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Biomaterials and the Future of Medical Devices

Biomaterials and the Future of Medical Devices

Marc HendriksRecently, I had a phone conversation with Marc Hendriks, R&D and technology director at DSM Biomedical. Hendriks had just announced over Twitter that he had recently given a guest lecture at the University of California, Berkeley and I was curious about the contents of his presentation.

While giving me a summary of his biomaterials lecture over the phone, It was clear that Hendriks, who has a doctorate in chemical engineering and holds 25 U.S. patents, is a real expert on the subject. By the end of our conversation, I had an invitation to send over a few questions, the answers to which I planned on sharing with our readers. 

The result of that exchange exceded my already high expectations. I present here his in-depth response to each of the four broad questions I asked: 

  1. How do you envision that biomaterials will help address medical applications in the near future and longer term?
  2. Could you explain what you mean when you refer to three generations of biomaterials?
  3. How has biomaterials research transformed orthopedics and cardiovascular devices?
  4. Could you give us an overview of biomaterials’ current and likely future role in tissue engineering?

Brian Buntz

Biomaterials' Role in Tissue Engineering

MD+DI: Could you give us an overview of biomaterials’ current and likely future role in tissue engineering?

Marc HendriksHendriks: The field of tissue engineering and regenerative medicine (TERM) has emerged as the result of reaching boundaries of what can be achieved within contemporary medicine. Surgical techniques moving tissue from one position to another have produced biological changes because of the abnormal interaction of the tissue at its new location. Techniques using implantable foreign body materials are associated with adverse events such as dislodgement, infection at the implant/tissue interface, fracture and migration over time. Transplantation from one individual into another has severe constraints, related to having access to enough donor tissue and organs, but also immunological problems that can produce chronic rejection and destruction over time.

TERM involves the fabrication of new and functional living tissue - either in vitro or in vivo (incl., in situ) - using biologically active cues (e.g., cells, growth factors, polynucleotides), which are usually associated with a matrix or scaffolding to guide tissue development.As a field, TERM has been defined only since the mid-1980s. TERM draws heavily on new knowledge from several interrelated, well-established disciplines, including cell and stem cell biology, biochemistry, and molecular biology, that individually and combined feed the understanding of complex living systems. Likewise, advances in materials science, chemical engineering and bioengineering allow the rational application of engineering principles to living systems. TERM literally is at the life science-materials science interface.

Significant progress has been realized since TERM’s principles were defined and its broad medical and socioeconomic promise was recognized. However, to date only relatively few TERM products have gained regulatory approval, and even less have achieved market penetration of any significance. Technical and economic hurdles must be overcome before TERM therapies will be able to reach the millions of patients who might benefit from them.

As said before, essentially there are no purpose-designed materials for tissue engineering and regenerative medicine. The promise of regenerative medicine will only be brought about when effort is put in design and development of biomaterials that are fit for that purpose.

There are multiple biomaterial forms that can be used for TERM purposes and the choice of these forms is dependent on the indication-for-use, with prime attention to challenges during surgery or for tissue development. I typically identify four primary materials-based product-categories for TERM:

1. Biomaterials for cell delivery. Cell therapy concerns the prevention or treatment of human disease by the administration of cells that have been selected, multiplied and pharmacologically treated or altered outside the body. Poor retention and integration of transplanted cells at the site of administration is a major challenge. It is thought that therapy improvement can be brought about by the use of polymer hydrogels that allow the injection or minimally invasive insertion of a combination of cells and polymer in a minimally invasive manner or surgically facile way. To do so effectively, hydrogels must meet a number of design criteria to function appropriately and promote new tissue formation. These criteria include both physical parameters (e.g., degradation and mechanical properties) as well as biological performance parameters (e.g., biocompatibility and cell adhesion). Inappropriately meeting these design criteria could cause undesirable tissue formation. Thus key to development of such biomaterials is a firm understanding of surgical procedures proposed and manipulations prior to surgery.

2. Materials for controlled delivery of growth factors. Contrary to cell therapy, use of growth factors (proteins or hormones) focuses on harnessing the regenerative potential of the endogenous tissues. These substances are aimed at regulating a variety of cellular processes at the site of administration: recruitment, growth, proliferation and differentiation.

