What’s next in sealants, glue, hemostats…and why?

From July 2016 published Report #S290.

Here are six key trends we see in the global market next in 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”.

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.

Medical and Surgical Sealants, Glues, and Hemostats, to 2022

There are several different classes of surgical sealants, glues and hemostatic products used to prevent or stop bleeding, or to close a wound or reinforce a suture line. These include fibrin sealants, surgical sealants, mechanical hemostats, active hemostats, flowable hemostats, and glues. Both sealants and medical glues are increasingly used either as an adjunct to sutures or to replace sutures.

Medical Sealants

Fibrin sealants are made of a combination of thrombin and fibrinogen. These sealants may be sprayed on the bleeding surface, or applied using a patch. Surgical sealants might be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates.

Sealants are most often used to stop bleeding over a large area. If the surgeon wishes to fasten down a flap without using sutures, or in addition to using sutures, then the product used is usually a medical glue.

Source: MedMarket Diligence, LLC; Report #S290.

Hemostatic Products

The surgeon and the perioperative nurse have a variety of hemostats from which to choose, as they are not all alike in their applications and efficacy. Selection of the most appropriate hemostat requires training and experience, and can affect the clinical outcome, as well as decrease treatment costs. Some of the factors that enter into the decision-making process include the size of the wound, the amount of hemorrhaging, potential adverse effects, whether the procedure is MIS or open surgery, and others.

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 flowable putty that may be applied to the bleeding area.
Mechanical hemostats, such as absorbable gelatin sponge, collagen, cellulose, or polysaccharide-based hemostats applied as sponges, fleeces, bandages, or microspheres, are not included in this analysis.

Source: MedMarket Diligence, LLC; Report #S290.

Medical Glues

Sealants and glues are terms which are often used interchangeably, which can be confusing. In this report, a medical glue is defined as a product used to bond two surfaces together securely. Surgeons are increasingly reaching for medical glues to either help secure a suture line, or to replace sutures entirely in the repair of soft tissues. Medical glues are also utilized in repairing bone fractures, especially for highly comminuted fractures that often involve many small fragments. This helps to spread out the force-bearing surface, rather than focusing weight-bearing on spots where a pin has been inserted.

Thus, the surgeon has a fairly wide array of products from which to choose. The choice of which surgical hemostat or sealant to use depends on several factors, including the procedure being conducted, the type of bleeding, severity of the hemorrhage, the surgeon’s experience with the products, the surgeon’s preference, the price of the product and availability at the time of surgery. For example, a product which has a long shelf life and does not require refrigeration or other special storage, and which requires no special preparation, usually holds advantages over a product which must be mixed before use, or held in a refrigerator during storage, then allowed to warm up to room temperature before use.

Source: MedMarket Diligence, LLC; Report #S290.


From “Worldwide Market for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.” See details at link. Order online.

Hemostat Sales to 2022

Owing to their ease of use, ease of handling, and general clinical utility, hemostat sales will almost double worldwide between 2016 and 2022:

Source: MedMarket Diligence, LLC; Report #S290. Order online.

Hemostat sales are exceptionally strong in the well developed economies (Japan, Australia, Korea) of Asia, and will continue to expand there with the rapidly growing contribution of China’s hemostat sales.

Source: MedMarket Diligence, LLC; Report #S290. Order online.

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Wound closure and healing via sealants, glues, hemostats in development

Natural tissue healing is a highly complex dance of processes that need to be working properly in order for the body to heal. Mammals have developed the ability to heal wounds rapidly through a cascade of processes that starts with hemostasis (blood clotting) to slow or stop the loss of blood. From the moment of injury, platelets start to aggregate, as well as starting to release cytokines, chemokines and hormones. Vasoconstriction takes place as the body tries to limit the loss of blood, and several vasoactive mediators come into play, including, norepinephrine, epinephrine, prostaglandins, serotonin, and thromboxane. Activated platelets lead to formation of a clot. Next, the inflammatory steps kick in, targeting and killing microbes and launching a natural internal debridement process, which serves to clean up any damaged tissue so that reconstruction may occur. Last in the cascade are the proliferative and maturation phases. These involve the deposition of new tissue matrix materials, and are intended to lead to reconstruction of tissue organelles and cellular structure. These healing steps actually overlap one another, and do not have strict times when each process begins or ends.

