Materials used in sealants, glues, and hemostats

Sealants are most often used to stop widespread, diffuse internal bleeding. The product may be sprayed on a bleeding surface, or applied internally using a patch. Sealants are considered inappropriate for heavy bleeding. Surgical sealants may be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates. Fibrin sealants are made of a combination of thrombin and fibrinogen. Sealants may also be made from a patient’s blood (autologous), which limits immunological and other risks.

Although the terms ‘glues’ and ‘adhesives’ are frequently used interchangeably, medical glues are products used to make two tissue surfaces adhere securely to each other without coming apart under normal physical stress. The definition of medical glues does not include medical adhesives such as those coating a bandage to make it stick to the skin.

A hemostat is commonly used in both surgery and emergency medicine to control bleeding, such as from a torn blood vessel. Active hemostats contain thrombin products which may be derived from several sources, such as bovine pooled plasma purification, human pooled plasma purification, or through human recombinant manufacturing processes. Flowable-type hemostats are made of a granular bovine or porcine gelatin that is combined with saline or reconstituted thrombin, forming a putty that may be applied to the bleeding area. Mechanical hemostats, which generally require pressure to stop the bleeding, include items such as hemostatic clamps, absorbable gelatin sponge, collagen, cellulose, or polysaccharide-based hemostats applied as sponges, fleeces, bandages, or microspheres, and do not contain thrombin or any other active biologic compounds.

Global Market for Wound Sealants, Glues and Hemostats, 2015-2022

img_2645

Source: “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.” (report #S290.)

Six Key Trends in Sealants, Glues, Hemostats Markets to 2022

From July 2016 published Report #S290.

Here are six key trends we see in the global market for surgical sealants, glues, and hemostats:

  1. Aggressive development of products (including by universities, startups, established competitors), regulatory approvals, and new product introductions continues in the U.S., Europe, and Asia/Pacific (mostly Japan, Korea) to satisfy the growing volume of surgical procedures globally.
  2. Rapid adoption of sealants, glues, hemostats in China will drive much of the global market for these products, but other nations in the region are also big consumers, with more of the potential caseload already tapped than the rising economic China giant. Japan is a big developer and user of wound product consumer. Per capital demand is also higher in some countries like Japan.
  3. Flattening markets in the U.S. and Europe (where home-based manufacturers are looking more at emerging markets), with Europe in particular focused intently on lowering healthcare costs.
  4. The M&A, and deal-making that has taken place over the past few years (Bristol-Myers Squibb, The Medicines Company, Cohera Medical, Medafor, CR Bard, Tenaxis, Mallinckrodt, Xcede Technologies, etc.) will continue as market penetration turns to consolidation.
  5. Growing development on two fronts: (1) clinical specialty and/or application specific product formulation, and (2) all purpose products that provide faster sealing, hemostasis, or closure for general wound applications for internal and external use.
  6. Bioglues already hold the lead in global medical glue sales, and more are being developed, but there are also numerous biologically-inspired, though not -derived, glues in the starting blocks that will displace bioglue shares. Nanotech also has its tiny fingers in this pie, as well.

See Report #S290, “Worldwide Sealants, Glues, and Hemostats Markets, 2015-2022”.

USA and Asia/Pacific Size Versus Growth in Sealants, Glues, Hemostats

The market dynamics in Asia/Pacific stand apart from those in the U.S. In the case of surgical sealants, glues, and hemostats, what stands out is the Size versus Growth metric.

Much of the potential in China, in particular, remains untapped (low volume, high growth), while in the U.S., these markets are more well established and, therefore, more penetrated.

Below are the size/growth “bubbles” for, alternating, the U.S. and Asia/Pacific.

output_dYHN2K

Source: MedMarket Diligence, LLC; Report #S290.

Surgical Procedures with Potential for Sealants, Glues, Hemostats

See the published report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”.

Sealants, glues, and hemostats must offer benefit to be adopted in clinical practice, or surgical procedures. Benefits can fall into a number of categories. These range from preventing serious complications from surgery (blood loss), improved patient outcomes (fewer complications, reduction in repeats), reductions in procedure time or other time- or cost-saving benefits, or improved aesthetic and perceived benefits. See these detailed below.

