Untapped potential for sealants, glues, hemostats in wound caseloads and procedures

Today’s surgeon has a broad range of products from which to choose for closing and sealing wounds. These include sutures, stapling devices, vascular clips, ligatures, and thermal devices, as well as a wide range of topical hemostats, surgical sealants and glues.

However, surgeons still primarily use sutures for wound closure and securement—sutures are cheap, familiar and work most of the time. Now, in addition to reaching for a stapling device, the surgeon must frequently decide at what point to augment or replace the commonly used items in favor of other products, which product is best for what procedure or condition, how much to use, and ease of use in order to achieve optimal patient outcomes. Because of budget pressures, the surgeon must also consider price when selecting a product. Of course in the USA, the product must also be FDA-approved, although the surgeon still has the choice of using a product off-label.

In the areas of sealants, hemostats and glues, there is room for both improvement and additional products.  There are a number of products already on the market, but the fact is that there is no one product that meets all needs in all situations and procedures. There are few products that stand out from the rest, apart, perhaps, from DermaBond® and BioGlue®. There are unmet needs, and companies having the necessary technology, or which may acquire and further develop the technology, can enter this market and launch novel items. These products have yet to significantly tap the potential for wound management and medical/surgical procedures.

Note: Log10 scale; Chronic wounds includes pressure, venous/arterial and diabetic ulcers.

Source: MedMarket Diligence, LLC; Report #S290.

Sealants, Fibrin and Others

Numerous variants of fibrin sealant exist, including autologous products. “Other” sealants refers to thrombin, collagen & gelatin-based sealants.

Fibrin sealants are used in the US in a wide array of applications; they are used the most in orthopedic surgeries, where the penetration rate is thought to be 25-30%. Fibrin sealants can, however, be ineffective under wet surgical conditions. The penetration rate in other surgeries is estimated to be about 10-15%.

Fibrin-based sealants were originally made with bovine components. These components were judged to increase the risk of developing bovine spongiform encephalopathy (BSE), so second-generation commercial fibrin sealants (CSF) avoided bovine-derived materials. The antifibrinolytic tranexamic acid (TXA) was used instead of bovine aprotinin. Later, the TXA was removed, again due to safety issues. Today, Ethicon’s (JNJ) Evicel is an example of this product, which Ethicon says is the only all human, aprotinin free, fibrin sealant indicated for general hemostasis. Market growth in the Sealants sector is driven by the need for improved biocompatibility and stronger sealing ability—in other words, meeting the still-unsatisfied needs of physician end-users.

High Strength Medical Glues

Similar to that of sealants, the current market penetration of glues in the US is about 25% of eligible surgeries. There are several strong points in favor of the use of medical glues: their use can significantly reduce healthcare costs, for example by reducing time in the surgical suite, reducing the risk of a bleed, which may mean a return trip to the OR, and general ease of use. Patients seem to prefer the glues over receiving sutures for external wound closure, as glues can provide a suture-free method of closing wounds. In addition, if glues are selected over sutures, the physician can avoid the need (and cost) of administering local anesthesia to the wound site.

Hemostats

Hemostats are normally used in surgical procedures only when conventional methics to stop bleeding are ineffective or impractical. The hemostat market offers opportunities as customers seek products that better meet their needs. Above and beyond having hemostatic agents that are effective and reliable, additional improvements that they wish to see in hemostat products include: laparoscopy-friendly; work regardless of whether the patient is on anticoagulants or not; easy to prepare and store, with a long shelf life; antimicrobial; transparent so that the surgeon continues to have a clear field of view; and non-toxic; i.e. preferably not made from human or animal materials.


Drawn from, “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.” Report #S290.

Add tick cement to the list of natural adhesives pursued for medical applications

In past posts, we have reported on multiple naturally-occurring substances or methods for strong adhesion that are being investigated for their potential to be exploited for medical or surgical adhesion. These include adhesives from remora, mussels, geckos, crab shells, barnacles, Australian burrowing frogs, spider webs, porcupine quills, sandcastle worms, etc.

