Commercial Evolution of Med/Surg Sealants and Adhesives

Product Development History

During the 19th century, surgeons began to experiment with materials designed to achieve hemostasis: gelatin, collagen, natural fabrics, and thrombin and fibrin materials. In the early 1980s today’s commercial products began to appear. They were rapidly adopted in Japan where bleeding is an extremely emotive issue, and also in Europe where local regulatory requirements allowed a sequential roll-out of product introductions. In the USA, early FDA concerns associated with disease transmission led to delayed launch of products derived from human sources. These regulatory delays, plus the perceived high cost of products and surgeons’ concerns regarding disease transmission risk, drove surgeons and hospitals to continue to look for alternative hemostats, sealants and glues. As a result, to this day, there is a tendency for hospitals to continue to prepare autologous fibrin (from the patient’s own blood taken before surgery) and to use a number of inferior haemostasis products.

Topical high strength glues were first used by the military, and to achieve immediate repair of sports injuries during professional sports like ice hockey, boxing and American football. These products became the subject of collaborative efforts between innovative suppliers and major suture manufacturing and marketing companies, keen to evolve their product portfolios to include next-generation closure materials.

During the 1990s, many technology-based companies began to target the huge unmet closure and sealant market. An extensive literature appeared, advising practitioners on specific methodology to create the ideal autologous fibrin sealant product and on applying these products to surgical indications. In addition, a number of specialist societies were established to support and advise on the process of preparing and using hospital-derived fibrin sealants.

There were also a growing number of companies developing medical devices and equipment specifically designed to allow the preparation of autologous fibrin sealant for surgical applications. All this effort led to a number of products being approved for use in the major surgical indications (see Exhibit). In 2006, sealant products were used in over three million surgical procedures. This represents up to 5 million units of commercially available fibrin sealant products, and approximately four million units of autologous fibrin prepared by hospitals. The autologous fibrin material, prepared using commercial medical devices, was used in approximately 70,000 surgical operations worldwide and represents a new market which has developed over the last five years. Similarly, the use of high strength glues for wound closure evolved since 1992 in Europe and since 1998 in the USA and Japan. High strength adhesives were used on approximately six million cuts, grazes and minor incisions in 2006. This usage is growing rapidly driven by greater awareness and cost effectiveness.

    Exhibit: U.S. FDA Approved Uses of Sealants, Glues, and Hemostats

     HemostatsSealantsAdhesive
    Cardiovascular

    Yes

    Yes

    No

    Orthopaedic

    Yes

    Yes

    No

    Neurological

    Yes

    Yes

    Yes

    Gastrointestinal

    Yes

    Yes

    No

    Pediatric

    Yes

    Yes

    No

    Thoracic

    Yes

    Yes

    No

    Pulmonary

    Yes

    Yes

    No

    Skin

    Yes

    No

    Yes

    Source:  MedMarket Diligence, LLC , Report #S145, “Worldwide Surgical Sealants, Glues & Wound Closure, 2007-1011.”

    Evolution of Commercial Markets for Sealants and Adhesives

    The use of fibrin and other hemostats expanded rapidly in the 1980s in Japan driven by the strong cultural desire to avoid the need for blood transfusions in that market. In addition, regulatory barriers to launching homologous pooled plasma-derived products in Europe were not as stringent as those imposed by the US FDA in the late 1980s and 1990s. As a result the scientific literature from Asia and Europe records many novel and experimental uses for sealant and haemostasis products across all surgical disciplines from ENT to major open heart surgery.

    In addition to commercial sources of sealant products, surgical centers in all regions of the world also prepare autologous fibrin for surgical procedures in efforts to save on commercial product costs, and to avoid potential for product-borne infection. Delays to the introduction of fibrin-based products in the USA led to a pent-up unmet need, which was addressed in the 1990s by the preparation of autologous fibrin in medical centers prior to surgical operations.

    Historically, closure of surgical incisions has been achieved through an ever-evolving portfolio of suture, staple and tape products. In the early 1990s physicians involved in sports medicine were the first non-military practitioners to adopt cyanoacrylate glues to achieve immediate closure of small cuts and lacerations, and an awareness of this opportunity developed in large multinational manufacturers of sutures and staples. Joint development efforts were commenced at Davis and Geck (now U.S. Surgical), and Ethicon (subsidiary of Johnson and Johnson), and in a number of companies manufacturing cyanoacrylates which ultimately resulted in topical cyanoacrylate closure products being launched around the world during the 1990s.

    Postoperative adhesion prevention evolved as a market in the early 1990s, and expanded with the addition of new entrant products from Genzyme, Focal, and others. Lifecore and Ethicon have developed a surgical adhesion prevention product based on hyaluronic acid. Angiotech, Fidia, Fziomed and Tissuemed all have adhesion-prevention products that are CE approved in the European Union.


    Report #S145, “Surgical Sealants, Glues & Wound Closure Worldwide, 2007-2011.” For details, see link.

