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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Record of Telephone Conversation, November 26, 2012 - EVARREST

Submission Type: BLA    Submission ID: 125392/0    Office: OBRR

Product:

Fibrin Sealant Patch [EVARREST]

Applicant:

Ethicon, Inc. (Ethicon)

Telecon Date/Time: 26-Nov-2012 04:50 PM        Initiated by FDA? Yes

Location: WOC 1, room 424N

Telephone Number: --b(4)---------

Communication Categorie(s):

1. Other - Labeling negotiations

 

Author: Kimberly Lindsey, Natalya Ananyeva

Telecon Summary:

Discussion with Applicant regarding revisions of Prescribing Information for EVARREST

FDA Participants:

Nisha Jain, M.D.

Kimberly Lindsey, M.D.

Natalya Ananyeva, Ph.D.

 

Ethicon:

Jessica Chung, Regulatory Affairs, Ethicon, Inc.

 

Trans-BLA Group: No

Related STNs: None

Related PMCs: None

 

Telecon Body

 

Dr. Jain called Dr. Chung to request additional revisions to the Prescribing Information (PI) dated 11.16.2012. Specifically Dr. Jain requested revisions to the following sections of the PI:

 

HIGHLIGHTS (The changes were to be made to the corresponding Full Prescribing information sections of the PI as well).

 

Dosage and Forms and Strengths:

Insert absorbable to indicate the dosage form for EVARREST:
i.e.  EVARREST absorbable Fibrin Sealant Patch consists of human fibrinogen and human thrombin embedded in a flexible…

 

Warnings and Precautions:

The Warning and Precaution statement about Creutzfeldt-Jacob disease was revised to state:

 

Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent (5.7)
 

Dr. Jain noted that the PI has been reviewed by the Office Director, Dr. Jay Epstein. He requested revisions to the adverse reactions (AR) table in section 6.1 of the PI. Specifically, Dr. Epstein noted that the table is misleading because the EVARREST group includes both the randomized and non- randomized, uncontrolled subjects who received EVARREST as part of an extended safety evaluation of EVARREST in the 400-07-002 study. The table will be more accurate if it specifically compares the subjects who were part of the controlled portion of the study. Therefore, the denominator for EVARREST in this table should reflect the controlled portion of the study.

 

Dr. Jain also stated that the Warnings and Precautions section (section 5.4) of the PI would need to be revised to address FDA’s concerns about the ----b(4)------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------- FDA asked Ethicon to propose language regarding use of ORC in gynecologic surgery where hemostasis is not optimal, and thus predisposing to adhesion formation, to be included in section 5.4.

 

Adverse Reactions

FDA requested that Ethicon re-calculate the AR’s in the table based on the controlled portion of the study and also report the overall safety population of subjects who received EVARREST (N=229), as it appears in the current table.
 

An option would be to include one table with 3 columns:
1) EVARREST (controlled study), 2) EVARREST overall and 3) Control.

 

Additional ARs may be added if they meet the following criteria: rate of ≥ 1% and greater incidence in the EVARREST arm compared to the control arm. The ARs should also be clinically relevant for EVARREST’s surgical indication and known mechanism of action. The table could be followed by a footnote stating that five of the six pulmonary embolic reported for EVARREST occurred in the open label uncontrolled section of the soft tissue bleeding study.

 

The following sentence was deleted from the immunogenicity section (section 6 Adverse Reactions):

 

The results demonstrated that the proportion of subjects having an immune response to human thrombin was within the expected range, i.e. within the 95% confidence interval, of the normal healthy population that had not been treated with thrombin products.
 

17 Patient Counseling Information

 

“Runny nose” was deleted from the described symptoms for parvovirus B19 infection, since this symptom occurs by way of a respiratory route. Parvovirus infection resulting from EVARREST would occur by means of systemic exposure.

 

Dr. Jain committed to send Ethicon a PI with track change revisions later this evening. A telecon will be set up for tomorrow, November 27, 2012 at 12:30 PM EST to continue working toward agreement on the final version of the PI.

 

END