Ideal medtech products

Drawing on specific examples of medical device, biotech, biohybrid, biomaterial and a wide range of other technologies I see at companies of all sizes, shapes and stages, I started an exercise to look at the “competitive advantage” sought by innovators pursuing new products in the big arena of medtech markets. Very clearly, there are companies I consider to fall in the “me, too” category, also known as 510(k), and there are companies whose products are much more PMA in that they are novel and unique, requiring more extensive data to demonstrate a heretofore undemonstrated capability. I was encouraged as I looked across the types of technologies and their target applications, since a great majority have been developed and are targeted at setting themselves apart in a market in which there is intense scrutiny on cost, which shows the resilience of innovators to rise to the challenge. At the same time, I continue to see a disappointing number of products that reflect an all too common view that being at least as good as anything on the market is adequate to succeed (hint: it isn’t).

This got me thinking about how innovators, consciously or not, are compelled to consider what their real competitive advantage is in medtech as they pursue product and market development in 2014.  This resulted in me distilling the common themes underlying new product development as pursued by the established and emerging companies I am tracking.

A key consideration is that market aware innovators recognize that their products are going to enter, in most cases, an existing market, which compels them to seek to develop their product from a relative standpoint, meaning its value is going to be judged relative to what is available, if there is any.

Screen Shot 2014-05-12 at 7.35.18 AMBelow are many of the common themes I see underlying the activities of medtech development. Again, note that, while there may be some absolutes (as in “cure”), most of the products’ performances are considered relative to existing products on the market. Combining multiple advantages is increasingly common, too, such as making a procedure less invasive and less costly, or simplifying the surgical procedure and reducing complications.

  • Allows treatment of patients who otherwise die with the available treatment limited to delaying death or ameliorating the suffering.
  • Cures the disease
  • Restores normal biologic function
  • Entirely eliminates the need for surgery
  • Eliminates need for reoperation to treat residual disease or address procedure failure rate
  • Increases the survival rate as bridge-to, or elimination of need for, organ transplant
  • Dramatically increases the specificity and intensity of treatment, especially for cancer, minimizing the impact to healthy tissue
  • Restores anatomic structural and functional integrity
  • Eliminates complications, side effects
  • Simplifies the procedure to reduce OR time
  • Shortens recovery time
  • Eliminates immunogenicity through highly efficient autologous cell technology
  • Reduces the invasiveness of the procedure by requiring fewer or smaller incisions via laparoscopy, transcatheter procedure, natural orifice endoscopy or completely externally (e.g., gamma knife)
  • Allows the treatment to be moved from acute care to an outpatient or office-based setting
  • Reduces cost by using a simpler device that can be manufactured less expensively, is less likely to break and require replacement or consolidates multiple treatment steps
  • Lowers the learning curve for physicians to adopt
  • Eliminates the need for later device removal; the product is absorbed or dissolved

This is a cursory view. As I review literally hundreds of medtech companies over the past decade, I can see a large number of common themes, but the ones above represent the bulk of them.

While it may seem trite, it is actually coincidental that the forces underlying most of the advantages are represented by a focus on one or more of these four C’s:

  • Cost
  • Complexity
  • Complications
  • Cure

If your efforts are in medtech and don’t touch on one or more of these themes, you have to ask yourself what your chances are of succeeding, even if you product is approved, even if your product gains reimbursement, even if a healthcare delivery system opts to contract to buy your product.


The sources on which these conclusions are drawn are advantages that are stated or implied by companies in the descriptions of their focus and the technologies they have under development or on the market, or the descriptions of patents, patent applications and other sources. This includes companies at all stages but, of course, earlier stage companies tend to have a focus on advantage that is more pronounced, at least in their intentions. Very early companies are therefore a particular interest of mine and I have been compiling data on startups for years and maintaining an active Medtech Startups Database (described at link).