“High Growth Medical Technologies” 2008

We have just updated our “High Growth Medical Technologies” white paper, as we expect to continually do in the immediate future, since the areas with growth keep changing, and new areas keep appearing.

As all white papers should be, it’s free.  Here’s the link so you can download it.

New Wound Closures Get Seal of Approval

From January 2008 issue of MedMarkets, with excerpts from Report #S145, "Worldwide Surgical Sealants, Glues & Wound Closure, 2007-2011."  This report has beeen updated by Report #S175, with forecasts for 2009-1013.

The market for surgical sealants is expected to grow in double digits over the next five years as aging populations drive increases in caseloads (see chart below). In addition, less morbidity and better outcomes are seen with the latest fibrin sealants, high-strength glues and adhesion prevention products, thus spurring increased adoption of these technologies over traditional wound closure methods.

There are several main categories of closure and securement devices in use in the OR: sutures and staples, tapes, hemostats, fibrin glues and sealants, adhesion prevention products, and soft tissue attachment products. Some leading companies in the modern wound closure market established their leadership positions when the market consisted exclusively of sutures, staples and tapes; others are new entrants based on expertise in areas such as adhesives. While the fibrin sealant market segment is dominated by Baxter Healthcare and CSL Behring, the high-strength glue segment is led by U.S. Surgical (now part of Covidien), Ethicon, and Aesculap (a B. Braun company). Key players in the market for adhesion prevention products are Ethicon, U.S. Surgical and Genzyme. Market shares for these companies are shown in the charts, “Leading Companies in the Sealants Market by Market Share.”

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Fibrin—The Body’s Sealant

Fibrin sealants are the most useful surgical hemostats because they can be used to clot blood but are also valuable for sealing around suture lines for organ transplants, mastectomies, and various resection procedures, as well as to prevent leakage of fluids and gases. A number of companies, including Harvest Technologies, Plasmaseal, ThermoGenesis, and Interpore Cross Medical, have developed active mixes of growth factors to aid repair and devices capable of preparing autologous fibrin and platelet formulations that can be used as sealants. In July 2007, ThermoGenesis announced that the FDA had approved the CryoSeal FS system, the company’s autologous fibrin sealant, as an adjunct to hemostasis in liver resection surgery. The product was already cleared for sale throughout the European Community (CE Mark) for any type of surgery. The CryoSeal FS system, an automated device with a companion sterile blood processing disposable, is used to prepare fibrin sealants from plasma in about an hour. The system produces a surgical sealant by harvesting, from a patient’s plasma, wound healing proteins including fibrinogen and Factor VIII, and the activating enzyme thrombin. When combined at the bleeding wound site, the two components form an adhesive gel that helps stop bleeding and bonds tissue. Thrombin is a predecessor of fibrin in the clotting cascade and is involved in converting (soluble) fibrinogen to (insoluble) fibrin. It is used in combination with fibrin for accelerated hemostasis. On January 10, 2008, Omrix Biopharmaceuticals announced that the FDA had granted an expanded indication for general hemostasis in surgery for Evicel liquid fibrin sealant (human). Evicel is the first liquid fibrin sealant to be indicated as an adjunct to hemostasis for use in patients undergoing surgery when control of bleeding by standard surgical techniques is ineffective or impractical. Ethicon is Omrix’s marketing partner and will actively promote Evicel for a wide range of surgeries.

High-Strength Medical Adhesives

Fibrin-based wound closure products achieve hemostasis and have moderate adhesive properties that can help sutures to keep wound edges in apposition. Where greater adhesive strength is required, cyanoacrylate products are the main form of high-strength surgical glue approved for human clinical use. They are replacing sutures in many procedures but do not represent the ideal alternative to suturing, an ideal technology that is still sought by researchers. Cyanoacrylate glues used for external skin closure are approximately five times less strong than sutures, and cyanoacrylates produce cytotoxic compounds as part of the curing process when used for securing torn or excised tissue. This has delayed the development and clinical evaluation of potentially useful materials for internal surgical procedures. Nonetheless, cyanoacrylate glues are marketed actively by a number of companies for topical wound closure in accident/emergency situations and in surgical closure. Leading products in this category include Dermabond, which is developed by Closure Medical and marketed by Ethicon. Dermabond is marketed in about 40 countries under EU- and FDA-approval for topical wound closure. For Ethicon, Dermabond represents the culmination of a five-year joint development program with Closure Medical that started in 1996. Closure Medical, which is now incorporated into Ethicon, also developed Omnex vascular sealant, a high-strength adhesive that received the CE mark in 2005.

