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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Information Request Email, February 13, 2012 - Bivigam

 

From:                    Rana, Pratibha
Sent:                      Monday, February 13, 2012 4:42 PM
To:                         'Matthew Vaughn'
Subject:                 STN 125389/0 Information Request
Dear Matt,

This is regarding your BLA submission STN 125389/0 for Immune Globulin Intravenous (Human).  FDA continues with the review of the referenced submission and requests BPC to provide the following information.          
 
1.     Please provide a flow chart of all the lot numbers used in validation and conformance lots for Phase I and Phase II from plasma units until the final container. 
 
2.     The full range of the following parameters is not validated:
  • --------------------------------------------------------(b)(4)---------------------------------------------------------------------.
  • --------------------------------------------------------------(b)(4)-------------------------------------------------------.
  • --------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------.
4.   The acceptance criteria used during your Robustness Studies were set at lower values then those used during the performance of your conformance lots. Please comment.
 
5.   Please describe how you calculated the -----(b)(4)---- values for -----(b)(4)------ in your response to Question 2C, Table 1, as compared to the data provided in sections 5.7.7 to 5.7.11 in the batch records.
 
6.   The Phase II conformance lots have a small increase in IgA at the ---(b)(4)--- stage (Phase II = ----(b)(4)----, Phase I = ---(b)(4)---). Please comment.
 
7.   Please submit a list of all the deviations encountered in Phase II manufacturing/validation.
 
8.   Please provide a table of the in-process tests and specifications which will be used in the routine manufacture of Biotest-IGIV.
 
9.   Regarding mixing instructions in the batch records:
a.      ------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------
b.     -----------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------
c.      ---------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------
d.     --------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------
 
10.       Your process-robustness data in Study VP-FR-3388 show ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
11.    Your most recent stability data (Report SP-DF-3036-4) indicates that the Bivigam formulation is unstable in that: 1) at (b)(4) storage temperature, --------(b)(4)------------------, anti-measles titer, -----------------(b)(4)------------------- all trend out of specification by --(b)(4)--, and --(b)(4)-- has fallen from -----------------(b)(4)--------------; and 2) anti-measles titer may trend out of specification by (b)(4) months shelf-life even at 2-8 ºC. In our experience, an optimized IGIV formulation will maintain the product’s critical quality attributes within release-specification acceptance ranges for at least two years at (b)(4). Please comment.
 
12.    Please provide the --------------(b)(4)---------------  data you have been accruing for Biotest-IGIV, in final- or interim-report form, with any analysis or interpretation that you have made to date.
 
Regarding Computer System
 
13.       Please verify that three validated computer systems -----------------(b)(4)---------------------- were used during manufacturing of last two conformance lots.
 
14.    Please provide rationale for not performing performance qualification for these new systems.
 
15.    Please provide copies of the protocol that lists all functional testing, sequential testing, stress testing and/or network testing that were performed as part of the ---(b)(4)- qualification including acceptance testing.
 
16.    Please provide all deviation and investigation reports relate to -----------------(b)(4)------------------- noted during conformance lots (for example -incident of power lost, data lost, wrong recipes used, tank overflows, computer lost connection with controller, system locks up, a list of critical alarms, wrong product pathway).
 
17.    We noted that you have experienced several deviations during IQ/OQ performance, please provide if you have run any additional tests to verify that system is working without any additional devotions/comments?
 
Regarding Transport Validation
 
18.       Please provide copy of study protocols and transport validation data for the minimum and maximum or worst case product load size including longest travel time for the multiple runs (typical three consecutive shipments tested on different days) to demonstrate that the product will remain under defined conditions during transport.
 
19.    Please provide copy of quality agreement and your plan to perform an audit of the vendor’s ((b)(4)) quality system.
 
 
Please submit a response to this request as an amendment to the file by February 24, 2012.
Thank you.
Pratibha Rana
 
Pratibha Rana, M.S.
Regulatory Project Manager
 
FDA/CBER/OBRR
Division of Blood Applications
1401 Rockville Pike
Rockville, MD 20852
Office: (301) 827-6124
Fax: (301) 827-2857
email: pratibha.rana@fda.hhs.gov
 
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