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Medtech Startups Hear Dour Diagnosis

"Funding has dried up over the last three years, especially for early stage companies--even later stage companies are getting hammered," said Mir Imran, a serial entrepreneur and chief executive of Modulus Inc. (San Jose), a contract medical design and manufacturing company. "Meanwhile, the regulatory process has become so convoluted it requires more funds to get products through it, so many of us have gone to Europe," he added.

As many as 40% of venture capitalists in medtech have been unable to raise new funds since the 2008 recession and are now holding money to keep their existing portfolio companies alive, said Imran who has started or funded dozens of medical electronics companies. Meanwhile deals are available to invest in late-stage companies at early-stage prices, he added.

"Our small fund has done two or three deals in the last year, but some have not done a single early-stage deal in the last year," Imran said. "Things are grim, and probably won't change for another year or two until things flush out," he said.
Long term prospects should improve. Big medtrech corporations such as Medtronic depend on acquiring startups as part of their product development process. A scarcity of early-stage startups now could lead to higher valuations for the few who make it to be acquisition targets in four or five years, said Imran...

Get the rest of the story at EETimes.

Rick Merrit is editor at large for EE Times

Titanium Hermetic Connectors Are Available for Use in Implantable Medical Devices

Titanium hermetic connectors feature glass-to-metal sealing and platinum alloy contacts, and are available for use in implantable medical devices. The company that manufactures the connectors also provides engineering design services and can produce versions with connector shells as small as 0.10 × 0.125 in. and with 0.010-in. contacts. If required, the connectors can also be supplied with a capacitive element for custom filtering.

Precision Hermetic Technology
Redlands, CA, 909/381-6011

Swiss Clamp System can be Used with Machine Tools in the Manufacture of Orthopedic Instruments and Components

Genevieve SwissA Swiss clamp system is used with machine tools in the manufacture of orthopedic instruments and components, including bone screws and implants. The EZR Swiss Clamp System ensures increased torque by achieving proper settings and enables fast, positive ER collet clamping. It eliminates wrench slippage and prevents the loss of clamping nuts in the machine sump-chin bin. Operators’ hands are kept clear of the sharp tools in the tooling zone. The system also prevents accidental breakage of ID microtooling. The Swiss clamp nuts can be tightened using standard box wrenches or a 3/8 -in. drive ratchet wrench with the EZR wrench adaptor or the EZR torque adaptor. Both adaptors engage and lock to the clamping nut with a specialized cam system on the face, delivering positive torque to the nut.

Genevieve Swiss Industries Inc.
Westfield, MA, 413/562-4800

Treating Medical Implants to a Surface Makeover

After a medical implant or implant component has been molded, extruded, or machined, it must still undergo surface treatments to prepare it for use in the body. Surface-treatment processes can be performed for a variety of reasons, including reducing friction to decrease surface tack, removing material imperfections caused during the micromachining process, enhancing a device's corrosion resistance or biocompatibility, and improving surface wettability prior to the application of an antimicrobial coating.

To achieve these ends, surface-treatment specialists have perfected a variety of process technologies, including microtexturing to create finely roughened surfaces, plasma treatments to promote the adhesion of dissimilar materials, and electropolishing to both polish and passivate metal surfaces. In all cases, manufacturers' choice of surface-preparation methods depends on the material in question, the product design, and the device's intended end-use application.

Microstructuring Tubing Surfaces

Hoowaki's microstructuring process transfers patterns from dies (top) to medical tubing (bottom).

In many implantable medical device applications, the physician's ability to insert and remove the device easily without friction is essential. To accomplish this goal, Hoowaki LLC (Pendleton, SC) specializes in the engineering of low-friction surfaces on extrusion dies, which are used to create microstructures on the outer surfaces of medical tubing. "We modify the surfaces of industrial tooling used to extrude medical tubing featuring microstructures," remarks Sarah Hulseman, Hoowaki's product development engineer. "These features transfer from the tooling to the product during standard manufacturing processes." The company's microstructured surfaces are not coatings, Hulseman adds. Rather, they are tiny features that are directly formed into the material of the product.