To read more on biomaterials, check out Hendriks's answers to the following questions:

How do you envision that biomaterials will help address medical applications in the near future and longer term? 

What do you mean when you refer to three generations of biomaterials? 

How has biomaterials research transformed orthopedics and cardiovascular devices?

Their first use entailed bolus injections – effective to some extent in animal studies – however, generally not confirmed in large controlled human clinical studies. Direct delivery of growth factors has the potential to stimulate tissue healing and growth, but is often associated with an initial burst of growth factors and a short half-life in vivo. The uncontrolled diffusion of growth factors may also cause undesirable side effects. Better-controlled spatial and temporal delivery that are enabled by novel materials-based technologies are required.

3. Tissue engineering scaffold materials. The most "simple" product category in TERM involves scaffold materials, typically processed into porous structures capable of supporting three-dimensional tissue formation. TERM scaffolds usually serve at least one of the following purposes:
  • Allow cell attachment and migration
  • Deliver and retain cells and biochemical factors
  • Enable diffusion of vital cell nutrients and expressed products
  • Exert certain mechanical and biological influences to modify the behavior of cells
The materials that have received most attention for use in fabrication of TERM products are aliphatic polyesters such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε-caprolactone) (PCL), and polycarbonates like poly(trimethylene carbonate) (PTMC), as well as their copolymers. These materials generally have shown to support cell adhesion and growth. Nonetheless, interaction between cells and synthetic polymers is not very strong. While cell adhesion can be facilitated by adsorption of proteins on the scaffold surfaces or by inclusion of bioactive compounds, in general these polymers are rather hydrophobic, do lack surface recognition sites and except for PTMC, upon degradation they form acidic products. All in all, these factors are severely limiting their further application.

Apart from these synthetic materials, natural biomaterials such as collagen or fibrin, polysaccharides, like chitosan and hyaluronic acid, but also calcium phosphate-based ceramics and decellularized tissues have found utilization as scaffold materials in TERM. The use of decellularized matrices is likely to expand, because they retain the complex set of molecules and three-dimensional structure of authentic tissues. Yet, decellularized matrices come with concerns of potential immunogenicity, presence of infectious agents, product variability, and the inability to completely specify and characterize the bioactive components of the material.

Apart from materials chemistry it should be noted that novel materials processing techniques comprise a prominent capability necessary to successfully develop TERM scaffolds. Fabrication methods like micro-extrusion and -injection moulding, electro-spinning and photolithographic techniques provide most powerful routes to fabricate scaffolds and 3D constructs with superb dimensional resolution, with some techniques moreover providing the ability to generate scaffolds with gradient properties (e.g., porosity and composition) in a directional manner.

4. Biomimetic materials. The fourth category of biomaterials involves so-called biomimetic materials. New regenerative strategies are developed through the application of bionanotechnology. Materials designed with specific structure and function mimicking complex biological molecules provide for structural and functional infrastructure serving as matrix for (endogenous) cells, participate in biological signaling, and – optionally – to efficiently deliver proteins and drugs. Different materials have been explored pre-clinically. This technological approach holds high promise, but still is in embryonic stage-of-development, and is yet to be proven beyond early pre-clinical stage. Biomimetic materials are the quintessential third generation bio-interactive biomaterials, where biological principles have been incorporated in biomaterials design.

The Legacy of Biomaterials in Medicine

MD+DI: How has biomaterials research transformed orthopedics and cardiovascular devices, and other medical applications? 

Marc HendriksHendriks: The use of biomedical materials has a long and fascinating legacy characterized by creativity, innovation and positive medical outcomes. Since the dawn of civilization, mankind has been exploring ways in which natural materials might replace or enhance the natural functions of the human body. Archaeological evidence suggests, for example, that the ancient Egyptians used sea shells to replace missing teeth and linen to close wounds—creating what may have been the first dental implants and sutures.

Natural materials have been the key source of biomedical materials throughout much of the history of their use—from the coconut shells used to close holes in skulls, as was practiced in Tahiti, to the elephant ivory that was used to create the first recorded hip implant in 1891.

The real revolution in biomedical materials began in the second part of the 20th century, with the introduction of synthetic materials that enabled medical device makers to break free from many of the limitations and risks associated with relying solely on natural materials. 

