Status: approval withdrawn; replacement in Phase III trials

Organizations involved:

Haemacure Corp. – Manuf.; R&D; Tech.; World mark.

CSL Bioplasma GmbH – R&D; Tech.

CSL Ltd. – Parent

Baxter AG – Manuf.; R&D; Tech.; Former

BioProducts Laboratory – R&D; Former

Cross ref: See the Fibrin Sealant Products entry (#735), and the entry above for Two-Component Fibrin Sealant, Vapor Heated or Tisseel VH Kit (#737).

Description: See the entry above for Tisseel VH Kit (#737), which is substantially identical to this product.

Nomenclature: Fibrin Sealant/Haemacure [BIO]; Haemaseel APR [TR]; Haemaseel HMN [TR]; Fibrin Sealant, Two-Component Fibrin Sealant, Vapor Heated Kit [FDA; former]; Fibrin Sealant (Human) [FDA; recently adopted]; fibrin sealant kit [SY]

Companies.: Haemacure Corp. acquired U.S. marketing rights to Hemaseel APR in 1997 from Immuno AG (Vienna, Austria) as part of the acquisition of Immuno AG by Baxter Healthcare Corp. As a condition for allowing Baxter Health-care Corp. to acquire Immuno AG, the Federal Trade Commission (FTC) ordered Immuno/Baxter to divest its Tisseel fibrin sealant product manufacturing and U.S. marketing rights to another company (to make sure another company markets the same or equivalent product in the U.S.). Haemacure received manufacturing and marketing rights to the Tisseel fibrin sealant product, which it markets under the trade name Hemaseel APR. Haemacure launched Hemaseel APR commercially in the U.S. in June 1998.

The FTC required Baxter to provide Haemacure with packaged Hemaseel (relabeled as Tisseel) at cost until Haemacure receives FDA approval for its own new manufacturing facility (originally estimated 3rd quarter 2004). Baxter also transferred all Tisseel-related technology. The FTC provided Haemacure up to seven years to assume manufacturing and gain FDA approval for its own product. The FTC has the right to terminate the license agreement, if FDA approval appears unlikely.

In early 2000, Haemacure concluded an agreement with BioProducts Laboratory (BPL; Elstree, England), a subsidiary of the U.K. National Health Service. BPL was developing a plasma fractionation facility for dedicated manufacture of the fibrinogen and thrombin components of Hemaseel APR. Haemacure assumed the costs of facility improvement and equipment and obtaining regulatory approval. The plant is designed to produce over 500,000 vials each of fibrinogen and thrombin annually. Construction was completed in Jan. 2002, with final FDA approval expected in 2004. Haemacure would then have its own manufacturing source and FDA approved product, and would, presumably, be released from the FTC consent/license agreement.

In Nov. 2003, Haemacure discontinued marketing and distribution of Hemaseel APR to concentrate on development of its 2nd generation product, Hemaseel HMN (in Phase III trials; see R&D section below). Haemacure terminated its 1997 agreement with Baxter for manufacture and supply of Hemaseel APR, with Baxter paying Haemacure $3.4 million by Jan. 2004 and $2 million by Jan. 2006, plus $915,000 for purchase of specialized equipment. Haemacure also terminated its agreement with BioProducts Lab. for company-dedicated manufacture of Hemaseel APR, with Bio-Products forgiving Haemacure’s debts in exchange for the Hemaseel APR equipment installed at BioProducts, Haemacure paying BioProducts $675,000, and granting BioProducts warrants to purchase up to 300,000 common shares of stock at $3.00 during the next two years.

Fibrijet syringe application system, with canula tip and manual spray accessories is supplied by Micromedics, Inc.

In Dec. 2005, it was reported that Fisher Biosciences, through its HyClone business, had partnered with Alfa Laval to provide single-use bioprocessing systems for Haemacure’s new manufacturing facility for Hemaseel products under construction in in Sarasota, FL. These bioprocessing systems are marketed and sold by Alfa Laval under an exclusive agreement with HyNetics, a joint venture between Alfa Laval and HyClone. In the HyNetics system, all of the parts that will come in contact with product materials are designed for single use (i.e., disposable). The contract with Haemacure marks one of the first major installations of HyNetics technology for large-scale bioprocessing. Haemacure has selected Alfa Laval to provide all of the detailed engineering for its new facility as well as selection of the production equipment. The core bioprocessing equipment for the operation will be the HyNetics single-use mixing technology, which features control fixtures and hardware manufactured by Alfa Laval and disposable elements manufactured by HyClone. The systems will be used to produce Haemacure’s fibrin-sealant and thrombin products sold under the Hemaseel brand.

FDA class: Biologic BLA

CBER class: Blood And Blood Derivatives

Approvals: Date = 19980501; first approval, BLA (for Tisseel, an identical product, not Hemaseel APR)

Date = 20000600; medical device, 510K [equivalence to current product (Tisseel)] Indication = approval of HemaMyst, a disposable aerosol applicator for Hemaseel

Indications: See the Tisseel entry (#737).

Status: Haemacure had submitted a BLA for a new frozen formulation – Hemaseel APR (Frozen Formulation), and projected approval in second quarter 2001. Approval of the new BPL manufacturing facility required consistent manufacture of three lots to be used in clinical trials, expected to be completed in 3rd quarter 2003. However, as discussed above, Heamacure halted manufacture of Hemaseel APR, and is now concentrating on Hemaseel HMN, the next generation product (discussed below).

Tech.: As part of the FTC consent/license agreement, Haema-cure will receive all Tisseel (fibrinogen and thrombin)-related technology from Immuno AG/Baxter.

Market: Sales of Hemaseel APR in FY2001 were $12.9 million, and ~$18.7 million in 2001. In Feb. 2001, Haemacure acquired exclusive U.S. marketing rights for the Gelfoam hemostatic product line, products used with fibrin sealants, from Pharmacia Corp. (now Pfizer Inc.).

The Average Wholesale Price (AWP) is not available (not in 2007, 2005 or 2004 Red Book). Presumably, prices for Hemaseel APR were similar to those for Tisseel.

R&D: In 1999, Haemacure entered in an agreement with the Central Laboratory Blood Transfusion Service (ZLB), Swiss Red Cross, now CSL BioPlasma AG. ZLB (CSL ) received exclusive worldwide development, manufacture and marketing rights for a second generation second-generation fibrin sealant product in development by Haemacure, Hemaseel HMN. Hemaseel HMN involves fractionation of fibrinogen and thrombin from plasma, with epsilon-amino caproic acid (EACA) used instead of aprotinin or tranexamic acid to eliminate undesirable plasminogen. This is claimed to provide higher purity, yields and enhanced safety. CSL Ltd. acquired ZLB in Sept. 2000, ZLB/CSL then withdrew from the 1999 agreement, and a new technology licensing agreement was subsequently concluded (with Haemacure receiving $7.1 million in milestone fees and ZLB/CSL receiving a 3% royalty on Hemaseel HMN for 10 years). Hemaseel HMN is now in Phase III trials.