Record of Telephone Conversation, August 23, 2012 - EVARREST
RECORD OF TELEPHONE CONVERSATION
Submission Type: BLA Submission ID: 125392/0 Office: OBRR
Fibrin Sealant Patch [EVARREST]
Telecon Date/Time: 23-Aug-2012 09:00 AM Initiated by FDA? Yes
Telephone Number: —b(4)--------, Participant Code: --b(4)---------
1. Other – Proper Name discussion
Author: TRACY TILGHMAN
Teleconference to discuss the proper name justification with Ethicon.
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
The purpose of this external teleconference with Ethicon, Inc. (Ethicon) was to continue negotiation on the proper name convention for EVARREST. FDA evaluated Ethicon’s proposal for the proper name, --b(4)---------------------------------------- submitted by e-mail on 21 August 2012. FDA did not find it acceptable for the following reasons:
· It is CBER's position that the use of the term, "Matrix" in the product's proper name will imply that EVARREST has activity or interactions with the treatment site that go beyond hemostasis, which is the proposed indication for this product. In the majority of FDA-approved products that use the term "Matrix", this term is associated with the wound healing activity of the product; such as, "tissue or organ repair and regeneration," "natural healing," "revascularization," "scaffold" or "cell (fibroblast) infiltration". As previously discussed, such wound healing activity for EVARREST has not been demonstrated in adequate and well-controlled clinical studies. Therefore, the evidentiary standard for this claim has not been met. FDA views the use of the term “Matrix” in the proper name as misleading and promotional [21 CFR 202.1(e)(6) and 21 CFR 312.7].
· CBER has established a proper name classification - Fibrin Sealant - for products containing both fibrinogen and thrombin. CBER has also established a proper name classification - Fibrin Sealant Patch - for combination products intended for use as adjuncts to hemostasis that consist of fibrin sealant (i.e., fibrinogen and thrombin biological substances) deposited onto a backing layer, i.e., a medical device support (e.g., collagen in the case of TachoSil or PG910/ORC-based support in the case of EVARREST). Section 508 of the Food, Drug and Cosmetic Act authorizes FDA to designate a single, useful proper name to products considered to be substantially equivalent in design and purpose. As Ethicon’s product belongs, by design and intended use, to the class of fibrin sealant products, it is CBER’s current position that the proper name "Fibrin Sealant Patch" be assigned to EVARREST.
Ethicon clarified that their intention was not to promote a wound healing claim but rather propose a name that most accurately describes their product. It is Ethicon’s opinion that the definition ---b(4)------------------------------------------- directly states the active biological components, and the term “matrix” most accurately describes the device component. Moreover, the term matrix has been used for similar hemostatic products to restrict blood loss at the wound site, such as FloSeal Hemostatic Matrix (Baxter) and SURGIFLO Hemostatic Matrix Kit (Ethicon).
FDA stated that these examples are devices reviewed and approved by CDRH and are exceptions. FDA does understand the scientific justification provided by Ethicon, Inc. for their proposed term. However, in clinical practice the use of the term “matrix” with this product may present confusion. Based on precedents with other similar products, FDA has established the term “patch” to mitigate this potential confusion.
Ethicon invited FDA to discuss the challenges with applications for combination products stating that having both a device and biological components in composition could warrant more than one mode of action, including the active role of the device component. Based on this concept, Ethicon would advocate for including the term “matrix” in the proper name of their product.
FDA emphasized that the Office of Combination Products assigned review of this application to CBER based on the assessment that the primary mode of action is provided by the biological components of EVARREST. CBER views the device component as a mode of delivery of the biologics to the wound site. However, this does not exclude the contribution of the backing layer in the mechanism of action of EVARREST which is reflected in the Prescribing Information under "Mechanism of Action": “…the formed fibrin clot integrates with the fibers of the backing layer and adheres to the wound surface thus providing a physical barrier to bleeding”.
Ethicon stated that they would accept “Fibrin Sealant Patch” as a proper name at this time but inquired if the proper name can be re-visited in the future, and what information should be provided to FDA.
FDA stated that if Ethicon provide the data from clinical trials to show evidence of wound healing attributes of their combination product, then that may be justification for FDA’s considering the proper name change. Ethicon can follow the guidance for industry or request a dedicated meeting with FDA to discuss respective trial design.
Ethicon and FDA agreed that the discussion of this telecon will be documented in the meeting minutes by both sides, and no additional statements will be needed.
Ethicon also stated that they will send the request for waiver for the pediatric study.
Ethicon also requested a follow-up telecon to clarify some aspects of the Lot Release process.