Criteria for Adjunctive Use of Hemostats, Sealants, Glues and Adhesion Prevention Products in Surgery

Screen Shot 2016-05-02 at 8.24.47 AM

Source: MedMarket Diligence, LLC; Report#S192.

We have assessed surgical sealants, glues, and hemostats for their potential in general surgery, aesthetics, neurology, urological, gastroenterology, orthopedics, and cardiovascular medicine.

Untitled-2

Source: MedMarket Diligence, LLC; Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”.


See the published report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”.

Surgical Sealants and Glues in the Balance of Wound Closure

Sealants and glues are emerging as important adjunctive tools for sealing staple and suture lines, and some of these products also are being employed as general hemostatic agents to control bleeding in the surgical field. Manufacturers have also developed surgical sealants and glues that are designed for specific procedures – particularly those in which staples and sutures are difficult to employ or where additional reinforcement of the internal suture/staple line provides an important safety advantage.Suture-line-pixelated

Surgical sealants are made of synthetic or naturally occurring materials and are commonly used with staples or sutures to help completely seal internal and external incisions after surgery. In this capacity, they are particularly important for lung, spinal, and gastrointestinal operations, in which leaks of air, cerebrospinal fluid, or blood through the anastomosis can cause numerous complications. Limiting these leaks results in reduced mortality rates, less post-operative pain, shorter hospital stays for patients, and decreased health care costs.

Although some form of suturing wounds has been used for thousands of years, sutures and staples can be troublesome. There are procedures in which sutures are too large or clumsy to place effectively, and locations in which it is difficult for the surgeon to suture. Moreover, sutures can lead to complications, such as intimal hyperplasia, in which cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point. This increases the risk of a blood clot forming and obstructing blood flow. In addition, sutures and staples may trigger an immune response, leading to inflamed tissue, which also increases the risk of a blockage. Finally, as mentioned above, sutured and stapled internal incisions may leak, leading to dangerous post-surgical complications.

These are some of the reasons why surgical adhesives are becoming increasingly popular, both for use in conjunction with suture and staples and on a stand-alone basis. As a logical derivative, surgeons want a sealant product that is strong, easy-to-use and affordable, while being biocompatible and resorbable. In reality, it is difficult for manufacturers to meet all of these requirements, particularly with biologically active sealants, which tend to be pricey. Thus, for physicians, there is usually a trade-off to consider when deciding whether or not to employ these products.

Screen Shot 2014-12-29 at 9.28.14 AMClosure of general surgical wounds (internal or external) is largely accomplished by a combination of surgical tapes, sutures & staples and, increasingly, surgical sealants and glues. For the reasons discussed, the rates of technology development and adoption among these causing a relative but not absolute decline of sutures and staples revenues worldwide.

Surgical sealants, glues, and hemostats can be divided into several different categories based on their primary components and/or their intended use. From a practical standpoint, they may be subdivided by composition into products containing biologically active agents, products made from natural and synthetic (nonactive) components, and nonactive scaffolds, patches, sponges, putties, powders, and matrices used as surgical hemostats.


Data drawn from MedMarket Diligence, LLC, Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018.” See link.

 

Growth of High Strength Medical Adhesives

The market for high strength medical adhesives is growing, and is expected to continue to grow due to regulatory approvals and steady ongoing research and development. Active programs are currently under development in three areas for high strength surgical adhesives:

  • The use of cyanoacrylate adhesives and new application devices for new internal surgical procedures
  • New adhesive products based on existing biomaterial adhesives such as fibrin and albumin compounds
  • New polymer adhesives based on entirely new chemistries (e.g., polyurethanes, proteins from living organisms).

The global market for high-strength medical adhesives is forecast to show strong double-digit growth during the forecast period, growing from roughly $713 million in 2011 to $1.72 billion by 2017. The USA represents, by far, the largest share of the global high strength medical adhesives market, and this is not expected to change during the forecast period.

Worldwide Market for High Strength Medical Adhesives, 2010-2017

Source: MedMarket Diligence Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2017.”

Although some form of suturing wounds has been used for probably thousands of years due to their ease of use and strength of closure, but sutures’ simplicity can also be limiting. There are procedures in which sutures are too large or clumsy, and locations in which it is difficult for the surgeon to suture. They can lead to complications, such as intimal hyperplasia, in which cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point. This increases the risk of a blood clot getting stuck and obstructing blood flow. In addition, sutures may trigger an immune response, leading to inflamed tissue that also increases the risk of a blockage. These are some of the reasons why surgical adhesives are becoming increasingly popular.

