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Vaccines, Blood & Biologics

Record of Telephone Conversation, November 10, 2011 - Flublok


Submission Type: BLA    Submission ID: 125285/0    Office: OVRR
Influenza Vaccine
Protein Sciences Corporation
Telecon Date/Time: 10-Nov-2011 12:30 PM        Initiated by FDA? Yes
Telephone Number: ---b(4)-------------------------
Communication Categorie(s):
1. Advice
Telecon Summary:
Discussion of fill validation issues.
FDA Participants: Timothy Fritz, Maryna Eichelberger, Deborah Trout, Rajesh Gupta, Rakesh Pandey
Non-FDA Participants: Manon Cox, Penny Post, Clifton McPherson, Tim Fields, Sam Simons,     --b(4)-------------------------------, Tanima Sinha (BARDA), Sheng Li (BARDA), Lou Mocca (BARDA)
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Telecon Body:
PSC said that they investigated potential sources of error for the SRID assay and found that the main source of error is reference antigen variability. Based on this result, PSC indicated that it:
  • Had identified a new lot of H3
  • Will use b(4) vials of reference antigen for potency determination
  • -----b(4)-----------------------------------------------------------
  • --b(4)--- ----------------------------------
CBER asked whether H3 –b(4)---- was used for PV3. PSC said yes and that it was also used for PV4. CBER expressed concern that PSC did not notify CBER of the problem identified with lot –b(4)- to address this problem. PSC acknowledged that it did not realize that there would be such variability between reference antigen vials and are now implementing measures to trend and track potency measurements and qualify reference antigen used for potency measurements.
CBER asked PSC for an update on SRID for A/Cal/2009 H1 rHA. PSC said that the ---b(4)-- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------and that PSC should communicate with CBER if PSC encountered problems with SRID measurements.
CBER asked if PSC had tests in place to monitor proper HA folding prior to lyophilization. PSC asked if CBER was referring to specific tests such as trypsin sensitivity. CBER replied that it did not have specific tests available to monitor folding but wanted to know whether PSC had developed such tests---b(4)-- --------------------------------------------------------------.
CBER asked if PSC had an explanation for the difference between the –b(4)------------------- B strain SRID potency for PV4. PSC said that the variability may have been because of the time difference between the 2 measurements: ----b(4)---- ----------------------------------------------------------------------------------------
CBER stressed that PSC must be confident that the product will meet release specifications prior to performing the next fill validation.
PSC asked if its proposed change to the drug product release specification were acceptable. CBER said that the proposed specification was not acceptable and that a determination of the appropriate specification based on the number of samples to be tested by PSC could be made in a subsequent discussion. CBER referred PSC to SOP 333.
CBER asked what volumes PSC was targeting for their process and fill validations and their engineering run. PSC stated that they were targeting –b(4)- volumes for the process and fill validations and –b(4)- for their engineering run.
CBER asked if PSC could explain the volume accountability for PV4. PSC referred CBER to Table 4-1 of the material provided. CBER asked what methods were used by Hospira for volume determination. PSC explained that Hospira had –b(4)-- ------------------------------------------------------------------------------------------------------------------------------------------------------------ -------test performed at Hospira is a 100% visual inspection for visible particulates or glass defects.
CBER advised PSC that 3 successful runs would be needed for fill validation and that at least 1 of these runs would need to be performed at full scale (b(4). CBER asked if PSC would send samples to CBER for testing from the validation runs. PSC said yes.
PSC asked whether the other drug substance and drug product specification changes proposed by PSC in their Sept 16 submission were acceptable. CBER said that the changes to total protein, triton X-100, DNA concentration and b(4) were acceptable and that the addition of the –b(4)----------------------- test was acceptable.
CBER noted in response to an earlier question e-mailed to CBER that PSC would need to send samples to CBER even if influenza strains did not change from one year to the next.
CBER apologized that a trivalent sample submitted by PSC had not been tested, and stated they have taken steps to correct this error.  CBER asked PSC to make a note of this as an amendment to the BLA, or to note the shipment in a direct communication with Dr Rajesh Gupta.

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