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Articles from 2003 In December

Spinal Surgery on the Verge of a Breakthrough

Originally Published MDDI December 2003


Erik Swain

Nonfusion disk arthroplasty has the potential to revolutionize the spinal surgery market, attendees to an industry summit learned in October.
A number of such technologies will hit the U.S. market starting in about 18 months, and they could provide patients with an alternative to spinal fusion, presenters at HealthPoint LLC's spine industry summit said. 

“These technologies are being shown to relieve the pain without fusing the spine, allowing patients to maintain normal motion,” said Robin Young, managing director of research for HealthPoint, a research and private equity firm devoted exclusively to orthopedics. “Clinical trial results for this approach show it relieves pain better than fusion. And since [the surgery] can restore the back's normal motion, it looks like a home run. The data have gotten everyone excited. It could be a game-changing technology.”

The market for such products could be vast, Young said, since more than 500,000 spinal surgeries are performed each year, and 300,000 of them are spinal fusions. He noted that industry has spent about $1 billion in the past year on research, development, and acquisitions in this area. None of the technologies are yet available in the United States, but some are in Europe, where sales have quadrupled in 2003 over 2002. 

Questions remain over which manufacturers will be able to capture the market. There could be as many as 10 players, and four considered among the closest to a U.S. debut presented data at the HealthPoint summit. The four products described were the SB Charite Artificial Disc from DePuy Spine Inc. (Raynham, MA), a Johnson & Johnson company; the ProDisc from Synthes-Stratec (Oberdorf, Switzerland); the PDN-SOLO Prosthetic Disc Nucleus from Raymedica Inc. (Minneapolis); and the Dynesys from Zimmer Holdings Inc. (Warsaw, IN).

“All of these lend themselves to a minimally invasive approach,” Young said. “Most of them are disk products that fit between the disk and the vertebra. Raymedica's looks like a tiny pillow. But all are like joints for the spine.”

But, he said, what attendees wanted to know most was which product would be the first to achieve U.S. market entry and which would offer patients the best performance in the long run. “The summit helped clarify that Charite will likely be first, with ProDisc right behind it. But no one's saying who's best yet. All we know is that all the products are better than fusion.”

Copyright ©2003 Medical Device & Diagnostic Industry

Combined Inspections:FDA’s Third-Party Carrot

Originally Published MDDI December 2003


Combined Inspections: FDA's Third-Party Carrot

To ensure the success of its voluntary third-party inspection program, FDA is counting on concurrent inspections to be enough incentive for industry.

FDA readily admits it can no longer keep up with inspections. So, with a third-party inspection program in place, FDA is pulling out all the stops to encourage industry to actually use it.

Under the program, device manufacturers can now arrange for FDA and other conformity inspections to occur at the same time. That is, of course, provided that the inspecting firm—one of the 15 newly appointed Accredited Persons (APs)—is also a conformity assessment body.

FDA is touting this benefit as a really big carrot for industry. The third-party inspectors can perform audits and inspections to the requirements for multiple nations—something FDA can't do. Instead of scheduling multiple audits to show compliance with nearly identical requirements, manufacturers could reduce the number of inspections by combining them.

CDRH director David Feigal Jr. says that such incentives should encourage industry to use the program, which he calls industry's best avenue to “eventually developing multipurpose inspections.” 

“It is highly unlikely that FDA will ever have the resources to allow our inspectors to grant a CE mark, but it may be possible for a third-party
inspector to do that,” Feigal noted at the Regulatory Affairs Professionals Society (RAPS) conference in Baltimore in October. Allowing third-party inspections was “the most important legislative change for Congress to make” last year, Feigal said at an AdvaMed meeting last March.

Feigal acknowledges that the program has limitations. Under the program, FDA must conduct every third inspection, and the agency must conduct all preapproval inspections. An added hurdle requires that manufacturers show that the law in a country where the device will be marketed recognizes FDA inspections. No country currently has such a law, which means that FDA must now figure out how to address this legislated requirement that asks manufacturers to do the impossible.

The good news is that FDA is actively tackling these limitations in its industry presentations and guidance documents. FDA wants to ensure that the program can get off the ground. If enough device manufacturers use the new third-party program, it would free FDA to allocate its limited resources more strategically, including increasing the number of facilities it inspects.

