Date: September 8, 2010 Time: 1:00PM – 2:00 PM
From: Nannette Cagungun, CBER/OBRR/DBA, HFM-380
To: STN 125385/0
Subject: First Committee Meeting for CSL Behring’s BLA for Factor XIII Concentrate (Human)
Nisha Jain – by phone
Martha O’Lone – by phone
Jennifer Schmidt- by phone
Daniela Vanco - absent
The meeting began with introductions. Dr. Ze Peng, the scientific lead, asked the review committee to notify him and the RPM about any deficiencies with the BLA before the filing meeting. The review committee agreed to do away with the filing meeting scheduled for October 5, 2010 and file the BLA if no major deficiencies are identified by then.
Dr. Nisha Jain represented Dr. Daniela Vanco, the clinical reviewer, who was on leave. Dr. Jain informed the committee that a recommendation for accelerated review was approved. So far, the clinical section appears to be acceptable. She noted that the applicant implemented suggestions made by the FDA at the pre-BLA meeting.
As agreed upon during the pre-BLA meeting, CSLB did not submit an integrated clinical trial safety summary (ISS) for CSLB's non-IND studies (eight studies), Dr. Nugent's IND study and CSLB's one completed IND study (pivotal PK trial BI71 023_2002). In addition, they did not submit an ISS of Dr. Nugent's IND study and CSLB's one completed IND study (pivotal PK trial BI71 023_2002) because some FXIII Concentrate (Human) non-IND CSLB sponsored clinical studies involved a different indication (i.e. -------(b)(4)------) and Dr. Nugent's IND study, (BB-IND (b)(4)), was not designed by CSLB, there is little commonality in the study design and data structures between these studies and CSLB's pivotal PK Study No.BI71 023_2002. CSLB provided in Module 2 a separate summary of safety and efficacy for each individual study and an overall narrative of the safety profile of FXIII Concentrate (Human) that emerges from the individual study reports.
A PMR study for safety and efficacy has already been initiated. Discussion for a Phase 4 study in support of US Licensure was initiated in March 10, 2010, during a pre-BLA meeting.
Dr. Jain noted that PREA is not required because the product has an orphan designation. She informed the committee that management is now reviewing CRB’s recommendation to waive presentation at the Blood Products Advisory Committee (BPAC) meeting.
Dr. Peng reminded the review committee that they will need to prepare a mid-cycle review memo and an executive summary of their review for the Summary Basis for Regulatory Action.
With regard to the pre-license inspection, DMPQ proposed to waive the inspection because no issues were identified at the most recent inspection of the Marburg facility in March 2010. Capt. Martha O’Lone informed the committee that she requested clarification from CSLB regarding the timeline for the planned prior approval supplement (PAS) that will include the three conformance lots made with an --------------(b)(4)------------------. She noted the IND lots are manufactured under GMP and that CSLB plans to market lots produced with the ---------(b)(4)----------------- process described in the BLA.
Dr. Peng indicated that he had discussed the lot release testing plan with appropriate personnel in the PRB and the DPQ branches.
Mr. Dennis Cato stated that BIMO will select three sites for inspection after the BLA is filed. Zhen will then send a notification regarding the selected sites to the clinical reviewer.
Dr. Alan Ou stated that he will give a more in depth look at the pharmacovigilance plan.
Dr. La’Nissa Brown indicated that the preclinical material submitted seems acceptable.
Dr. Renee Rees noted that she could not open the datasets for the efficacy studies as well as the PK datasets. (This was later resolved).
Mr. Michael Brony indicated that he had no issues with the carton and labeling.
After the submission is filed, CBER will ask the applicant which lots are available for submission to the Product Release Branch, and the relevant lot release protocol to be submitted to PRB and OBRR for review.
The review committee will provide their filing memos to Nannette Cagungun and Ze Peng by September 30, 2010.