 

Aesthetics and Reconstructive Surgery: A Market in Transformation

Aesthetic and reconstructive surgery has been undergoing a transformation over the past ten years.  A wide range of forces are changing the dynamics of clinical practice and the market for products used.  The drivers and limiters behind this have been and, to some degree, will continue to be:

  • Aesthetic or purely cosmetic procedures are growing among all demographics (male/female, old/young).
  • The economic hits of the 2008 recession were severe, especially for aesthetics, but have begun to be replaced by new procedure volumes.
  • Aesthetics have become a more complex clinical practice employing surgery, a wide range of implant types and materials, topicals and physician driven procedures.
  • Reconstructive medicine has advanced through developments in autologous tissue engineering, extracellular matrices, and other technologies that address bone defects and other orthomusucloskeletal problems.
  • The advances in reconstructive medicine have begun to trickle-down to aesthetic procedures, stimulating increasingly volume of cosmetic procedures paid out-of-pocket.

There has been a series of shifts in aesthetics/reconstruction procedure volumes commensurate with these and other forces. The result is a wide swing in procedure volumes over the past decade, much of which is expected to continue. See the table below.

Percent Change in Aesthetic/Reconstructive Procedures, 2002 to 2012

Screen Shot 2014-05-07 at 10.34.34 AM

Source: MedMarket Diligence, LLC; Report #S710.

Other forces behind transformation in aesthetics and reconstruction are fundamental advances in cell biology, continued progress in biomaterials development, advances in wound sealants, glues and wound closure, and others.


The topics in this post are the subject of the comprehensive MedMarket Diligence report, “Global Markets for Products and Technologies in Aesthetic and Reconstructive Surgery, 2013-2018.” See link for further details.

Product types, uses in wound management

The sheer number of products in wound management provides many options for the clinician in deciding what is suitable per patient, but the choices also set up a challenge. Considering dressings alone, clinicians must match the balance of the properties of each wound and its needs for healing with the right type of dressing. Although there are hundreds of dressings to choose from, all dressings fall into a few select categories. Dressings within a particular category can then be chosen according to availability and familiarity.

Composite, or combination dressings may be used as the primary dressing or as a secondary dressing. These dressings may be made from any combination of dressing types, but are merely a combination of a moisture retentive dressing and a gauze dressing. Use on: a wide variety of wounds, depending on the dressing. These products are widely available and simple for clinicians to use.  However, these may be more expensive and difficult to store, affording less choice/flexibility in indications for use.

Other dressings available on the market include dressings containing silver or other antimicrobials, charcoal dressings and biosynthetic dressings.

Traditional gauze dressings are the least occlusive type of dressing and would lie at one extreme of the continuum. Then, in order of increasing occlusion would follow calcium alginate, impregnated gauze, semi-permeable film, semi-permeable foam, hydrogels, hydrocolloids, and finally latex as the most occlusive dressing type.

Most wounds can be managed the use of different dressing types, even multiple types as the wound slowly heals and demands different conditions for optimal healing. However, due to patient status (e.g., age, circulatory status, presence of concomitant conditions like diabetes, etc.) a growing number of wounds become non-healing or simply chronic, demanding more sophisticated intervention to be healed (see link for discussion of the factors affecting wound healing). For this reason, a range of new technologies have been introduced, with others in development, to address the deficiencies in traditional wound management approaches.

The range of wound products that are in use or under development are illustrated in the following table.

Wound Management Product Types

Screen Shot 2014-05-06 at 9.03.45 AM
Source: MedMarket Diligence, LLC; Report #S249.

Factors Affecting the Pace and Level of Wound Healing

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.

Extrinisic 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

Intrinsic factors affecting wound healing include:

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

s249-size-growthThese are discussed in detail in “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.” Report #S249.

Product Development in Surgical Glues

Surgical closure and securement products range from simple suture products to sophisticated biomaterial aids for hemostasis, sealant activity, and for adhesion prevention. Within the hemostasis field, products have the objective of rapidly achieving hemostasis and acting to seal in the presence of high pressure blood flow or air flow.