FDA is required by law to conduct routine inspections every two years. However, for device manufacturers of lower-risk technologies, the agency has been able to perform such inspections only every five to seven years, according to AdvaMed.

Feigal also says it would be nice to build the program to the point where FDA could even allow third-party preapproval inspections. He is calling on industry to take advantage of the benefits of the third-party program. The sooner that happens, he says, the sooner FDA will have the confidence necessary to allow APs to conduct preapproval inspections as well.

Now it is up to industry to determine whether the carrots being offered are big enough. If so, industry needs to state loud and clear to the APs that the incentive of grouped inspections would make the program worth using. The time and money saved could be substantial.

Much of the onus, however, falls on the newly named APs to develop systems for concurrent inspections. It may take some time for them to mesh existing assessment programs with FDA requirements. The inspection program is voluntary, and its success rests squarely on the shoulders of the medical device industry.

The Editors

Copyright ©2003 Medical Device & Diagnostic Industry

Appreciating the Microcultures of a Product Development Team

Originally Published MDDI December 2003

Product Development Insight

Recognizing differences among team members can enhance team performance.

Richard Rosen
Battelle Memorial Institute

Much has been written about the style differences that exist between company employees who work in the general areas of research and development, manufacturing, sales and marketing, finance, and general management. Recognizing the communication differences that exist between such personnel is critical to success in the development and launch of a new product. As a manager of R&D or engineering staff responsible for new product innovation, you know that differences don't stop at departmental or functional area lines.

In the product development area, teams are most often comprised of interdisciplinary technical groups that collectively represent the technologies required in the end product. Consider a typical product development team for a new diagnostic instrument. Experts in biotechnology, chemistry, and microbiology combine with engineers in software, electronics and controls, mechanical, polymer, and manufacturing disciplines. They in turn work with quality system and regulatory staff to accomplish the program goals. 

Frequently, the only common bond existing between the members of these groups is one of analytical methodology or mathematical foundation. Yet all too often, the technical groups are viewed and evaluated collectively, without recognizing their inherent dissimilarities. So how can you prevent such differences from negatively affecting the team's performance?

Researchers have coined the term microcultures to acknowledge the differences in style, values, and communication preferences that exist among small groups within a company. While they exist on many levels, it is useful to focus on the microcultures that exist within technical disciplines of an engineering or R&D unit. When harnessed, the diversity of multiple viewpoints gives rise to innovative new-product ideas. However, an interdisciplinary technology team is equally fertile ground for communication problems and style differences, which must be properly managed to achieve product success.

Does This Sound Familiar?

Consider the following example to see if it has a familiar ring. Your company has several product development efforts ongoing in its product pipeline. One team is performing very well and seems to deal effectively with each unanticipated problem without missing a beat. A second team is struggling to make progress and frequently makes such statements as “It's software's fault that we're behind,” “The quality system is limiting our ability to make quick decisions,” “Don't blame the sensor; the assay doesn't behave like it is supposed to,” and so on. Yet, both teams work in the same company, use identical process systems and operating procedures, and are guided by the same business objectives. Why is there such a difference in performance? One explanation for the variation is ineffective interactions of microcultures within the two teams.

Research from well-known sources such as Myers-Briggs and “The Art of Thinking,” by Harrison and Bramson, have shown that individuals think and communicate from diverse perspectives. Appreciating and harnessing this diversity can be the source of high performance. Ignoring these traits can be the source of problems, at both the individual and team level.

Look for these warning signs that can indicate when a team or an effort is headed for trouble:

• A problem or conflict remains unresolved, despite repeated efforts to correct the situation.
• Disgruntled “finger-pointing” exists, embodied in statements such as, “Software is always our problem.”
• An individual becomes overly dominant, to the point of being disruptive, yet he or she is highly valuable and critical to the project's outcome.
• A project team reaches a stage of near burnout on a long, grueling project, and there is still considerable work ahead before it will be finished.
• A project seems stalled in a particular phase of its effort, despite good intentions and continued hard work on the part of the team.

Resources and Tools

It is important to recognize that technical team leaders have a long history of accomplishment as technical contributors, but often have little training in interacting with others, team dynamics, and appreciating how communication differences impact progress. 

