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Review of Amendment 53 Memo, Flublok


Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Compliance and Biologics Quality
Division of Manufacturing and Product Quality
To:                  File STN 125285/0/53
From:             Deborah Trout, Committee Member, OCBQ/DMPQ, HFM-675
Through:        Carolyn Renshaw, Branch Chief, OCBQ/DMPQ, HFM-675
Subject:          Review of amendment 53 for CMC updates to various BLA sections submitted February 24, 2012 by Protein Sciences Corporation (hereafter referred to as PSC).
Action Due Date: There is no action due date at this time. The application review is currently under a complete response letter.
Recommendation: No action required at this time.
Summary of the updates/changes are noted below.
Section 3.2.S.2.2.2 Cloning of HA Genes and Generation of WVBs
  • Information on cloning and production of working virus banks by an Sf9-cell and ----–b(4)-- serum-free method for the 2011-2012 vaccine formulation.
Defer to product reviewer
Section 3.2.S.2.2.4 Downstream Purification (Table 3.2.S.2.2.4-18)
  • Removal of baculovirus DNA in-process test from –b(4)---- step.
Defer to product reviewer
Section 3.2.S.2.3.8 WVB (w/Strain-specific rHA Inserts)
  • The WVB for the 2011-2012 season rHAs are derived from the same strains as those for the previous season. Clone changes related to replacement of 2010-2011 working virus banks with new Sf9- and serum-free working virus banks for the 2011-2012 vaccine formulation.
Defer to product reviewer
Section 3.2.S.2.3.9 Raw Materials & Prep. of Solutions for Production/Media
  • Raw Material and vendor updates
Defer to product reviewer
Section 3.2.S.5 Reference Standards or Materials
  • Update of SRID reagents to reflect new supplies from CBER
Defer to product reviewer
Section 3.2.A.1.1 Protein Sciences Corporation – Facilities
The following changes have been incorporated into the BLA since its filing on April 17, 2008:
  • A warehouse was added to the –b(4)------------------------------------------------------------------------------------------------------------------------------- (Figure 3.2.A.1.1-12). The new raw material flow is described and arrows showing ingress into –b(4)-------- from the new         -b(4)------- warehouse have been added to Figure 3.2.A.1.1-4.
In addition, the following minor modifications were made to diagrams that were previously submitted.
  • Figure 3.2.A.1.1-4. Raw Material Flow. Raw materials are not stored in –b(4)-------------------------- This arrow was removed from the flow diagram.
  • Figure 3.2.A.1.1-5. Buffer Flow. Buffer is not transported through -------------b(4)---- and is not returned to Room b(4) and therefore these arrows were removed. Solutions are transported into Room b(4)Media Prep for media preparation. An arrow was added to clarify this.
  • Figure 3.2.A.1.1-6. Media Flow. Media is –b(4)-------------------------------------------. An arrow was added to show exit of media from Room –b(4)--. Prepared media is not transported through pass through b(4) or Rooms –b(4)--------------. These arrows were removed.
  • Figure 3.2.A.1.1-7. Waste Flow. Some waste that has not had baculovirus contact, but is generated in the baculovirus area of the facility, is not compatible with autoclaving (i.e. -    -b(4)----------------------). Solid waste that has not had baculovirus contact is removed from the building –b(4)--------------------------. Arrows were added to this map to indicate this.
  • Figure 3.2.A.1.1-11. HVAC Air Pressure Cascade. Room b(4) Cell Culture has –b(4)---- pressure with respect to Room b(4) Incubation. Arrow was corrected to point from Room ---b(4)-------------
  • Figure 3.2.A.1.1-12. Floor Plan of Quality Control Areas in Building b(4).The conference room was converted to offices.
  • Minor corrections were made to the base maps to wall locations in the –b(4)---------- as well as door swings in the manufacturing facility and adjacent areas.
The following correction is made:
  • -b(4)---vials of cells are transported into the facility through –b(4)---- and not through Material –b(4)------. (Found in description of product flows on page 6.)
The corrections and additions to the facilities section appear minor. No further review is needed.
Section 3.2.A.2 Adventitious Safety Evaluation
  • CoA and CoO for ---b(4)----------------------------------------------------------------------------------------------------------
Defer to product reviewer