Researchers from MedUni Vienna and Vienna University of Technology are now investigating 300 different ticks for the “cement” used by the parasites to attach to hosts. The goal is to study the composition of the natural tick “dowel” used by the mouthparts of ticks and determine how it might serve as a template for new tissue adhesives.

The Vienna research also notes other natural adhesives are similarly being investigated for medical and surgical use:

Other potential “adhesive donors” are sea cucumbers, which shoot sticky threads out of their sac; species of salamander, which secrete extremely fast-drying adhesive out of skin glands, if attacked; or insect larvae, which produce tentacles or crabs, which can remain firmly “stuck,” even under water.

The incentive for studying natural adhesives is that they have been driven by evolution to provide strong adhesion without toxicity in various wet or dry conditions that are challenging for existing synthetic or existing natural glues (e.g., fibrin glues, cyanoacrylates, etc.). Surgical glues currently in use have some limitation arising from lesser strength, ease of use, toxicity, and other shortcomings. New glues will gain wider adoption, capturing procedure volume used with sutures, clips and other closure methods, particularly in internal use, if they are stronger and/or provide tighter seals (without needing to be combined with sutures on the same incision/wound) and do not cause the toxicity that some high strength medical glues do (e.g., synthetics like cyanoacrylates; “super glues”). The biologically-derived glues (or the surfaces structures of gecko feet) avoid the toxicities of synthetics and have often proven to have very high tensile strength. (The fast-curing cement used by barnacles has been shown to have a remarkable tensile strength of 5,000 pounds per square inch.)

Edit: See also, Biomimetic Glue, based on shellfish natural adhesive.


MedMarket Diligence tracks the technologies, clinical practices, companies, and markets associated with medical and surgical sealants and glues, with the most recent coverage in, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022,” (report #S290).

Factors Affecting Wound Healing

Excerpted from, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”, Report #S251.

A delicate physiological balance must be maintained during the healing process to ensure timely repair or regeneration of damaged tissue. Wounds may fail to heal or have a greatly increased healing time when unfavorable conditions are allowed to persist. An optimal environment must be provided to support the essential biochemical and cellular activities required for efficient wound healing and to remove or protect the wound from factors that impede the healing process.

Factors affecting wound healing may be considered in one of two categories depending on their source. Extrinsic factors impinge on the patient from the external environment, whereas intrinsic factors directly affect the performance of bodily functions through the patient’s own physiology or condition.

Preparation of the wound bed (WBP) is essential for the support of efficient and effective healing, especially when advanced wound care products are to be used. WBP involves removing localized barriers to healing, such as exudate, dead tissue or infected tissue.

Wound Bed Preparation: the TIME and DIMES acronyms

WBP involves debridement, reduction and neutralization of the bioburden and management of exudate from the wound. The TIME acronym provides a systematic way to manage wounds by looking at each stage of wound healing. The goal is to have the best, thoroughly-vascularized wound bed possible.

TIME stands for:

  • T: Tissue, non-viable or deficient.

The wound care professional should look for non-viable tissue, which includes necrotic tissue, tissue which has sloughed off, or non-viable tendon or bone.

  • I: Infection or Inflammation

Examine the wound for infection, inflammation or other signs of infection. Are there clinical signs that there may be a problem with bacterial bioburden?

  • M: Moisture Balance

Is the wound too dry, or does it have excess exudate?

What is the objective of topical therapy: absorption or drainage?

  • E: Edge of wound—non-advancing or undermined

Examine the edges of the wound. Are the edges undermined, or is the epidermis failing to migrate across the granulation tissue?

The DIMES acronym is very similar to TIME:

  • Debridement (autolytic)

For wounds with the ability to heal, adequate and repeated debridement is an important first step in removing necrotic tissue. Debridement may also help healing by removing both senescent cells that are no longer capable of normal cellular activities and biofilms that may be shielding bacterial colonies.

  • Infection/Inflammation

The level of bacterial damage may include contamination (organisms present), colonization (organisms present which may cause surface damage if critically colonized) or infection. Treatment needs to make a match between the individual patient’s wound and the appropriate product.

  • Moisture balance

Clinicians need to create a careful balance in the wound such that the environment is neither too wet nor too dry. The environment itself will change as the wound heals.

