Naturally sticky: Biologically-based medical glues dominate

Medical glues are either biologically-based, cyanoacrylate, or other synthetic. The bulk of global sales of medical glues are biologically-based, (includes fibrin, thrombogen, and others), cyanoacrylate-based glues, and other synthetic glues.

Cyanoacrylate-based glues, include those from Ethicon, Adhezion Biomedical, B. Braun, Meyer-Haake, and others. Cyanoacrylates provide strong adhesion, but biologically-based glues have found more applications, both topically and internally. “Other” glues are of a variety of synthetic types; these glues have yet to gain more than 4% share globally.

Below is illustrated the growth of biologically-based glues by region, showing that most growth in this segment will be from Asia/Pacific markets, which are consistently demonstrating higher growth than in western markets.

Global Markets for Biologically-Based Medical Glues, 2015-2022, USD MillionsSource: MedMarket Diligence, LLC; Report #S290. (Order online)

 

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”.

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.

Regional Markets for Surgical Sealants, 2015 and 2022

The fastest growth in the sales of surgical sealants over the next decade will be in the Asia-Pacific region, driven primarily by very strong healthcare market growth in China, and reaching a CAGR (2016-2022) of at least 13.97%. The growth rate in China would be even higher, but will be dampened for the time being by the lack of surgeons trained in the proper use of these products, as well as the limitations of reaching a dispersed patient population. Nonetheless, the A/P share of the global sealants market will double in the next seven years!

Below illustrates the geographic distribution of surgical sealants (fibrin and others) in 2015.

Regional Markets for Sealants, Fibrin and Other Sealant Products,
2015 & 2022, USD Millions

2015screen-shot-2016-11-11-at-8-52-44-am

2022

screen-shot-2016-11-11-at-8-53-17-am

Source: MedMarket Diligence, LLC; Report #S290.


Report #S290 may be purchased online for PDF download or print delivery; in single, site, or global licenses.

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.)

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.

To request a set of report excerpts, click here.

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.