Screen Shot 2014-04-23 at 3.49.13 PMDevelopment Timelines
Natural hemostats such as gelatin, collagen and thrombin were first developed as hemostatic agents, followed by mixes and fibrin sealants. More recently, companies have introduced synthetic sealants and hemostats that accelerate the process of blood clotting and provide a stronger seal that will withstand greater pressures. These products employ various synthetic polymer chemistry systems. Glues are required to secure tissue firmly under substantial forces. In extreme cases such as musculoskeletal repair, these glues need to withstand high tension and pressure forces. Fibrin and other sealants are not strong enough for these applications and have been used as adjuncts to sutures and staples. Cyanoacrylate glues have sufficient strength for most procedures but are not yet cleared for use in the majority of internal applications due to toxicity concerns. They also lack sufficient flexibility for use in many procedures.

Efforts are progressing to develop new biomaterials capable of gluing tissues with high strength, low toxicity, and sufficient flexibility to avoid breakage of the bond. In addition, cyanoacrylate manufacturers are examining the possibility of improving cyanoacrylate technology to overcome the existing challenges of toxicity and brittleness. Despite this huge challenge, one or both of these two approaches are likely to establish new products in the next decade. In addition, the evidence of research work suggests it should be possible to create a glue technology that incorporates hemostatic properties to further enhance the role of this technology.

Apart from fibrin-based sealants and cyanoacrylate-based high-strength glues, there are three other main categories of closure/attachment products in use or in development at present.

Collagen and Thrombin Combination
Screen Shot 2014-04-23 at 3.54.26 PMCollagen is a major protein found in most mammals; the form of collagen that is generally used for wound sealant and closure is a white water-soluble fiber containing several key amino acids. In most sealants, collagen forms a matrix on which thrombin (but also fibrin, polyethylene glycol (PEG) polymers, or other compounds) are attached. The role of the collagen matrix is to channel blood with its various clotting proteins to the compounds attached to the matrix (thrombin, etc.), triggering a clotting cascade.

Polyethylene Glycol Polymer (PEG)
Screen Shot 2014-04-23 at 3.55.52 PMPolymers such as polyethylene glycol polymer (PEG) can absorb fluids and are the basis for products to seal and join tissues. CoSeal (Angiotech Pharmaceuticals, marketed by Baxter BioSurgery) and FocalSeal (Genzyme) are two products of this type. They are completely synthetic and offer quick sealing of the wound with the flexibility to expand and contract. Because these sealants are synthetic, they do not pose the risk of viral infection spreading from one person to another.

Albumin Cross-Linked with Glutaraldehyde
Screen Shot 2014-04-23 at 3.58.05 PMAlbumin, the protein that forms egg white, is one of the strongest natural adhesives in the market. Albumins are water-soluble and will coagulate when heated or combined with certain acids. When combined with glutaraldehyde, albumin forms a strong adhesive for internal surgery. The albumin/glutaraldehyde compound forms a cross-link with the tissues to be bonded that can even be stronger than the underlying tissues. In fact, the compound has been shown to withstand pressures of 500 mm–800 mm of mercury, which is more than four times normal human blood pressure.

CryoLife’s BioGlue is a widely used albumin/glutaraldehyde glue. It begins to set within 20–30 seconds of application and reaches its ultimate bonding strength within two minutes.

It is unlikely that any one formulation of tissue glue will be adequate for all applications. For example, fixing fragments of bone after significant bone trauma is likely to require an adhesive with a different modulus and strength to that required for adherence of pericardium during cardiovascular surgery. It is also likely that the sealant and hemostatic properties of these two products will need to be different. For example, to stick pericardial tissues together, the surgeon will be concerned with avoiding surgical adhesions and excessive fibrosis that might lead to problems during revision surgery. In the example of bone repair, rapid rehabilitation and avoidance of non-unions during fracture healing is a major challenge: this would suggest looking for a glue that encourages osteoblast activity and does not form an impenetrable barrier for cellular in- growth, but which can also tolerate the static and dynamic forces put upon bone.