Today, thanks to continued innovation and advancement in the biomaterials field, healthcare providers and device makers are finding solutions with the potential to address key problems associated with one of the greatest challenges facing the world today: our aging population.

What follows are a few examples of the transformative role of biomaterials technology in medical device design:

In the cardiovascular space, the introduction of heparin coatings has clearly had a positive clinical outcome in patients demonstrating extracorporeal circulation during open heart surgery. The response to extracorporeal circulation extends far beyond a simple derangement of hemostasis. It can be associated with a severe systemic inflammatory response. Heparinized circuits have demonstrated to decrease inflammation, particularly during extended cardiopulmonary support.

To read more on biomaterials, check out Hendriks's answers to the following questions:

How do you envision that biomaterials will help address medical applications in the near future and longer term? 

What do you mean when you refer to three generations of biomaterials? 

Could you give us an overview of biomaterials’ current and likely future role in tissue engineering? 

Another example concerns the treatment of vascular stenoses. Biomaterials technology enabled the design and development of angioplasty balloon catheters, the performance of which was further improved by the application of hydrophilic lubricious coatings, such as the DSM ComfortCoat--which helps improve the maneuverability of the catheters. Materials selection for design of the balloon catheter itself has gone through several iterations to end up with the minimal profile catheters and high-performance balloons we have today.

Balloon angioplasty, associated with a relatively high rate of restenosis, was rather quickly replaced by stenting. If we look at first-generation stents versus today’s stents, we clearly see how biomaterials technology has enabled the creation of progressively smaller stents. As a third technology wave in treatment of vascular stenosis, the so-called drug eluting stents were introduced. Biomaterials technology has played and still plays a key role in providing for the drug eluting coating. In successfully designing a polymer-based drug delivery solution, many polymer performance requirements come together. Think of such design criteria as biocompatibility, drug elution rate, drug compatibility, film-forming properties, surface adhesion, packaging requirements, and there are several more. More recently, biodegradable polymers were introduced for development of drug eluting stent coatings, such as a proprietary amino acid based–drug carrier for Svelte’s new all-in-one drug-eluting stent system.

In the orthopedic space, the total artificial joints, most notably for replacement of the hip and the knee, have been the most striking clinical successes enabled by advancements in biomaterials technology. Today, more than a million hip and knee replacements are done annually, bringing improved quality of life and the return to activity to many patients.

"Clearly, biomaterials technology has had a transformative role on modern medicine..."

Dyneema Purity fibers are one of the most recent advances in the biomedical materials industry. These Ultra-high-molecular-weight polyethylene (UHMwPE) fibers are proving effective in moving implants beyond the limitations of more-traditional orthopedic fibers and sutures. Conventional fibers such as polyesters, polypropylene, or nylon have a moderate strength and will show a fairly large stretch (elongation) before they ultimately break. The UHMwPE fibers are the opposite: their strength is much higher—on weight basis, the fibers are more than 10 times as strong as steel, and a braid or suture made from these fibers has the potential to be twice as strong as a comparable polyester product. At the same time, the elongation is hardly noticeable—when ultimately reaching the breaking strength, the elongation is just about 3%. These materials characteristics enable the design of improved and novel medical devices. Currently, Dyneema Purity is, for instance, successfully used in orthopedic sutures for rotator cuff repair and in ligament fixations where the very low stretch results in a very rigid fixation, improving the chance for fast readhesion of the torn ligaments back to the bone.

These are just a few examples and there are many more. Clearly, biomaterials technology has had a transformative role on modern medicine, and I’m convinced continued innovation in biomaterials technology will foster further improvement in the safety and efficacy of medical technology as well as, going forward, in enabling more beneficial health economics.

Three Generations of Biomaterials

Marc HendriksHendriks: If we look at the evolution of biomaterials technology then we can see that, initially, the choice of biomedical materials for use in the body was based on achieving a suitable combination of physical properties to match those of the replaced tissue with a ‘biopassive’, minimal toxic response in the host. This “do no harm” paradigm is very well illustrated by the way professor David Williams defined biocompatibility in 1987: “The ability of a material to perform with an appropriate host response in a specific application”.