Post-Surgical Adhesion Prevention

Post-operative adhesions tend to arise when internal connective tissues are exposed to air and instrumentation during the surgical procedure and any irritation caused to internal organs. Abdominal surgery often leads to some form of adhesion formation, as does cardiovascular surgery. There are roughly 8 million–9 million abdominal surgeries, more than 2 million gynecologic surgeries, and 9 million cardiovascular surgeries every year, with about 1.7 million procedures associated with some risk of critical adhesion formation. Thus there is enough risk for adhesions from these procedures to encourage the use of adhesion prevention products in approximately 10% of the cases over the next decade. Among companies that have led the growth in adhesion prevention products are Johnson & Johnson/Ethicon with its Interceed brand, and Genzyme Biosurgery, which launched Seprafilm approximately five years after the J&J product. Interceed (made out of neutralized oxidized regenerated cellulose by the company’s Noramco chemical synthesis business) and Seprafilm both provide a bioresorbable protective layer between tissues susceptible to adhesion formation. Other contenders in this field include Omrix Biopharmaceuticals, which has developed an anti-adhesion product named Adhexil; an IND for Adhexil was filed in December 2006. Meanwhile, SyntheMed has developed the Repel-CV bioresorbable adhesion barrier; the company announced favorable results from a pivotal trial in neonatal patients in September 2006. When Angiotech acquired Cohesion Technologies, it inherited the Adhibit sprayable adhesion prevention product. In April 2006, the company announced data from a 71-patient human clinical study (conducted in the EU) designed to assess the safety and efficacy of Adhibit for preventing adhesions in patients undergoing a myomectomy procedure. The trial data indicated that the use of Adhibit reduced post-operative adhesion. Baxter Healthcare has been granted exclusive worldwide (excluding the United States) marketing and distribution rights to Adhibit. In July 2007, Protein Polymer Technologies (PPTI) announced it had entered into an agreement with an unnamed multinational biotechnology device company in which PPTI will provide genetically engineered protein polymer biomaterials for use in the prevention of post-surgical adhesions. PPTI believes its protein polymer materials can improve the outcome of abdominal and gynecological surgery by substantially reducing adhesions. PPTI is also in discussions with several U.S. and international biotechnology and medical device companies, which are evaluating PPTI’s surgical sealant and drug delivery product applications. These products are intended to aid in the closure of surgical incisions and tissue trauma reducing, for example, the incidence of post-operative bleeding and the local delivery of therapeutic agents.

Market Potential

The commercial importance of wound closure and adhesion prevention products is directly linked to clinical need, which is reflected in the numbers of procedures that can benefit from improved closure and adhesion-prevention technology. Approximately 10 million cardiovascular procedures in the United States have the potential to benefit from improved hemostasis, sealants and glue products. In an estimated 1.5 million procedures, these products can make a major contribution to the work of the surgeon in carrying out a safe procedure with minimal risk from blood transfusion and complications associated with loss of blood. Procedures that fall into this category include open heart bypass procedures with vein harvesting and many heart revascularization procedures, aortic valve replacements, mitral valve replacements, carotid endarterectomy, femoral distal bypass, and femoral popliteal bypass. Of more than 9 million musculoskeletal surgical operations worldwide, a large number (approximately 4 million) involve minimally invasive arthroscopy or are closed fractures in which hemostats, sealants and glues cannot be used. However, open trauma cases, knee reconstruction, total knee replacement, some hip reconstruction procedures, and all spine fusion procedures have the potential to benefit from improved appropriate use of hemostat, sealants and glues. Some of these procedures cause the patient to lose substantial quantities of blood. Effective use of sealants/hemostats can prevent loss of time during surgery, reduce the requirement for replacement blood products, and significantly improve rehabilitation due to reduced morbidity. Also there are 450,000 fusions and 432,000 discectomies performed in the United States each year. Particularly in the case of fusion, patients may require replacement of up to half the blood in their bodies. These procedures can take up to six hours to perform, and effective hemostasis can significantly improve cost effectiveness by saving surgical theater time and related costs, improving recovery and outcomes for the patient (e.g., reduced risk of infection) and reducing morbidity. There are approximately 2.5 million joint reconstruction procedures worldwide. Although minimally invasive procedures have reduced the burden of these procedures, reconstructive surgery is likely to increase with the growth of the aging population and with increased recreational activity. These procedures can benefit from improved use of closure and hemostatic products. Typically, tourniquets are used to prevent excessive bleeding during many of these procedures; it is assumed that lack of blood flow results in morbidity of tissue and delayed recovery as well as leading to increased complications, although the reduced need for blood transfusion is thought to outweigh these disadvantages. The introduction of effective sealants and hemostats offers the possibility of selectively reducing bleeding at sites of reconstruction without the concomitant effect of increased morbidity. It seems realistic to expect that a new category of procedure-enabling high-strength glue products will evolve and enable gluing of ligaments, tendon and bone in the orthopedic arena. Although there are a number of cement and bone graft substitute materials that have glue-like characteristics, none yet have the weight-loading potential or the torque-strength characteristics to meet the demand to fix bone fragments together without hardware support. Gynecological and urological procedures include transurethal prostate resections, bladder surgery, prostatectomy, hysterectomy and surgical resection of adhesions, as well as cesarean sections. Hemostasis and sealing in these procedures is critical to prevent complications that can result from excessive bleeding. Neurosurgery (4 million procedures annually in the United States) is highly vulnerable to the effects associated with healing: inflammation, angiogenesis, and generation of fibrous tissue—all attributes of normal tissue repair—cause problems for neural tissue. Effective hemostasis and sealing of blood can avoid these traumatic effects and are vital to reduce morbidity. Most traumatic wounds offer potential to be appropriately treated with hemostats, sealants and glues. Many lacerations can be adequately treated with high-strength glue products; this would avoid a secondary visit to a medical center for removal of sutures with associated costs. For example, conservative estimates of ER costs for closure of a small bleeding trauma laceration with sutures, (including local anesthetic, antibiotic cream and suture removal kit) are approximately $75 before labor and time are included. Further, in U.S. acute care hospitals, 5%–10% of patients develop hospital-acquired (nosocomial) infections, many of them in wounds. The cost per wound ranges from $3,000 to $27,000.

