Date: October 30, 2007
Time: 10:30 PM – 11:30 AM
From: Nannette Cagungun
To: STN 125267/0
Re: LevPharma’s C1 Esterase Inhibitor BLA
Dave Doleski - Absent
Jean Mackie - Absent
On October 15, 2007, FDA received LevPharma’s response to the September 25, 2007 information request. The sponsor has just submitted an amendment containing clinical data for the prophylaxis indication as well as manufacturing data on October 29, 2007.
The discussion ensued immediately after the arrival of Dr. Golding. The scientific lead, Felice D’Agnillo, stated that everyone in the review team had submitted their mid-cycle memo. He informed the review team about the forthcoming inspection of the firm’s Amsterdam and Belgium facilities toward the end of November through the beginning of December. Robert Wesley stated that there will be BIMO inspection of three clinical sites. Everyone voiced their concern about the limited time left to do the review of the submission with the most recent amendment having arrived midway through the review.
Felice D’Agnillo noted that the lot release plan has been prepared and will be sent to Debbie Jansen. However, he still needs to provide justification for why FDA does not need a lot release testing plan after approval. Lot release protocols will be required, however. The firm will have to submit conformance samples for testing potency, purity (-(b)(4)-) and to look for dimers and monomers.
Paul Buehler recommended revisions to the labeling pertaining to the repeat dose toxicology and pregnancy category. Iftekhar Mahmood also had PK labeling comments.
Felice D’Agnillo said there were no CMC showstoppers for this BLA. Mahmood Farshid stated that the firm has to check source material qualification for B19 and the manufacturing log should not exceed (b)(4) logs. He said the firm cannot make a labeling claim by referencing literature.
Felice D’Agnillo mentioned that Jean Makie (APLB) found the proprietary name acceptable.
Boris Zaslavsky and Charles Maplethorpe noted that they have only done a partial review because the prophylaxis data have just come in. Charles Maplethorpe noted that the data submitted by the firm should be more detailed. He will recommend an additional study because of statistical issues. However, this could change based upon the outcome of his review of the prophylaxis data. The firm should check for robustness in their sensitivity analysis. They did not include information on the site where patients were randomized. Sites with less than one subject in either treatment groups were pooled for all analyses.
Nannette Cagungun reminded the review committee that the press release and PI should all be in place by December 21, 2007. She will send an information request to the firm early next week.
The meeting adjourned.