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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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CMC Related Information Request, August 26, 2011 - Gintuit

 

1.      MCB isoenzyme and karyology (cytogenetic) analysis
 
a.       Please provide the complete set of testing results for the isoenzyme and karyology (cytogenetic) analysis performed by --b(4)-------------------------------------------------------------- for all HDF and HEP MCB banks. These data should include results for all parameters evaluated at each passage for each cell type.
 
b.      Please also comment on any trends identified in the data set and their relevance, for example, if there were any observed changes in the karyology of keritinocytes.
 
c.       Please clarify which passage number is used for each cell type and describe the passage in reference to stage of manufacture (e.g. number of passages prior to use, passage of use, and senescence). There are inconsistencies in the BLA application for this information.
 
2.      Please provide further details regarding tumorigenicity testing of the MCBs          [--b(4)---------------------------], and if available, the SOP and the assay validation report (including a validation summary table). If formal analytical method validation per ICH guidelines has not been performed for this assay, please provide a rationale and any qualification data that demonstrate this assay is suitable for its intended use and will provide consistent and reliable results.
 
3.      Please provide a more in-depth justification for the acceptance criteria –b(4)----- for the collagen biosynthesis assay for HDF WCB release testing, especially as it relates to values obtained during previous manufacture. For example, in Table 7 of –b(4)------Apligraf Manufacturing--b(4)- (retrospective process validation report for cell banking), the mean value for Collagen Biosynthesis (--b(4)---) was –b(4)--, approximately –b(4)----------- than the acceptance criteria. The justification should describe how the current specification, with a seemingly acceptance criteria, provides sufficient control of manufacturing quality and consistency.
 
4.      Similary, please provide a more in-depth justification for the acceptance criteria of --b(4)--- for the involucrin assay for HEP WCB release testing, especially as it relates to values obtained during previous manufacture.
 
5.      The laboratory listed as the donor testing facility under FEI----b(4)------- could not be located in the Human Cell and Tissue Establishment Registration (HCTERS) database. Please verify the FEI# is correct and/or provide further information for the laboratory which conducts the donor testing.