Revenue Implications

Fibrin-Based Sealants: The world market for fibrin-based sealants and similar products is estimated to be worth roughly $1.5 billion per annum, with annual growth rates in low double figures. Most fibrin and similar sealant products were first used for internal surgical hemostasis and sealant effects. This is now changing with the realization that appropriate hemostasis and gluing of surgical wounds results in reduced infection rates and better cosmesis. Growth rates in the synthetic and biological adhesives segment of the market will be relatively modest because these technologies have the most potential in niche opportunities, competing with established use of autologous and allogeneic fibrin products from major established players and a number of new device suppliers, as well as future recombinant human fibrin producers such as PPTI. Fibrin sealant usage worldwide is forecast to increase steadily during the coming years, driven by such factors as the requirement to use these materials in new procedures and an increasing caseload. One market in which these products are of special interest is Japan, where the loss of blood and avoidance of transfusion are extremely emotive issues. Growth rates here for autologous products and sealants not derived from blood may be delayed by long approval mechanisms, but will be rapid once these products appear on the Japanese market. In addition, this growth rate will be supported by the sales of new devices for the preparation of autologous fibrin sealants. High-Strength Glues: Cyanoacrylate products are the primary form of high-strength surgical glues approved for human clinical use in the worldwide market. A number of new materials are under development for internal use in particular, but these represent new chemical entities and their commercialization is likely to be delayed by regulatory requirements. Even though cyanoacrylate glues are not the ideal replacement for sutures, such a perfect replacement has yet to be fully developed, leaving room for cyanoacrylate glues to replace conventional sutures in many procedures over the next 10 years. To that end, cyanoacrylate glues are marketed actively by a number of companies for topical wound closure in accident/emergency situations and in surgical closure. The $500 million world market for high-strength surgical glues is growing vigorously and expected to more than double in value over the next five years, driven by increased incidence of surgery, greater adoption of cyanoacrylate and newer adhesive products for internal surgical applications, and the need for improved, fast-acting and easy-to-use products for use in minimally invasive procedures. Also, it is increasingly recognized that these products have a role to play in reducing infection and improving cosmesis of superficial surgical wounds, which will also drive the value of this market segment.

Adhesion Prevention

The market for products to prevent post-surgical adhesions is driven by the introduction of new technologies, by impressive data on product effectiveness, by increasing caseload and by growing acceptance of this type of product. World sales of products in this category are forecast to increase by solid double-digit annual growth rates from a value around $700 million to something approaching $1.5 billion in five years’ time.


Links: Advanced Medical Solutions (Winsford, U.K.; http://www.admedsol.com) Aesculap (Center Valley, PA; http://www.aesculap.com) Angiotech (Vancouver, Canada; http://www.angiotech.com) B. Braun (Melsungen, Germany; http://www.bbraun.com) Baxter Healthcare (Deerfield, IL; http://www.baxter.com) Chemence (Corby, U.K.; http://www.chemence.com) Closure Medical (Raleigh, NC; http://www.closuremed.com) Covidien (Norwalk CT; http://www.covidien.com) CSL Behring (King of Prussia, PA; http://www.cslbehring.com) Daiichi Sankyo (Montvale, NJ; http://www.daiichius.com) Ethicon (Somerville, NJ; http://www.ethicon.com) GEM (See Synovis Life Technologies) Genzyme Biosurgery (Cambridge, MA; http://www.genzyme.com) GluStitch (Delta, Canada; http://glustitch.com) Harvest Technologies (Plymouth, MA; http://www.harvestech.com) Interpore Cross Medical (Irvine, CA; http://www.interpore.com) Johnson and Johnson (Somerville, NJ; http://www.ethus.jnj.com) Kaketsuken (Kumamoto, Japan; http://www.kaketsuken.or.jp) MedLogic Global (See Advanced Medical Solutions) Nissui Pharmaceutical (Tokyo, Japan; http://www.nissui-pharm.co.jp) Omrix Biopharmaceuticals (Kiryat Ono, Israel; http://www.omrix.com) Pharming Group (Leiden, The Netherlands; http://www.pharming.com) Plasmaseal (San Francisco, CA; http://www.plasmaseal.com) Protein Polymer Technologies (San Diego, CA; http://www.ppti.com) Synovis Life Technologies (St. Paul, MN; http://synovislife.com) SyntheMed (Iselin, NJ; http://www.synthemed.com) SysCore (E-mail: Helmut.Kranzmaier@cnc-communications.com) ThermoGenesis (Rancho Cordova, CA; http://www.thermogenesis.com) U.S. Surgical (Norwalk, CT; http://ussurg.com)  


The complete report on Surgical Sealants, Glues & Wound Closure is described in detail here.   This report may be purchased in its entirety online or via Google Checkout, below.