As our understanding of the pathophysiology of implanted devices at the cellular and molecular levels has increased, so too has our emphasis on better management of the material’s biointerface. Rather than trying to exclusively achieve the bioinert tissue response, the biomaterials field is focusing instead on incorporating bioactive components in the design of biomaterials that could elicit a controlled action and reaction in the physiological environment. Very prominent examples of these second generation “bioactive” biomaterials are heparin coatings for improved blood compatibility, and drug eluting stent coatings for prevention of vascular restenosis.

To read more on biomaterials, check out Hendriks's answers to the following questions:

How do you envision that biomaterials will help address medical applications in the near future and longer term? 

What do you mean when you refer to three generations of biomaterials? 

How has biomaterials research transformed orthopedics and cardiovascular devices? How about other medical applications?

Now third-generation biomaterials are being designed to stimulate specific cellular responses at the molecular level. These biomaterials take our contemporary understanding of molecular and cell biology steps further by actually incorporating biology into materials design and are helping to achieve the objective regeneration as opposed to repair. For example, molecular modifications of polymer systems can elicit specific interactions with cell surface integrins and thereby stimulate direct cell proliferation, differentiation, and extracellular matrix production and organization. These third-generation "bio-interactive" biomaterials stimulate regeneration of living tissues.

Circling back to the definition of biocompatibility, some 20 years after his original definition, the same professor David Williams revised the original definition of biocompatibility to now read: “The ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy”. Clearly this reflects the evolution of biomaterials into second and third generations, where materials have increasingly more activity and interaction with the biological environment. With regard to biocompatibility, the next generations of biomaterials not only focus on “doing no harm”, but actually have the ability obtain a beneficial response.

Biomaterials: Addressing Medicine's Future Needs

Marc HendriksMark Hendriks: Biomaterials technology will help the industry and the medical community successfully address some of the most significant issues and trends in healthcare delivery today and in the future, including:

  1. Costs. 
  2. Minimization. 
  3. Infection prevention. 

On Costs. The pace of growth in healthcare expenditures is not sustainable and reimbursement of medical device products is under increasing cost-pressure. Obviously, such pressures will trickle down to the level of biomaterials technology suppliers and solutions providers. As a biomaterials solutions provider this is a concern; however, it can also be seen as an opportunity for innovation.

For example, [at DSM,] we have embedded innovation in the way we develop and market our novel medical coatings technologies. We focus on developing best-in-class coating chemistry, as well as developing a robust coating process for application of that chemistry. Moreover, we help transfer this coating process to our customer through an on-site process validation. This creates a comprehensive solution for our customers, which helps keep the total cost of ownership very competitive.

To read more on biomaterials, check out Hendriks's answers to the following questions:

What do you mean when you refer to three generations of biomaterials? 

How has biomaterials research transformed orthopedics and cardiovascular devices?

Could you give us an overview of biomaterials’ current and likely future role in tissue engineering?

Another example relates to our novel implant-grade polyurethanes. Through careful design of the chemistry of this class of medical polymers we can provide a material with desirable characteristics – such as hydrophilicity, or antimicrobial activity —which may allow developers to omit a final coating step altogether. In other words, a surface-modified medical device can be designed immediately from the raw material, which also helps to keep costs competitive.

On Minimization. Medical devices are getting smaller and smaller. We have seen the various clinical fields increasingly turn to percutaneous therapies or minimally invasive procedures. The reasons are obvious: Smaller devices help to reduce trauma, speed recovery time, and shorten hospital stays; all which reduce the burden on our healthcare system and patients as well as increase cost effectiveness.

Needless to say, reducing the size of medical devices raises the bar on what can be expected from traditional biomaterials in regards to meeting design specifications. One cannot keep decreasing the wall thickness of a polymer tubing made from traditional materials, for instance, and expect the same mechanical performance and endurance as before.

From the perspective of medical device designers, this means that they will need biomaterials that can enable decreasing device size without compromising on strength and durability.