Hoowaki's microstructured surfaces serve to reduce friction on the surface of medical tubing partially by reducing the tubing's area that contacts the body or other outer surfaces and partially by changing the geometry of the surface at the interface. By lowering surface friction, the technology reduces tack, making it easier for doctors to insert the tubing and reducing the potential for tissue damage.

Based on the work of William King, a professor in the nanoengineering laboratory at the University of Illinois at Urbana-Champaign, Hoowaki's microstructuring technology combines microfabrication capabilities and industrial manufacturing. Like most microstructuring technologies, the company's methods start with silicon, Hulseman explains. But then, depending on the desired feature size, the company employs several different proprietary methods for creating the microstructured surfaces.

"First, we work with our customers to understand their application and to identify the types of improvements they require on their product," Hulseman says. "We then design and engineer the appropriate surface to achieve those attributes." This process includes determining the appropriate die material and how the manufacturing process will affect the geometry of the final product. It also requires that the die undergo adjustments to achieve the correct specifications for the end product. "Generally, we are able to amend the customer's extrusion dies to achieve the desired results," Hulseman says. "We often provide engineering assistance during the initial trials, since the new tooling may require new maintenance procedures."

The company's surface-modification processes allow medical implant makers to use their preferred materials almost independently of their surface function, Hulseman comments. Based on the specific material and application, these techniques are used to custom design features, taking into account material shrinkage, drawdown, and the device's end-use application. Demonstrating up to a 15% reduction in dry sliding conditions and up to an 80% reduction in lubricated sliding conditions, Hoowaki's technique boosts the surface capabilities of standard polymers, according to Hulseman. In addition, its process can engineer the internal surfaces of tubing to improve flow or to reduce drag.

Engineered with features ranging in size from 0.8 to 400 µm, depending on the needs of the application, the company's linear or 3-D microstructured surfaces can accommodate a variety of tubing materials, including silicones, rubber, polypropylene, polyethylene, fluoropolymers, and nylon. Typical extruded tubing or device dimensions range from 0.5 to 50 mm in diameter or width.

The technology promotes process improvements as well. For example, using Hoowaki's technology, catheter manufacturers can fabricate smaller-diameter products that exhibit increased flow rates. "Our technology enables medical device and component manufacturers to enjoy performance improvements without changing their manufacturing methods," Hulseman notes.

Plasma Promotes Adhesion
In many medical implant applications, dissimilar materials must be bonded to each other. For example, coatings must adhere to device substrates, and components made from different thermoplastic polymers must be combined to form the finished device. To adhere such dissimilar materials, plasma processes are often employed to prepare material surfaces for subsequent bonding steps.

Plasma Etch's PE-100 system produces hydrophilic surfaces to facilitate bonding of dissimilar materials.

But dissimilar materials often cannot be bonded easily, remarks Tom Chill, marketing manager systems engineer at Plasma Etch (Carson City, NV). To bond disparate materials, it is first necessary to create wettable surfaces, a processing step that is accomplished using plasma technology. "Our surface treatment enables significantly improved wettability prior to applying coatings or bonding materials. This capability ensures that the coating will not delaminate and prevents the parts from separating." The typical process gases used in the company's plasma processes--argon and oxygen--ensure hydrophilicity, Chill adds. "Argon mechanically removes organic contaminants from all medical devices materials, while oxygen is used to chemically react with plastic surfaces, making them very hydrophilic."

Incorporating both a plasma etching mode that can perform reactive ion etch (RIE) anisotropic-type etching and a cleaning/etching mode that can perform isotropic-type cleaning, Plasma Etch's convertible PE-100 system is used to produce hydrophilic surfaces required for adhering dissimilar materials. "Hydrophobic surfaces cause adhesives to bead off," Chill says. "Hydrophilicity does exactly the opposite. By treating plastic surfaces with oxygen, a chemical reaction takes place whereby hydroxyl sites are formed. This promotes adhesion."

The PE-100's RIE mode produces a directional plasma stream, Chill notes. This function produces high etch rates and etching patterns that allow the system to eliminate difficult-to-remove organic materials. "While RIE is primarily associated with semiconductor fabrication processing for etching patterns in integrated circuits, it can also be used to remove thick polymers and heavy organic contamination from the oils that are used in some medical device fabrication operations," Chill says. "The system's isotropic conversion electrode kit, on the other hand, enables large quantities of parts to be surface-treated in a batch process in which the plasma affects the parts from all directions."

