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Vaccines, Blood & Biologics

Information Request, April 05, 2012 - Bivigam


From:                    Tilghman, Tracy
Sent:                      Thursday, April 05, 2012 10:19 AM
To:                         ''
Cc:                         Rana, Pratibha; Cagungun, Nannette
Subject:                 Information Request
Importance:           High
Dear Mr. Vaughn:
This information request is being sent on behalf of Pratibha Rana. 
This is regarding your BLA submission, STN 125389/0, for Immune Globulin Intravenous (Human). We determined that the following information is necessary to continue our review:
1.     Please submit the investigation associated with ALR 11-WF-005, observed during qualification of your WFI system.
2.     For major process equipment, as outlined in the Appendices of Module 3, submitted in response to the CR letter, please specify the exact use of each piece of equipment. For example, you provide a general description of the use of ---------(b)(4)------------, but you should be explicit in describing the equipments’ function. If this information is present elsewhere in the BLA, please specify that location.
3.     With respect to Cleaning Validation:
a .      Please justify use of (b)(4) cleaning validation acceptance criteria of either (b)(4) (final rinse sample) --- (b)(4) (--(b)(4)-- sample) for cleaning of all product contact equipment used from (b)(4) of the manufacturing process on. Similarly, please justify use of a bioburden acceptance cleaning validation criteria in excess of        -------(b)(4)--------- specifications for all product contact equipment used from      -(b)(4)- of the manufacturing process on. Finally, please justify use of a                ----(b)(4)---- acceptance criterion of --(b)(4)-- for all process equipment.
b.      Please define the method by which you choose locations ---(b)(4)--- sampled for (b)(4) and Bioburden.
c.       Please specify that all equipment was soiled with a worst case soil with respect to what the equipment is used for.
d.      You state that due to Deviation DEV-7307 associated with the Final Report for the Cleaning Validation of the --(b)(4)-- Cleaning of Fractionation Miscellaneous Equipment and Components, you will need to complete a, t least one additional cleaning validation run in 2012. Please specify if this run has been performed, and submit the results of this run.
e.       Please provide all actual numbers that are listed as “(b)(4)” from all Cleaning Validation reports if those numbers were associated with any (b)(4) negative control value deviation.
f.      You state that you “utilized a family approach to accomplish cleaning validation. Multiples of like equipment that are equivalent, in both process use and physical structure, were grouped into like equipment groups. After grouping, representative worst case units were selected for use in the testing. Once the cleaning validation is completed and approved, all units included in the group are considered as validated.” Please define all individual equipment that cleaning has not been actually validated for. 
g.      In relation to deviation DEV-7133, you state that the (b)(4) Rinse Control was collected from port ---(b)(4)--- on 3-11-2011. On the same day as the failure, a sample was collected from a different port ----(b)(4)----. Please justify using results from a different (b)(4) port to establish that port contamination of the port you actually used had not occurred.
h.      Please specify that, for any alteration of cleaning methodology found necessary to meet cleaning validation acceptance criteria, you have incorporated the necessary alteration into your routine practices.
4.     Please define all tests performed as part of your -----------(b)(4)--------------- Test, as noted in your report entitled, “Final Report for the Installation/Operational Qualification of the --------------------(b)(4)--------------------.” Additionally, please define the key performance aspects of the --------------------(b)(4)--------------------, and state how you determine that the system met these aspects’ acceptance criteria.
5.     For the --------(b)(4)------------, please define all process steps where --(b)(4)-- is in contact with the product, and if --(b)(4)-- is filtered through a --(b)(4)-- filter either systemically, or at points of use. 
6.     For the --------------------------(b)(4)---------------------------, please specify environmental conditions required while these cleanrooms are in use, and then provide data that demonstrates that you are able to achieve said environmental conditions.
7.     For your empty chamber temperature distribution study performed in support of Validation number VP-FR-3242-2 for Autoclave (b)(4), please define your temperature setpoint, and please explain the large temperature variation between thermocouples, more than (b)(4), observed during the study.
8.     With respect to the -------------(b)(4)---------------, please define normal --------(b)(4)---------, and then relate this normal --------(b)(4)-------- to the (b)(4) evaluated in the     --------(b)(4)-------- (see section 6.2.8, Table 7)
9.     For all ----(b)(4)----- units, please specify ---------(b)(4)---------- storage conditions, and provide data that support number of maximum uses for the ----(b)(4)----.
10. Please provide evidence that the -------(b)(4)------ at the ------------------------(b)(4)-------------------------- steps were part of the originally validated process, as you claim in your response to CR question 4. You may direct us to previously submitted process descriptions to respond to this question.
Please submit your response to this information request as an amendment to this file by close of business on Wednesday, April 11, 2012, referencing the date of this request. 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 April 26, 2012.
If you have any questions, please contact Ms. Rana at (301) 827-6124. 
Tracy Tilghman, MPH
Lieutenant, United States Public Health Service
Regulatory Project Manager
U.S. Food & Drug Administration
WOC1, RM 556N, HFM-380
Rockville, MD 20852
Phone: 301-827-9427
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