  • Edge/Environment

The clinician should carefully examine and monitor the wound edge. If the wound edge is not migrating after appropriate wound bed preparation, and if healing appears to be stalled, then more advanced wound care therapies should be considered.

  • Supportive Products and Services

There are additional products which support wound healing yet don’t fall into one of these steps. For example, proper nutritional support is important to achieving the goal of a fully healed wound.

Extrinsic Factors

Extrinsic factors affecting wound healing include:

  • Mechanical stress
  • Debris
  • Temperature
  • Desiccation and maceration
  • Infection
  • Chemical stress
  • Medications
  • Other factors such as alcohol abuse, smoking, and radiation therapy

Mechanical Stress

Mechanical stress factors include pressure, shear, and friction. Pressure can result from immobility, such as experienced by a bed- or chair-bound patient, or local pressures generated by a cast or poorly fitting shoe on a diabetic foot. When pressure is applied to an area for sufficient time and duration, blood flow to the area is compromised and healing cannot take place. Shear forces may occlude blood vessels, and disrupt or damage granulation tissue. Friction wears away newly formed epithelium or granulation tissue and may return the wound to the inflammatory phase.

Debris

Debris, such as necrotic tissue or foreign material, must be removed from the wound site in order to allow the wound to progress from the inflammatory stage to the proliferative stage of healing. Necrotic debris includes eschar and slough. The removal of necrotic tissue is called debridement and may be accomplished by mechanical, chemical, autolytic, or surgical means. Foreign material may include sutures, dressing residues, fibers shed by dressings, and foreign material which were introduced during the wounding process, such as dirt or glass.

Temperature

Temperature controls the rate of chemical and enzymatic processes occurring within the wound and the metabolism of cells and tissue engaged in the repair process. Frequent dressing changes or wound cleansing with room temperature solutions may reduce wound temperature, often requiring several hours for recovery to physiological levels. Thus, wound dressings that promote a “cooling” effect, while they may help to decrease pain, may not support wound repair.

Desiccation and Maceration

Desiccation of the wound surface removes the physiological fluids that support wound healing activity. Dry wounds are more painful, itchy, and produce scab material in an attempt to reduce fluid loss. Cell proliferation, leukocyte activity, wound contraction, and revascularization are all reduced in a dry environment. Epithelialization is drastically slowed in the presence of scab tissue that forces epithelial cells to burrow rather than freely migrate over granulation tissue. Advanced wound dressings provide protection against desiccation.

Maceration resulting from prolonged exposure to moisture may occur from incontinence, sweat accumulation, or excess exudates. Maceration can lead to enlargement of the wound, increased susceptibility to mechanical forces, and infection. Advanced wound products are designed to remove sources of moisture, manage wound exudates, and protect skin at the edges of the wound from exposure to exudates, incontinence, or perspiration.

Infection

Infection at the wound site will ensure that the healing process remains in the inflammatory phase. Pathogenic microbes in the wound compete with macrophages and fibroblasts for limited resources and may cause further necrosis in the wound bed. Serious wound infection can lead to sepsis and death. While all ulcers are considered contaminated, the diagnosis of infection is made when the wound culture demonstrates bacterial counts in excess of 105 microorganisms per gram of tissue. The clinical signs of wound infection are erythema, heat, local swelling, and pain.

Chemical Stress

Chemical stress is often applied to the wound through the use of antiseptics and cleansing agents. Routine, prolonged use of iodine, peroxide, chlorhexidine, alcohol, and acetic acid has been shown to damage cells and tissue involved in wound repair. Their use is now primarily limited to those wounds and circumstances when infection risk is high. The use of such products is rapidly discontinued in favor of using less cytotoxic agents, such as saline and nonionic surfactants.

Medication

Medication may have significant effects on the phases of wound healing. Anti-inflammatory drugs such as steroids and non-steroidal anti-inflammatory drugs may reduce the inflammatory response necessary to prepare the wound bed for granulation. Chemotherapeutic agents affect the function of normal cells as well as their target tumor tissue; their effects include reduction in the inflammatory response, suppression of protein synthesis, and inhibition of cell reproduction. Immunosuppressive drugs reduce WBC counts, reducing inflammatory activities and increasing the risk of wound infection.