Capable of removing organic contaminants from metals or plastics and suitable for preparing the surfaces of catheters, pacemakers, and other medical implants, Plasma Etch's surface-treatment processes are employed in a variety of prebonding applications. For example, by plasma treating a customer's polyethylene-based catheter and a polyethylene terephthalate balloon, the company was able to increase the completed device's bond strength by more than 50%, according to Chill.

Electropolishing Imperfections
The micromachining processes used to fabricate medical implantable devices such as nitinol stents often result in surface imperfections that can affect device performance in the operating room. To remove such imperfections, Pulse Systems (Concord, CA) offers electropolishing services that enhance the smoothness, corrosion resistance, and biocompatibility of implantable devices.

"The main reasons for electropolishing medical devices is to round their edges, smooth their surfaces, and improve their fatigue performance and corrosion resistance," explains Brock Groth, electropolishing manager at Pulse Systems. "Whereas electroplating adds a layer of metal to an existing part, electropolishing removes material from its surface." Electropolishing, Groth adds, removes material preferentially. "In general, more material is removed from high points than from low points, translating into edge rounding, surface smoothing, an overall reduction in the size of such features as strut widths, and an increase in the size of such features as holes."

Nitinol, according to Groth, is always covered with an oxide layer, but not all oxide layers are equal. Depending on its thickness, this layer can be amber, blue, or even dark gray. Poorly structured, such thick oxide layers are susceptible to cracking. In contrast, the oxide layer created during the electropolishing process is basically transparent, allowing the nitinol's silver color to show through. While it is thin, this well-structured layer is also durable, enabling it to bond well to the bulk material and offering a shield against corrosion. "Thin and adherent--that's the catchphrase for electropolished nitinol oxide," Groth comments.

In addition to ensuring corrosion resistance and enhancing fatigue performance, electropolishing promotes medical device biocompatibility. "When a stent is implanted in the body, blood rushes past it," Groth comments. "Anything you can do to inhibit the platelet cascade--the process that starts the formation of a blood clot--is a step you want to take. That's one example in which removing material from the surface of a component or device can pay dividends in terms of biocompatibility." Furthermore, because electropolishing passivates device surfaces, it causes devices to become more neutral toward the body, Groth adds. Because of the passivation factor, electropolishing impedes cell growth and other biological phenomena on the implant surface.

But electropolishing has yet another purpose, according to Groth: aesthetics. Surgeons associate shiny, silver objects with cleanliness, sterility, and high performance. Although a nitinol part with a blue or amber oxide surface may perform perfectly well in certain applications, those who have to handle such devices may not respond positively to them. "Looks sometimes matter," Groth adds.

To electropolish a nitinol stent, the component is first fixtured to a conductive material and then immersed in a bath containing the appropriate electrolyte and electrodes. In the bath, the part and its fixturing act as the positive side of the electrical circuit, while the electrodes are attached to a power supply with negative leads. When power is applied to the circuit, the current flows through the electrolyte via the ions that shed off the component. This process results in material removal.

Like medical devices themselves, electropolishing is specific to the application, according to Groth. For electropolishing nitinol, Pulse Systems offers four basic setups involving four different chemistries, temperatures, and power settings. Custom electropolishing options are also available. While some setups are better for removing more material, others are more suitable for removing less. While some perform well at rounding corners, others are better at maintaining dimensional ratios during electropolishing. And while some setups are used to polish inside small gaps, others are preferable for polishing component inner diameters.

"It's hard to say why one component may need lower material-removal amounts than another without knowing the function or design of the component in question," Groth remarks. "But in general terms, permanently implanted devices will likely require more material removal than devices that remain in the body for a few hours during surgery." Permanently implanted devices, Groth adds, simply have a higher bar to clear when it comes to corrosion and fatigue performance.

Top Stories of 2011

As we near the end of another eventful year in the medtech world, MPMN takes a look back at the most-popular stories from our daily blog, Medtech Pulse. Covering topics ranging from metal-on-metal hip implants to the artificial pancreas to implant hacking, these 10 stories, counting down to the most-popular post of the year, represent the medical device design and development issues that captivated you most during the past 12 months.

