Ethicon/Omrix's EVARREST Update Email, September 19, 2012
Tilghman, Tracy


From: Hornatko-Munoz, Adrienne

Sent: Wednesday, September 19, 2012 10:35 AM

To: Tilghman, Tracy

Subject: FW: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update - a few brief comments

FYI-

This was addressed and resolved in a t-con that OBRR had with CDRH later that evening. A

From: Blyskun, Elaine

Sent: Thursday, August 30, 2012 8:18 AM

To: Lerner, Herbert P.; Whang, Joyce M; Fisher, Benjamin

Subject: FW: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update - a few brief comments

Good morning,

I would like to inform you of an item that you may wish to discuss with Christy at your 1â€?onâ€?1

this morning:

CBER is planning on approving the Ethicon EVARREST Patch in September. It has the following Indications: “an adjunt to hemostasis for soft tissue bleeding during retroperitoneal, intraâ€? abdominal, pelvic, and thoracic surgery when control of bleeding by standard surgical methods of heomostais (e.g. suture, ligature, cautery) is ineffective or impractical.”

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

We learned about this from Roxy Horbowyj. According to our meeting with her yesterday, the sponsor has provided very limited clinical data to support this BLA, and the primary clinical study only involved a phone call at 1â€?year postâ€?procedure. Therefore, I am concerned that will cause significant problems, not only for patients (i.e., adhesions), but also for us in the regulation of ----(b)(4)--------

Below you will see the only response that I have received since I informed CBER that---(b)(4)----------------------------------I am concerned that they are underestimating the potential impact of this approval, and I would appreciate any insight that you and Christy may have regarding a path forward.

Thank you, Elaine

Sent: Wednesday, August 29, 2012 5:54 PM

To: Blyskun, Elaine; Horbowyj, Roxolana; Melhem, Randa; Waites, Nancy; Brown, La'Nissa; Lindsey, Kimberly; Scott, John; Cato, Dennis; Campbell, Karen M; Nguyen, Loan; Khuc, Kristine;

Barash, Faith

Cc: Tilghman, Tracy; Shields, Mark; Krause, David; Francis, Jacqueline; Andrews, Sharon M; Sewell, Catherine

Subject: RE: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update - a few brief comments

Dear Elaine,

According to the information provided in the BLA, the ORC used in EVARREST Fibrin Sealant Patch is----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

I hope this information is helpful. Thank you.

Natalya (Product Reviewer)

Natalya Ananyeva, Ph.D. Senior Staff Fellow FDA/CBER/OBRR/DH/LH Office: 301-827-6165

E-mail: Natalya.Ananyeva@fda.hhs.gov

From: Blyskun, Elaine

Sent: Wednesday, August 29, 2012 5:39 PM

To: Horbowyj, Roxolana; Ananyeva, Natalya; Melhem, Randa; Waites, Nancy; Brown, La'Nissa; Lindsey, Kimberly; Scott, John; Cato, Dennis; Campbell, Karen M; Nguyen, Loan; Khuc, Kristine; Barash, Faith

Cc: Tilghman, Tracy; Shields, Mark; Krause, David; Francis, Jacqueline; Andrews, Sharon M; Sewell, Catherine

Subject: RE: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update - a few brief comments

Hello,

Would you please let us know if the ORC in this product is -------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------

---------------------(b)(4)------------------------------

Thank you,

Elaine Blyskun

Chief, Obstetrics-Gynecology Devices Branch

Division of Reproductive, Gastro-Renal, and Urological Devices

ODE/CDRH/FDA

10903 New Hampshire Ave. WO66-G202 NEW

Silver Spring, MD 20993-0002 (301)796-6533

(301)874-8111 Fax

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From: Horbowyj, Roxolana

Sent: Monday, August 27, 2012 1:32 PM

To: Ananyeva, Natalya; Melhem, Randa; Waites, Nancy; Brown, La'Nissa; Lindsey, Kimberly; Scott, John; Cato, Dennis; Campbell, Karen M; Nguyen, Loan; Khuc, Kristine; Barash, Faith Cc: Tilghman, Tracy; Shields, Mark; Krause, David; Francis, Jacqueline; Blyskun, Elaine

Subject: RE: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update - a few brief comments

Hi - thank you - few brief comments. EVARREST is a combination product:

The Matrix component consists of a knitted oxidized regenerated cellulose (ORC)

backing layer under a layer of polyglactin 910 (PG910) non-woven fibers.

Each 4 x 4 in. (10.2 x 10.2 cm) unit of EVARREST contains (nominally) 50.3 mg/in2 (7.8 mg/cm2) Human Fibrinogen and 203.2 IU/in2 (31.5 IU/cm2) Human Thrombin.

The proposed labeling raises several concerns including the device components which are ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- it seems possible that the EVARREST labeling may impact future device labeling

To my knowledge, -----------------------(b)(4)----------------------------------------- as well as the subject combination product ---------(b)(4)---------(polyglactin), human fibrinogen & thrombin) have not been studied in any procedures that were not open, or any pediatric or oncologic population, and manual pressure is a key condition of EVARREST use.