Other Extrinsic Factors

Other extrinsic factors that may affect wound healing include alcohol abuse, smoking, and radiation therapy. Alcohol abuse and smoking interfere with body’s defense system, and side effects from radiation treatments include specific disruptions to the immune system, including suppression of leukocyte production that increases the risk of infection in ulcers. Radiation for treatment of cancer causes secondary complications to the skin and underlying tissue. Early signs of radiation side effects include acute inflammation, exudation, and scabbing. Later signs, which may appear four to six months after radiation, include woody, fibrous, and edematous skin. Advanced radiated skin appearances can include avascular tissue and ulcerations in the circumscribed area of the original radiation. The radiated wound may not become evident until as long as 10-20 years after the end of therapy.

Intrinsic Factors

Intrinsic factors that directly affect the performance of healing are:

  • Health status
  • Age factors
  • Body build
  • Nutritional status

Health Status

Chronic diseases, such as circulatory conditions, anemias and autoimmune diseases, influence the healing process as a result of their influence on a number of bodily functions. Illnesses that cause the most significant problems include diabetes, chronic obstructive pulmonary disease (COPD), arteriosclerosis, peripheral vascular disease (PVD), heart disease, and any conditions leading to hypotension, hypovolemia, edema, and anemia. While chronic diseases are more frequent in the elderly, wound healing will be delayed in any patient with a pre-existing underlying illness.

Chronic circulatory diseases which reduce blood flow, such as arterial or venous insufficiency, lower the amount of oxygen available for normal tissue activity and replacement. Anemias such as sickle-cell anemia result in reduced delivery of oxygen to tissues and decreased ability to support wound healing.

Normal immune function is required during the inflammatory phase by providing the WBCs (white blood cells) that orchestrate or coordinate the normal sequence of events in wound healing. Autoimmune diseases such as lupus and rheumatoid arthritis interfere with normal collagen deposition, and impair granulation.

Diabetes is associated with delayed cellular response to injury, compromised cellular function at the site of injury, defects in collagen synthesis, and reduced wound tensile strength after healing. Diabetes-related peripheral neuropathy (DPN), which reduces the ability to feel pressure or pain, contributes to a tendency to ignore pressure points and avoid pressure relief strategies.

Acquired Immune Deficiency Syndrome

Patients with acquired immunodeficiency syndrome (AIDS) have significant impact on the wound healing market as their numbers rise and their average life expectancy increases. Patients in the latter stages of the disease experience drastic reductions in mobility, activity, and nutritional status, placing them at high risk for the development of pressure ulcers. Minor scrapes or abrasions are at high risk for infection and may progress to full-thickness wounds requiring antibiotic therapy and aggressive wound management. Skin tumors, such as Kaposi’s sarcoma, lead to surgical incisions closed by secondary intention requiring the use of appropriate dressings.

The skin of AIDS patients becomes drier as the syndrome progresses. As the CD4+ T cell count falls below 400/mm3, pruritus increases and erythematous patches appear on the skin, progressing to ichthyosis and appearing as large polygonal scales, especially on the lower limbs. Histological changes include hyperkeratosis and thinning of the granular layer of the epidermis. As skin becomes more fragile, care must be exercised in the selection of tapes and adhesive dressings to avoid skin stripping and skin tears.

Age Factors

Observable changes in wound healing in the elderly include increased time to heal and the fragile structure of healed wounds. Delays are speculated to be the result of a general slowing of metabolism and structural changes in the skin of elderly people. Structural changes include a flattening of the dermal-epidermal junction that often leads to skin tears, reduced quality and quantity of collagen, reduced padding over bony prominences, and reduction in the intensity of the immune response.

Body Build

Body build can affect the delivery and availability of oxygen and nutrients at the wound site. Underweight individuals may lack the necessary energy and protein reserves to provide sufficient raw materials for proliferative wound healing. Bony prominences lack padding and become readily susceptible to pressure due to the reduced blood supply of wounds associated with bony prominences. Poor nutritional habits and reduced mobility of overweight individuals lead to increased risk of wound dehiscence, hernia formation, and infection.