Recently, new technologies have appeared on the market to address the need for adhesion prevention. These products have been formulated to be approvable by the FDA through device regulation routes; thus, in addition to providing a physical barrier, these products also may have some subsidiary active mechanism to achieve their objective.

Delivery Systems

Screen Shot 2014-04-23 at 4.01.16 PM
Source: CryoLife

In parallel with new products, in several instances new delivery systems have had to be developed. Surgeons also experiment with these products in an effort to produce superior results. A surgeon may, for example, mix a sealant with a few ml of saline to gain greater control over product application. Development of these delivery systems may be driven by several factors, such as: to improve the speed and ease of surgical procedures; to facilitate complex procedures that would otherwise be less successful; to better access a particular tissue; or to avoid premature mixing of two components, thus providing better control of the gluing process. New delivery systems have evolved to spray liquid hemostat solutions such as thrombin onto surgical sites to improve speed of hemostasis. Fibrin sealant is supplied as two powders that need to be solubilized and then mixed immediately prior to application to the surgical site. This has led to the development of a number of sophisticated medical delivery devices, and companies like Baxter aredeveloping single component systems that are already solubilized for immediate use in the surgical theater.

Cyanoacrylate adhesive for surgical closure is a topical-only treatment that eventually sloughs off the top surface of the wound. The product is applied to the surface of the skin to form a glue film that secures apposition of the cut edges of the incision. Currently, the cyanoacrylate is supplied in a device that aids the curing of the adhesive and ensures its safe handling and application.

Several fairly sophisticated delivery systems for new sealant and glue products have been developed or are currently under development. As new procedures are developed for cyanoacrylate and new glues, new devices will be required to aid the procedure. The devices will contribute an increasing proportion of the value associated with the gluing process.

Sophisticated surgical instruments are being developed to facilitate the application in each new indication for new high-strength glue products. High-strength glues are increasingly being utilized to repair vascular joints in coronary bypass operations. Customized instrumentation is designed to hold vessels in place and facilitate the application of exact amounts of adhesive and to avoid subsequent delays from leakage, or imperfect integration of the grafted tissues.


Source: MedMarket Diligence, LLC; Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2017.”

Applications, global markets in tissue engineering and cell therapy

Screen Shot 2014-04-17 at 7.37.44 AMThe market for tissue engineering and cell therapy products is set to grow from a respectable $8.3 billion in 2010 to nearly $32 billion by 2018. This figure includes bioengineered products that are themselves cells or are actively stimulating cell growth or regeneration, products that often represent a combination of biotechnology, medical device and pharmaceutical technologies. The largest segment in the overall market for regenerative medicine technologies and products comprises orthopedic applications. Other key sectors are cardiac and vascular disease, neurological diseases, diabetes, inflammatory diseases and dental decay and injury.

Cell-tissue-applications

Factors that are expected to influence this market and its explosive growth include political forces, government funding, clinical trial results, industry investments (or lack thereof), and an increasing awareness among both physicians and the general public of the accessibility of cell therapies for medical applications. Changes in the U.S. government’s federal funding of embryonic stem cell research has given a potentially critical mass of researchers increased access to additional lines of embryonic stem cells. This is expected to result in an increase in the number of research projects being conducted and thus possibly hasten the commercialization of certain products.

regional-forecast

Source: Report #S520, “Tissue Engineering, Cell Therapy and Transplantation: Products, Technologies & Market Opportunities, Worldwide, 2009-2018.”

Another factor that has influenced the advancement of regenerative technologies is found in China, where the Chinese government has encouraged and sponsored cutting-edge (and some have complained ethically questionable) research. While China’s Ministry of Health has since (in May 2009) established a policy requiring proof of safety and efficacy studies for all gene and stem cell therapies, the fact remains that this research in China has spurred the advancement of (or at least awareness of) newer applications and capabilities of gene and stem cell therapy in medicine.

