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
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).