As a logical derivative, surgeons want a product that is strong, easy-to-use and affordable, while being biocompatible and resorbable. TissuGlu (Cohera Medical), a urethane adhesive suited for plastic surgery procedures, is both biocompatible and resorbable, making it ideal for internal applications. It is also strong, user-friendly, and does not contain human/animal product derivatives. TissuGlu is currently only available for sale in Germany, but the company is rapidly preparing to sell in the other major markets of the EU.

One of the top five plastic surgery procedures performed in the United States is abdominoplasty, which has a reported post-operative complication rate of 15-52%. The most common complication is the formation of seroma. Usual methods to combat seroma formation include the placement of closed suction drains, use of compression garments around the tissue, use of progressive tension sutures, and use of fibrin sealants to reduce fluid accumulation. However, most of these methods can still lead to further complications such as leakage from drain sites, skin necrosis and inconsistent adhesion. High strength glues like TissuGlu and other products can solve this problem and garner significant caseload.

Medtech market competitor consolidation on the rise

The healthcare industry faces a less daunting period of recession compared to many industries (we’ve covered it here and here), but still faces different and tough dynamics during this period.

Although demand for healthcare is more inelastic than other products and services, new business in healthcare (development and innovation) requires financing, a particularly  scarce commodity during the recession.  Well established companies with existing revenue streams are able to draw on those streams to fund new development.  However, early stage and startup companies demand financing from 3F ( "family, friends and fools"), since they do not yet have other revenue streams.  So, an obvious polarity is set up:  big companies with money seeking innovation versus small companies with innovation but little money.

Hence, the young startup has become a very real acquisition target by established companies.

If we look at one of our favorite markets, for surgical sealants, glues, hemostats, wound closure and anti-adhesion, here is a past list of acquisitions in this arena, a robust amount of activity before the financial meltdown took place: 

 

 

Company

Year Acquired

Omrix Biopharmaceuticals

2008

Altana Pharma

2007

American Medical Instruments

2006

Berlin Heart

2006

Biomet

2006

Confluent Surgical

2006

Quill Medical

2006

Surgical Specialties

2006

Closure Medical

2005

Aventis Behring

2004

Interpore Cross

2004

Onux Medical

2004

PPL Therapeutics

2004

Cohesion

2003

Gliatech

2003

Fusion Medical Technologies

2002

Medlogic Global

2002

Focal

2001

Source: MedMarket Diligence, LLC, Report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure Market, 2009."

In early 2009, we have already seen some struggles among young companies in this sector, such as Haemacure, in financing their operations and continued development.  Given that there are so manny active companies in this area (our report #S175 profiles over 135 companies), we anticipate in 2009 a significant amount of interest and potentially acquisitions by the well established players.

See our report #S175 table of contents, including companies profiled, for potential acquisition targets.

 

Growth, development and consolidation in the sealants, glues, wound closure and anti-adhesion industry

In the last few years, there has been a significant consolidation in the sealants, glues, wound closure and anti-adhesion industry (the "securement industry") as venture-based companies have been acquired and assimilated into larger market-based corporations with critical mass in their sales effort. This represents a welcome development for investors in leading-edge technologies, which are now being developed into marketable ventures. Examples are seen in the full range of deal structures from exclusive distribution deals and joint development agreements with exclusive marketing licenses to full acquisitions of companies.

Recent Acquisitions in the Securement Industry

sealant-consolidation1

Source: MedMarket Diligence, Report #S175.

 

Potential caseload in sealants, glues, hemostasis and anti-adhesion

For completing our most recent worldwide analysis of the market for sealants, glues, and related products, we assessed their current and potential uses globally. We found the strongest uptake of fibrin sealants in Asia; also in Europe, particularly in Italy where GEM has established a 12-item application list for its high-strength glue product.

Approximately 12 million cardiovascular procedures in the United States have the potential to benefit from improved hemostasis, sealants and glue products. Of these, we estimate that in 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.

