Counting Down To Patent Reform

Although President Obama signed the Leahy-Smith America Invents Act into law on September 16, 2011, most of the changes that will affect Patent Office Practice will not take effect until September 16, 2012 or March 16, 2013. Nevertheless, now is the time to prepare for these changes. This article highlights what will change in September and how medical device companies can prepare for the first-to-file changes that will take effect in March.  
New Inventor Oath/Declaration Options

As of September 16, 2012, patent applicants will be able to satisfy the inventor oath/declaration requirement by submitting an assignment document that includes the mandated oath/declaration language. While this option may be convenient for inventors who will need to execute only a single document, medical device companies should approach this option with caution For example, while an assignment document may encompass future improvements of the invention (including those claimed in continuation-in-part applications), an inventor oath/declaration is tied to the text of a specific application (each inventor must acknowledge having reviewed and understood the application). Inventors may be more willing to execute additional oath/declaration documents for future applications than they would be to execute new combined assignment-oath/declaration documents, especially if they have changed employment.

Another change due to take effect in September relates to when the inventor oath/declaration must be submitted. The new law provides for submission before a Notice of Allowance is issued, but the Patent Office’s proposed rules still would require an executed inventor oath/declaration before substantive examination. The Patent Office is reconsidering its proposal in view of public comments opposing that approach, and may announce a different timeframe in the final rules. Even if the Patent Office permits applicants to satisfy the requirement later, medical device companies should strive to obtain executed inventor oath/declaration documents as soon as possible in case the inventor changes employment or otherwise becomes less willing to cooperate with the application process.
 
New Ability Of Third Parties To Submit Prior Art During Prosecution

As of September 16, 2012, third parties will be able to submit prior art in any pending patent application that has not yet received a Notice of Allowance, as long as the application was published within six months of the submission or has not yet received a first Office Action on the merits. As outlined in the proposed rules, the Patent Office will treat these submissions similar to an Information Disclosure Statement. Applicants will not have to respond to the submissions directly, but will have to respond to any examiner rejections based on information that was included in a submission. Offensively, medical device companies may want to monitor their competitors’ published applications and consider whether there is relevant prior art that they want to ensure is considered during prosecution. Defensively, medical device companies may want to consider expediting examination of important applications under the Track I program, to increase the odds that a Notice of Allowance will issue before a competitor has an opportunity to prepare a prior art submission. Medical device companies also may want to monitor the status of their own applications on the Patent Office’s PAIR Web site, because the Patent Office will not provide notice of a submission until a copy is provided with the first Office Action.
 
New Ability To Request Supplemental Examination Of A Patent

As of September 16, 2012, patent owners will be able to request a supplemental examination of any of their own patents to obtain consideration or reconsideration of any information believed to be relevant to the patent, or to correct any information believed to be relevant. Although the ultimate review process will be conducted under the reissue application framework, a request for supplemental examination will not have to aver any defect in the granted patent. Moreover, supplemental examination will shield the patent owner from charges of unenforceability (e.g., inequitable conduct) based on any information considered during a supplemental examination proceeding, as long as the request is filed before the charge is raised by a third party in litigation or in an Abbreviated New Drug Application paragraph IV filing.
 
New Ability To Request Inter Partes Review Of A Patent

On September 16, 2012, inter partes reexamination will be replaced with inter partes review. Although the proceedings will be similar, there are some significant differences, including explicit estoppel provisions and provisions governing the relative timing of inter partes review and district court litigation. Medical device companies may be particularly interested in the class of patents that can be challenged by inter partes review. While inter partes reexamination is only available for patents granted from applications filed on or after November 29, 1999, inter partes review will be available for patents granted from earlier applications. Medical device companies may want to consider whether this new opportunity to challenge an old patent is of strategic interest. On the other hand, the transition to inter partes review will impose a delay in challenging new patents because a request for inter partes review cannot be filed until nine months after the patent is granted. This time period will complement the time period during which post-grant review can be requested once post-grant review becomes available, but creates a gap in time for patents that are not subject to post-grant review (which only will be available against patents subject to the first-to-file changes, which do not take effect until March 16, 2013). If a medical device company is considering requesting ex parte reexamination of a recently issued patent, it may want to do so by September 15, 2012, in order to avoid the restrictions associated with the new inter partes review proceedings.
 
