RECORD OF TELEPHONE CONVERSATION
Submission Type: BLA Submission ID: 125392/0 Office: OBRR
Fibrin Pad [EVARREST]
Ethicon, Inc. (Manufacturer: Omrix Biopharmaceuticals Ltd.)
Telecon Date/Time: 11-Apr-2012 01:00 PM Initiated by FDA? Yes
Telephone Number: -------(b)(4)------
1. Other - Evaluation of Ethicon's response to the Complete Response letter dated 19 September 2011
Author: TRACY TILGHMAN
Telecon Background and Summary:
Review of the original BLA for Fibrin Pad resulted in issuance of a Complete Response (CR) letter by FDA on September 19th, 2011. The CR letter cited, among other items, outstanding cGMP-related issues identified during the Pre-License Inspection of Omrix Biopharmaceuticals Ltd. on May 11-19th, 2011. Ethicon submitted Amendment #11 to the BLA with their responses to the CR letter received by FDA on March 30th, 2012. The purpose of the telecon was to alert Ethicon of a number of incomplete responses to FDA Form 483 items, and to request additional information to permit review of the amendment.
Natalya Ananyeva, OBRR/DH
Randa Melhem, OCBQ/DMPQ
Destry Sillivan, OCBQ/DMPQ
Raina Dauria, Group Director Regulatory Affairs, Johnson and Johnson Wound
Christiana Bielinski, Group Director Quality and Compliance, Johnson and Johnson
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
The FDA Form 483 observations during the Pre-License Inspection of Omrix’s manufacturing facilities included inadequate cleaning validations and programs for facility and equipment, inadequate environmental monitoring program, inadequate qualification of equipment (--------------(b)(4)-------- unit), and inadequate shipping validation and procedures.
On a cursory review of the March 30th amendment, FDA determined that Ethicon/Omrix’s corrective actions described in the responses to 483 items are incomplete at this time. Specifically, not all final cleaning validation reports have been submitted as some studies have been completed only recently. FDA has concern that the manufacturing process for Fibrin Pad will be implemented without having a validated process for cleaning that has been deemed acceptable by the FDA.
Another FDA concern is related to the inadequate validation of the clean hold times for the equipment. The claimed ---(b)(4)--- clean hold time is not supported by the data or documentation. The validation of clean hold time should determine prospectively the maximal time during which each piece of the equipment remains clean after the cleaning procedure – and should not rely on assumptions, extrapolations from use in other processes, or waived if equipment is not currently dedicated to the Fibrin Pad production process. FDA pointed out that all the claims in the license must be validated for the particular process at the time of submission of the application.
Ethicon stated that they are willing to complete the cleaning validation to meet the FDA standards. Ethicon also stated that their current clean hold times are based on industry practices and standards, and the supporting documentation can be provided.
Ethicon emphasized the importance to move forward with the application and asked if FDA permit Ethicon to submit additional information during the review process in order to avoid voluntary withdrawal of the amendment.
FDA stated that during the 14-day evaluation period FDA will decide whether or not Ethicon’s responses to the CR letter can be accepted as complete. This decision will determine whether or not the review clock can be started. FDA re-stated that the current responses are deficient in addressing the cGMP-related issues listed in the CR letter. Final reports of all cleaning validation activities are required. The Regulatory Project Manager will consult with the supervisory managerial level whether FDA allow Ethicon to submit deficient information within 30 days, i.e. by 30 April 2012, as another amendment to the BLA, to avoid the stop of the application. FDA will notify Ethicon whether Amendment STN 125392/0.11 was accepted for review in the Acknowledgement letter due by April 13th, 2012.