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. Factors which strongly affect wound healing include smoking, diabetes, age, oxygenation, stress, obesity, certain medications, alcoholism and nutrition.

Timescales for Development of
Sealants, Glues and Hemostat Products

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Source: MedMarket Diligence, LLC; Report #S290.

While product development continues apace, and companies are launching their products in new countries, launches of actual new products has been relatively slow. This is due most likely to the highly technical (read: expensive) nature of the product development, as well as the cost and time involved in running clinical trials, and the strong patent protection which has been erected, especially by the leading companies. The need for the products is there, but the required clinical testing is putting a brake on the markets.

In July 2015, HyperBranch announced the product launch of Adherus® AutoSpray Dural Sealant in the US. FDA clearance to market the product was obtained in March 2015. The absorbable sealant is intended for use in brain surgery and is applied over the sutures for dura repair to prevent cerebrospinal fluid from leaking out of the incision site. The Adherus® AutoSpray Dural Sealant is made of two solutions: a PEG ester solution and a polyethylenimine (PEI) solution. When mixed together, the solutions combine to form a sealant gel that is applied to the incision site. According to the company, the sealant is fully absorbed in about 90 days.

Cohera Medical launched its TissuGlu® in select US cities in November 2015. At this point, TissuGlu® is available in ten cities in the USA, while B. Braun is the distributor for the product in Germany, Spain and Portugal.

Sanyo Chemical launched its first medical device, Hydrofit, in February 2014. The company obtained the approval of the medical device under the Pharmaceutical Affairs Law in December 2011, filing it as a novel surgical hemostatic agent intended for anastomosing the arterial blood and artificial blood vessel in surgical procedures. According to the company, the product will be produced by Sanyo and marketed by Terumo.

In 2014, Cohera Medical, Inc. launched Sylys Surgical Sealant, which can be used in gastrointestinal surgery to decrease anastomotic leak. In the same year, Baxter also gained the FDA permission for Tisseel® fibrin sealant, which, according to the company, is used in almost all types of surgical procedures.

Mallinckrodt will invest in the commercial launch and ongoing market development of both PreveLeak and Raplixa in FY 2016. According to the company, both products are faster to prepare and easier to use and store than competing products. PreveLeak, a surgical sealant, is allegedly more flexible than hemostasis glue products. It is indicated for use in vascular reconstructions to achieve adjunctive hemostasis by sealing areas of leakage. PreveLeak is currently marketed in Europe through distributors.

In an example of a delayed launch, CryoLife has been working towards launch of PerClot in the US, but ran into litigation trouble with Medafor, a wholly-owned subsidiary of CR Bard. In November 2015, CryoLife announced that it had entered into a resolution with Medafor to end the patent dispute in the US District Court for the District of Delaware between the companies regarding PerClot. Under terms of the resolution, all parties agreed to end the litigation, jointly dismissing all claims and counterclaims with prejudice and waiving all appeal rights in this case.  Each party is to pay its own attorneys’ fees and costs associated with the litigation.  However, the court’s preliminary injunction entered March 31, 2015 with respect to CryoLife’s marketing and sale of PerClot in the US will remain in effect until the expiration of Medafor’s US Patent No. 6,060,461 (the “‘461 Patent”) on February 8, 2019. CryoLife management says that this will not upset their plans, as CryoLife does not expect to receive FDA market approval for PerClot before 2018, if then.


From “Sealants, Glues, Hemostats to 2022” (#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”.

The Demand for Sealants, Glues, and Hemostats in 2016

The following is drawn from “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.” Report #S290.