Some abdominal aortic aneurysm treatments also fall into this category along with some pacemaker insertion procedures. The vast majority of cardiovascular procedures (84%) fall into categories II and III. These procedures can use new surgical closure and securement products to improve cost-effectiveness by reducing infection and post-surgical fibrous adhesion formation; they reduce morbidity by improving procedure effectiveness and cutting down surgery time. Although cosmetic improvement can also result, this is rarely the driver for using these improved products within the cardiovascular arena.

Many coronary angioplasty, cardiac catheterization, and carotid endarterectomy procedures fall into Category III procedures as they have potential to benefit from the appropriate use of these products.

Of more than 9 million musculoskeletal surgical operations worldwide, a large number (approximately 4 million) involve minimally invasive arthroscopy or are closed fractures that are not currently addressable by hemostats, sealants and glues. However, open trauma cases, knee reconstruction, 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, as well as total knee replacement 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. As a result, most of these procedures fall into the categories I, II, and III (shown below), as would be expected. These treatments may benefit from improved securement and soft tissue bioresorbable securement products.

 

Criteria for Adjunctive Use of Hemostats, Sealants, Glues and Adhesion Prevention Products in Surgery

 

Category I: Important and Enabling 

Category II: Improved Clinical Outcome 

Category III: Cost-Effective and Time-Saving 

Category IV: Aesthetic and Perceived Benefits 

Also there are 450,000 fusions and 432,000 discectomies (with and without disc replacement) performed in the Untied States per year.
Particularly in the case of fusion, patients may require replacement of up to half of the blood in their bodies. These procedures can also take up to six hours to perform, and effective hemostasis can significantly improve cost-effectiveness by saving surgical 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 procedures worldwide to reconstruct joints. Minimally invasive procedures have recently reduced the burden of these procedures, but reconstructive orthopedic procedures are likely to increase with growth of the aging population and with increased recreational activity. These procedures can benefit from improved use of products covered by this report and we forecast a compounded annual growth rate of 6% in this category. 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.

A relatively small number of procedures (1.0 million) such as synovial fluid replacement and minimally invasive discectomy offer potential to benefit from improved closure; these currently fall into Category IV. We expect a new group of procedure-enabling high-strength glue products to evolve, which will in the future enable gluing of ligaments, tendon, bone etc. within the orthopedic arena. Although a number of cement and new bone graft substitute materials exist 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.

A number of digestive tract procedures such as colon surgery and appendectomy can benefit from the use of improved hemostats and sealants. In these cases, loss of blood is not the major challenge, but infection and appropriate securement of the repaired alimentary organ is essential. Most of the potential in this category falls into Categories II and III.

Urological and gynecological procedures include transurethal prostrate 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 (Category II). In a number of cases, effective hemostasis can prevent excessive loss of blood and is essential for safe and effective outcomes. There are also a large number of procedures (for example, cesarean sections) for which cosmetic outcome is important. In addition, there is an increasing number of minimally invasive procedures for which this range of products appears to offer no advantage.

Neurosurgery (3.8 million procedures in the United States) represents the surgical field most 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, so most of these procedures fall into Categories I and II.

Of the 11.1 million cosmetic surgery procedures worldwide, a small number (including some breast augmentation/reduction procedures) require effective hemostasis and sealing to prevent blood loss and resultant transfusion, with approximately 60,000 also benefiting from improved clinical outcomes (e.g., faster healing) associated with this hemostasis. The potential in the cosmetic arena comes from improved cosmesis and reduced scarring after surgery (particularly facelifts, abdominoplasty, and augmentation procedures).

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 accident and emergency costs for closure of a small bleeding trauma laceration with sutures, local anesthetic, antibiotic cream and suture removal kit are approximately $75 (before labor and time are included). In acute care hospitals in the United States, 5%–10% of patients develop hospital-acquired (nosocomial) infections, many of them in wounds. The cost per wound has been estimated as ranging from $3,000 to $27,000.

Cyanoacrylate products can be used without anesthetic and without sutures. In addition, because cyanoacrylate sloughs off the skin surface, there is no need for a removal kit.

 Below are estiamtes of the total potential procedures, by major clinical area, that could ultimately be targeted for the application of sealants, glues, hemostasis and other wound closure and anti-adhesion products.

caseload-sealants

Source:  MedMarket Diligence, LLC; Report #S175.

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)  


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