
Information Request Email, November 06, 2009 - Flublok

 
 
 

From: Fritz, Timothy

Sent:    Friday, November 06, 2009 3:18 PM

To:      Penny Post (penny.post@proteinsciences.com)

Cc:      Manon Cox

Subject:           Information Request for STN 125285 (FluBlok BLA)

 

Importance:    High

Dr. Post-

 

CBER’s review of BLA 125285 and Protein Science Corporation’s response to CBER’s October 1, 2009 Information Request is ongoing. CBER has the following requests for additional information. The headings and numbering below reflect those used in CBER’s October 1, 2009 Information Request.

 

1. Concerning process validation

 

We note that H1 lots –b(4)------------------------------- had potency results either Out of Trend or Out of Specification. Please submit your investigation reports, making sure to include the cause of the failures, remedial actions undertaken and conclusions regarding these incidents.

 

Regarding your final down-stream process validation report submitted October 6th, 2009:

 

·           Please provide chromatograms -----b(4)---------------------------------------------------------------------- columns of each validation run (H1, H3 and B) to enable us to evaluate the consistency of your chromatography performance steps. Please indicate initiation of wash, load and elution steps on each chromatogram. Also, identify the chromatograms that will be or were used as reference during manufacture of subsequent batches.

 

·           We note that you commit to providing additional information to support consistent manufacture of B rHA. The data you provide should include evidence from more than one run that your corrective action (i.e. -----b(4)--------------------) has resolved the inconsistency in yield and –b(4)------------- obtained following b(4) chromatography.

 

·           Your process does not include a test to demonstrate consistency in --------b(4)----. ---------------------------b(4)------- or an alternative method should be added as a QC test for monovalent bulk, with a suitable release specification set to identify the --------------------------b(4) in each lot.

 

4d. Concerning stability of monovalent bulks

 

C)        We do not agree with the use of –b(4)--------------- as the means to determine drug substance shelf-life. We recommend that you determine shelf-life by a specified percent decline in potency (as measured by SRID). The percent decline should be based on product stability and assay variability.

 

5cii. Concerning Adventitious Agent Testing

 

a.         --------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------

 

b.         ------------------------------------------------------------b(4)-----------------.

 

c.         ------------------------------------------------------------b(4)-----------------.

 

Additional requests/comments

 

1. Concerning the B/Brisbane/60/2008 HA gene sequence

 

A key advantage of PSC’s manufacturing approach is the ability to use a HA sequence that is identical to that present in early virus isolates. When the sequence is not identical to an appropriate reference (as is the case for B/Brisbane/60/2008), it is imperative to demonstrate antigenic similarity between the selected rHA and recommended vaccine strain. We request that you provide your proposed method to demonstrate antigenic similarity and results to support antigenic relatedness of your B/Brisbane/60/2008 to the recommended strain rHA preparation.

 

If you have any questions, please contact the Regulatory Project Managers, Katherine L. Matrakas or Timothy A. Fritz at 301-827-3070.

 

 

Timothy A. Fritz, Ph.D.

Microbiologist

FDA/CBER/OVRR/DVRPA/RRB2

WOC1 HFM-478 Suite 371N

1401 Rockville Pike

Rockville, MD 20852

Phone: 301-827-3070

Fax: 301-827-1597

 

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