Submission Type: BLA Submission ID: 125392/0 Office: OBRR
Fibrin Sealant Patch [EVARREST]
Ethicon, Inc. (Ethicon)
Telecon Date/Time: 27-Nov-2012 12:30 PM Initiated by FDA? Yes
Telephone Number: --b(4)------; Participant Conference Code: --b(4)-------
1. Other – Revisions to the Prescribing Information (PI) for EVARREST
Author: TRACY TILGHMAN
Discussion on revised labeling based on FDA recommendations from 26 November 2012
Ethicon, Inc. Participants:
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
FDA scheduled a follow-up teleconference with Ethicon to discuss the draft version of the PI for EVARREST revised based on FDA recommendations of 26 November 2012.
1. Ethicon revised HIGHLIGHTS and section 3 in the Full Prescribing information, Dosage and Forms and Strengths, to indicate the dosage form for EVARREST:
“EVARREST absorbable Fibrin Sealant Patch consists of human fibrinogen and human thrombin embedded in a flexible patch component… “
FDA recommended that the dosage form (absorbable patch) be stated in the following sentence: “Each 4 x 4 inch (10.2 x 10.2 cm) absorbable patch contains…”
The above sentence should be reverted back to “EVARREST Fibrin Sealant Patch” (to reflect the proper name).
2. Ethicon requested clarification on the additional wording in Section 5.4 (Adhesions) suggested by FDA: “Postoperative adhesions may occur in gynecological procedures with the use of an adhesion barrier that consists of –b(4)-------- oxidized regenerated cellulose, if meticulous hemostasis is not achieved prior to application.” The paragraph was extended to emphasize potential risk of adhesion formation due to the presence of oxidized regenerated cellulose in the composition of EVARREST, and for consistency of the warnings for EVARREST and for ----b(4)---------------------------
Ethicon stated that this wording may be confusing, and proposed three alternative options. The following wording was found most adequate by FDA: “Meticulous hemostasis should be achieved, particularly in gynecological procedures, to reduce the potential for postoperative adhesions.”
3. FDA re-stated their recommendation to revise the Adverse Reactions (AR) Table 1 to include the AR incidence specifically in the randomized subjects. The current version of Table 1 is misleading because it compared all subjects treated with EVARREST (N = 229 including both randomized and non-randomized subjects) with control subjects which is not an accurate comparison. The denominator for EVARREST in the revised table should reflect the controlled portion of the study.
FDA also recommended re-calculating the AR incidence to see if any additional reactions need to be added to or deleted from Table 1. Ethicon should follow the same rule: to include those reactions with incidence equal or higher than 1% and higher in the EVARREST arm than in the Control arm. Ethicon is amenable to these changes.
4. Following 26 November 2012 recommendation of FDA, Ethicon revised the immunogenicity section of the PI by deleting the comparative statement with the normal healthy (untreated) population and focusing only on comparison of patients treated with EVARREST and other thrombin products. FDA found the changes to be acceptable.
FDA requested that Ethicon submit a revised PI by email no later than 28 November 12, followed by a formal submission of the PI as an amendment to the file, STN 125392/0.