On Infection Prevention. It is well known that reimbursement agencies have said that the cost of treating hospital-acquired infections will no longer be reimbursed by CMS. The consequences of a device-associated infection can be dramatic. It typically means surgery to remove the infected device and concomitant intense treatment with antibiotics to eradicate the infection. Depending on the clinical indication, after the infection has been eradicated, another intervention may be necessary to replace the medical device. Costs associated with a device-associated infection can be dramatic. Literature has reported that treatment of a device-infection can easily cost six times the price of the original device placement.

"In the future, biomaterials technology will continue to provide solutions to improve clinical success in both drug delivery—notably delivery of protein therapeutics—and regenerative medicine."

Therefore, it is no surprise that the change in reimbursement policy has created greater demand for antimicrobial materials technologies. To meet that demand, biomaterial technology developers are focusing on the development of innovative materials including non-biofouling coatings, “contact-killing” surfaces and antibiotic-releasing materials.

In the future, biomaterials technology will continue to provide solutions to improve clinical success in both drug delivery—notably delivery of protein therapeutics—and regenerative medicine.

Though controlled and sustained delivery of protein therapeutics meets a clear clinical need, at present, there are few tangible solutions where active therapeutic protein can be delivered for more than one month. The biodegradable polyester-based materials that are currently used are not fully suitable because of their bulk degradation and local acidity problems. Biostable polymer delivery systems are generally not suitable for protein delivery as the molecules are too large to be released by diffusion. As a result, there is a clear and growing need for materials that can protect the protein payload from the degradation mechanism of the body, yet allow for it to be released in a fully functional and non-aggregated form.

As professor Tony Mikos of Rice University once told me: “There are no purpose-designed materials for tissue engineering and regenerative medicine.” For example, instant hydrogels for cell delivery; materials for tissue engineering scaffolds; and, as mentioned before, materials for controlled delivery of protein therapeutics, such as growth factors. The promise of regenerative medicine will be advanced as more developers focus their efforts on the design and development of biomaterials that are fit for that purpose.

A Perspective on Invention, Innovation, and Regulation of Medical Devices

A Perspective on Invention, Innovation, and Regulation of Medical Devices

  1. Invention is the act of creating, or improving, something that is new.
  2. Innovation is the act of successfully commercializing something that has been invented; it will be successful, if it has real (utilitarian) or perceived (aesthetic) value. This definition is consistent with the over half century of published work on diffusion of innovation. Innovation cannot include commercializing dangerous or defective products. If you want to protect your profitability, make sure your products are safe (each won’t cause harm) and effective (each will do what you claim).
  3. Regulation (in the medical device sector) is a control mechanism for protecting the public (health).

Yes, regulation can impact invention. If there is little or no opportunity to benefit from your intellectual property, then it is likely that you will focus your energies elsewhere. Regulation can also impact innovation; in fact, that is exactly FDA’s congressionally-mandated mission. Congress established that FDA regulates manufacturers—not inventors, practitioners, or consumers. Practitioners are regulated by each individual state. Congress charged FDA with protecting the health of consumers.

FDA regulation, like everything else in life, has its preferred attributes and disliked attributes. For example, from the manufacturer’s point of view, FDA regulation’s preferred attributes include shielding from civil liability when a product is approved (but not if it is administratively cleared via 510(k)), protecting proprietary design and manufacturing information, and dramatically reducing competition; not just any firm can jump into the medical device sector. On the other hand, it demands modern engineering practices (including design controls and risk management for hardware, software, and human factors), it demands accountability (such as complaint handling and medical device reporting), and it is believed to be slow to complete clearances and approvals. From the consumer’s point of view, FDA regulation’s preferred attributes include requiring best practices and accountability from manufacturers and its disliked attributes include shielding manufacturers from civil liability, not divulging critical proprietary information related to design and manufacturing flaws, limiting the possible number of manufacturers available to innovate (due to the high barrier imposed by regulation), not vigorously enforcing accountability, and being too quick to complete clearances (in other words, without clinical trials). Yes, that’s right: what one side likes, the other side dislikes.