Nutritional Status

Healing wounds, especially full-thickness wounds, require an adequate supply of nutrients. Wounds require calories, fats, proteins, vitamins and minerals, and adequate fluid intake. Calories provide energy for all cellular activity, and when in short supply in the diet, the body will utilize stored fat and protein. The metabolism of these stored substances causes a reduction in weight and changes in pressure distribution through reduction of adipose and muscle padding. Sufficient dietary calories maintain padding and ensure that dietary protein and fats are available for use in wound healing. In addition, adequate levels of protein are necessary for repair and replacement of tissue. Increased protein intake is particularly important for wounds where there is significant tissue loss requiring the production of large amounts of connective tissue. Protein deficiencies have been associated with poor revascularization, decreased fibroblast proliferation, reduced collagen formation, and immune system deficiencies.

Reduced availability of vitamins, minerals, and trace elements will also affect wound healing. Vitamin C is required for collagen synthesis, fibroblast functions, and the immune response. Vitamin A aids macrophage mobility and epithelialization. Vitamin B complex is necessary for the formation of antibodies and WBCs, and Vitamin B or thiamine maintains metabolic pathways that generate energy required for cell reproduction and migration during granulation and epithelialization. Iron is required for the synthesis of hemoglobin, which carries oxygen to the tissues, and copper and zinc play a role in collagen synthesis and epithelialization.

Adequate nutrition is an often-overlooked requirement for normal wound healing. Inadequate protein-calorie nutrition, even after just a few days of starvation, can impair normal wound-healing mechanisms. For healthy adults, daily nutritional requirements are approximately 1.25-1.5 g of protein per kilogram of body weight and 30-35 calories/kg.  These requirements should be increased for those with sizable wounds.

Malnutrition should be suspected in patients presenting with chronic illnesses, inadequate societal support, multisystem trauma, or GI or neurologic problems that may impair oral intake. Protein deficiency occurs in about 25% of all hospitalized patients.

Chronic malnutrition can be diagnosed by using anthropometric data to compare actual and ideal body weights and by observing low serum albumin levels. Serum prealbumin is sensitive for relatively acute malnutrition because its half-life is 2-3 days (vs 21 d for albumin). A serum prealbumin level of less than 7 g/dL suggests severe protein-calorie malnutrition.

Vitamin and mineral deficiencies also require correction. Vitamin A deficiency reduces fibronectin on the wound surface, reducing cell chemotaxis, adhesion, and tissue repair. Vitamin C is required for the hydroxylation of proline and subsequent collagen synthesis.

Vitamin E, a fat-soluble antioxidant, accumulates in cell membranes, where it protects polyunsaturated fatty acids from oxidation by free radicals, stabilizes lysosomes, and inhibits collagen synthesis. Vitamin E inhibits prostaglandin synthesis by interfering with phospholipase-A2 activity and is therefore anti-inflammatory. Vitamin E supplementation may decrease scar formation.

Zinc is a component of approximately 200 enzymes in the human body, including DNA polymerase, which is required for cell proliferation, and superoxide dismutase, which scavenges superoxide radicals produced by leukocytes during debridement.


From, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”. Report #S251. Available online.

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.

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Source: MedMarket Diligence, LLC; Report #S290.

Sealants, Glues, Hemostats to 2022

 

Below is our bubble chart giving the segment size (bubble size and horizontal axis position) and growth (vertical axis position) of the products detailed in our 2014 report #S192.

Source: MedMarket Diligence, LLC; Report #S192 (published Oct. 2014)

Given the interest by companies actively involved in sealants, glues, and hemostats, we are publishing Report #S290 (June 2016), “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.”

From Skitch

Wound Care Technologies: Sales Growth, Change, Global Forecast

MedMarket Diligence is hours away from publishing its 2015 report on the worldwide wound management market.

The report is entitled, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”. The report is described in detail at link.

The very diverse field that is wound management encompasses technologies from gauze to bioengineered skin and skin substitutes and many in between. Growth rates range from flat to over 15% annually through 2024.