Preparing For First-To-File

The first-to-file system (embodied in a new version of 35 USC § 102) will not take effect until March 16, 2013, but medical device companies should understand the complicated effective date and applicability provisions of the revised statute and begin preparing now for patenting under the first-to-file system.

There are several reasons why medical device companies will want to shield their patent applications from the first-to-file system for as long as possible. For example, applications under the first-to-file system will be subject to more secret prior art because published U.S. patent applications and PCT applications that designate the United States will qualify as prior art as of the filing date of any earlier priority application “that describes the subject matter at issue,” potentially reaching back an additional 12 months. Unlike other first-to-file countries, like Europe and Japan, where such secret prior art only can be used in a novelty rejection, U.S. examiners are likely to continue to retroactively cite patent applications in obviousness rejections as well.

Of course, applications subject to the first-to-file system will not be able to avoid third-party prior art by establishing an earlier date of invention. Although limited exceptions will be available under new 35 USC § 102(b), those will require evidence establishing that the disclosure at issue “was obtained directly or indirectly” from an inventor or previously had been disclosed by an inventor or another who obtained the subject matter directly or indirectly from an inventor. Additionally, applications subject to the first-to-file system will not be able to avoid the prior art effect of an earlier-filed third party application by establishing priority in an interference proceeding. Instead, the only possible recourse against an earlier-filed copending application will be in a derivation proceeding, which will require proof that the other inventor “derived the claimed invention from an inventor named in the petitioner’s application.”

Another reason to avoid the first-to-file system is that only patents granted from first-to-file applications will be subject to the new post-grant review proceedings. Third parties will be able to request a post-grant review within nine months of a patent’s grant date or reissue date in order to challenge the validity of a first-to-file patent under a preponderance of the evidence standard “on any ground that could be raised” under 35 USC § 282(b)(2) or (3). This includes issues pertaining to 35 USC § 101 and 35 USC § 112, which cannot be raised in reexamination or inter partes review proceedings.

Despite these important reasons to file new U.S. patent applications by March 15, 2013, medical device companies need not file all planned patent applications by that date. For example, continuation and divisional applications filed on or after March 16, 2013 will remain under the current first-to-invent system, as will new U.S. applications that claim priority to earlier filed foreign or PCT applications, as long as all claims are entitled to a priority date of March 15, 2013 or earlier. On the other hand, brand new application, continuation-in-part applications, and new non-provisional applications may fall under the first-to-file system.

To ensure the availability of the current first-to-file system for as many inventions as possible, medical device companies should confer with their inventors and mine their invention disclosures to identify inventions that may be ready for patenting so that patent applications can be filed by March 15, 2013. Looking ahead, once the first-to-file system takes effect medical device companies should exercise care when filing an application that adds disclosure to a previously filed application, and should consider strategies that could preserve the applicability of the current first-to-invent system to the earlier subject matter. For example, original and new subject matter could be segregated in different applications, with one application claiming only original subject matter (and thus remaining under the first-to-invent system) and the other application claiming new subject matter (and thus falling under the first-to-file system). Medical device companies also should ensure that their inventors and business development teams understand the importance of filing a patent application before any disclosure or offer for sale of technology embodying a new invention because the new grace period exceptions will be both narrower and more difficult to establish than options currently available under the first-to-invent system.

Ready For Take-Off

There are a number of steps medical device companies should consider taking before September 16, 2013, with more to do before March 16, 2013. By understanding the different provisions of the America Invents Act, medical device companies can identify which changes are most relevant to their intellectual property programs and business objectives, and take appropriate measures. Savvy medical device companies will be able to position themselves to mitigate the impact of unfavorable provisions of the new law, while preparing to take advantage of the new opportunities that the law has to offer.

Courtenay C. Brinckerhoff is a partner of Foley & Lardner LLP, Chair of the firm’s IP Law & Practice, and editor of PharmaPatentsBlog.com. The views expressed herein are the author’s own, and may not represent those of Foley & Lardner LLP or its clients.
 