From the regulator’s perspective, it is constrained by federal law and historically promulgated regulations, it is constrained by congressionally-mandated budgets, and it can be whipsawed by the push and pull of manufacturers, practitioners, consumers, and their political allies. Yes, of course, it is a bureaucracy: just like every other unit of federal, state, and local government and most units of large corporations. The Institute of Medicine’s (IOM) recent recommendation essentially to dismantle the 510(k) premarket notification system, a central FDA/CDRH program, was certainly scientifically and technically correct, based upon the specific questions they were asked (Is the 510(k) process optimal and, if not, what should be done?); but from a managerial, commercial, and consumer perspective, it was totally untenable. We already knew it was not optimal; suggesting it be replaced, rather than offering how to transform it, seems to me to be counterproductive. Bureaucracies just aren’t that agile and likely never will be.

I have had the opportunity to work both inside and outside the FDA. My impression from inside the agency is that the vast majority is well-educated, well-meaning, and operates within their regulatory and legal constraints as interpreted by their management. For the last 15 years, I have worked with a wide range of medical device manufacturers: from new startups to global multinationals (most of who are just aggregates of small and medium size firms, which were once new startups). As John Dew recently pointed out in an article on transforming organizations to improve quality, they may be characterized as “tribal cultures”, with compartmentalized units across which knowledge isn’t shared, power is hoarded, and formal rules (the ones the FDA inspectors audit) aren’t enforced. This is nothing new; Deming, Juran, and other management luminaries have long bemoaned it. The onset, over the past more than two decades, of mechatronics in medical devices illustrates the problem with such regressive management and communication structures. Interdisciplinary development of medical devices in internal silos, without clear understanding and communication of the inherent risks and critical interactions associated with hardware and software systems, and human factors, is creating quality problems of increasing complexity. But we all have heard that “ignorance is bliss” and there is usually a good chance nothing bad will happen—until consumers are injured and the plaintiff’s bar comes to visit.

A more recent example is health information technology (HIT). Here we have more or less standard hardware with highly complicated software and historically little attention to human factors engineering and usability issues. In an era when virtually all owners of HIT were contractually prohibited from publishing adverse reports and only now are we beginning to see a burgeoning repository of adverse event reports directly resultant from HIT implementations, the IOM’s recommendation that HIT avoid FDA regulation defies logic. As correctly stated by Richard Cook, these are Class III medical devices no matter how hard vendors try to shift the burden onto user organizations by requiring them to “customize” each system (and the IOM should be reassured they will not be subject to the 510(k) process). Expediting their deployment with federal incentives in the hope of improving national healthcare delivery efficiency, but without adequate assurance of their safety and effectiveness, runs the risk of more than doubling the IOM’s prior estimate of avoidable medical errors. HIT needs to be properly regulated and subject to design controls, risk management, complaint handling, and medical device reporting; it can still be profitable, while being safe and effective. Whether or not HIT will always improve efficiency in healthcare delivery is not yet known; information technologies in other industrial sectors have had mixed results.

It is my opinion that the argument “the FDA is too slow” is almost always without merit. I have seen PMA, IDE, and 510(k) submissions from the inside and from the outside (both from clients and during discovery as an expert witness). The ones that did (or should have) encountered problems actually had defects in the submissions: ignorance or misunderstanding of FDA regulations, consensus standards, and guidance documents; missing or defective elements such as risk analyses, software documentation, human factors testing, no clue what engineering verification or engineering validation really mean, or defective biostatistical test designs and analyses; and, in a small number of cases, misrepresenting the facts, not withstanding a declaration that the submission was truthful, accurate, and complete.

This is not intended to be a pitch for regulatory consultants, but a lot of these problems (excluding those misrepresenting facts) would not have arisen with competent advice—given at the beginning of the product development process and then actually followed. I subcontract to a fair number of regulatory consulting firms; I know these folks and I know that there is no dearth of competent advice available to anyone who is willing to listen. In my experience, firms rarely experience delays, if they are not just looking to “git ‘er done” and are careful to meet all the submission requirements. I also think that the regulator still has room to improve communication and outreach, but not just with postings on the Web, social media, or an occasional visit. It is humans who are developing and manufacturing medical devices and it is humans who are regulating medical devices. A continual, reliable way for these people to better appreciate the other’s expectations and point of view is essential, so that safe and effective medical devices can be efficiently commercialized. It is not only industry that needs to inculcate human factors principles and practices.

