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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

Review of Amendment 53 Memo, Flublok

 

Memorandum
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