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Vaccines, Blood & Biologics
Submission Type: BLA Submission ID: 125392/0 Office: OBRR
Fibrin Sealant Patch
Telecon Date/Time: 28-Nov-2012 04:30 PM Initiated by FDA? Yes
Telephone Number: —b(4)-----
1. Other - Labeling negotiations
Author: LEIGH PRACHT/ Kimberly Lindsey, Natalya Ananyeva
Discussion with Applicant regarding revisions of Prescribing Information for EVARREST
Kimberly Lindsey, MD
Natalya Ananyeva, PhD
Jessica Chung, Regulatory Affairs
Trans-BLA Group: No
Related STNs: 125392, EVARREST Fibrin Sealant Patch
Related PMCs: None
1). FDA sought clarification regarding the denominator of 158 for all subjects randomized to Fibrin Pad (FP, former name for EVARREST used in the clinical studies) in the controlled portions of studies 400-07-002, 400-08-002 and 400-10-001.
FDA noted that the integrated safety summary in module 2.7.4 outlined the treatment allocation for the individual studies as follows:
Study No. subjects treated No. subjects
with FP treated with control
400-07-002 N=111 N=30
400-08-002 N= 59 N=32
400-10-001 N=59 N=45
Integrated Safety N=229 N=107
FDA acknowledged that Study 400-07-002 had 60 FP subjects in the randomized portion of the study and 51 non-randomized subjects which gives the denominator of 178 for randomized subjects.
Ethicon confirmed the above numbers in Study 400-07-002, and confirmed that all subjects in Study 400-08-002 were randomized. Ethicon also pointed out that Study 400-10-001 had 39 subjects treated with EVARREST FP in the randomized, controlled portion of the study, whereas remaining 20 run-in subjects were non-randomized and treated with EVARREST FP. This resulted in 71 non-randomized subjects in all three studies. FDA agreed with Ethicon that the denominator of 158 was indeed correct.
2). FDA requested that Ethicon reorder the columns (left to right) in the adverse reactions Table 1 as follows:
Column 1: EVARREST Total; Column 2: EVARREST Randomized; and Column 3: Control.
3). FDA also requested that Ethicon put a footnote at the bottom of Table 1 to explain that there were an additional 71 subjects treated with EVARREST who were not randomized.
4). FDA stated that the following line in Table 3 of the package insert should be bolded to be consistent with the presentation in Table 2: (i.e. Manufacturing Step HIV-1 SBV BVDV PRV EMCV HAV CPV)
5). FDA requested revisions to section 5.7:
Change “ Because this product is made from human plasma…” to “Because the biological components of this product are made from human plasma…”
6). Ethicon asked if the package labeling should be modified to reflect the dosage form of EVARREST as an “absorbable patch”. FDA commented that they would need to consult with the APLB colleagues and provide a definitive answer in the first part of the day of 29 November 2012.
Ethicon committed to defer submitting the official responses to FDA’s information requests until FDA confirmed immediate supervisory concurrence with the revisions (i.e. Dr. Nisha Jain). FDA did reiterate to Ethicon that additional revisions to the package insert may be requested pending the upper management review.