 

Drivers, Forces and New Thinking that Redefine Medtech Market Outlook

From the December 2007 edition of MedMarkets

Never before, or so it seems, have there been so many widely different dynamics in medical technology markets that determine whether a company will be successful, or if successful, to what degree. Science, its application in technology, and its commercialization in healthcare has traditionally been driven by a narrow scope on a limited number of specific functions provided by the product — the expanded coronary artery lumen, the successfully implanted artificial hip, the endoscope that delivers good images. However, as the famous Greek philosopher Heraclitus said, “You can never put your finger in the same river twice.” So, the target changes as businesses seek greater commercial success with products that deliver more functions better. Third party payers strain to ensure coverage even while premiums grow out of control, so they demand better, more cost effective performance from a longer term perspective. Enabling these perspectives, or even driving them, is technology development that increasingly redraws boundaries of what is possible. And the overarching force that accelerates change is globalization of markets. Here we consider in the space allotted just some of the specific drivers and forces that are redefining the medtech market outlook.

Redefining the product. Market opportunity and technology development operate hand-in-hand. In 2007, the development of products is limited in scope seemingly only by imagination, due to the spectrum of opportunities created by materials technology, information technology, product hybridization and others, enabling manufacturers to focus on the fullest possible achievement of clinical outcome delivered by their products. (We have frequently addressed this issue; the dissolution of boundaries between devices, drugs, pharmaceuticals.) Realizing this is necessary means realizing that a whole slew of other companies out there looking at that same clinical outcome, often from a very different perspective. Of course, this sometimes means being opportunistic to recent developments, such as in stent developers adapting development (or maybe just their marketing message) to address a sudden hot button issue like late stage thrombosis. As comfortable as it may be to lean on one’s existing technology platform, unless that platform is predetermined to anticipate the wide range of competition possible, manufacturers must think beyond the platform and focus on the clinical solution, redefining the product in all its forms to simply reach that solution more effectively.

Redefining the process. There is always another way to get the job done, the “job” being the development, regulatory approval, manufacturing, marketing, sales, and distribution of medical products. It is a safe bet to say that no manufacturer has optimized that entire process. And even if a manufacturer has done so, the process remains a moving target, with new options emerging on all fronts. New vendors appear, regional/national/international economics change, and technologies create new possibilities to get the “job” done. Every step of the process then demands regular scrutiny to adjust: what is the appropriate balance between in-house development versus acquired innovation, what are the current sensitivities of regulators as to specific demands for market approval, what new options exist for OEM and how do they measure against the costs, how have marketing channels changed to create opportunities and challenges in product/price/placement/position, what are specific healthcare systems’ new requirements for purchasing new technology, are products reaching the market through distribution channels that optimize the market penetration given associated delivery cost? These questions only scratch the surface.

Never taking an eye off of “cost”. In the most optimistic view, the issue of cost has to be view through the lens of opportunity. Cost must be considered from the most relevant perspective. Can you make the argument that this new device/product is more effective than competitive alternatives? Although you believe your product is not only competitive against similar technologies but is it also competitive against different technologies targeting the same patient population(s) — and do third party payers really see it this way? Can you make an effective case?

Competition is a chameleon. Be careful what you consider to be your competition, because accurate though you may be today, your competition could be entirely different tomorrow. Competition of course is any entity serving the need of your current/potential customers by any method and from any source. You know the companies with like technologies currently going head-to-head with you in the geographic markets in which you market/sell product, but are you considering the bigger picture of any potential alternative technology on the market or under development, currently active in your territories or looking at yours from across the border? The corollary to this is, of course, that one must also look aggressively at those new technologies that will open up patient populations to be served and also look back across those geographic boundaries to markets that are attractive enough, and/or with barriers low enough to make it worthwhile for one to compete there as well.

Do not limit your potential. Once a manufacturer decides the product and market opportunity that will be pursued, it becomes a sort of self-imposed limit. We frequently witness innovative medtech startups who dare to assume that they need not limit their market introduction to the U.S. or Europe, or that even though they have only a handful of employees, they are capable of competing with multi-nationals who who have million- or billion-dollar budgets. To assume any limitation is to make it real, so one best make the biggest reasonable assumptions about market potential.

