in-bag sensors will be placed inside 
  -------------------------------------------------------------------(b)(4)-----------------------------------------------------------------------------------------------------------------.Pleasee
    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.

  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.
  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)----------------.
  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.

  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)---------.
  Please explain how you decided the locations to place the BIs within the 
  system in the studies.
  Please provide the certificate of analysis for the BIs in Study LAB/VR/039/06 
  and their D115 values.
  Please provide the D115 values for all of the BIs used in Study VP/031/LAB/09.
  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.
  Please explain if there were any changes to the autoclave or load 
  configuration between the initial validation and the revalidation.
  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.
  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.
  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.
  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:

 
  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.
  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.

 

Transportation:

 
  Please provide the transportation SOP that will be used for routine 
  manufacturing.
  Please clarify if your transportation validations address the worse case 
  shipping conditions to demonstrate the product would not be compromised.
  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.

  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.

 

Sincerely,

 

 


Sonday L. Kelly, M.S.

Regulatory Project Manager

FDA/CBER/OBRR/DBA/RPMB

 

 

 
