Surgical Sealants, Glues, and Hemostats with Bioactive Agents

Excerpt from Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018″.

Biologically 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.

Note: Status of products detailed in Report #S192.

Source: MedMarket Diligence, LLC

Surgical Sealants: Advanced Technologies in Well Developed Markets

Advanced technologies are frequently developed in well developed economies, then migrate to other economies over time. Consequently, relatively new technologies tend to be more dominant in the well developed economies while relatively old technologies tend to be more dominant in the developing economies.

Case in point, surgical sealants for wound management versus surgical tapes, the former relatively new (and advanced) and the latter relatively old.

Screen Shot 2015-03-21 at 12.45.52 PM

Source: MedMarket Diligence, LLC; Report #S192

Competitive Landscape in Wound Sealants and Closure

The global market for products used in wound closure encompasses sutures/staples, tapes, specialized vascular closure devices, hemostats, and surgical sealants. Some well known companies dominate some segments, but the market remains open to innovations by others. As a result, the balance of control of each segment has continued to shift. Below is illustrated the overall market shares of companies in this market.

Screen Shot 2015-03-12 at 8.36.00 AM

A: 3M
B: Abbott Vascular
C: Access Closure
D: B.Braun
E: Baxter
F: C.R. Bard
G: Covidien
H: CryoLife
I: CSL Behring
J: Equimedical BV
K: Ethicon/J&J
L: Pfizer
M: St. Jude Medical
N: Others

Source: MedMarket Diligence, LLC; Report #S192.

 

Wound Closure Technologies Fragmented, But Growing through 2018

Wounds have been closed and secured through the use of sutures and bandages since ancient times, using equipment ranging from threads made of a variety of organic materials, to tight wrappings. In the modern medical age, suture materials have evolved through a succession of stages from non-resorbable, to resorbable, to stapling devices. Surgeons still primarily use sutures for wound closure and securement—sutures are cheap, familiar and work most of the time. However, it is important to discuss this class of products and their relationship with adjunctive measures, and with newer products under development.

There are six major device markets in the field of wound closure:

  • Sutures and Staples
  • Vascular Closure Devices
  • Surgical Sealants and Glues
  • Surgical Hemostats
  • Cyanoacrylate Glues for External Closure
  • External Closure Tapes and Strips

The markets for some segments in wound closure, especially sutures and staples, surgical tape, hemostats, and sealants and glues, are highly fragmented. There are literally hundreds of companies with products that fall into the wound closure arena. Barriers to entry are low for some segments, such as medical tapes, sutures and staples, and high for others, such as fibrin and others. In addition, many companies purchase from the original equipment manufacturers (OEM), and rebrand the products to sell under their own name. While this may obscure who the market leaders are, there no little doubt, however, that the overall market leader for the products in wound closure is Johnson & Johnson (JNJ), which markets devices that fall under six of the seven product categories. JNJ is followed by Covidien and B. Braun/Aesculap, which together make up the three largest players in this space.

Global Market Shares in Wound Closure 2014

Screen Shot 2015-02-23 at 4.02.15 PM

Source: MedMarket Diligence, LLC; Report #S192.

Growth in this market is still driven by new technologies with potential to not only penetrate well-established wound closure technologies but also gain procedure volume in novel applications. Below is illustrated the relative compound annual growth rates in sales of each of the major types of wound closure technologies.

Sales Growth in Wound Closure Types, 2014-2018

Screen Shot 2015-02-23 at 4.08.14 PM

Source: MedMarket Diligence, LLC; Report #S192.

Surgical Sealants and Glues Sales Growth

Aside from demonstrating clinical utility in wound sealing and closure on their own, 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.

Sales of surgical sealants and glues have become as common in some surgical procedures as sutures and staples in well developed markets (U.S., Europe and Japan), but their use continues to expand in both stand alone and adjunctive use with other wound closure. Emerging markets, especially in Asia will drive nearly double these growth rates. All told, the global surgical sealants and glues market will eclipse $2 billion by 2018 on compound annual growth of 9.4%.

Screen Shot 2015-01-27 at 2.45.11 PMSource: MedMarket Diligence, LLC; Report #S192.

 

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.

 

New technologies at Medtech Startups, November 2014

Below is a list of the technologies under development at companies recently identified and included in the Medtech Startups Database.

  • Handheld ultrasound, MRI imaging device.
  • Needle-free injection drug delivery.
  • Lenses designed to correct imbalance between eyes and brain that cause certain migraines.
  • Continuous blood glucose monitoring in diabetes.
  • Customized prosthetic aortic valve.
  • Cystoscope-implanted, stent-like device to treat urinary obstruction associated with benign prostatic hypertrophy.
  • Endovascular treatment for abdominal aortic aneurysm.
  • Respiratory therapy device based on “high frequency chest wall oscillation” for treatment of COPD, other respiratory disorders.
  • Treatment of arrhythmia.
  • Medical device commercialization company active in cardiovascular care, tissue ablation, medical infusions, hand surgery and laparoscopic surgery.
  • Surgical visualization systems.
  • Arthroscopic bone tunneler and other orthopedic surgical instrumentation.
  • Brain stimulation to treat multiple disorders.

See link for a month-by-month listing of the technologies at companies in the Medtech Startups Database.