We must admit that this view of the medtech market outlook can be accused of being myopic, since it only considers a limited number of possibilities in the list of possible market drivers, and only briefly touches on them. Competing in medical technology markets these days can be an overwhelming proposition because all of the possibilities must be explicitly considered or they will be implicitly made so. The most compelling advice to be offered is that the successors in medtech markets rarely view these market drivers as daunting challenges, but instead view them as invigorating opportunities.

New report from MedMarket Diligence:  Worldwide Wound Management 2007

Wound Types and Advanced Wound Products, Worldwide

From the Executive Summary (excerpt) from “Worldwide Wound Management 2007-2016 ,” report #S245, published November 2007. See link.

The skin is our protection from the environment. Far from being just a physical barrier, the skin is a complex organ, protecting our bodies from chemical, biological and physical insult, keeping organs and tissues in their place, and regulating various secretions including sweat (to control temperature), and pheromones (to act as sexual attractants). It is constantly renewed and maintained. Injuries to the skin cause the potential for infection and significant disruption to the healthy functioning of the tissues beneath. Healing of the skin has been an essential pre-requisite for evolutionary and individual survival, and complex biochemical systems have evolved for repair of the skin.

Acute Wounds

Surgical wounds account for the vast majority of skin injuries. There are almost 100 million surgical incisions every year which require some wound management treatment. In approximately 80% of these cases, some form of wound closure product is used: sutures, staples, and tapes. Many require hemostasis (blood clotting) promoters, and of course the use of fabric bandages and surgical dressings is almost universal.

Traumatic wounds occur at a rate of about 1.4 million cases every year. Lacerations are a specific type of trauma wound that are generally minor in nature and require only cleansing and dressing for a shorter period. Lacerations occur frequently (approximately 19 million cases a year), as a result of cuts and grazes. They can usually be treated in the doctor’s surgery, outpatient medical center, or hospital accident and emergency department.

Burns

Burn wounds can be divided into minor burns, medically treated, and hospitalized cases. Out- patient burn wounds are often treated at home, at the doctor’s surgery, or at outpatient clinics. As a result a large number of these wounds never enter the formal health service system. We estimate that approximately 3.1 million burns in this category do enter the health service system and receive some level of medical attention. These burns are mostly treated using hydrogels and advanced wound care products, or even with consumer based products for wound healing.

Medically treated burn wounds get more specialist levels of care to remove heat from the tissue, maintain hydration, and prevent infection. Advanced wound care products are used on these wounds. There are approximately 6.0 million burns like this treated medically every year.

Hospitalized burn wounds are rarer and require more advanced and expensive care. These victims require significant care, nutrition, debridement, tissue grafting and often tissue engineering where available. They also require significant nursing care and rehabilitation to mobilize new tissue, and physiotherapy to address changes in physiology.

Chronic Wounds

Chronic wounds generally take longer to heal, and care required is enormously variable, as is the healing time. There are approximately 5.2 million pressure ulcers in the world that require treatment every year. Optimally, these wounds receive advanced wound management products and appropriate care to address the underlying defect that has caused the chronic wound. Pressure ulcers are caused by compression of the skin and underlying tissues, as when a patient is bedridden and the buttocks are pressed onto the mattress; a number of advanced devices exist to reduce pressure for patients.  Other skin ulcers are caused by poor circulation, even without the added complication of pressure. There are approximately 7.6 million venous ulcers, and approximately 7.0 diabetic ulcers in the world requiring treatment.

Chronic wounds are growing in incidence due to the growing numbers of elderly individuals in the population, and the caseload is also increasing due to improved diagnosis and education. At present these factors are contributing to growth of this pool of patients faster than new technologies are reducing the incidence of wounds by healing them.

Wound management techniques are also used for a number of other conditions including amputations, carcinomas, melanomas, and other complicated skin cancers, which are all on the increase.

Products Used in Advanced Wound Management

Dressings can be divided into categories using a number of different classification systems. In report #S245, “Worldwide Wound Management 2007-2016,” we focus our product, marketing, and technology review on the category known as Advanced Wound Management. This includes Film dressings, Hydrocolloids, Foam Dressings, Alginate Dressings, Hydrogels, Non-Adherent Dressings, Antimicrobial dressings, Cleansing and debridement products, Tissue engineered products, Pharmacological products, (including Pain control, Antibiotics, Growth Factors, Non-Growth Factor Modulators, Gene Therapy, and Scarring Modulators), Physical treatments (like pressure devices, hydrotherapy, electrical stimulation, electromagnetic stimulation, ultraviolet therapy, hyperbaric oxygen therapy, mechanically assisted wound closure devices, ultrasound, laser and information systems. Some of these product categories are well established; others are in development.

(Excerpted from “Wound Management 2007-2016,” report #S245, published November 2007.)