I have a similar opinion regarding the other argument that “the FDA is too quick.” If you don’t like the rules under which industry and the regulator must operate, change the rules rather than trying to change just a small part of the process. But make sure you focus beyond just the short term and don’t tip the balance too far in one or the other direction; you will get unanticipated and undesirable consequences. Federal regulation is for the small number of bad actors; unfortunately, since there is no way to know a priori who that is at any point in time, everyone has to be subject to regulation. Instead of fighting it or dodging it, if firms followed best practices, I suspect we would have fewer problems, greater product safety and effectiveness, and greater profitability— but, someone always thinks they are special and can take the shortcut! I believe it is that behavior which contributes to stifling medical device innovation (and often leads to defective or dangerous medical devices). Well-engineered products whose submissions are technically complete and correct, logically presented, and meet all the stated regulatory requirements, relevant international consensus standards, and guidance documents are rarely delayed by the regulatory process.

Manufacturers that are primarily interested in innovating high-quality medical devices to promote excellence in patient care should ensure that no one in their organization is permitted to take shortcuts; following this advice will maximize their profitability in the long term and expand job opportunities as the medical device industry grows. Product quality (top level attributes: safety, effectiveness, efficiency, and user satisfaction) is the result of careful engineering and attention to details. Time to market may be expedited by taking shortcuts, but this often undermines quality and, ultimately, profitability; engineers know this and impatient managers need to learn this.

GM Samaras is a biomedical scientist and engineer at Samaras & Associates Inc. (Pueblo, CO). Trained as an electrical engineer, he has doctorates in physiology and industrial engineering and is a licensed professional engineer, board-certified human factors engineer, and an ASQ-certified quality engineer. He has a number of biomedical patents and publications in physiology and engineering (hardware, software, human factors, and quality). He has worked at the FDA/CDRH as a reviewer and manager, was a medical school and engineering graduate school professor, and founded an engineering firm that he ran for a decade.

Disclosure:  Even with the background described above, he still succumbed to editor Brian Buntz’s request for an article on the controversial subject of medical device innovation. The opinions given here are solely those of the author and are subject to change as a result of new data.

Weekly Vitals: Medtech in 2011, Making a Medtech Mt. Rushmore, and More

As the end of 2011 draws nigh, medical device editors everywhere are busy compiling year-end lists for a bit of reflection on the medical device industry and the events of the past 12 months. And we're no exception. Covering topics ranging from metal-on-metal hip implants to the artificial pancreas to implant hacking, MPMN's gallery of the 10 most-popular stories of the year represent the medical device design and development issues that captivated you most during the past 12 months. Our colleagues at MD+DI also take a look back at some of the recurring issues or topics that dominated the headlines this year. Read more about these lists and other top stories of the week in the below roundup.

Misunderstanding of FDA Device Classification Is Widespread

FDAThe device classification scheme is an important component of the U.S. regulatory system for medical technology. Introduced in the Medical Device Amendments of 1976 to the Federal Food, Drug, and Cosmetic Act, the system assigns devices to one of three categories: Class I, Class II, or Class III. It is widely believed that Class I is comprised of devices that represent the least risk while Class III represents the highest risk. Presumably, Class II is for devices that are moderately risky. That characterization, however, is incorrect—even though it is sometimes described that way by FDA employees and by other authorities on the matter.

“[T]he classification system is not based on the inherent riskiness posed by the devices, but on their complexity and function,” explains device attorney Larry Pilot in a document titled “Stifling Medical Device Innovation.” Pilot helped write the Medical Device Amendments of 1976. “Even for a Class III device, the FDA confirms by approving the PMA application that the product does not pose a ‘high risk,’ but in fact is reasonably safe and effective for its intended use,” Pilot writes in the document.

“I don’t know when [the confusion surrounding device classification] began or who generated that process of transforming what is clear in the legislative language into something that is not supported by that language,” Pilot said in a phone interview.

The best way to understand device classification is to read the legislative language behind it, recommends Pilot. “[In Section 513(a) the FD&C Act (21 USC §360c),] there are several paragraphs that describe the three classifications that are relatively easy to understand," Pilot says. "The [language] was understood before the [Act's] enactment date, clearly after the enactment date, and for many, many years after that,” Pilot says.

So, if the system isn’t based on risk, what is it based on? It is, as the Amendments explain, a measure of the level of controls that are “sufficient to provide reasonable assurance of the safety and effectiveness.” 