Source: MedMarket Diligence, LLC; Report #S251.

The highest growth segments in medical technology sectors typically derive their high growth from modest absolute changes on very small volume and therefore rarely can sustain that growth over time. However, in wound management, the use of bioengineered skin and skin substitutes will result in the highest cumulative sales compared to all segments from 2015 to 2024 — excluding, that is, the high volume segments of traditional adhesives, gauzes, and non-adherent dressings.  Also noteworthy is the second highest cumulative sales over this period was for antimicrobial dressings, despite this segment having relatively modest growth on a percentage basis, but proceeding from significant sales in 2015 (already at over $1.5 billion).

Source: MedMarket Diligence, LLC; Report #S251.

During the forecast period, the most significant change evident in sales is the jump in the share of the market represented by bioengineered and other skin replacements, as noted above. But with compound annual growth rates (to 2024) in sales in the different wound segments ranging from near 1% to nearly 20% — for segments with 2015 sales at a low of $300 million and a high of $15 billion — there is considerable shifting of shares of the global wound market.

Source: MedMarket Diligence, LLC; Report #S251.

On a geographic basis, wound care technology migration, efforts to secure underserved patient caseload, and other forces result in growth rates that vary by country or region. The well-developed USA market therefore does not compare in uptake of both old and new technologies within growth markets like China and others in the Asia/Pacific region.

Source: MedMarket Diligence, LLC; Report #S251.

Growth in Sealants, Glues, Hemostats, and Wound Closure is Absolute, Relative

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)

Of late, I have needed to re-emphasize the difference between absolute and relative growth in medtech markets (and its importance). So, here it is again, this time regarding surgical sealants and other wound closure products.

The lowest relative rate of growth in this industry is the well-established sutures and staples segment. Sales of these products globally, even supported by innovations in bioresorbables and laparoscopic delivery technologies, are only growing at a 5.6% compound annual growth rate from 2013 to 2018. By comparison, growth of sales of surgical glues and sealants is at 9.4% for 2013-2018.

But from an absolute sales growth point of view, sales of sutures and staples will go from $5.2 billion to $6.9 billion, or absolute growth of $1.7 billion. Simultaneously, the relatively high growth in surgical glues and sealants translates to the absolute growth from 2013 to 2018 of only $0.9 billion.

Obviously, both absolute and relative growth are of interest.

Screen Shot 2015-07-23 at 2.31.03 PM

Source: MedMarket Diligence, LLC; Report #S192.

Bioactive Agents in Wound Sealing and Closure

See updated analysis in Report #S290, “Sealants, Glues, Hemostats to 2022”.

Screen Shot 2015-03-30 at 10.14.59 AMBiologically active sealants typically contain various formulations of fibrin and/or thrombin, either of human or animal origin, which mimic or facilitate the final stages of the coagulation cascade. The most common consist of a liquid fibrin sealant product in which fibrinogen and thrombin are stored separately as a frozen liquid or lyophilized powder. Before use, both components need to be reconstituted or thawed and loaded into a two-compartment applicator device that allows mixing of the two components just prior to delivery to the wound. Because of the laborious preparation process, these products are not easy to use. However, manufacturers have been developing some new formulations designed to make the process more user friendly.