Wound Management Worldwide: Huge Market Plus High Growth Sectors

Wound Management Market Growth by Segments, 2007-2016Technologies developed and in use for the management of acute and chronic [tag]wound[/tag]s have diversified from traditional dressings, bandages and wound closure techniques to include an increasing number of diverse technologies ranging from tissue engineering, growth factors, physical therapies (e.g., negative pressure) and others. Traditional dressings and bandages have evolved to contain more active elements contributing to wound healing, with products including films, [tag]hydrocolloids[/tag], foams, [tag]alginates[/tag], hydrogels, non-adherents and antimicrobials. [tag]Wound closure[/tag] is a specific area of intense development and market growth beyond traditional suturing and more recent stapling technologies and has seen proliferation and high market growth for [tag]surgical sealants[/tag], glues and hemostasis products.

The size of the worldwide wound management market is ultimately driven by the clinical need for advanced wound management products. That need is most clearly reflected in the prevalence of chronic wounds and burns. Current estimates put the total annual incidence of chronic wounds at almost 9 million worldwide, and there are 177 million cases of [tag]diabetes[/tag] worldwide; 10-15% of diabetic patients will develop ulcers at some point. The market for products used in the management of venous stasis (as in chronic [tag]venous ulcers[/tag]) is put at over $3 billion, while the decubitus ulcer (e.g., bedsores) market is in excess of $2 billion. Sales of products used to treat diabetic foot ulcers are estimated around $1.5 billion, and the market for burns dressings is approximately $60 million.

It should be noted that a large proportion of worldwide wound product sales are accounted for by traditional types of wound management products. An estimated two-thirds of the world’s physicians are not making routine use of advanced [tag]wound management[/tag] products, with availability playing only a minor role in limiting their use. Conversely, while the U.S. healthcare market is characterized by an almost overindulgent attitude toward new technologies, U.S. physicians are much more conservative in their approach to advanced wound healing technologies than their European counterparts. For this reason, the European share of the advanced wound care market is significantly higher than the U.S. share.

Market Growth in Wound Management Product Segments
Until recently, the product categories with most growth potential were alginates and foams; both have substantial shares of the total market and both are set to increase their shares substantially between 2007 and 2016. Hydrocolloids had a considerable market share in 2007 but their star is in decline; it is anticipated that they will lose several percentage points in the market share table by 2016. (Segment growth in chart from MedMarket Diligence report #S245, “Worldwide Wound Management, 2007-2016,” publishing November 2007. See link for description, table of contents.)

The most significant market entrants are growth factors and, even more dramatically, physical therapies – specifically, negative pressure (also known as VAC therapy) devices. This market sector grew from a small base to gain $1.2 billion by 2007 and is set to capture an estimated 20% of the advanced woundcare market by 2016.

Films, antimicrobials and non-adherent dressings will maintain steady growth although their shares of a vigorously expanding market will decline.

The (Medtech) World is Getting Smaller

It has already been said that medical technology is getting complicated. Now it’s time to point out that the world is getting strikingly small(er).

Even the youngest startup has to consider market opportunity on a global scale. So a little medtech startup with not much more than a patent (and sometimes not even that) and with a staff you can count with one hand, is highly likely to be considering their moves based on global markets. The opportunities are all too apparent and tangible.

A caseload of 100,000 U.S. patients annually as prospects for a new device can be reasonably attractive if the device offers a measurable clinical advantage over alternative approaches  — approaches that may include a device, a drug, a hybrid of both or just a lifestyle change — and if that advantage is tangible and can be sold as such. But if the real potential market is any healthcare system sophisticated enough to use the device, willing and prepared to pay for the device and one reachable by distribution systems, then that U.S. caseload can actually represent a minor share of the total. The “rule of thumb” is that for most medical device markets, the U.S. represents roughly 50% of the world market, and while clearly the U.S. healthcare system is ready, willing and able to pay for medical technology that sometimes shows only marginal clinical advantage, that remaining 50% is comprised of an awful lot of Westernized, democractic, and capitalistic geographies, with sophisticated distribution systems, well established reimbursement schemes and, not least of which, painfully favorable currency exchange rates against the dollar. Combine this with increasingly sophisticated manufacturing and design companies capable of producing prototypes, CRO’s capable of generating clinical data, and tax structures, work forces and economies globally just begging for outsourcing opportunity and it seems a rather foolish notion to limit market consideration to the U.S., does it not?

Then there is that other earth-shrinking force, information technology. Time was when my business’s worldwide focus meant a rather heavy FedEx bill to deliver reports to Europe, Japan, China, Australia, Korea and the Middle East, but thankfully, the idea of the “paperless” world is getting more and more real, since now the vast majority of business reports are ordered and delivered electronically within 30 minutes from start to finish. It’s only the deliberative dialogue that takes longer as clients decide on the relevance of report content and that process takes place largely electronically, of course.

Worldwide markets MedMarket Diligence have covered recently:

Obesity (final edits in process)
Ophthalmology
Surgical Sealants
Orthopedic Biomaterials
Micro/Nanotechnology
Diabetes
Wound Management

Tags: medtech

Surgical Procedures Worldwide with Potential for Use of Hemostats, Med/Surg Glues & Sealants and Adhesion Prevention

Sealant, Glues, Hemostats Potential ProceduresSurgical wounds are projected to increase in number at an annual rate of 3%, but overall the severity and size of surgical wounds will continue to decrease over the next five years as a result of the continuing trend toward minimally invasive surgery.