Numerous points of view are sought in brainstorming sessions because of the value of diverse opinions and viewpoints. But in other team settings, managers are sometimes intolerant of certain types of communication or interactive styles because they seem disruptive or distracting. Team leaders should pay attention to managing the softer side of technical functions, and increase their listening and perceptive skills to help them more effectively manage an interdisciplinary team.

Here are some approaches to enhance a high-performing team, or to energize a stalling team. These approaches can also help when undertaking an effort where the parties or people are new and unfamiliar to one another.

• Conduct a session, through the human resources department or through outside facilitation, designed to raise the awareness of different styles of communication and interaction. Techniques such as Myers-Briggs type indicators and The Forté Institute are well-known and helpful in this regard.
• Set aside time at the outset of new projects to bring significant senior leadership together with the entire team, no matter how large, to express appreciation for the effort and to share background information that is important to the project.
• Wherever possible, bring customers and success stories directly to employees, so that individuals can remember who the real beneficiaries of your products are.
• Invest in training key team members, such as project managers, in leadership techniques and differences in communication style. Make accomplishing this training an element of their performance appraisal.
• Support efforts that encourage staff to appreciate diversity in all dimensions as it relates to their fellow coworkers.
• Conduct readiness exercises and focused workshops as projects progress through different stages to actively ensure that the staff works from common understandings, instead of differing interpretations of what is most important to the project's success.
• Establish safety-net programs that offer nonintrusive support systems from other teams, individuals, or senior management to create and sustain environments conducive to success.
• Perform surveys to provide fact-based benchmarks and serve as early-warning systems about trends that could be destructive to achieving goals.

A summary of these concepts is shown in Table I.

Table I. Certain approaches can enhance a team's performance, or energize a stalling team (Click to enlarge).

These concepts do not only apply to projects within your own company; they apply to company-to-company relationships as well. Statistics show that alliances and collaborations between companies rarely fail because of technical problems. The cause for failure almost always involves some form of communication breakdown. Likewise, strong strategic alliances perform well because there is an alignment of goals, an atmosphere of mutual trust, and an appreciation of each other's business constraints.


Raising awareness among R&D and engineering staff managers can have a significant impact on product development team effectiveness. Appreciating and harnessing the differences of multidisciplinary teams is a source of important innovation and progress, not to mention a way to provide a more fulfilling work environment for all involved.

A seasoned manager of a device R&D group once spoke at a conference on leadership and said, “Anyone can manage when times are good; the true test of leadership comes in the face of conflict, and how you respond and learn from those challenges.” It is risky to wait until problems arise and assume that your product development leaders are adept at mobilizing a diverse technical team to solve the problems. Taking steps to train team leaders about the dynamics of interdisciplinary microcultures is one case where an ounce of prevention is truly worth a pound of cure. 

Copyright ©2003 Medical Device & Diagnostic Industry

FDA Enforcement Deeds Don’t Match Words

Originally Published MDDI December 2003


FDA Enforcement Deeds Don't Match Words

The current perception of an “aggressive” FDA is inconsistent with the agency's own annual analysis.

James G. Dickinson

What FDA Can and Can't Do with PMAs | Misys Recalls Defective Software | Identification Sought on Reprocessed Devices | ASR Makers Seek DNA Guidance Clarification | FDA Closer to Approving Silicone Implants 

As high-ranking regulatory attorneys met in September to discuss what they and many of their clients deemed a newly “aggressive” FDA, the agency itself issued its annual analysis of enforcement performance. Ironically, FDA's report confessed continuing decline.

The apparent dichotomy reflects, in part, the approaching election season, during which the administration will seek to portray itself—among its many national-security concerns—as strong on enforcing laws that protect healthcare products. Such posturing explains the current rash of bold proclamations about security arrangements for FDA-supervised distribution pipelines and new collaborations between domestic and foreign trade agencies at ports of entry.

However, when John Scharmann, a former FDA Denver District director, looked into FDA's Enforcement Story for fiscal year 2002 (the latest available), he found a significant across-the-board reduction in three out of four measures of enforcement performance during the latest three-year period. Only court injunctions had increased, from 11 to 15. Criminal prosecutions had declined from two to zero, warning letters from 1154 to 756, and seizures from 36 to 13.

On the other hand, these reductions occurred in tandem with a 42% increase in product recalls, from 3532 in fiscal year 1998 to 5025 in fiscal year 2002.