As we near the end of another eventful year in the medtech world, MPMN takes a look back at the most-popular stories from our daily blog, Medtech Pulse. Covering topics ranging from metal-on-metal hip implants to the artificial pancreas to implant hacking, these 10 stories, counting down to the most-popular post of the year, represent the medical device design and development issues that captivated you most during the past 12 months.

The Skinny on Thin-Strut Stents

When it comes to stents, thin is in. In order to meet clinical demands for enhanced stent delivery and flexibility, medical device OEMs are striving to push the envelope and produce platforms with increasingly thin struts. But as these diminutive designs hit the market, emerging issues such as shrinkage and longitudinal compression are beginning to cast a shadow on the performance and reliability of some thin-strut stents.

A case series published online in the journal EuroIntervention proved to be the catalyst for a recent industry frenzy focused on a potential flaw found in some thin-strut stents. Conducted by two UK-based physicians, the series drew attention to the observed vulnerability of Biosensors International's BioMatrix, Boston Scientific's Promus Element, and Medtronic's Endeavor stent to longitudinal compression.

"The move over the years has been for stents to have thinner struts and to have different designs that would make them more flexible and deliverable in very tortuous and calcified coronary arteries," Simon Walsh, a physician involved in the study, told the "That's been the trend across the industry--and it's been an advance--but we're starting to see that once we use the stents in some of our more challenging subsets of patients, there are some limitations."

Building on the buzz, organizers of the Transcatheter Cardiovascular/Therapeutics (TCT) conference tacked on several talks about longitudinal compression to the agenda mere days before the event. But while presenters at TCT relayed anecdotes of longitudinal compression in various stents, most downplayed the issue as relatively rare and cautioned against getting caught up in the hype. Several speakers also noted that stent design may not be the sole culprit--surgical technique may also be a factor.

The safety of thin-strut stent designs was again called into question, however, in a recent case report and accompanying editorial in the Journal of Interventional Cardiology. In the report, the journal's editor Cindy Grines, a cardiologist, and her colleagues detail a case in which a patient suffered a heart attack as a result of the deformation of a Boston Scientific Ion coronary stent. The thin-strut Ion paclitaxel-eluting platinum-chromium coronary stent system, which obtained FDA clearance in April, demonstrated deformation, accordioning, and shortening of about 35%, according to Grines. She described this stent shrinkage in her editorial as "disturbing."

Although Boston Scientific may have some explaining to do on behalf of its Ion system, other manufacturers of thin-strut stents don't need to go on the defensive just yet. But experts do seem to be attributing these performance issues to thin-strut stent platform designs. And in light of this heightened scrutiny, OEMs would be wise to reevaluate next-generation stent designs to ensure that, by pursuing thinner struts, they are not compromising longitudinal strength and integrity. Companies should also consider heeding TCT presenters' suggestions to adopt standardized longitudinal strength-testing protocols in order to allay cardiologists' concerns. After all, being thin isn't everything.

Guest Blog: When to Leak Test

When designing a device or an assembly line that involves testing, it’s important to know the various forks in the road that will affect the ultimate testing costs.

Testing takes time and money. If your medical device is leak sensitive, the data you need to model is how testing various subassemblies and/or final assemblies will impact both costs and product quality.

One example is the great number of medical devices or components made from molded plastic parts that also have internal chambers. For example, think of a device with one pathway for irrigation and another for aspiration. Too often, Uson’s medical device testing team has been approached to test such devices as a fully assembled single unit. But for the device to function properly, internal wall leakage is just as important.

The lowest cost testing solution in many such cases would involve first leak testing a subassembly. Yes, leak detection equipment can be configured to do both internal (common) wall and external leak tests. But the time you take to isolate test circuits, do physical crimping of tubes or connections, and so forth, during testing adds cost, lengthens test cycles, and may require more expensive leak detection equipment than would be required if testing of the subassembly were done first.

The good news is that a company like Uson has “been there, done that” for your type device—even if it is a totally new “mousetrap”. You don’t need to figure these type of decisions out on your own. All you need to know is to call testing experts who have grappled with your type leak detection challenges many times before.

