Surgical sealants and fibrin glues are biologically-based products designed to aid in the process of clot formation. Clotting is the first naturally occurring process in wound repair, and affects many subsequent biochemical processes in the wound healing cascade.
During the wounding event, blood from capillaries at the damaged tissue site seeps out and reacts with tissue proteins and air to cause platelets and complement factors to trigger the cleavage of pro-thrombin into thrombin which then changes fibrinogen into fibrin, the main insoluble component of a blood clot.
It was natural for practitioners, looking for effective haemostasis, to look at fibrin as a source of effective haemostatic activity. In the 19th century, physicians used fibrin powder to stop bleeding. During the period from 1940 to 1960, understanding of blood fractionation and the development of processes for preparing blood fractions, meant that a pure form of fibrin could be prepared and manufactured in a stable format.
Fibrin sealants represent the most useful of surgical hemostats. These products can be used to clot blood but are also used to seal around suture lines for organ transplants, mastectomies, and various resection procedures, to prevent leakage of fluids and gases. A number of companies have developed devices capable of preparing autologous fibrin and platelet formulations that can be used as sealants, and active mixes of growth factors to aid repair. Harvest Technologies, Plasmaseal, Thermogenesis, Biocoral Inc, and Interpore Cross Medical (Autologous Growth Factors product) are four companies with products designed to address this need.
Because sealants are often available as multicomponent systems that need to be mixed immediately prior to surgical application, several innovative devices have been developed to facilitate application. During product manufacture, the thrombin component and the Factor XIII/fibrinogen components are kept separate until required. Addition of fibrin product to a bleeding surface primed with the other component results in accelerated hemostasis and a sealing effect on the bleeding surface.
(From “Worldwide Surgical Sealants, Glues and Wound Closure Market, 2007-2011.” Published February 2007, MedMarket Diligence, LLC. For more information see report description, table of contents.)
Exhibit ES-8:Â Selected Sealant Product Companies and Their Strategies
Products and Prices
Focal division of Genzyme Biosurgery
Focal Seal L $30 per ml
Available for lung resections in Europe and as an adjunct for non-hemostasis sealing in the USA. Focal exploiting light activated hydrogel IP. Focal is strategically focused on exploiting unique sealant capability of its products in neurological, cardiovascular, gastrointestinal, and thoracic applications.
CoStasis (Dynastat) $50 per ml
A sprayable liquid hemostat adjunct for use in surgical procedures to control bleeding in specific clinical applications. Five year agreement with Tyco for a broad range of indications in the USA, Europe, Latin America, Middle East, Australia, New Zealand, and India. Cohesion provides unique products for sealing and hemostasis targeted at the full range of surgical procedures.
Fusion Medical Acquired by Baxter
Floseal $28 per ml
Non-sealant hemostat for all hemostasis as an adjunct, including problematic bleeding. Strategy is to develop patented products which combine technologies incorporating a number of processed mammalian biomaterials and have hemostatic benefits for surgery in demanding actively bleeding procedures, and lead to rehabilitation and re-operation benefits by reducing adhesion formation.
Tisseel $65 per ml
Homologous pooled fibrin, human thrombin, and bovine aprotinin. Adjunct for hemostasis in an expanding range of indications. Baxter focuses on biopharmaceuticals, vaccines, biosurgery and transfusion products and provides products for medication delivery and dialysis. The bioscience division of Baxter provides innovative solutions for biosurgery, tissue regeneration and surgical hemostasis.
Bioglue $45 per ml
Haemostatic adjunct for aortic dissection during surgery and may also be used during lung procedures; contains proprietary mixture of bovine albumin and glutaraldehyde. CryoLife focuses on providing donated human tissue for surgical procedures. Recently has focused on developing synthetic and engineered products as replacements for donated tissue. CryoLife will continue to target Bioglue at procedures which require a strong hemostatic tissue sealant, and compete on product benefits with Tisseel etc.
Haemaseel $65 per ml
Hemostat adjunct identical to Tisseel. Strategy to become a fully integrated supplier of haemostatic and sealant products and to evolve these into new uses such as drug delivery.
