Status: approved; marketed

Organizations involved:

Orthovita, Inc. – Manuf.; R&D; Tech.; World mark.

Angiotech Pharm., Inc. – R&D; Tech.; Former

Cohesion Technologies, Inc. – Former

U.S. Surgical – Former

Tyco Healthcare – Parent; Former

Cross ref.: See the Thrombin Products entry (#919). See also the entry for Gelatin Matrix Hemostatic Sealant (FloSeal) (#808), another thrombin plus collagen hemostatic product.

Description: Vitagel Surgical Hemostat is a sprayable liquid hemostatic product composed of bovine thrombin and bovine collagen that is mixed with autologous (patient’s own) blood-derived Plasma. Vitagel works by combining the thrombin/collagen suspension with the patient’s own plasma to form a fibrin/collagen clot. Joined syringes, one holding Plasma (Human) from the patient, and the other an aqueous mixture of bovine thrombin and collagen, mix these components for spraying onto bleeding wounds. As with other thrombin-containing hemostasis sealant products, the thrombin reacts with endogenous fibrinogen (in the Plasma) to form fibrin polymers which, along with the collagen matrix, forms a surface physical barrier to blood flow. Besides adding mechanical strength to the resulting gel matrix, collagen is a potent platelet activator and assists with clotting. Vitagel is approved in the U.S. for use only in conjunction with the the Cellpacker autologous plasma collection system from Orthovita.

The Vitagel syringe contains a 5 mL of a suspension of 20 mg/mL bovine collagen and at least 300 U/mL bovine thrombin (Thrombin-JMI) in 40 nM calcium chloride (CaCl2) buffer.

Vitagel contains highly purified bovine collagen and bovine thrombin sourced from U.S. cattle only. Presumably, Orthovita uses Thrombin-JMI from GenTrac, Inc. (see entry #920). The fibrinogen for clot formation is a component of the patient’s own plasma (obtained by centrifugation of whole blood from the patient). Heparinized patient’s blood can be used to prepare the plasma.

The process for use of Vitagel involves: drawing the patient’s whole blood into the Cellpacker plasma collection system; centrifuging the blood; transfering the plasma from the collection system to the sterile syringe; attach the sterile plasma and Vitagel-containing syringes to the joiner; assembly of the delivery device; and application of Vitagel by spraying onto bleeding areas.

Nomenclature: Thrombin/Collagen Spray [BIO]; Vitagel Surgical Hemostat [TR]; CoStasis Surgical Hemostat [TR former]; DynaStat Surgical Hemostat [TR former]

Biological.: Vitagel affects the clotting cascade through multiple mechanisms. The thrombin initiates the conversion of fibrinogen to fibrin, which forms a matrix (clot) to inhibit blood flow. The collagen is incorporated into this matrix and gives it additional strength. The collagen and thrombin are both potent platelet activators. Preclinical animal studies show the material is completely resorbed in a few weeks after treatment.

The Vitagel biologically active three-dimensional matrix provides elasticity, strength and adherence to inhibit blood flow; contains microfibrillar collagen which studies show to be conducive to cell ingrowth; and is resorbed in ~30 days. Vitagel contains a physiologic fibrinogen concentration. Excessive levels of fibrinogen may form dense fibrin films, which have been reported to impede healing.

Companies.: CoStasis was originally developed and manufactured by Cohesion Technologies, Inc. CoStasis was the company’s first product. It ws exclusively marketed in the U.S. by U.S. Surgical, a subsidiary of Tyco Healthcare.

In Feb. 2003, Angiotech Pharmaceuticals, Inc. completed acquisition of Cohesion Technologies. In June 2004, Angiotech granted Orthovita, Inc. exclusive marketing rights for CoStasis, which was rebranded as Vitagel Surgical Hemostat, and Orthovita commenced sales in 2005.

In Oct. 2005, Orthovita, Inc. acquired all remaining, including manufacturing, rights for Vitagel. In March 2006, manufacturing obligations for the Vitagel (and Cellpacker) were shifted from Angiotech to Orthovita. Orthovita commenced manufacturing Vitagel in July 2006.

In Dec. 2006, Orthovita acquired full rights to Vitagel and Cellpacker, and no longer pays royalties to Angiotech. Angiotech has retained all development and commercial rights for a drug-loaded (therapeutics delivery) versions of this product.

FDA class: Medical device; PMA

Approvals: Date = 20000613; PMA, first approval

Date = 20060516; PMA (P050044); Indication = approval for manufacture by Orthovita at subcontractor facilities in Malvern, PA

Date = 20070122; PMA supplement; Indication = approval of Cellpacker plasma collection system for use with Vitagel

Indications: [full text of "Indications for Use” of product insert/labeling]:

Vitagel surgical hemostat has been tested and shown to be clinically effective in the following applications:

Anastomotic Bleeding: Bleeding that is encountered at the anastomotic sites, during coronary artery bypass grafting, or vascular procedures.

Cancellous Bone Bleeding: Bleeding encountered during cardiothoracic procedures (sternal edge) or orthopedic procedures such as iliac crest bone harvest site.

Capillary Bed Bleeding: Bleeding that is encountered from cut surface of liver, retroperitoneal bed, epidural bleeding, or any other type of diffuse capillary bleeding.

Status: The PMA was approved in June 2000, and CoStasis was launched in the U.S. in July 2000. CoStasis received CE mark (European Union medical device approval) in Sept. 1998, and it was launched in Europe in early 1999.

Tech. transfer: The product insert cites U.S. 5,290,552; 6,096,309; and 5,997,811. U.S. 6,096,309, “Compositions containing thrombin and microfibrillar nanometer collagen, and methods for preparation and use thereof,” originally assignd to Cohesion Technologies, Inc., has the exemplary claim (no. 1), “A hemostatic composition comprising thrombin and a mixture of non-microfibrillar collagen and microfibrillar collagen in an aqueous medium wherein said microfibrillar collagen has an average fibril diameter of about 3-30 nm.” Other claims include the composition and manufacture of Vitagel components. U.S. 5,290,552, “Surgical adhesive material,” concerns preparation of fibrinogen- and clotting factor-containing preparations from autologous plasma.

Trials: Vitagel has been clinically tested in cardiovascular, general, hepatic and orthopedic surgeries. Vitagel was shown to be effective in controlling bleeding in hepatic, general, cardiac and orthopedic surgical procedures. The most common adverse events observed in the treated patients were fever, pain, nausea and collapse of a lung (atelectasis).

Medical: Vitagel is used in surgical procedures (other than neurological, eye, and urinary tract surgery) to help in the control of bleeding. Vitagel is a topical hemostat and is applied only to the tissue surface. Vitagel is sprayed directly onto the bleeding site, where it adheres to tissues and stops bleeding during surgery. It functions without the need for manual pressure or the need to hold the material in place.

Blood collection and separation of plasma are performed at the start of surgery and take about five minutes. Final assembly of the device can be done immediately prior to use (~2-3 minutes). Vitagel Surgical Hemostat (thrombin and collagen component syringe assembly) is ready to use from the package and can remain unopened until needed. Vitagel can be used (sprayed) multiple times throughout a procedure without clogging for up to two hours. Extra spray tips and cannulas are provided for easy replacement.

Market: Average Wholesale Price (AWP) not available (product not in 2007, 2005 or 2004 Red Book).

Product sales under Orthovita’s VITAGEL product platform were $5.6 million for first three quarters of 2006, equivalent to sales of about $7.45 million/year.

Orthovita has approximately 40 direct sales representatives and clinical specialists in the U.S. and operates a network of independent distributors in selected countries in the European Union.