The need for surgical sealants, glues and hemostats is directly related to the clinical caseload and procedure volumes, as well as to the adoption of these products for multiple uses, such as the use of one product for sealing, hemostasis and anti-adhesion. It is fair to say that use of these products has become routine in the surgical suite and in other clinical locations. Procedure volumes are in turn driven by demographic forces, including global aging populations, while regulatory changes will continue to influence uptake of these products.

wound-prevalance

Source: MedMarket Diligence, LLC; Report #S290.

Medical Sealants

Fibrin sealants are made of a combination of thrombin and fibrinogen. These sealants may be sprayed on the bleeding surface, or applied using a patch. Surgical sealants might be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates.

Sealants are most often used to stop bleeding over a large area. If the surgeon wishes to fasten down a flap without using sutures, or in addition to using sutures, then the product used is usually a medical glue.

Hemostatic Products

The surgeon and the perioperative nurse have a variety of hemostats from which to choose, as they are not all alike in their applications and efficacy. Selection of the most appropriate hemostat requires training and experience, and can affect the clinical outcome, as well as decrease treatment costs. Some of the factors that enter into the decision-making process include the size of the wound, the amount of hemorrhaging, potential adverse effects, whether the procedure is MIS or open surgery, and others.

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 flowable putty that may be applied to the bleeding area.

Medical Glues

Sealants and glues are terms which are often used interchangeably, which can be confusing. In this report, a medical glue is defined as a product used to bond two surfaces together securely. Surgeons are increasingly reaching for medical glues to either help secure a suture line, or to replace sutures entirely in the repair of soft tissues. Medical glues are also utilized in repairing bone fractures, especially for highly comminuted fractures that often involve many small fragments. This helps to spread out the force-bearing surface, rather than focusing weight-bearing on spots where a pin has been inserted.

Thus, the surgeon has a fairly wide array of products from which to choose. The choice of which surgical hemostat or sealant to use depends on several factors, including the procedure being conducted, the type of bleeding, severity of the hemorrhage, the surgeon’s experience with the products, the surgeon’s preference, the price of the product and availability at the time of surgery. For example, a product which has a long shelf life and does not require refrigeration or other special storage, and which requires no special preparation, usually holds advantages over a product which must be mixed before use, or held in a refrigerator during storage, then allowed to warm up to room temperature before use.

 

Recent Merger and Acquisition Activity in Sealants, Glues and Hemostats

Growth in sealants, glues, and hemostats markets has been strong enough for long enough to have attracted a lot of players. With growth slowing as the untapped potential is reducing more rapidly, consolidation has now appeared in the natural order of things.

Recent Merger and Acquisition Activity in Sealants, Glues and Hemostats

Original Company/ ProductAcquiring or Collaborating CompanyDate of Acquisition/Collaboration DealFinancial Details (where revealed)
Bristol-Myers Squibb/ Recothrom¨ Thrombin topical hemostatThe Medicines Company2012/2014$105 million collaboration fee
Cohera Medical/TissuGlu¨Collaboration with B. Braun Surgical S.A. to distribute in Germany, Spain and Portugal.Jan. 2015B. Braun Surgical S.A. will exclusively market and sell TissuGlu in the territories of Germany, Spain and Portugal through its existing Closure Technologies commercial teams.
Profibrix/ FibroCapsThe Medicines Company2013$90 million, with $140 million contingent upon milestones
Medafor/Arista¨ AH Absorbable Hemostatic ParticlesCR Bard (Bard Davol)2013$200 million upfront payment
Tenaxis Medical, with ArterX (among other products)The Medicines Company2014$58 million in upfront payments
The Medicines Company/ PreveLeakª (formerly known as ArterX), Raplixaª(formerly known as FibroCaps) fibrin sealant, Recothrom¨ Thrombin topical (Recombinant) sealantMallinckrodt plc2016The entire deal has a potential value of $410 million.
Xcede Technologies, Inc./Resorbable Hemostatic PatchCollaboration with Cook BiotechJan-16Signed three collaboration agreements with Cook Biotech, including a Development Agreement, a License Agreement and a Supply Agreement to complete development, seek regulatory clearance and produce XcedeÕs resorbable hemostatic patch.

Source: MedMarket Diligence, LLC; Report #S290.

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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