U.S. FDA perspective on the regulation of cyanoacrylate polymer tissue adhesives in clinical applications

Currently, tissue adhesives and glues are an alternative technology in clinical applications that are important both to the medical industry and surgical profession. Many of these emerging tissue adhesives could modify difficult surgical procedures by stabilizing tissue surfaces through hemostasis, sealing of wounds, and fixation of tissue in areas inaccessible to staples, clips, and suture placement. Currently, physicians are relied heavily on sutures, clips, and staples which have an estimated annual worldwide market of over $ 2.5 billion for wound closure alone. There have been significant advances in this technology because of excellent clinical research and development in this field during the last 15 years. In a broad sense, tissue adhesives and glues can be categorized into biologic, composite (hybrid) biologic, synthetic and genetically engineered polymer protein glues. A biologic tissue adhesive is a natural substance consisting of blood products, for example, Fibrin Sealant (Tisseel® VH Kit). It is used as “an adjunct to hemostasis in surgeries involving cardiopulmonary bypass and treatment of splenic injuries due to blunt or penetrating trauma to the abdomen, when control of bleeding by conventional surgical techniques, including suture, ligature, and cautery, is ineffective or impractical; also indicated as an adjunct for closure of colostomies...”. Tisseel is manufactured using fibrinogen as the main ingredient (a protein from human blood that forms a clot), thrombin (another blood protein that facilitates blood clotting), bovine fibrinolysis solution, and other clotting factors or additives. An example of a composite (hybrid) biologic tissue adhesive is BioGlue Surgical Adhesive. It is a two-component (natural and synthetic substance) system consisting of purified bovine serum albumin and glutaraldehyde. It is indicated for use “as an adjunct to standard methods of achieving hemostasis (such as sutures and staples) in adult patients in open surgical repair of large vessels (such as aorta, femoral, and carotid arteries)”. Synthetic tissue adhesives include cyanoacrylate tissue adhesives such as DermabondTM, IndermilTM Tissue Adhesive, Histoacryl® Blue* (*Sold widely in Canada and Europe only), and polymeric sealants such as FocalSeal-L Synthetic Absorbable Sealant and CoSeal Surgical Sealant. Genetically engineered polymer protein glues are based on protein engineering and DNA gene technology, which are still at experimental stages.