Surgical procedures generate a large number of uncomplicated acute wounds with uneventful healing, and a lower number of chronic wounds such as those generated by wound dehiscence or post-operative infection. On the skin surface, surgical wounds are most often closed by “primary intent”, using products such as sutures, staples, or glues, where the two sides across the incision line are brought close and mechanically held together. The use of glues for closure has rapidly become adopted for treatment of minor cuts and grazes over the last decade, and products in this category are now being promoted for use in theatre where they offer certain advantages over sutures. Benefits for use on the skin surface include reduced need for anesthesia, reduced infection, and reduced scarring.

A growing number of wounds created as part of the surgical procedure are becoming infected by pathogens that exhibit some resistance to antibiotics. Recent figures indicate that an average of 8% of wounds are infected in the hospital during surgical procedures. Adjunctive surgical closure and securement products have been shown to reduce infection levels, and, for example, cyanoacrylate adhesives have been approved in the USA for use to prevent post surgical infections.

Surgical hemostats, [tag]tissue sealant[/tag]s, and glues are used for a spectrum of surgical procedures ranging from closure of skin wounds to significant hemostasis to prevent blood replacement during major surgical procedures.

Hemostats are used to reduce bleeding during surgical procedures. These products work by coagulating blood quickly and accelerating the normal clotting mechanisms. Blood clotting is part of the body’s natural defense mechanism. After tissue damage, blood invades the damaged area. Platelets are activated to convert prothrombin into thrombin, which converts fibrinogen in the blood to form viscous polymers of fibrin. The fibrin is subsequently cross-linked by activated factor XIII to further bind the fibrin polymers into a viscous three-dimensional mat of fibrin. This is the basis of a blood clot which prevents further bleeding. Later in the healing process the fibrin clot is acted on by the enzyme fibrinolysin which breaks up fibrin as this material is no longer required. Fibrinolysis begins a cascade of healing by releasing fibrino-peptides which act to stimulate angiogenesis and cell-activated-repair.

The natural clotting process has been used by manufacturers to design new products that can mimic the body’s hemostatic action. Hemostatic products have been developed using collagen and degraded collagen (gelatin) to stimulate the hemostasis cascade. These hemostatic products depend on a cascade of blood factors to initiate and drive the full clotting process; they therefore tend to be slower-acting than products based on fibrin and thrombin which act later in the cascade to produce immediate hemostatic results. In addition, synthetic polyanionic materials (such as Johnson & Johnson/Ethicon’s Surgicel) and some naturally occurring biological polymers (such as calcium alginate and chitosan) have been developed to stimulate the same cascades; companies have recently evolved these simple hemostatic materials to develop hemostasis products that can also seal bleeding tissues.

[tag]Fibrin sealant[/tag]s and synthetic [tag]sealants[/tag] offer a significant advantage over pure hemostats because they do not rely on the full complement of blood factors to produce hemostasis. Sealants provide all the components necessary to prevent bleeding and will often prevent bleeding from tissues where blood flow is under pressure, and the damage is extensive.

In addition to [tag]hemostats[/tag] and sealants, a number of companies have developed tissue glues to reduce (and in some cases replace) the requirement for sutures. These products are capable of providing a degree of repair strength which is at least an order of magnitude greater than that achieved with [tag]fibrin[/tag] and synthetic sealants.

It is recognized that these products have potential to replace sutures in some cases where speed and strength of securement are priorities for the surgical procedure. Tapes, sutures and staples are also applicable to a growing range of procedure-specific internal securement cases

Approximately 70 million surgical and procedure-based wounds are created annually worldwide that offer potential for use of adjunctive surgical closure and securement products; over 20 million of these wounds are created during surgical procedures in the USA.

Although healing of all these wounds might be improved through use of adjunctive surgical closure and securement products, it is likely that increased usage of these products will be limited, on economic grounds, to a fraction of procedures. It is realistically estimated that some 10-15% of these procedures would benefit from increased use of newly-developed adjunctive surgical closure and securement products.

Tags: sealant, fibrin, hemostat, wound

See Report #S145: “Worldwide Surgical Sealants, Glues and Wound Closure Market, 2007.” Description and table of contents here.

Medical/Surgical Sealants; Worldwide Growth

Sealants GrowthSurgical 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.)

Tags: medtech, sealants, fibrin, cyanoacrylate

Selected Medical/Surgical Sealant Product Companies and Their Strategies

Exhibit ES-8:  Selected Sealant Product Companies and Their Strategies

Company

Products and Prices

Strategy

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.

Angiotech

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.

Baxter
Healthcare

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.

CryoLife

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.

Haemacure

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; 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.

 

See http://mediligence.com/rpt/rpt-s145.htm.

Tags: sealant, fibrin, cyanoacrylate