Have attached the subject files here and cc'd CDRH - PRSB BC (re hemostasis and -(b)(4)-aspects), OGBD BC (re ---(b)(4)--- aspects) and Jackie Francis, MD (re pediatric aspects).

<< File: EVERREST, proposed-tracked-changes.pdf >> << File: ped-waiver-neonates.pdf >>

<< File: Current US -----(b)(4)------------.pdf >> << File: ----------(b)(4)------------.pdf >> << File: Omrix FP draft-annot-labeling-text (2), rih.docx >>

http://www.ethicon360.com/products/coated-vicryl-polyglactin-910-suture

Very briefly, the sponsor appears to have made somewhat substantive changes to labeling (submitted track changes version attached).

- As to the IFU, Contraindications, Warnings and Precautions: there are

2 sets of these: on page 1 of 8, and again on page 2 (IFU) and 4 of 8. The language is not consistent (e.g.: some words and or phrases added or omitted) in the 2 sets, which is confusing and potentially misleading. It seems that these should be consistent. Below please find preliminary comments.

- Data for all clinical trials submitted to support this application does not seem to be in the labeling.

As to the IFU (p1/8):

- It is misleading to drop 'with manual compression' because this was very much a condition of investigational use in clinical trial. EVARREST has not been studied without manual compression and likely would have a very different (worse) outcome if used without manual compression. Dropping 'with manual compression' implies use in other than open procedures.

- Dropping the term 'non-cardiac' expands use to the cardiac surgery population. From the CBER perspective, has such use been justified? From the CDRH perspective, polyglactin is contraindicated as a suture in cardiovascular and neurological procedures.

- for clarity, the IFU should likely be specific to use in open procedures; laparoscopic and endoscopic procedures were not studied, the last sentence on the page 2 IFU is omitted on page 1, which often happens when there are multiple sentences and is misleading.

As to Contraindications (p 1/8):

'Do not use to treat bleeding from large defects in large arteries or veins. (4.1)'

- It would be useful to define large defects and large arteries, e.g., greater than 2mm, edit to e.g.,

Do not use to treat bleeding from defects in large (greater than 2mm diameter) arteries or

veins. (4.1)

'Do not use in individuals known to have anaphylactic or severe systemic reaction to human blood products, ------------(b)(4)-------------------------

The sponsor proposed to -------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------

However, the sponsor does not include contraindications as to AE the matrix device components could cause and this may affect future device labeling. Please see the current labeling

for INTERCEED: http://www.ethicon360.com/sites/default/files/products/Current%20US%20INterceed%20IFU%200910_0.pdf

For Polyglactin 900 suture:

http://www.ethicon360.com/sites/default/files/products/Coated%20VICRYL%20EPI.pdf

As to Warnings (p1/8) The sponsor has added

'• ---------------------(b)(4)---------------------------------------------------------------------

However, considering data to support the marketing application, It seems that this should be modified to state ------------------------------------------------------------(b)(4)-------------------------------------------------------------------------

As to 'Topical'

This labeling uses 'topical' to mean 'on top of any surface', whereas

CDRH use has been 'external, on top of skin'. To minimize confusion

and potentially misleading / misunderstood labeling, it would be useful to discuss CBER and CDRH use of this term and come to consensus on how to best assure that labeling clearly conveys intent.

Will send more detailed comments shortly.

From: Ananyeva, Natalya

Sent: Monday, August 27, 2012 12:16 PM

To: Melhem, Randa; Waites, Nancy; Brown, La'Nissa; Lindsey, Kimberly; Horbowyj, Roxolana; Scott, John; Cato, Dennis; Campbell, Karen M; Nguyen, Loan; Khuc, Kristine; Barash, Faith

Cc: Tilghman, Tracy; Shields, Mark; Ananyeva, Natalya Subject: BLA STN# 125392/0 - Ethicon/Omrix's EVARREST - Update Importance: High

Dear All,

During the 23 August 2012 telecon, we reached agreement with Ethicon/Omrix regarding the proper name for their hemostatic product EVARREST.

Please use the proper name "Fibrin Sealant Patch" in your review memoranda and executive summaries for SBRA.

We are moving towards approval; however, there are a few pending issues, and we will keep you updated.

Please note that presentation of the BLA at the PeRC was moved to 5 September 2012.

Please continue to follow the established schedule in finalizing your reviews and executive summaries to be included in the SBRA.

T-30 date is 30 August 2012. Your response by COB 27 August 2012 (for executive summaries only) would be highly appreciated.

Thank you very much. Natalya

Natalya Ananyeva, Ph.D. Senior Staff Fellow FDA/CBER/OBRR/DH/LH Office: 301-827-6165

E-mail: Natalya.Ananyeva@fda.hhs.gov