Meanwhile, stricter regulations in other areas of Asia (particularly Japan) will serve to temper the overall growth of commercialized tissue and cell therapy–based products in that region. Nonetheless, the growth rate in the Asia/Pacific region is expected to be a very robust 20% annually.


MedMarket Diligence’s Report #S520 remains the most comprehensive and credible study of the current and project market for products and technologies in cell therapy and tissue engineering.

Technologies and Areas of Clinical Focus for 2014 Medtech Startups

Since January 1 of this year, we have identified 42 medical technology startups and added them to the Medtech Startups Database. As is the case with all of the companies in this database, these recently added companies represent a wide range of focus in clinical practice and technology:

Screen Shot 2014-04-16 at 8.12.15 AM

(Note: Multiple categories possible per company, such as minimally invasive and surgery)
Source: MedMarket Diligence, LLC

Below is a list of the technologies under development by these startups:

  • Ophthalmology prescreening technology for detection of diabetic retinopathy, cataract, glaucoma, cornea problems and refractive errors
  • Tissue engineered scaffolds to generate synthetic tracheas
  • Embolectomy devices
  • Resorbable embolization material for use in interventional radiology and drug delivery.
  • Time-varying electromagnetic fields for the treatment of inflammatory, autoimmune and degenerative diseases
  • Tissue attachment technology
  • Devices and procedures to improve nasal breathing
  • Devices for minimally invasive, augmentative or reconstructive mastopexy
  • Ocular stent for treating age-based vision changes
  • Ophthalmic device company focusing on age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, hemianopia, and glaucoma
  • Neuroscience-based technology (neuromodulation) for enhancing performance on cognitive tasks, for the healthy and impaired
  • Portable, ultrasound-based device non-invasive, transcranial diagnosis of stroke
  • Temporary cardiac pacing as treatment for reversible symptomatic bradycardia
  • Product to improve treatment of kidney stones and product to reduce pneumonia in intubated patient and ventilated patients in the ICU
  • Biometric medical device for orthopedic and other diagnostic applications
  • Technologies for treating urological conditions and disorders
  • Use of biomaterials in aesthetics for non-surgical temporary & permanent breast and buttock enhancement, facial rejuvenation solutions and adipose tissue engineering related therapies
  • Custom surgical implants including using 3D printing
  • Targeted, localized drug delivery
  • Protein-free tissue sealants in surgery, initially targeted to vascular applications
  • Hemostatic dressing for non-compressible hemorrhage
  • High resolution imaging in cancer
  • Image-guided surgery
  • Cardiac assist device for patients otherwise needing transplant
  • Implant to restore some sight for patients with retinitis pigmentosa
  • Device to harvest bone grafts
  • Device and method for self-collection of samples to screen for HPV, chlamydia, and gonorrhea
  • Implantable neuromodulation device for the treatment of chronic pain and overactive bladder
  • Encapsulated pancreatic cells for treatment of type 1 diabetes
  • Embolization device
  • Deep brain stimulation for Alzheimer’s and other cognitive disorders.
  • Magnetoencephalography and magnetocardiography
  • Technologies to manage core temperature in critical care and post-surgical patients
  • New method to use pulse wave velocity to measure arterial stiffness as indicator of heart attack risk
  • Autologous cell therapy delivered at the intraoperative point of care
  • Minimally invasive hip implants and other orthopedic implants
  • Orthopaedic implants
  • Tactile stimulator to work with fMRI, a dermatome for skin grafts and other technologies
  • Carbon nanotube fiber material to treat ventricular arrhythmia
  • Devices for cardiac and vascular procedures designed for easier use and lower cost
  • Knotless suture technology

For a historical list of technologies at medtech startups in the full database, see link.