Source: MedMarket Diligence, LLC
From “Worldwide Surgical Sealants, Glues and Wound Closure Market, 2007-2011,” published February 2007. Click for details.
This report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, from tapes, sutures and staples to hemostats, fibrin sealants/glues and medical adhesives. The report examines the clinical and technology developments underlying this huge and rapidly growing worldwide market, with data on products in development and on the market; market size and forecast;Â competitor market shares; competitor profiles; and market opportunity.This report is a market and technology assessment and forecast of products in wound closure. The report details the current and emerging products, technologies and markets involved in wound closure and sealing using sutures and staples, tapes, hemostats, fibrin and sealant products and medical adhesives. The report provides a worldwide current and annual forecast to 2011 of the markets for these technologies, with particular emphasis on the market impact of new technologies through the coming decade. The report provides specific forecasts and shares of the worldwide market by segment for the U.S., Europe (United Kingdom, German, France, Italy, BeNeLux), Latin America, Japan and Rest of World.
The report provides background data on the surgical, disease and traumatic wound patient populations targeted by current technologies and those under development, and the current clinical practices in the management of these patients, including the dynamics among the various clinical specialties or subspecialties vying for patient population and facilitating or limiting the growth of technologies. The report establishes the current worldwide market size for major technology segments as a baseline for and projecting growth in the market over a ten-year forecast. The report also assesses and projects the composition of the market as technologies gain or lose relative market performance over this period.
Not every start-up succeeds. But every single successful medical technology company was once a start-up. From a primary consideration, start-up companies have been founded based on: (1) what technologies they consider possible, and (2) the need for clinical solutions to problems that exist in health care. For this reason, we look at the range of technologies under development, the common themes that exist among them and what this implies about the future medical product industry.The two drivers of start-ups — current technology possibilities and current/emerging/future clinical need —can often drive each other, with technology possibilities creating demand, and with changing clinical need (e.g. the aging population) demanding technology solutions. Predicting the future can, therefore, often be accomplished by anticipating the technology response to the clinical need or, conversely, predictingÂ the emerging demand resulting from new technologies.
The Range of Clinical and Technology Focus at Startups
Taking a sampling of newly formed medtech start-ups (see Database), one can see the trends and the opportunities emerging. In the MedMarket Diligence Medtech Startups Database, which categorizes companies by areas of clinical and/or technology focus, common threads appear in the technologies of start-ups, indicating the clinical demand and technology possibilities. While the categories below do not reflect all categories of clinical/technology focus in medtech (nor all categories in the Medtech Startups Database), they are illustrative of a broad range of technologies at start-ups.
BLOOD, ORGAN & TISSUE. This represents an enormously active area, principally because of steady advances in cell biology, tissue engineering and the ever-controversial stem cell therapy. These include advances in basic science that, in turn, precipitate commercial development, as well as advances by medical technology entrepreneurs in applying blood, organ and tissue technologies to clinical problems. Two areas of significant activity are in: (1) dermatology, wound management and plastic surgery, and (2) application to treatments of ischemic heart disease.
In the first case, the application of tissue/cell technologies to aesthetics and wound management come as the result of the relative ease of developing tissue that replaces skin, fills dermal defects or accomplishes less challenging functional goals than is the case with tissue-engineered internal organs (pancreas, kidney, liver). In the second case, ischemic heart disease is one which, despite (or simply because of) the enormous market success of CABG and interventional cardiology (angioplasty, stenting), there remains strong demand for effective clinical solutions. The recent late stage thrombosis problem associated with drug-eluting stents simply furthers the drive for new technology solutions.
Common threads: – Dermatology/aesthetics/plastic surgery, wound management and plastic surgery – Cardiac applications (e.g., treatment of ischemia) – Organ replacement technologies (e.g., pancreas, kidney, liver)
CARDIOVASCULAR THERAPEUTICS. Heart disease represents a huge market potential that will remain until â€œcuresâ€ are possible, and while genome therapeutics may one day accomplish this, for now there remains tremendous demand for medical technology device solutions. The drivers behind development are to reduce restenosis (without late stage thrombosis), create solutions that are increasingly less invasive (e.g., percutaneous bypass or valve replacement) and further penetrate the surgery-only option with minimally invasive approaches (e.g., percutaneous treatment of chronic total obstruction).