 

Treating Cancer Using Protein-Synthesizing Nanoparticles

Nanoparticles can produce proteins when ultraviolet light is shone on them. In this case, a green fluorescent protein was used. (Image by Avi Schroeder)

The development of new drug-delivery platforms, especially those for treating cancers, has long been a major goal of the medical device industry. Now,  researchers at the Massachusetts Institute of Technology (MIT; Cambridge, MA) have developed a nanoparticle that can synthesize proteins on demand. After the particles reach their designated targets, protein synthesis can be initiated by shining ultraviolet light on them. This technique, the scientists hope, could eventually serve as an effective drug-delivery method for curing cancer.

"This is the first proof of concept that you can actually synthesize new compounds from inert starting materials inside the body," says Avi Schroeder, a postdoc in MIT's David H. Koch Institute for Integrative Cancer Research and lead author of a paper appearing in the journal NanoLetters.

Endeavoring to discover new ways to attack metastatic tumors, the researchers decided to mimic the protein-manufacturing strategy found in nature. Cells store their protein-building instructions in DNA, which is then copied into messenger RNA. mRNA carries protein blueprints to cell structures called ribosomes, which read the mRNA and translate it into amino acid sequences. Amino acids are strung together to form proteins.

The researchers designed the new nanoparticles to self-assemble from a mixture that includes lipids--which form the particles' outer shells--and a mixture of ribosomes, amino acids, and the enzymes needed for protein synthesis. Also included in the mixture are DNA sequences for the desired proteins. The DNA is trapped by a chemical compound called DMNPE, which reversibly binds to it. This compound releases the DNA when exposed to ultraviolet light.

"You want to be able to trigger it so the system turns on only when you want it to work," Schroeder comments. "When the particles are hit by light, the DNA is released from a caging compound and then can enter the cycle of producing the protein."

In this study, particles were programmed to produce either green fluorescent protein (GFP) or luciferase, both of which are easily detected. Tests in mice showed that the particles were successfully prompted to produce protein when UV light shone on them.

The researchers are now working on particles that can synthesize potential cancer drugs. While some of these proteins are toxic to both cancerous and healthy cells, using this delivery method could spare healthy cells. The team is also working on new ways to activate the nanoparticles. Possible approaches include production triggered by acidity level or other biological conditions specific to certain body regions or cells.

The grass isn’t always greener when it comes to medical devices

It’s interesting (and even comforting) to note that issues with the FDA, or the governing body of whatever country you happen to be in, appear to be universal. At least that’s the case in Japan, with its PMDA, or Pharmaceuticals and Medical Devices Agency. The leaders of two different groups acknowledged that the PMDA is a conservative, slow-moving organization that’s reluctant to change.
 
But there is certainly no shortage of “lobbyist” groups, or associations that act in a fashion similar to a lobbyist group. For example, the Japan Association for the Advancement of Medical Equipment (JAAME) is working closely with the automotive industry to align medical device technology with automotive technology. One such application of the union would put sensors into the car’s steering wheel. Such sensors could detect blood pressure, heart rate, etc., keeping a close eye on the driver. Not surprisingly, the funding for JAAME and groups like it come mainly from industry.
 
Another key issue that’s rankling many is the split, or more importantly the non-split, of the PMDA into two separate groups, one to deal with the pharmaceutical industry and one to deal with medical devices. Proponents of the split say that the limited crossover between medical devices and pharmaceuticals, combined with the increasing number of devices looking for approval, makes the split a no-brainer. It’s a discussion that’s been taking place for quite a few years, and finally appears to be on the agenda. But even the most optimistic estimates say it’ll be at least a few years before there’s any significant action taken.
 

Ensuring the Stability and Viability of Combination Products

Many of the testing procedures used to validate combination products are borrowed from the pharmaceutical industry. Since combination products are produced using CGMP-type manufacturing standards, manufacturers must employ such CGMP testing protocols as those used to test incoming raw materials. But in addition to incoming tests, developers of combination products must also often perform mechanical and physical testing on a sampling of manufactured devices.

A drug-dissolution apparatus at Exova can be employed to determine the API release rate from combination devices, a critical performance measurement used for performing product specifications.

Drugs administered to the body via combination products often begin as solid products. Hence, the rate at which such drugs dissolve into the body becomes a crucial issue. Therefore, manufacturers of combination medical devices must perform a range of drug-dissolution tests to measure the dissolution, or release, rate of the pharmaceutical agent from the device platform. And as in the case of standard pharmaceutical products, manufacturers must understand the degradation rates of the products they produce--both in terms of the pharmaceutical agents themselves and the material matrix, which is typically made from such polymer materials as PLGA.

When developing combination products, manufacturers must also perform a host of stability tests to determine the shelf life of the pharmaceutical agents used in their products. Such testing involves placing a sample into a chamber and then withdrawing small amounts of it at established time intervals--perhaps every three months. Then, the samples are subjected to a battery of tests to determine whether they have changed over the course of time.

As in the case of testing pharmaceutical agents, it is important for medical device manufacturers to test the stability of the material matrix itself. Assuming that a combination device's material platform is a polymer-based material, manufacturers must analyze it to determine whether it contains residual monomers or extractables and leachables that might elute from the product into the body. The goal of such testing is to determine the toxicity effects such by-products may have. Does the polymer degrade over time? Does it need to be protected from light or from excess humidity or temperature? These questions must be answered during the process of developing and manufacturing combination products.

The procedures used by manufacturers to test existing product lines are also suitable for use in developing new products. Hence, when a manufacturer proceeds to develop new combination products, it is important to have all of the requisite analytical tools at hand because many of the design changes and optimizations that take place during the development phase can affect product stability or viability.

Combination Products: Marrying Materials, Medicines, and Manufacturing

Combination products are becoming increasingly important in the medical device space. Defined as products composed of any combination of a drug, device, or biological agent, combination products are predicted to become market leaders in the future, perhaps totaling 50% of all U.S. medical device activity in the next few years, according to the Medical Development Group.

SSF's UV curing chamber enables the processing of combination products.

An array of combination products--including drug-eluting stents, pacing leads with steroid-coated tips, and antimicrobial catheters--are developed using raw materials to which active pharmaceutical ingredients (APIs) are added during the manufacturing process. However, the complex partnering of such materials as polymers and plastics with APIs can often be achieved only by overcoming a variety of technological challenges associated with determining drug-elution rates, preventing mechanical stresses, and avoiding excessive heat. Solving these issues requires not only expertise in unifying materials and drugs but also the active collaboration of materials experts and medical device manufacturers.

Living in a Material World
Manufacturing combination products requires a delicate balancing act between a material matrix and the pharmaceutical agent it releases into the body. Thus, to ensure success, combination products must be designed with matrices that can release drugs at the rate required by the medical application. The drug-release rate, in turn, is affected by the material's degradation and mechanical properties.

"OEMs seek to market products that will deliver a certain amount of a drug at a certain rate," remarks Bryan Wickson, manager, polymers and medical devices at Exova (Mississauga, ON, Canada). "Or they may want to develop a device with a coating that is expected to dissipate completely over a certain period of time." In both cases, determining the rate at which the drug must be released has an important bearing on the type of material that will be selected for the application.

When developing materials for such combination products as stents or wound dressings, the first criterion for the materials supplier is to determine how the API will be released from the material, Wickson says. For example, in the case of a matrix made from poly(lactic-co-glycolic acid), or PLGA, drugs may dissolve or may be be leached or extracted out of the matrix.

The next critical issue, according to Wickson, involves adjusting the drug-release rate. In the case of PLGA, one method is to adjust the PLGA-copolymer ratio, which affects the degradation rate of the matrix and, therefore, the drug-release rate. The other is to change the porosity or the crystallinity of the material. If the combination device material features both amorphous and crystalline properties, changing the ratio of amorphousness to crystallinity can affect the drug-release rate.

"Let's say you are developing a combination product that is supposed to elute an API relatively quickly," Wickson comments. "You can choose a base matrix material with rapid dissolution or degradation properties, accelerating drug release. Or you can change the matrix to make it somewhat porous, providing more surface area to release the drug quicker." For example, if the base matrix consists of a semicrystalline material combining both amorphous and crystalline properties, the drug would likely be in the amorphous phase, Wickson says. Changing this ratio to boost the concentration of the drug in the amorphous phase results in accelerated drug release. Conversely, decreasing the concentration of the drug in the amorphous phase slows the drug-release rate. The correct drug-release rate is essential, Wickson adds, because it enables the device to remain in the body until the revascularization process is complete.

The drug-release rate of a combination product is also dependent on the base material's mechanical properties, including its radial, flexural, and tensile strength. "Sometimes, a drug can act essentially as a filler," Wickson notes. "In such cases, when you load a drug into a base resin such as an elastomer, the mechanical or physical properties of the resin change. For example, the drug can make the material stiffer and less elastomeric."

When designing materials for combination products, suppliers often do not know what the drug-loading levels will eventually be, Wickson notes. "Thus, a materials specialist may assume at the outset of a project that a device will have a drug-loading level of 10% whereas it will, in fact, turn out to be 30%. That difference will have a huge effect on the mechanical properties of the material." For example, different drug-loading levels can change a material's elastic, flexural, or radial-strength properties. While higher levels can improve a material's stiffness in some situations--in effect promoting greater reinforcement capability--they can also make the material too brittle, rendering it too unstable to be implanted in the body.

Hot Products
Manufacturing combination products presents a host of processing challenges, one of the most difficult of which is working with heat-sensitive APIs. Exova, for example, experienced extrusion-related problems when developing a material for a cardiovascular stent. "Extruding polymers generally involves high temperatures," Wickson says, "but high temperatures can cause the API to degrade. However, using a low temperature to reduce thermal degradation exposes the API to shear forces." The company solved this problem by adding an ingredient to the polymer to lower its melt temperature, enabling the manufacturer to process the combination product below 100°C, instead of closer to 200°C.

Also dedicated to addressing the problem of API heat sensitivity, Momentive Performance Materials (Columbus, OH), has developed a material specifically designed for extruding combination products and components at low temperatures. "The active ingredients in combination products can often be degraded by exposure to the high temperatures that are required when curing silicone elastomers by conventional thermal methods," explains Mel Toub, the company's applications development manager, elastomers. "Our method for overcoming this limitation is to provide UV-curable materials, an alternative curing system that does not require high temperatures and, therefore, may be more compatible with heat-sensitive additives."

UV-curable silicone elastomers consist of a silicone rubber base and a photoactive platinum catalyst that yield a cured silicone rubber part when blended together and briefly exposed to UV light, a process that requires little thermal input, Toub explains. "As with all platinum-catalyzed silicone elastomers, UV-curable silicone rubber is cross-linked by a hydrosilylation reaction. This reaction results in a vulcanized part with no cure by-products, making it particularly well suited for healthcare applications." In addition, the physical properties of cured silicone rubber are similar to those of silicone elastomers that have undergone heat curing, making them suitable for combination products.

To develop extrudable materials suitable for manufacturing API-containing medical devices, Momentive collaborated with Specialty Silicone Fabricators (SSF; Tustin, CA), a contract molder and extruder of combination products that grappled with the temperature-stability issues associated with pharmaceutical agents and the narrow process window this limitation places on manufacturers. "While liquid-silicone and high-consistency rubbers can be molded or extruded at any temperature, high-temperature processes destabilize the drug," remarks Mark Paulsen, SSF's director of business development. "On the other hand, processing these materials at low temperatures extends the curing cycle from a half hour to an hour or even longer. Momentive's UV-curable material enables us to cure materials at close to room temperature--a work-around that represents a big breakthrough."

Mixing and Matching
When using standard thermal-cure materials for molding or extruding components used in combination products, SSF begins the manufacturing process by sourcing the API and then confirming its identity, as stipulated in Title 21, Section 211 of the Code of Federal Regulations. The identity of the API, Paulsen notes, is typically confirmed using Fourier transform infrared spectroscopy.

Regardless of whether the API will be added to a thermoplastic or silicone material, most molding or extrusion processes involve elevated temperatures. Thus, the next step involves determining the drug's temperature stability using differential scanning calorimetry.

Once the contract manufacturer knows the pharmaceutical agent's maximum processing temperature, it selects an optimal matrix material in collaboration with clients--such as a thermoplastic, bioresorbable thermoplastic or silicone material. "We pick the optimal matrix material with an eye toward three things: API compatibility, elution-rate targeting, and the fabrication method and scalability," Paulsen remarks.

After selecting the material and determining the maximum processing temperature, the manufacturer optimizes the process for mixing the API and matrix material together, depending on the process most appropriate to the application. Several different types of mixing equipment are available for performing this step, including two- and three-roll mills; a speed mixer that provides dual asymmetric centrifugal forces; a machine that mixes materials using low-frequency, high-intensity acoustical energy; and low- to high-viscosity mixers.

"Typically, the drugs used in combination products are supplied in their purest forms as powders," Paulsen explains. "The challenge is, how do you mix it into a silicone that, for example, is the consistency of Vaseline? And how do you do it without having to hand-stir the mixture? Thus, we're always looking for mixing processes that are hands-off and can be easily validated."

Having chosen a material, determined the material's temperature stability, and mixed the ingredients, SSF validates the mixture using in-house high-performance liquid chromatography testing to ensure that it is homogenous. Testing includes, but is not limited to, total-drug-content and elution-rate profiling. Employing rheometry to measure how the liquid mixture will flow in response to applied forces, the company then determines the appropriate time-temperature parameters required to completely cure the product. Before processing commences, the company develops acceptance criteria, typically in collaboration with the client.

Living with Imperfections
While Paulsen will not venture to say whether combination products represent the future of medicine, he affirms that they are becoming a growing part of the medical device sector. However, in the quest to optimize materials and corresponding processing techniques for this burgeoning area, it is incumbent upon materials developers and manufacturers alike to ensure that their materials and processes remain commercially viable.

Highlighting the occasional disconnect between developing manufacturing processes and the demands of doing business, Wickson notes that startups often approach Exova to produce prototypes for combination products based on processes that are simply not cost-effective. And in other cases, established companies use manufacturing processes that fly in the face of commercial realities.

"Some manufacturers use processes that can yield products with the desired properties, go into clinical trials, and even complete much of the FDA clearance procedure," Wickson says. "But sometimes, they have to go back to the basics and completely redo their fabrication processes with cost consciousness in mind."

For example, manufacturers often overlook the fact that the materials used in production-scale fabrication processes are likely to be impure. When polymers are manufactured, such residual chemicals as monomers, solvents, or catalysts containing heavy metals can form. However, when using such polymers for commercial purposes, it would be very expensive to purify them. "While it is acceptable in a university setting or in very small runs to distill monomers before commencing with polymerization, this is out of the question in the commercial world," Wickman says. "Manufacturers are going to buy them in bulk, and they're not going to redistill and purify them to 99.99% purity. It's just not feasible. So, you have to design devices from the get-go based on knowing that you're working with impure starting materials."

The price for failing to understand the impacts of material impurities are potentially steep. "Impurities in the material could degrade the drug," Wickson says, "or they could prevent drug release." To prevent such issues, manufacturers should be aware of the effects of material purity levels on material-drug interactions. If they fail to do so, they may have to develop purification procedures after the fact, show that the degradation products caused by the impurities are safe, or modify the design of the combination device to change the release rate. "However, all of these options are commercially unviable," Wickson adds.

Thinking ahead will become even more critical as companies developing combination products increasingly turn to the use of biologics such as peptides, Wickson notes. "I think that biologics are going to find their way more and more into combination products. However, this move will be challenging because the biotech industry has completely different manufacturing demands from those in the pharmaceuticals sector. Their testing and QC-type procedures are also different." Thus, as the industry pioneers new combination products, it will have to rise to the challenge of meeting new technological demands.

TEDMED Recap

TEDMED Recap

Last week’s TEDMED 2012 event in Washington, DC, brought together experts from a variety of disciplines—the sciences, media, business, and the arts—to brainstorm solutions to the world's most pressing healthcare problems.

People working in healthcare tend to connect in silos, with specialists interacting mainly with others in their specific fields, said TEDMED curator and emcee Jay Walker. The goal of conference, he said, was to assemble a diverse crowd to focus on innovation, imagination, and inspiration.

“People from the front lines of medicine across all fields are here,” Walker said.

The four-day conference addressed topics ranging from next-generation medical technologies to how to pay for treatment. Speakers included medical device company executives; the director of the NIH; professors in the fields of genomics, computer science, cardiology, and neurology; and even Sesame Street's Cookie Monster.

MD+DI editors attended TEDMED Live sessions throughout the week. Check out our coverage of the event:

TEDMED Opens with Call to Think Outside the Box to Solve Healthcare Problems

TEDMED Update: Why the Future of Medical Electronics Is Flexible

To Move Forward, Medical Science Needs Imagination and Collaboration

TEDMED Live: The Promise of Stem Cells While Regulations Stifle Innovation

TEDMED 2012: Telling Health Stories Through Mobile Data Collection

Harnessing the Power of Play for Medical Problem Solving
 

Jamie Hartford is the associate editor of MD+DI and MED. Follow her on Twitter at @readMED.

Legos Form Building Blocks of Automated Process for Making Synthetic Bone

Engineering researchers at the University of Cambridge (UK) have turned playtime into productivity. In a burst of creativity, the team employed Lego robotics to build a simple, inexpensive robot that effectively automates processing of synthetic bone.

Using hydroxyapatite-gelatin composites, the engineers are developing synthetic bone that boasts low energy costs in addition to closely resembling real human tissue. But achieving such a material can be labor intensive and rather tedious, according to the researchers. "To make the bone-like substance, you take a sample. Then, you dip it into one beaker of calcium and protein, then rinse it in some water and dip in into another beaker of phosphate and protein-you have to do it over and over and over again to build up the compound," explains Daniel Strange, a PhD student involved with the research.

Looking to automate the process, the engineers determined that the ideal solution would be a robot that could be left unattended to perform the necessary tasks for creating the synthetic bone material. Rather than purchasing an expensive, off-the-shelf kit, however, the team decided to experiment with the use of a Lego Mindstorms robotics kit. Containing microprocessors, motors, and sensors that can be programmed to perform repeatable basic tasks, the kit enabled the researchers to create a crane to which the sample is attached. The crane then carries out the task of dipping the sample into the different solutions, creating an automated solution that removes the burden of tedious labor from the researchers.

"The great thing about the robots is once you tell them what to do, they can do it very precisely over and over again," Strange adds. "So, a day later, I can come back and see a fully made sample." See a video of the novel automation solution below.

UBM and Cambashi Survey Investigates How to Improve Medical Device Manufacturing

Research and consulting firm Cambashi (Cambridge, UK and Boston, MA), with the support of UBM Canon, has launched a new research survey with the aim of better understanding the best practices used by medical device industry leaders to improve margins and grow market share. This study is focused on the challenges medical device manufacturers face in seeking to grow and increase quality and financial performance in the face of complex and changing regulatory requirements. The confidential questionnaire covers respondents’ current situation, challenges, and approaches for improvement, as well as performance improvement accomplishments. Questions also ask about processes, suppliers, software technologies, information flows, and strategic actions to support reliable, safe, and high-quality medical device manufacturing through the global supply chain and the product lifecycle. 
 
A sneak preview of the findings will be presented at MD&M East, May 21-24 in Philadelphia. Lead researcher Julie Fraser will share data from the study to highlight best practices and approaches for success. She will also be available to answer questions and discuss issues with event attendees.
 
Researches are requesting individuals who either work for or supply materials to medical device manufacturers to participate. Those interested can participate in the survey here through April 30.

Asahi Intecc Is Big Winner at MEDTEC Japan Innovation Awards

The long and winding road from auto parts supplier to medical device manufacturer has been a fruitful journey for Asahi Intecc, Japan's leading maker of PTCA (percutaneous transluminal coronary angioplasty) guiding catheters. The company's international reputation for quality, service and low cost was recognized at MEDTEC Japan, where it received the Grand Award during the MEDTEC Japan Innovation Awards ceremony on April 18. Organised by UBM Canon, the MEDTEC Japan tradeshow and conference is held in Yokohama, Japan, on April 18 and 19.

Winners in other categories included Misuzu Industries, which plays a key role in the manufacture of an implantable left ventricular assist system, and Charmant Group, which fabricates titanium-based products for ophthalmological applications.

For more about the event and the winners, read the full report filed by editor Miki Anzai on the MEDTEC Connection website.

— Norbert Sparrow

Federal Scrutiny of Implant Hacking Continues: Is Increased Regulation on the Horizon?

There was a time when the mere suggestion of hacking or some sort of intentional security breach of a software-controlled medical implant would be laughable. But no one's laughing now--not Medtronic or other medical device manufacturers, not government officials, and especially not patients. As the issue of medical device security continues to gain prominence, officials are now zeroing in on this emerging threat to patient safety and peace of mind. And with the Information Security and Privacy Advisory Board now joining the growing chorus of voices expressing concern and supporting action regarding medical device security, it's becoming increasingly clear that connectivity may soon require cutting through more red tape.

medical device hackingImplant security vulnerabilities were first prominently exposed in 2008 when a group of university researchers detailed their success in hacking into a Medtronic implantable cardioverter-defibrillator (ICD). The researchers tampered with the device, achieving extraction of patient data, depletion of battery power, device inaction, and fibrillation. The impetus for a federal probe and rising concern, however, came courtesy of Jay Radcliffe, who famously demonstrated the ability to hack his own Medtronic insulin pump at last year's Black Hat security conference. Then, as recently as February, implant security, specifically insulin pump vulnerabilities, once again made news when McAfee research architect Barnaby Jack presented at the RSA conference on a method he developed for remotely triggering a lethal attack on a diabetic.

These heavily publicized, analyzed, and criticized public demonstrations of implant security breaches collectively appear to be the catalyst for change, however. Two members of the Energy and Commerce Committee requested a report from the Government Accountability Office after Radcliffe's presentation detailing the extent to which FCC was overseeing and evaluating software-controlled medical device security risks. A GAO spokesperson recently told Wired that the report would be released in July.

Further representing impending change are the recent observations and subsequent recommendations regarding medical device security made a few weeks ago by the Information Security and Privacy Advisory Board (ISPAB) to the U.S. Office of Management and Budget. The board observed: a lack of government accountability and oversight of medical device security attributed to a diffusion of government responsibility; reporting methods that are not currently designed to reflect device security problem indicators; the increased vulnerability of medical devices employed in the home to cybersecurity issues; and that the means to address such issues are, in fact, currently within government's ability.

Based on these observations, ISPAB suggested that:

"1. A single federal entity (such as FDA) should be assigned responsibility for taking medical device cybersecurity into account during premarket clearance and approval of devices and during postmarket surveillance of cybersecurity threat indicators at time of use.

2. FDA should collaborate with NIST scientists and engineers to research cybersecurity features that could be enabled by default on networked or wireless medical devices in federal settings.

3. Government should assign a lead entity to establish better training and education that informs users, healthcare organizations, and manufacturers about the risks associated with networked and wireless medical devices.

4. Because medical devices are increasingly Internet-based, U.S. Computer Emergency Readiness Team should create defined reporting categories for medical device cybersecurity incidents.

5. Further study is needed to determine whether additional policy or legislative changes are necessary to promote medical device security."

As the security of software-controlled medical devices is increasingly called into question, the next step could very well be increased regulation and oversight of such devices, as indicated in recommendations one and five. And while increased regulation and hurdles to FDA clearance are likely the last thing medical device manufacturers want, they need to be prepared. Identifying potential security risks or vulnerabilities in medical devices and incorporating measures to prevent such breaches should become an essential aspect of software-controlled device design if it hasn't already.

In addition to preparing for likely change, software-controlled medical device manufacturers should take the initiative to protect patients against such potential threats. Although some examples of medical device hacking do seem rather farfetched, the reality is that the more attention this issue gets, the more likely it is to actually happen. And other instances of viruses and other security breaches resulting from wireless or Internet connectivity do seem like viable threats. Patient safety should be paramount in device design.

Commenter MattWB, who identified himself as a medical device engineer, on the Wired piece summed it up nicely: "Wireless transmission risks should definitely be considered...It is possible to make the connection secure enough to minimize foreseeable risk to the patient. And, unlike 99% of electronic consumer goods companies, profit is not the only thing medical devices companies care about. We do care about the patient and his/her safety, and wellbeing is always at the forefront of most employees' minds. Mistakes do happen (metal-on-metal hip implants, bad cardiac defibrillator leads, etc.), but the best we can do is learn from mistakes and keep improving."

Read more about medical device hacking and security in MPMN's archived articles, "Device Hacking Continues: Medtronic, Others 'Lacked Foresight," "Mitigating Risk in Software-Controlled Devices," "Preventing Medical Device Hacking, a Nightmare in the Making," "Software: The Brains Behind the Medical Device," and "Securing Change for Implants." --Shana Leonard