Human fibrinogen + human thrombin

319935004

Refrigerated Storage

Tisseel · Baxter

Baxter
Tisseel
Ready to use solution for sealant

The product literature states that the product should be stored in a freezer (at ≤-18°C) and the cold storage chain must not be interrupted until use. Once thawed, unopened pouches may be stored for up to 72 hours at controlled room temperature (not exceeding 25°C) after removal from the freezer. If not used within 72 hours after thawing, the product must be discarded.

Contact Baxter for additional information on cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Thawed solutions should be given an expiry of 72 hours from when the product was removed from the freezer.
No
17th April 2019
London MI Service

New Medicines

Raplixa · Haemorrhage; intra-surgical - supportive treatment in adults where standard surgical techniques are insufficient for improvement of haemostasis

Information

Raplixa
New formulation
Mallinckrodt
Mallinckrodt

Development and Regulatory status

Licence withdrawn
Licence withdrawn
Licence withdrawn
01. Aug 13: Plan to file in EU Q4 2013 and in US Q1 2014 [6]
02. Oct 14: Trade name changed from Fibrocaps to Raplixa™. [9]
03. Nov 13: Filed in the EU. The complementary spray delivery device to assist surgeons in the accurate application of the dry powder Fibrocaps was recently granted a European CE mark. The company plan to file for approval of Fibrocaps in the US in Q1 2014 [7].
04. Apr 14: Filed in the US to aid in haemostasis during surgery, where control of mild or moderate bleeding by conventional means is ineffective or impractical. A decision on approval expected by Jan 31, 2015 [8].
05. Jan 15: EU positive opinion for Raplixa as supportive treatment where standard surgical techniques are insufficient for improvement of haemostasis in adults. Raplixa must be used in combination with an approved gelatin sponge [10].
06. Mar 15: Approved in the EU. The marketing authorisation is valid in the 31 countries of the European Economic Area, which includes all 28 EU Member States, plus Norway, Iceland and Liechtenstein [11].
07. Mar 15: The Medicines Company is seeking potential partners to support supply of Raplixa during 2015 and beyond [11].
08. Apr 15: Approved in the US [12].
09. May 16: The complementary spray delivery device for the application of the powder has been granted a European CE mark. Product launch is anticipated by 2016 [13].
10. May 16: Mallinckrodt plc acquired the haemostasis portfolio of The Medicines Company in Feb 16 [14].
11. Nov 16: Mallinckrodt annual report does not disclose marketing plans, but presume launch in EU countries & the US will follow [15].
12. Mar 18: Raplixa is not currently available in the EU. Mallinckrodt does not have a timeline for availability [16].
13. Dec 18: Licence withdrawn [17]

Category

Dry powder formulation of fibrinogen and thrombin derived from human plasma
In cardiac surgery, severe bleeding occurs in approximately 7% of cases; approximately 7% of percutaneous coronary interventions performed emergently in pts with acute coronary syndrome result in major bleeding. Mortality rates approaching 20% have been observed in elective vascular patients with severe bleeding complications [2].
Haemorrhage; intra-surgical - supportive treatment in adults where standard surgical techniques are insufficient for improvement of haemostasis
Topical

Trial or other data

01. Feb 12: NCT01527357 (Finish-3) A PIII, international randomized, single-blind, controlled trial of topical Fibrocaps™ plus gelatin sponge vs gelatin sponge alone, for achieving hemostasis in 500 subjects with mild to moderate surgical bleeding during spine, liver, vascular or soft tissue surgery. The primary outcome is Time to Hemostasis (TTH) within 5 minutes. The study will start May 12 and is due to complete May 13 [1].13/02/2012 09:14:15
02. ProFibrix BV is developing Fibrocaps®, a dry powder formulation of fibrinogen & thrombin derived from human plasma, for treatment of acute and severe bleeding associated with elective surgery or trauma. Thrombin is a highly specific protease that transforms fibrinogen into a fibrin clot. Fibrocaps® is formulated using spray drying, which makes small, hollow microspheres of thrombin and fibrinogen. Trehalose carbohydrate is also added during formulation to ensure that the active proteins remain stable and rapidly dissolve in solution. The powder is stored at room temperature and can be applied to the wound without preparation as soon as bleeding starts [3].
03. Apr 13: Enrolment completed of PIII FINISH-3 on schedule [4].
04. Jun 13: The Medicines Company will purchase ProFibrix. subject to a satisfactory review of the pending PIII FINISH-3 trial results of ProFibrix´s lead biologic, Fibrocaps. FINISH-3, has completed enrollment of 719 surgical patients with mild to moderate surgical bleeding and results are expected 3Q 2013. If favorable, FINISH-3 is expected to be sufficient to support a filing for marketing approval in the EU and US [5].
05. Aug 13: Results of the PIII FINISH-3 study reported. The study met all primary and secondary haemostasis efficacy endpoints in four surgical indications of spinal surgery, hepatic resection, soft tissue dissection and vascular surgery. ProFibrix has developed a complementary dry powder spray delivery device to assist surgeons in the accurate application of Fibrocaps. Recently the ProFibrix quality management system for the design, development and control of manufacture of sterile biological haemostat delivery systems and their accessories was granted ISO 14385: 2003 certification. Applications for a European CE mark and for an FDA 510k review for the device are underway [6]
06. Aug 13: The Medicines Company has purchased ProFibrix following the positive results from FINISH-3. The Company believes that Fibrocaps are complementary to Recothrom® ProFibrix also has a proprietary recombinant fibrinogen development program that will potentially allow development of the first recombinant thrombin and recombinant fibrinogen combination products [6].
07. Oct 14: Positive data from FINISH-3 presented. In this randomised (2:1), single-blind, controlled PIII pivotal trial, pts with mild-moderate surgical bleeding were treated with Raplixa™ (n=480, sprayed on in 50% of cases) or gelatin sponge (n=239) while undergoing spinal (n=183), vascular (n=175), hepatic (n=180), or soft tissue (n=181) procedures. Raplixa™ significantly reduced time to haemostasis (TTH) vs. gelatin sponge; hazard ratios: 3.3, 2.1, 2.3, and 3.4 for the four surgical indications, respectively (each p<0.001; primary endpoint) and significantly reduced median TTH for each indication (p<0.0001). Adverse event incidences were similar between treatment arms. Non-neutralizing, anti-thrombin antibodies developed in 2% and 3% of pts on Raplixa™ vs. gelatin sponge-treated patients respectively. [9]

Evidence based evaluations

EPAR

VeraSeal · Haemorrhage in adults undergoing surgery

Information

VeraSeal
New formulation
Grifols

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
None

Sep 17: EU positive opinion for supportive treatment in adults where standard surgical techniques are insufficient: • for improvement of haemostasis. • as suture support in vascular surgery. It is proposed that the use of VeraSeal is restricted to experienced surgeons who have been trained in the use of the medicinal product [1].

Category

VeraSeal will be available as solutions containing the active substances human fibrinogen (80 mg/ml) and human thrombin (500 IU/ml).
Acute coagulopathy with significant blood loss is frequent in major vascular procedures. The problem is confounded by the high prevalence of antithrombotic agent use among patients undergoing vascular surgical procedures and intraoperative heparin administration [2].
Haemorrhage in adults undergoing surgery
Topical