Selected Biologically Active Sealants, Glues, and Hemostats 

CompanyProduct NameDescription/
(Status*)
Asahi Kasei MedicalCryoSeal FS SystemFibrin sealant system comprising an automated device and sterile blood processing disposables that enable autologous fibrin sealant to be prepared from a patient's own blood plasma in about an hour.
BaxterArtissFibrin sealant spray
BaxterTisseelBiodegradable fibrin sealant made of human fibrinogen and human thrombin. For oozing and diffuse bleeding.
BaxterFloSealHemostatic bioresorbable sealant/glue containing human thrombin and bovine-derived, glutaraldehyde-crosslinked proprietary gelatin matrix. For moderate to severe bleeding.
BaxterGelFoam PlusHemostatic sponge comprising Pfizer's Gelfoam hemostatic sponge, made of porcine skin and gelatin, packaged with human plasma-derived thrombin powder.
Behring/NycomedTachoCombFleece-type collagen hemostat coated with fibrin glue components.
Bristol-Myers Squibb/ZymoGenetics (Sold by The Medicines Company in the US and Canada)RecothromFirst recombinant, plasma-free thrombin hemostat.
CSL BehringBeriplast P/Beriplast P Combi-SetFreeze dried fibrin sealant. Comprised of human fibrinogen-factor XIII and thrombin in aprotinin and calcium chloride solution.
CSL BehringHaemocomplettan P, RiaSTAPFreeze-dried human fibrinogen concentrate. Haemocomplettan (US) and RiaSTAP (Europe).
J&J/EthiconEvicelEvicel is a new formulation of the previously available fibrin sealant Quixil (EU)/Crosseal (US). Does not contain the antifibrinolytic agent tranexamic acid, which is potentially neurotoxic, nor does it contain synthetic or bovine aprotinin, which reduces potential for hypersensitivity reactions.
J&J/EthiconEvarrestAbsorbable fibrin sealant patch comprised of flexible matrix of oxidized, regenerated cellulose backing under a layer of polyglactin 910 non-woven fibers and coated on one side with human fibrinogen and thrombin.
J&J/EthiconBIOSEAL Fibrin SealantLow-cost porcine-derived surgical sealant manufactured in China by J&J company Bioseal Biotechnology and targeted to emerging markets.
J&J/EthiconEvithromHuman thrombin for topical use as hemostat. Made of pooled human blood.
Pfizer/King PharmaceuticalsThrombin JMIBovine-derived topical thrombin hemostat.
Stryker/OrthovitaVitagel SurgicalBovine collagen and thrombin hemostat.
Takeda/NycomedTachoSilAbsorbable surgical patch made of collagen sponge matrix combined with human fibrinogen and thrombin.
Teijin Pharma Ltd/Teijin Group (Tokyo, Japan)KTF-374Company is working with Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) to develop a sheet-type surgical fibrin sealant. Product combines KAKETSUKEN's recombinant thrombin and fibrinogen technology with Teijin's high-performance fiber technology to create the world's first recombinant fibrin sealant on a bioabsorbable, flexible, nonwoven electrospun fiber sheet.
The Medicines Company (TMC)Raplixa (formerly Fibrocaps)Sprayable dry-powder formulation of fibrinogen and thrombin to aid in hemostasis during surgery to control mild or moderate bleeding.
The Medicines Company (TMC)In development: Fibropad patchFDA accepted company's BLA application for Fibrocaps in April 2014 and set an action date (PDUFA) in 2015. In November 2013, the European Medicines Agency agreed to review the firm's EU marketing authorization application. Status update in report #S192.
Vascular SolutionsD-Stat FlowableThick, but flowable, thrombin-based mixture to prevent bleeding in the subcutaneous pectoral pockets created during pacemaker and ICD implantations.

Source: MedMarket Diligence, LLC

Note: Status of products detailed in Report S192. See UPDATED analysis in 2016 report #S290. Available online.

 

Wound Sealant and Securement Procedure Volumes by Clinical Area and End-Point

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)

Sealants, glues, hemostats, and other products in wound closure and securement offer benefits that vary by clinical area, but the nature of that benefit also varies by the type of end-point (benefit) the product achieves — does it provide a life-saving benefit? A time-saving? Cost-savings? A cosmetic or aesthetic benefit?

Accordingly, by examining the volume of procedures for which closure and securement products provide which kind of benefit is crucial to understanding demand, especially between competitive products.

Below is a categorization of benefits ranging from the critical (I) to the aesthetic (IV).

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

Screen Shot 2015-06-23 at 7.24.29 AM

Source: MedMarket Diligence, LLC (Report #S192)

Considering these different categories, below are the volumes of procedures distributed by category across each of the major clinical disciplines.

Surgical Procedures with Potential for the Use of Hemostats, Sealants, Glues and Wound Closure Products, Worldwide (Millions), 2014

 

 

 

 

Screen Shot 2015-06-23 at 7.28.36 AM

Source: MedMarket Diligence, LLC (Report #S192)

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)