Safety, of course, is part of the explicit definition behind the three classes. “And as you read the Act, you’ll see the term ‘risk’ mentioned in the context of Class I and Class III,” Pilot acknowledges. “But it’s in the context of exception.”

Brian Buntz 

The Most Important Stories you Missed in 2011

Sometimes really big stories fall through the cracks. This is especially true on the Web, where important ideas get overlooked in favor of flashier gimmicks. So we’ve decided to present our picks for the most important stories of the year. Some of them got your attention, but others might have been overlooked. Here is a second chance to get up to speed on these critical stories.

Wireless Security Questioned When User Hacks His Own Insulin Pump

The security of wireless medical devices was an abstract concern until this year, when security researcher and diabetic Jay Radcliffe hacked his insulin pump on stage at a tech conference. The fallout included a response from Medtronic, the maker of Radcliffe’s device, and calls from members of Congress for an investigation of FCC’s attempts to protect devices from hacking.—Jamie Hartford

Industry Is Excluded from Harmonization Table

It was a small story, but the industry not having a seat on the global harmonization task force is indicative of a larger trend of exclusion hidden under the cloak of impartiality. The expert opinions and real-world concerns of stakeholders should not be discounted simply because they are attached to business. Industry should fight to have a say in harmonization. We’ve seen that the result of noninvolvement can be disappointing, as with IOM choosing not to have industry involved in its 510(k) report, or disastrous, as with industry choosing not to be involved with healthcare reform. —Heather Thompson

IOM’s take on the 510(k)

I don’t think that abandoning the 510(k) program and moving to a completely new program will ensure that safe and effective devices enter the market. Did industry learn anything from the IOM report? It seems like a lot of time and energy was spent to produce a report that had no constructive results. I call it the big disappointment for 2011.—Maria Fontanazza


An Exclusive Interview with Medtech Pioneer, Thomas Fogarty

MD+DI’s chat with medtech industry luminary Thomas Fogarty, MD provided insight into some of the most-pressing issues facing the sector today. Fogarty explained his thoughts on FDA, which he says “has been a large obstruction in getting devices to the marketplace.” —Brian Buntz

Chemists Create Nanomaterial-Purifying Molecular Traps

Tiny nanotubes created by chemists are able to trap molecules of different sizes, filtering and separating different particles and molecules. Traps resembling tube-shaped hairbrushes have been created by a team of chemists at the University of Buffalo (Buffalo, NY) to capture and purify nanomaterials.

Uniformity of particle size is an important factor when creating advanced materials, so the ability to separate proteins by size and charge, or separating large and small quantum dots, could aid in material developments, and could also lead to advancements in fluid filtration devices. By creating what the scientists call a "bottle-brush" molecule, the tubes can selective encapsulate only positively charged particles, and can differentiate between a particle sizes.

To create the trap, the team stitched together several of the bottle brush molecules, which have molecular bristles sticking out all around the molecular backbone. After the molecules were stitched, the center of each bottle-brush molecule was hollowed out since the structures used for the heart of each molecule disintegrate in water. A layer of negatively charged carboxylic acid groups were then attached around the core, resulting in a nanotube with negatively charged inner walls that can trap positively charged particles.

To test the trap, a two-layered chemical cocktail was created, with a heavier chloroform solution containing the nanotubes on the bottom, and a thinner, water-based solution containing positively charged dyes floating on top. The team shook the mixture, and after five minutes, the dyes, which would otherwise not mix in the chloroform solution, were trapped by the nanotubes, changing the color of the entire solution.

Researchers discovered in another test that certain sizes of positively charged molecules called dendrimers could be extracted from an aqueous solution by the nanotubes. The dendrimers that were 2.8 nanometers in diameter were trapped, and the ones just 1.5 nanometer larger were not. To release the dendrimers from the nanotube traps, the pH of the chloroform solution was lowered, which shut down the negative charge in the traps, allowing the captured particles to escape.

The researchers reported the findings in the Journal of the American Chemical Society, and are continuing to test bottle-brush molecules in nanomembranes for water filtration and also in creating polymers able to reflect visible light in a way similar to butterfly wings.