The perception of increased FDA aggression was expressed by attorneys during FDLI's recent annual Conference on Enforcement and Litigation. Most of the meeting focused on a handful of high-profile GMP cases in which FDA has pioneered profit-disgorgement penalties.

FDA deputy chief counsel for litigation Eric Blumberg staunchly defended the strategy of seeking court orders to force companies to surrender to the U.S. Treasury any profits gained from selling violative products.

He called it “a long-recognized equitable remedy developed to prevent unjust enrichment and to deprive a defendant of ill-gotten gains.” He said this legal remedy is intended as a “deterrent” to future violations and should not be viewed as a “penalty.”

Pointing to a 1999 consent decree with Abbott Laboratories that provided for disgorgement, and a record-breaking $500 million disgorgement in a consent decree obtained from Schering-Plough Corp. in 2002, Blumberg said such settlements are designed “not only to remove incentive to break the law, but to reduce any incentive to delay compliance.”

Although some have disputed FDA's authority to seek disgorgement (it is not specifically provided for in the Federal Food, Drug, and Cosmetic Act), Blumberg cited at least three U.S. Supreme Court cases that he said uphold the agency's position. Included among these was Porter v. Warren, a 1946 decision the agency views as definitive.

Michael Labson of the Washington law firm Covington & Burling objected to Blumberg's application of the term ill-gotten gains to GMPs. Labson argued that GMP violations are not those to which this remedy has traditionally been applied. He also took issue with FDA's practice of naming individuals in consent decrees, stating that this can unfairly jeopardize their future employment prospects.

Blumberg retorted, “Why would anyone want to hire an . . . executive that had been involved in a major violation anyway?”

By not addressing the declining number of FDA enforcement actions and instead focusing on the perceived severity of the few actions that do occur, the FDLI conference discussions illustrated the Bush administration's enforcement philosophy: Get the “biggest bang for the buck” in an environment in which FDA simply cannot afford to even try to catch every violation.

Indeed, it may be fairly observed that by focusing on the “biggest bang” philosophy of enforcement, FDA is tacitly admitting that in the absence of human injury, most of the smaller, day-to-day breaches of its myriad regulations don't matter in the real world.

What FDA Can and Can't Do with PMAs

FDA's Center for Devices and Radiological Health and Center for Biologics Evaluation and Research have issued a new guidance, FDA and Industry Actions on Premarket Approval Applications (PMAs): Effect on FDA Review Clock and Performance Assessment. The guidance lists criteria for the various actions FDA can take during and after a PMA review, and the effect of each on the review clock and performance criteria set forth in the Medical Device User Fee and Modernization Act of 2002 (MDUFMA).

The guidance states that MDUFMA performance goals contain both cycle and decision goals for original PMAs, original expedited PMAs, panel-track supplements, and 180-day PMA supplements. After reviewing an original or supplemental PMA and considering any applicable advisory-panel recommendations, FDA can issue a written letter indicating that the application is approved, approvable, not approvable, or denied.

FDA should issue an approval order once it feels reasonably assured that the device is safe and effective for its intended use as prescribed in the product labeling, the guidance explains. Issuance of an approval order is also contingent upon the agency determining that the device company's manufacturing facilities, methods, and controls are in compliance with the quality system regulation. 

The agency should issue an approvable letter (different from an approval order) when it has determined that minor deficiencies remain that must be addressed before an approval order can be issued. If the agency has not yet determined whether the applicant's manufacturing facilities, methods, and controls are in compliance with the quality system regulation, it should issue an approvable letter as well.

The guidance says that FDA should issue a major-deficiency letter once it has determined that a PMA lacks any of the following necessary data: detailed reanalysis of previously submitted data, additional test data to demonstrate safety and effectiveness of the device, scientific justification for test data in the submission, new validation data and analyses, and/or any other substantive deficiencies that prevent FDA from making a determination about a device's safety and effectiveness.

A not-approvable letter, according to the guidance, tells a PMA applicant that FDA has completed a scientific review of the PMA and does not believe that it can be approved because of significant deficiencies identified in the letter. Applicants who receive a not-approvable letter may amend their PMA to address the deficiencies, withdraw the PMA, or consider the letter to be a denial of approval and request administrative review.

