RECORD OF TELEPHONE CONVERSATION
Submission Type: BLA Submission ID: 125392/0 Office: OBRR
Fibrin Sealant Patch [EVARREST]
Ethicon, Inc. (Ethicon)
Telecon Date/Time: 5-Oct-2012 02:00 PM Initiated by FDA? No
Telephone Number: ---b(4)---------, Participant Code: --b(4)-------
1. Other – Discussion of revised Prescribing Information for EVARREST
Author: TRACY TILGHMAN/Natalya Ananyeva
Teleconference to discuss additional revisions to the PI in preparation of the response to the Complete Response letter dated 28 September 2012
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
The 28 September 2012 Complete Response letter included FDA-recommended text of Prescribing Information (PI) and the package label for EVARREST. Ethicon requested this teleconference to discuss with FDA the additional revisions to the PI to ensure alignment with FDA recommendations in each section of the labeling, before the formal submission of the revised labeling is made.
Ethicon stated that they accepted majority of the FDA-recommended revisions to the PI, and requested clarification on additional aspects regarding the following sections: Dosage and Administration, Dosage Forms and Strengths, Warnings and Precautions, Adverse Reactions, and Prescribing Highlights.
FDA recommended that Ethicon revise the wording under the Warnings and Precautions section of the PI to include the word “can” and not “may”, as the latter undermines the potential risk associated with the product use, and there is no data to support the plausible claim. Ethicon agreed to use the word “can”.
Ethicon stated that they extended the list of the Adverse Reactions included in Table 1 in the PI and presented the AR incidence in decimal percentages. Ethicon asked FDA to clarify what the rule should be for including selected ARs in the table out of the whole list, and how the AR incidence in the percentages should be properly presented. FDA clarified that Adverse Reactions to be included in Table 1 should be those with an incidence (i) greater than or equal to 1%, and (ii) greater in the EVARREST arm versus the control arm. FDA also recommended removing the disclaimers from Table 1 and rounding the percentages to the nearest digit because there is no power for pooling for pre-specified endpoints. FDA stated that the changes to Table 1 will be reviewed in further detail by the review team, who can provide additional feedback to Ethicon.
Ethicon requested to clarify the wording of the statement under the Pediatric Use section 8.4 of the PI: “Safety and effectiveness in pediatric patients have not been established. Use of EVARREST in children under the age of one month may be unsafe or ineffective due to small size and limited ability to apply the patch as recommended. Slow absorption and possibility of adhesions can further complicate use of EVARREST in the neonates.” Ethicon stated that there is no data to suggest that adhesion formation is true for neonates. Ethicon would like to propose an alternative language for this section. FDA stated that per regulations, due to specifics of the pediatric age group, this statement must remain in the PI as agreed upon with the Pediatric Committee, and any revisions would result in the submission going back to PeRC for review. Ethicon agreed to keep the statement.
Under Indications and Usages, Ethicon would like to change the phrase “EVARREST is a fibrin sealant patch” to “Evarrest Fibrin Sealant Patch”. FDA will have to review the guidance and will provide the response to Ethicon during the review process.
Ethicon would like to incorporate the trademark symbol with the proprietary name (EVARREST) and a copyright symbol in their PI. FDA stated that they have no objections but the frequency of the trademark symbol in the PI should not be distracting; also the trademark symbol is not visible in SPL format.
FDA clarified that the package label has to have all the requirements as outlined in Section 610.61, and recommended that Ethicon review the guidance before formally submitting the revised labeling.
Ethicon stated that they will submit their response to the Complete Response Letter in PDF and Word formats for FDA to review, and asked if the review can be completed within 7-10 days. FDA stated that the revised labeling will need to be reviewed by the initial and supervisory reviewers as well as by the upper management, and the internal documents associated with this submission will need to be updated. FDA will try to expedite the review process but no commitment can be made. FDA asked that Ethicon route all correspondence related to this submission through the Regulatory Project Manager.