Common threads: – Stents, of course – Chronic total occlusion – Minimally invasive valve replacement/repair – Treatment of congestive heart failure
INTERVENTIONAL RADIOLOGY AND VASCULAR SURGERY. Interventional radiology/vascular surgery procedures, being the less demanding (i.e., less acute) caseload served by many of the same technologies used in interventional cardiology and cardiac surgery, still represents a strong area of potential, if only for the ability to retool (or just re-market) many technologies originally developed for interventional cardiology and cardiac surgery applications. For this reason, the use of peripheral stenting for vascular as well as nonvascular (e.g., ductal therapies as in urology) represent strong growth areas for the future. Separately, (and with no analogous cardiac application), there is strong demand for products in the treatment for deep vein thrombosis.
Common threads: – Deep vein thrombosis – Chronic total occlusions – Peripheral stenting
MINIMALLY INVASIVE THERAPY. Virtually all procedures that were accomplished previously by open surgery, and many that are already being performed by a less invasive approach, are targets of development to perform the same procedures even less invasively. With the increased sophistication of percutaneous technology, endoscope technology and the growing potential for non-device technologies to compete head-on with device technologies, there really is no stopping the â€œless invasiveâ€ juggernaut. It is driving growth in procedures and technologies in nearly every clinical sector.
Common threads: – Valve repair – Coronary artery bypass – Ablation technologies – Orthopedic/musculoskeletal surgery – Spine surgery
ORTHOPEDIC/MUSCULOSKELETAL. The orthopedic and musculoskeletal treatment arenas have seen challenges in reimbursement (read â€œreduction in profit marginsâ€) that have driven the pursuit of improvements in devices to sustain premium pricing (biocompatibility, less invasiveness of procedures) and/or lower the costs of innovation (to widen the margin). However, the market has also seen the innovative development of traditional orthopedic technologies (fracture fixation, joint replacement/repair) being applied to small bone and joints. These are not huge markets, but do represent upside for companies in orthopedics facing shrinking opportunity in traditional markets.
Common threads: – Small bone work – Small joint replacement/repair – Biomaterial (grafts, ceramics, polymers, etc.) – Tissue engineering, cell scaffolds
UROGENITAL. This category encompasses a wide range of clinical applications and technologies, many of which have strong growth potential. Treatments for urinary incontinence span bulking agents, surgical procedures, device solutions, drugs and others, all targeting a caseload that has been ill-served in the past, leaving much latent demand. Benign prostatic hypertrophy is the subject of many different technology solutions, from surgery, to various ablative technologies, to drugs, and even â€œwatchful waiting.â€ Until one or more technologies prove themselves far superior to alternatives, there will be incentive for new technologies. The urogenital arena is also particularly well-suited, given the sophistication of urologists in performing advanced clinical procedures, for the application of a whole range of ablative technologies (cryotherapy, RF, microwave, thermal therapy, laser, etc.) to treatments for fibroid tumors, endometriosis, BPH and others.
Common threads: – Incontinence – BPH – Fibroid tumors – Ablation therapies applied to urogenital applications (fibroid tumors, endometriosis, BPH)
New technologies and new solutions of any type to clinical demand are not the exclusive mandate of start-up companies. Indeed, companies like Medtronic, J&J, Boston Scientific and many others are highly proficient in developing new products that capitalize on new technology possibilities while competitively responding to clinical demand.
However, start-up companies hold a certain value in gauging future medtech markets for their tendency to focus on new technologies in which they see clinical opportunity as being so significant that they are not just introducing a new product, but they are founding a new company to do so. With such commitment being demonstrated, it is therefore well worth paying attention to their activities.
MedMarket Diligence’s Medtech Startups Database is a live resource of newly established medical product companies (adding 10-15 new companies per month and updating existing company data)Â with focus on medical devices, biotech, biomaterials and others competing in frequently overlapping clinical applications. (See details.) The complete listing of clinical/technologies covered include: