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Articles from 2012 In February


Device Hacking Continues: Medtronic, Others 'Lacked Foresight'

Medtronic and other medical device manufacturers may have been lulled into a false sense of security as the headline-grabbing insulin pump hacking controversy began to die down in recent months. But hacker Barnaby Jack plans to push the issue of medical device security vulnerabilities right back into the spotlight at the RSA security conference this week where he will demonstrate the ability to remotely launch a lethal attack against an insulin pump user. This mounting pressure from high-profile, hard-working hackers, coupled with the increasing prevalence of connected devices, is quickly catapulting the issue of medical device security to the top of the industry's priority list.

A consortium of university researchers initially called attention to device security flaws when it hacked into a Medtronic ICD and demonstrated the ability to maliciously control the implant back in 2008. However, the issue of wireless medical device hacking gained national media attention and launched a federal probe--in addition to eliciting mixed feedback from patients and the industry alike--when Jay Radcliffe hacked into his own Medtronic insulin pump at the Black Hat security conference last summer.

Launching his own investigation into insulin pump hacking, Jack, a McAfee research architect, engineered a means of remotely inducing a lethal attack on a diabetic. Although he revealed early results at the Hacker Halted conference in Florida last October, Jack claims to have strengthened his attack program, details of which he will share at the RSA conference.

Unlike Radcliffe's hacking attempts, Jack's program is capable of scanning a public space from up to 300 ft away, identifying Medtronic insulin pumps, and then directing them to dispense fatal doses of insulin, according to Bloomberg. His program does not require extra surveillance to obtain a serial number nor does the hacker have to be positioned particularly close to the victim. It also can disable security alerts on the insulin pumps.

These high-profile hacks of medical devices by Jack and Radcliffe, for example, certainly make for gripping presentations and stories. But they've also proven to be extremely polarizing. On the positive side, they help to initiate change, applying ample pressure on manufacturers to examine potential security vulnerabilities and address them for next-generation devices. They also help the companies in identifying some of these vulnerabilities.

On the other side of the coin, however, they are causing unnecessary public panic among some insulin pump users despite a low likelihood of a hacking event actually occurring. Furthermore, this glamorization of medical device hacking could potentially have the effect of actually inspiring a real-world medical device hacking attempt. Critics even go so far as to admonish the professional hackers for providing a blueprint of sorts and ideas for maliciously breaching device security.

Both sides have valid points. Bringing security vulnerabilities to the attention of medical device manufacturers could ultimately result in better devices and enhanced patient safety. But the continued public demonstrations of medical device hacking may be doing more harm than good. Security features of many current devices cannot be fixed or improved without issuing a recall, and a recall doesn't make sense if the threat is not immediate or great--not to mention largely theoretical.

And it's not like manufacturers were really acting irresponsibly at the time by not accounting for such threats in earlier designs. "[Jack] says the problems stem from a lack of foresight by device makers. Security, he says, wasn't a priority when the devices were designed," according to Bloomberg. So what, exactly, are these public demonstrations accomplishing, should they continue? If hackers are exploring medical device security for the welfare of patients, and not just for the headlines, they perhaps should proceed by working directly with manufacturers and perhaps FDA moving forward, unless a discovery unveils an immediate, concrete threat to patient safety.

Read more about medical device hacking and security in MPMN's archived articles, "Mitigating Risk in Software-Controlled Devices," "Preventing Medical Device Hacking, a Nightmare in the Making," and "Securing Change for Implants." Plus, check out a recent interview, below, with Jack by Bloomberg.--Shana Leonard

Book Review: Injection Molding Part Design for Dummies

Proto Labs has released a book “Injection Molding for Dummies,” written by Tom Tremblay. The group worked with the “For Dummies” people at Wiley & Sons Inc. to create an easy-to-understand guide to the injection molding process. And it pays off.

Is it everything you ever wanted to know about injection molding? Actually, yes, depending on your job description. The book provides a very thorough overview of the process designed to help medical device designers, for example, get enough information about the process to help them talk to molders intelligently. Proto Labs provides CNC machined and injection molded parts. Its Firstcut and Protomold services use proprietary computing technologies and automated manufacturing systems to provide prototypes and short-run production parts.

The book addresses the basics of molding, how to overcome common challenges, such as warping, design limitations, and materials selection. Particularly useful is the vocabulary discussion. If you don’t know what a boss or a rib might be, this is the book for you. I found chapter four, which describes the complex side of injection molding, the most informative—likely becuase I hadn't learned about some of the technologies prior to reading the book. This section discusses when to use side-action cams or shutoff molds.

The writing style is casual and direct, with some amusing metaphors and useful examples. One I liked was using model car parts, which most kids have seen, to illustrate what a gate looks like.

At 66 pages, the book is a quick read. Chapters are short, the illustrations useful, and the inevitable promotional content is kept to a minimum. I’m fairly certain that after reading this book that I can now design parts for an injection mold. And from a non-engineer, that’s pretty high praise.

Heather Thompson

To request a FREE "Injection Molding Part Design for Dummy’s” book visit www.protomold.com/book and enter code: MI12DB


 

Multitouch Gesture-Recognition Software Has Good Instincts

Ease of use is crucial to consumers of all types of electronic devices. Meeting the growing need for user-friendly medical devices, Grayhill Inc. (La Grange, IL) has developed a set of software tools based on gesture-recognition technology that offers technicians greater control of medical imaging applications. The Instinct suite of software tools suits a range of applications, including ultrasound equipment, medical imaging controllers, patient monitors, surgical equipment, and molecular imagers.

Grayhill gesture-recognition software
Finger positions on Grayhill's Multi-Touch Ring Encoder are interpreted by gesture-recognition
software.

Used in conjunction with the firm's hardware, Instinct software creates a more-intuitive human interface for users of medical imaging devices, says Jason Kandik, Grayhill's marketing manager. First, it enables a touchpad on the device's surface to recognize finger touches and motions, after which the gestures are transmitted via USB to a CPU. Then, the CPU decodes the gestures and sends them to the display on the medical device. "This method allows the user to get the benefits of gesture recognition without ever touching the display," Kandik adds.

Instinct, Kandik notes, is a set of multitouch gesture-recognition software tools consisting of a Windows driver and a separate gesture-recognition library. The Windows driver allows Windows-based systems to utilize the OS-internal human-interface commands and, in the case of Windows 7, gesture-recognition tools. But because not all systems are based on Windows, the company provides a separate gesture-recognition library that enables system integrators to incorporate gesture recognition directly into their drivers or applications.

When a user touches Grayhill's human-interface devices, the touch tracking information is sent to the system, Kandik explains. This information does not contain system-specific commands but simply indicates, for example, that two fingers flicked across the multitouch surface. After handling gesture recognition by monitoring incoming data, the driver or application triggers a command when a gesture is recognized.

The software can be integrated with the company's Multi-Touch Ring Encoder, an optical encoder with a multitouch surface measuring 50 or 70 mm in diameter. Capable of outputting a digital 2-bit quadrature code, the ring is available with 32 or 48 positions and features a surface that can track up to five finger positions simultaneously. "It's those finger positions that Instinct can interpret and act upon," Kandik says. Compact and user-friendly, the ring encoder is also easy to clean.

"We want to give customers flexibility," Kandik remarks. "It's up to them to define which types of inputs trigger which types of events or commands." Thus, one customer might prefer to use gestures to navigate through different screens, while another might prefer the ring encoder to scroll through many options or adjust audio or video settings. "Whatever functions they have in mind," Kandik says, "medical device OEMs can use Instinct to supplement or eliminate existing controls on their devices. Whichever route they choose, the goal is to make the use of their devices more intuitive."
 

"Rainbow Polymer" Could Be Used for Biomed Imaging, Disease Detection

Rainbow polymer, University of Buffalo
A rainbow-colored grating, about 25 millimeters wide, under sunlight. Enlarged microscope images show the graded surface, with the black bars indicating a length of 10 microns. Image: University of Buffalo

University at Buffalo (UB) reports that engineers at the school have developed a one-step, low-cost method for fabricating a polymer that, when viewed from a single perspective, is rainbow-colored, reflecting many wavelengths of light. Used as a light filter, this material could form the basis of handheld multispectral imaging devices that identify the "true color" of objects examined.

Such portable technology could have applications in biomedical imaging, including analyzing colors in medical images to detect disease, according to UB vice president for research and economic development Alexander N. Cartwright, one of the researchers who led the study.

The ease of producing the polymer could make it feasible to develop small devices that connect with cell phones to conduct multispectral imaging, said Qiaoqiang Gan, a UB assistant professor of electrical engineering and another member of the research team.

"Our method is pretty low-cost, and because of this and the potential cell phone applications, we feel there is a huge market for improving clinical imaging in developing countries," Gan said.

To create the rainbow material, Liu and Xu sandwiched a photosensitive pre-polymer syrup between two glass slides. Next, they directed a laser beam through a curved lens placed above the pre-polymer solution. The lens divided and bent the laser beam into light of continuously varying wavelengths.

As this light hit the solution, monomers in the solution began joining into polymers, forming a continuous pattern of ridge-like polymer structures. Larger ridges rose where the light struck with more intensity.

The resulting structure is a thin filter that is rainbow-colored when viewed under white light. This is because the periodic polymer layers reflect a continuous spectrum of colors, from red on one end to indigo on the other.

The single-step fabrication method -- shining a laser light through a curved lens -- is affordable and relatively simple. The UB Office of Science, Technology Transfer and Economic Outreach has submitted a provisional patent application detailing the production process.

The filter the researchers created was about 25 millimeters long, but the technique they used is scalable: It is possible to create filters of different sizes by shining the laser through lenses of different sizes.

Gan said the next step for the researchers is to improve the quality of the rainbow filter. The team is also beginning to explore ideas for incorporating the technology into handheld devices.

Cartwright and Gan's team's polymer fabrication technique was published online last week in the journal Advanced Materials. Coauthors of the study include UB students Ke Liu and Huina Xu and UB research scientist Haifeng Hu.

Continuous Extrusion Technology Simplifies Guide Catheter Fabrication

As the demand for minimally invasive procedures rises, so has the need for specialized guide catheters to properly deliver stents, balloons, and other such devices in the body. Fabricating these catheters, however, has traditionally required a hand lay-up manufacturing process to satisfy complex guide catheter shaft requirements. Eliminating this need for manual assembly, Putnam Plastics Corp. (Dayville, CT) has combined traditional coextrusion, braiding, and intermittent extrusion techniques, resulting in the Tri-Tie continuous process designed to enhance catheter reliability and lower costs.

Putnam Plastics Tri-Tie
The Tri-Tie extrusion process can enhance catheter reliability while lowering costs.

Conventional guide catheters consist of three distinct layers, states Dan Lazas, marketing director at Putnam Plastics. A braided stainless-steel matrix, designed to improve torque transmission and shaft support, is sandwiched between a lubricious inner PTFE layer and a smooth outer thermoplastic layer.

Despite the prevalence of this composite shaft construction, however, it can present some processing challenges. For example, variable flexibility of the outer thermoplastic layer--a commonly desired feature--requires hand assembly of discrete extrusions with varying durometers over the braided layer and subsequent thermal or adhesive bonding. But this approach, Lazas notes, can result in abrupt, unwanted discrete connection points. Furthermore, PTFE is highly lubricious and can be difficult to bond to the other layers. The PTFE layer also has to be manufactured via ram extrusion, which often requires the expertise of a specialty vendor. These issues, Lazas says, result in a multicomponent, labor-intensive process subject to considerable quality and validation challenges.

Seeking to improve this process, Putnam Plastics combined the use of its Tri-Layer, braiding, and total intermittent extrusion (TIE) processes to create the Tri-Tie extrusion technology. The former process is primarily employed to create the shaft in which guidewires are inserted. But instead of PTFE, the lubricious inner layer is made from polyethylene (PE), which is harder than PTFE and more resistant to digging in or 'plowing' of inserted devices, Lazas states. "Because PE is also lubricious and difficult to bond, we simultaneously extrude a bonding layer on top and an outer thermoplastic layer," he explains. "The result is three layers being extruded at the same time in an extremely small-diameter tube." Braiding immediately follows extrusion of the three layers.

The final step is the TIE process, a form of coextrusion. "But instead of pushing both materials at one time, you do one material after the other," Lazas says. He adds that the durometer of the guide catheter must be very soft and flexible at the distal end and stiffer at the proximal end to perform as desired. This method, he says, allows for the outer layer to transition from flexible to rigid construction, or from one color to another, in one seamless, automated operation.
 

FDA Reaches $1M Settlement with Medical Device Company

FDA has reached a $1 million civil money penalty settlement with Globus Medical Inc. (Audubon, PA) for the distribution of unapproved medical devices.

According to an FDA press release, the settlement requires Globus Medical to pay a $550,000 penalty and David C. Paul, the firm’s CEO, to pay a $450,000 penalty, for a total of $1 million.

During an inspection of Globus Medical in September 2010, FDA investigators learned that the company had marketed its NuBone Osteoinductive Bone Graft product without proper premarket approval or clearance, as required by law.

“The device-clearance process assures the quality and safety of devices before they reach the market. Firms can’t simply choose to sell devices that FDA has not found to be safe and effective,” said Steve Silverman, director of the Office of Compliance in FDA’s Center for Devices and Radiological Health. “We took action against Globus Medical to protect patients, and we are pleased with the outcome.”

Globus Medical had sought clearance of its NuBone product in January 2009, but FDA declined to clear the product after determining that it was not substantially equivalent (NSE) to legally-marketed products. FDA advised Globus Medical that it could not distribute the product, but the firm continued to do so, even after receiving the NSE letter in December 2009.

FDA then filed a complaint for civil money penalties against Globus Medical and the company’s CEO for distributing the NuBone product without proper FDA approval or clearance. The agency informed Globus Medical and Paul of this action in November 2011, and later participated in settlement discussions leading to the $1 million penalty agreement.

“This company ignored previous warnings by FDA and continued to produce and distribute unapproved medical devices,” said Dara A. Corrigan, associate commissioner for regulatory affairs. “By taking this enforcement action, FDA is demonstrating its commitment to protecting the public from the dangers of unapproved devices.”

-Richard Park

Rensselaer Researchers Develop Postsurgery Orthopedic Implant Sensor

Used to perform in vivo monitoring of orthopedic surgery sites, a sensor developed by Rensselaer researchers can be attached to a range of orthopedic implants.

An implantable sensor developed by researchers at Rensselaer Polytechnic Institute (Troy, NY) can transmit data wirelessly from the site of a recent orthopedic surgery. Developed by Eric Ledet, an assistant professor in the department of biomedical engineering, the sensor can provide surgeons with detailed, real-time information from the actual surgery site, an in vivo process that could lead to more accurate assessments of a patient's recovery or provide information about potential complications.

Measuring only 4 mm in diameter x 500 µm in thickness, the sensor does not require a battery, external power source, or electronics in the body. Instead, it is powered by the external device that is also used to capture sensor data. "Our new sensor will give surgeons the opportunity to make personalized, highly detailed, and very objective diagnoses for individual patients," Ledet remarks. "The simplicity of the sensor is its greatest strength. The sensor is inexpensive to produce, requires no external power source, yet it is robust and durable. We are very excited about the potential of this new technology." Having a stream of real-time in vivo data should take some of the approximation and subjectivity out of declaring a patient recovered and ready to return to work, Ledet adds.

Capable of being attached to commonly used orthopedic musculoskeletal implants such as rods, plates, and prostheses, the sensor looks like small coils of wire. Once it is implanted, it can monitor and transmit data about the load, strain, pressure, or temperature of the surgery site. In addition, it is scalable, tunable, and easy to configure, enabling it to be incorporated into many different types of implantable orthopedic devices.

The Latest Versions of IEC 60601-2-25:2011 and -2-27:2011: Big Changes to the Defibrillation Protection Test

In 2011, the latest versions of IEC 60601-2-25 ed. 2.0, Electrocardiographs; and IEC 60601-2-27 ed. 3.0, Electrocardiographic Monitoring Equipment, were released. Both standards have the identical test for defibrillation protection, and they have been significantly revised from their previous versions for this test. A new switch, named S3 in the standard has been added, a resistor value has been changed from 470k to 390k, and the circuit topology has been changed, for the common mode test. For both common and differential mode tests, the test requires that the test pulses be delivered in a proscribed time period of 20 seconds between pulses. For the common mode test, five pulses of each polarity are delivered with 20 seconds between pulses. For the differential mode test, the test is repeated for each lead wire in turn, until all lead wires are tested.

Jeff Lind

It also appears that the tolerance of the test components has been increased to ±1% for this test, see Para. 201.5.4. In the previous edition, we assumed a tolerance of ±5% was required by these components by reference to a similar Figure in IEC 60601-1 (see IEC 60601-1:2005 Fig. 9). This reference was necessary because it appeared to us that no tolerances were assigned to the load-carrying components making up the circuit (see IEC 60601-2-27:2005, Para 17h.101.3 and Fig. 108).

The new test package for -2-25:2011 and -2-27:2011 is quite a bit more stringent than the old test. Regulatory engineers will have to ensure that the resistor circuit value of 470kΩ is changed to the new value of 390kΩ. Since the topology of the common mode test has changed, regulatory engineers will also have to modify their defibrillation protection testers to add in S3 and lift the connection between the bottom node of the 100Ω resistor and ground while the common mode is connected, and replace the connection for the differential mode. Please note also that S3 is a in a high voltage, high current portion of the circuit and should be suitably sized.

Of greater concern is the new repetition rate of 20 seconds between tests. We have checked and we do not believe any cycle times have been assigned to this test in past versions of this standard, or other standards in the IEC 60601-x universe. If the test is conducted at this repetition rate using a tester not rated for this duty cycle, the resistors will heat and fall out of tolerance, making test results inconclusive.

Further, the accuracy of the resistors have gone from an assumed tolerance of ±5% to a required tolerance of ±1%. This is a big improvement for defibrillation protection testers because it is a brand new tolerance, much more stringent than the tolerance of similar circuits in tests described in the overall Standard IEC 60601-1.

Defibrillator
Emergency defibrillator image from Olaf on Flickr. 

Existing defibrillation protection testers will need to be updated to meet this new requirement.

A note on resistor tolerance: While it appears that the resistor tolerance noted in the new IEC 60601-2-25:2011 of ±1% is for the resistors at rest (cold, before testing), another important tolerance is the drift experienced by the resistor bank while it heats, during the test; which is not addressed in the IEC Standards. It’s important to keep the drift within a reasonable amount during the test sequence. (We have assumed that the drift of the resistor bank should stay within the specification noted in IEC 60601 during the pulsing cycle in the past, so we have assumed a 5% drift as being the requirement in our equipment.) Since the new 20 second duty cycle is faster than anticipated by defibrillation protection Testers currently on the market, regulatory engineers should test their defibrillation protection testers to see if the resistor bank will stay within comfortable tolerance. This test can be done by pulsing the defibrillation protection Tester every 20 seconds with nothing connected to the output, so the whole pulse appears across the 100Ω resistor. Repeat this test ten times to simulate the new common mode test. If a resistance measurement of the 100 ohm resistor is taken just before the next pulse is delivered, the engineer can see what tolerance can be held by the tester, and make a determination of acceptability.

As a final note, we are designing our defibrillation protection tester to meet the new requirements, and are assigning a resting tolerance to the 100Ω resistor of 1%, and a working tolerance of 5% over a duty cycle of 20 seconds continuous. We believe this is a valid interpretation of IEC 60601-2-25 and -27. Should discussion ensue we are most interested. 

—Jeff Lind

Jeff is the president of Compliance West USA (San Diego, CA)

Artificial Pancreas, Injection Sites, and Fast-Acting Insulin: Diabetes Trends and Challenges

 Artificial Pancreas, Injection Sites, and Fast-Acting Insulin: Diabetes Trends and Challenges

Bill BIll BettenBetten recently attended the 5th International Advanced Technologies and Treatments for Diabetes (yep, the poor guy just had to go to Barcelona). Afterwards, he was kind enough to provide MD+DI with his observations from the event, highlighting trends in the sector.

What were some diabetes trends that you noticed?

A keynote talk was given on “What Next for Diabetes Technology: Strategic Directions for the Next 10 Years,” by J. Pickup of London. The five highlighted buzzwords included cost effectiveness, nanomedicine, mobile health, optical sensing, and closed-loop insulin delivery. A point that he made is that insulin pumps, for example, have taken over 30 years to reach maturity, and continuous glucose monitors (GCMs) have been around since 1999 and are not yet beyond clinical trials. Even with insulin pumps, a lot of discussion was around a low glucose suspend (LGS) mode of operation, which allowed the pump to stop infusing insulin for up to a two-hour period as a mechanism for avoiding hypoglycemia. Apparently this mode is controversial enough that it is not yet approved in the United States. If this isn’t possible, then the prospect of going completely closed loop is still out in the future.

Many of the presentations centered around closed-loop monitoring of insulin patients, up to and including the creation of an artificial pancreas. Fundamental elements of closed loop systems are the sensors, a processing board with signal processing, an insulin pump, and a delivery mechanism for the insulin into the body.

 

Can you tell me more about the artificial pancreas technology?

There were a number of discussions associated with the creation of an artificial pancreas. In fact, there is a European sponsored project to focus on development of such a system. Common hardware configurations included the Dexcom Seven Plus CGM system plus an Insulet Omnipod pump. In between were a number of discussions about the hardware and signal processing designed to manage the entire loop. There were discussions about fuzzy logic, neural nets, and all kinds of management techniques designed to address the issues associated with closing the loop. At a very basic level the goal of such a system is to maintain the blood glucose level within an acceptable level (typically 70 – 140 mg/dL) while dealing with the disruptions of meals and physical activity. While this might seem to be a classical feedback control-loop problem, the difficulties start with the inaccuracy of the continuous glucose monitoring (CGM) sensor and relating that to actual glucose in the bloodstream. The difficulties continue with the lag times of insulin injection, impact on the body, and duration of the insulin in the blood stream. It is like trying to hit a moving target while the background conditions are continually changing. Draft guidelines exist from the US FDA and can serve as a framework for investigations into this area.

What are some other challenges to managing and treating diabetes?

The choice of site for injection of insulin is clearly an issue, given the different physiology of the body and how it takes the insulin into the blood stream. Injection into the subcutaneous tissue can have a different reaction time than deeper within the body. One of the key targets for insulin pumps is to keep a minimum dosing levels running as a background, and then using a larger bolus injection to address meals, exercise, etc.

A very definite need is faster acting insulin with shorter duration in the body. Numerous fast-acting versions exist, but long-term persistence remains an issue, increasing the risk associated with hypoglycemia (low blood sugar). The risks associated with hypoglycemia are short term from the perspective that too low of a blood sugar can cause a coma and death quickly (less than an hour), while the effects of hyperglycemia (high blood sugar) tend to be long term due to impact on blood vessels (nerve damage, poor circulation, loss of eyesight, potential amputation, etc.). Either condition is serious, but the emphasis is on prevention of hypoglycemia since it has more immediate consequences. In addition, inhaled insulin is being assessed as an alternative or enhanced method of delivery of the drug.

A critical aspect of both the measurement of blood glucose levels is the sampling location. The most representative sampling method is directly from the blood, hence the popularity of the blood glucose measurement sticks. The continuous glucose monitors sense the glucose in the interstitial layers underneath the skin, which is different than the level in the blood. Other methods, including optical, are being explored, but none of these seem to be acceptable yet.

Better sensors are required due to relatively poor accuracy, particularly in CGM, and need for increased reliability. The margin of error with CGM sensors is sufficiently broad that they must be calibrated via a blood stick typically at least every 12 hours and cannot currently be used for long term closed loop patient treatment.

Roche Diaport, courtesy of diabetesmine.comWere there any particular devices that caught your attention?

There was much discussion around the Roche Diaport system. Basically this is a port implanted in the body that allows connection to the insulin pump system. However, a key attribute of this system seems to be the placement of the catheter into a deeper portion of the body, nearer to the liver, to enhance the take up of the insulin into the body. One of the problems with injection of the insulin into the body as well can be adhesion and overgrowth along the injection site, limiting the ability to keep the site open and necessitating relocation of the injection location. The Diaport catheter is apparently designed to float within the abdomen and help allay such problems. In addition, there were discussions of injection of another drug with the insulin to facilitate the injection location’s ability to take up insulin as well as using a heating mechanism to do this as well.

—Heather Thompson

Further Reading

Product Teardown: Inside the Dexcom Seven Plus Continuous Glucose Monitoring System

Tech Review: JDRF’s Insulin Initiative: Afrezza, Roche’s DiaPort, Smart Insulin and More

Patient Perspectives: Tom Brobson: My Experience in the Artificial Pancreas Clinical Trials


 

OncoSec Could Revolutionize Oncology Therapy

OncoSec Could Revolutionize Oncology Therapy

The permeability of a cell membrane can be dramatically enhanced by applying  an external electrical field. This technique, known as electroporation, has a history of being used in research settings to introduce molecules into cells. Clinical applications of the technology, however, have been limited until recently. But electroporation could be a disruptive force in oncology, where it can be used in conjunction with a drug or DNA-based biologic to decrease side effects of active therapeutic agents.

Electroporation technology can result in a 4000- or 10,000-fold increase in movement of an agent into cells. 

A company known as OncoSec Medical Inc. (San Diego, CA) is working to become a trailblazer in the domain of medical electroporation technology. The firm is using the technology to dramatically facilitate uptake of drugs or biologics into cells through an increase in permeability of the cell membrane. “The treatment approach is very potent,” says Punit Dhillon, cofounder, president, and CEO of the firm. “We can see a 4000- to 10,000-fold increase in the movement of the agent into the cell,” he says. Substantially increasing the cellular uptake of chosen therapeutic agents can minimize the dose required to destroy cancer cells and spare healthy tissues. In addition, by enhancing the delivery mechanism of treatment, the side effects of non-targeted cancer-treatment protocols such as traditional chemotherapy can be drastically reduced.

Dhillon was formerly the head of operations and finance for Inovio Pharmaceuticals (Blue Bell, PA), which had been investigating the use of electroporation for chemotherapy, immunotherapy, and DNA vaccine applications. Inovio decided to focus on the use of electroporation for DNA vaccines. OncoSec was spun out of Inovio to use the technology to target solid tumors. 

At present, OncoSec is working on three phase II clinical trials, which will use its patented “electroimmunotherapy” technology to deliver DNA-based interleukin-12 (DNA IL-12) to patients with metastatic melanoma, Merkel cell carcinoma, and cutaneous t-cell lymphoma. “Our focus is to continue our immunotherapy approach, which we feel is very elegant for delivering DNA IL-12 locally,” Dhillon says. “We are exploiting the local response, and then we are getting a global systemic response.

  • June 2011: Received $3 million

     Focus Going Forward

    • Gather preliminary data for metastatic melanoma, Merkel cell melanoma, cutaneous T-cell lymphoma phase II trials.
    • Continuous partnering efforts in electrochemotherapy and additional data points.
    • Initiate and begin enrollment in CTCL electro-immunotherapy program.

    Highlights

    • February 2012: Initiation of Phase II melanoma study.
    • September 2011: Preliminary data  announced for chemotherapy programs.
    • June 2011: Phase I data announced for melanoma.

    “The key areas that we decided to focus on are very important. They are all lethal in cancer. Our flagship product is for metastatic melanoma. We are focused on stage 3 and stage 4 melanoma,” Dhillon says. Patients with this cancer have limited treatment options. “With these patients, we are now seeing an overall response rate of around 50%,” Dhillon continues. 

    Punit Dhillon 

    “This is really a next generation delivery technique. We are using electrical field energy to get the agent into the cell.”
    —Punit Dhillon, president and CEO 

    The company is also investigating the use of electroporation to treat Merkel cell carcinoma and cutaneous T-cell lymphoma. “Those are also very rare skin cancers and they are very lethal for these patients,” Dhillon says. “All of these treatment options are very amenable to using the DNA IL-12 combined with electroporation approach that we are doing.” 

    The company recently dosed the first patient in its phase II clinical trial for metastatic melanoma. “We are working toward completing enrollment in [our three clinical] studies in the next 12 months, and then we will have data to share with a partner,” Dhillon says. “In addition, we are also going to use that data to advance [our] programs.”

    Leadership

    Avtar Dhillon, MD, chairman
    Punit Dhillon, president and CEO
    James M. DeMesa, MD, director
    Anthony E. Maida, III, PhD, director

    Contact

    Oncosec Medical Inc.
    4690 Executive Dr # 250
    San Diego, CA 92121 | 858/558-8518
    www.oncosec.com

    OncoSec's technology was recently featured in a news broadcast by KIRO7:

    —Brian Buntz  

    Brian is the editor-at-large at UBM Canon's medical group. Follow him on Twitter at @brian_buntz.