Joe Pustka

Putska (pictured on the left) is a medical device leak testing technical support manager for Uson, which first developed high accuracy leak testing methods for NASA, and since 1963 has specialized in leak detection, leak testing, and non-destructive testing for the medical device and medical packaging industries, among others. Putska works with medical device companies throughout North and Central America and has worked with Uson in various technical capacities since 1980.

Software Tools Help Medical Device Makers Navigate Changing Global Regulatory Landscape

The medical device industry has benefited greatly from the growing availability of financial and enterprise resource planning (ERP) software over the years. But is has suffered from a noticeable lack of software resources aimed at providing business intelligence and decision support, according to Peter von Dyck, CEO of e-Zassi  (Fernandina Beach, FL). Responding to this unmet need in the marketplace, e-Zassi has developed proprietary software tools that help outline a clear regulatory pathway for medical product design and development and partnered with to increase accessibility to the medical device community.

"Design and development have typically focused more on performance and efficacy and been less dependent  on regulatory aspects of the product, but those days are over," von Dyck says. "We now have to design and develop products with global regulatory classifications in mind, especially since the initial clinical studies and commercial entry point may be outside the United States. This has required that those involved in the earliest phases of product design and development [increasingly] take into consideration the regulatory and reimbursement  aspects of a product or you risk having a product that is not commercially viable."

Developed to accommodate these changing market needs, e-Zassi's Web-based tools are designed to promote efficiency, accelerate product development, and foster collaboration within the medical device sector. Providing in-depth insight into a product's global regulatory pathway, e-Zassi's InnoVision assessment software, for example, generates detailed product analysis based on information provided by the user. The resulting report helps predict both U.S. and EU regulatory classifications and identify end-user call patterns. It also identifies reimbursement and manufacturing burdens, as well as other critical market requirements, to help medical device developers make more-informed product development and commercialization decisions.

Touting the motto 'open innovation with IP protection,' e-Zassi also enables fast, secure online collaboration between medical device innovators and funding sources or OEMs. While fears of over disclosure have historically hindered online collaboration within the medical device industry, e-Zassi's InnoVision software allows the conversion of confidential material to nonconfidential information that can be readily shared earlier in the development phase between all parties, according to von Dyck.

Offered as part of the purchased InnoVision software or as a simplified, standalone tool free to Qmed users is the company's FDA Calculator. Supplying FDA classification and product codes, the tool is designed to assist foreign medical device companies with navigating the complex U.S. regulatory and reimbursement environment. "With all the reforms and uncertainty, the United States has become one of the most complicated markets to enter," von Dyck notes. "Companies located outside of the United States need to quickly understand where they stand in terms of entering the U.S. marketplace--which regulatory classification they need to be a part of and which clinical endpoints they need to satisfy. Without this kind of data, their ability to enter the marketplace will be hindered and it will take much more time and money to do."

The regulatory calculator also proves useful to U.S.-based companies operating in the current controversial regulatory climate, von Dyck comments. "Because FDA is under reform, it's [often] very difficult to understand what's going to happen," he says. "Having an FDA tool that provides decision support during this healthcare reform really allows U.S. designers and developers to embed that regulatory element into their design today on new products they intend to launch in the coming months or years."

Essentially, von Dyck notes, e-Zassi's tools have the potential to expedite the product development process for all potential stakeholders in a project. Inventors or entrepreneurs can put the information obtained via the software to use in raising capital, for example, while more-mature companies can employ the tools to more-accurately forecast launch dates and development requirements for new products they have in the pipeline. "And for the venture funds and very large companies, they can use the InnoVision tool for more-rapid due diligence purposes to screen and assess new product opportunities submitted from outside parties," von Dyck says. "They can do much more with much less time and effort and also without confidentiality agreements needing to be in place because all the content is nonconfidential." -Shana Leonard

Why Don't CDRH Reviewers Always Greet You Warmly on the Phone? They Are Stressed, Says Former FDA Insider

At a conference session at Biomedevice at San Jose, president of CardioMed Device Consultants (Baltimore) Semih Oktay, PhD gave a broad overview of CDRH and FDA, drawing on his own experience at the agency as an expert mechanical engineer and scientific reviewer of cardiovascular devices.

Oktay explained that working at the agency can be very stressful and the salary opportunities are limited. The workload at the CDRH can be daunting, he explained. "They are dealing with more than 11,000 submissions every year," he said. Also consider the volume of investigational device exemptions that are submitted to reviewers, Oktay recommended. "[Reviewers] have 30 calendar days to review them," he added. On top of that, reviewers must go to frequent meetings and training events. "All of these things these guys are doing under limited salary. Imagine how much pressure they are under," he said. Oktay added that the stress level at the agency is the reason people in the industry often are not greeted warmly when phoning a reviewer at CDRH. And the workload combined with the limited pay is one of the reasons for high employee turnover at the agency.

This issue has been getting a fair amount of attention in recent years, as the agency has been increasingly criticized for slow review times, inconsistency, and other problems. Last year, senator Al Franken released a document explaining his thoughts on CDRH recruitment, arguing in the beginning of the document that:

While there are varied opinions on many Food and Drug Administration (FDA) issues, the good news is that everyone seems to agree on one matter: that FDA, and its Center for Devices and Radiological Health (CDRH) in particular, need to make some changes in workforce recruitment and retention strategies.

Advice for Medical Device Professionals on Dealing with FDA

Although I found the first-person perspective on Oktay's experience at the agency to be especially interesting—considering how frequently the agency is criticisized for inefficiency and lack of transparency, the bulk of his conference session provided background information about the industry and advice on how to best deal with CDRH. Here's a summary of one portion, which was designed to offer advice on how to get the most out of dealing with the agency:

  • Be up front about your proposed submission strategy. FDA does not like surprises, Oktay says.
  • Good record keeping is important—document all of your communications with FDA every e-mail, every phone conversation should be recorded and kept track of.
  • It is important that you deal with the appropriate FDA reviewing branch—do your homework, he advised. And make sure you communicate well with that branch.
  • Getting FDA interaction early is a key to your success, he said.
  • Honor the commitments you made with the agency. Try to make their lives easier; you need to have FDA staff as friends.

Related Content

Brian Buntz

Top Medtech Stories in 2011: FDA, the Big Three, China, India, and the Future

Top Medtech Stories in 2011: FDA, the Big Three, China, India, and the Future

We're getting closer to 2012, and it seems like a good time to look at what MD+DI articles resonated with you the most. This year, the stories fell into rather distinct categories.

From this list we can tell that you are interested in FDA, the world, and the costs of running your business. But you are also interested in what other companies are doing, particularly about the big three (J&J, Boston Scientific, and Medtronic). And then in some cases, you are interested in random stuff that doesn't really fit into any categories. For example, a 1998 article from Karl Hemmerich, on general aging theory and accelerated aging was among the top 50 articles this year.

Go figure.

And while you help us figure that one out, here some of the top articles from 2011, arranged by category:

Stories about the Future

•    Which Devices Will Hit Big this Year? —January
•    Theoretical Physicist Michio Kaku Predicts the Future of Healthcare  —November

Stories about The Big Three

•    Boston Scientific CEO Disparages St. Jude's, Medtronic's Products —May
•    Shipment of Boston Scientific Devices Stolen — May
•    MD+DI's Manufacturer of the Year: Johnson & Johnson —November
•    For J&J, Drug-Coated Stents Were an Albatross —June
•    'Economist' Casts Medtronic CEO Ishrak as Savior of Device Industry —September

Stories about FDA

•    ReGen to Sue FDA —June
•    Panel Pressures FDA to Expedite Development of Artificial Pancreas —August
•    Epic Fail: IOM Disappoints in 510(k)s by Not Doing Its Job —July

Stories about Standards

•    The New (and Scary) Standard for Medical Electronic Equipment —January
•    National Deviations to IEC 60601-1 —February

Stories about Business and Costs

•    Outsourcing in Device Industry Not Big, But Getting There —February
•    The Most Expensive Place to Make Medical Devices; Plus the Least —May

Stories about the World

•    India, China, and the Future of the Medical Device Industry  —September
•    Waiting for a Superman: China Could Save Medical Device Sales —March

Any theories on why general aging and acceleration got so hot this year? Drop me a line.

Heather Thompson