The guidance indicates that for original and panel-track supplements, a not-approvable letter is issued after FDA has conducted a complete review of the PMA application, including any recommendations by an FDA advisory panel, if applicable, and determined that the available data in the PMA do not support a determination of reasonable assurance of safety and effectiveness. Generally, according to the guidance, FDA has provided the applicant with an opportunity to address its concerns in a major-deficiency letter before the agency issues a not-approvable letter.

For 180-day supplements, a not-approvable letter is issued when an application lacks substantial information needed for FDA to complete its scientific review and render a final decision on the supplement, or after FDA has conducted a complete review of the supplement and determined that the available data do not support determination of a reasonable assurance of safety and effectiveness.

The guidance defines a denial order as a letter telling a PMA applicant that the agency has completed its scientific review of a PMA and, based on the review, has decided not to approve the PMA. Like a not-approvable letter, a denial order includes all deficiencies that must be adequately addressed by an applicant to bring the PMA into approvable form.

FDA may issue a denial order if (1) after reviewing an amendment submitted by an applicant in response to a not-approvable letter, the agency determines that a PMA still does not support a determination of reasonable assurance of safety and effectiveness; (2) FDA has received a written response from an applicant to a not-approvable letter stating that the applicant has decided not to submit an amendment; or (3) an applicant decides to regard a not-approvable letter as a denial and petitions for review.

An abandonment letter tells an applicant that FDA considers its PMA abandoned. FDA can issue it when it deems the PMA voluntarily withdrawn because an applicant failed to respond to a request for additional information contained in a major-deficiency or not-approvable letter. The agency can also issue an abandonment letter when other circumstances indicate that the applicant is not undertaking additional measures regarding the PMA, and when an applicant fails to communicate with FDA within seven days of the date on which the agency notifies the applicant that the PMA appears to have been abandoned.

To view the guidance, visit  

Misys Recalls Defective Software

FDA said in October that Misys Healthcare Systems (Raleigh, NC) had recently recalled three versions of its laboratory software because of a defect that could lead to inaccurate results. The software compiles information from blood and urine tests and performs a quality assurance check to determine whether all procedures have been carried out properly. Misys said a software patch is available from the company to fix the glitch. No injuries have been reported as a result of the problem, FDA said.

To view FDA's notice, visit  

Identification Sought on Reprocessed Devices

In comments submitted to an open docket, the Association of Medical Device Reprocessors (AMDR) told FDA that the agency should require identification of the OEM or the reprocessor on all devices as mandated by the Medical Device User Fee and Modernization Act of 2002. 

When the legislation was being drafted, OEMs sought a provision requiring identification of the reprocessor on reprocessed devices. However, AMDR argues that the provision was written to apply to all devices, reprocessed or otherwise. AdvaMed and the Medical Device Manufacturers Association have each argued that AMDR's interpretation of the provision places a significant burden on their members with no apparent benefit. But to require that the provision apply only to reprocessors would be “arbitrary and capricious,” according to AMDR.

To view their comments, visit  

ASR Makers Seek DNA Guidance Clarification

FDA needs to clarify that its draft guidance titled Multiplex Tests for Heritable DNA Markers, Mutations, and Expression Patterns does not apply to clinical assays that incorporate multiple analyte-specific reagents (ASRs), according to the American Clinical Laboratory Association (ACLA). In recent comments to the agency, ACLA argued that the guidance should apply only to “devices that incorporate multiplex technology and are complete ‘test systems.'” 

ASRs currently are exempt from premarket approval, but the group is concerned that the guidance may reverse the exemption. It asks FDA to clarify the boundaries of the draft guidance by stating in the final version that it is “not intended to revise the ASR rule and does not mandate FDA approval of multiplexed reagents where each of the multiplexed reagents otherwise meets the definition of a Class I ASR.”

To view these comments, visit  

FDA Closer to Approving Silicone Implants

Renewed FDA approval of silicone breast implants moved a step closer in October. A highly publicized meeting of the agency's General and Plastic Surgery Devices Panel resulted in a vote of 9 to 6 to recommend approval of a silicone-gel implant PMA from Inamed Corp. (Santa Barbara, CA). 
Marketing of such devices stopped in 1992 because of complaints that toxic silicone migrations from ruptured implants made the devices unreasonably unsafe.

FDA's panel now says that marketing could resume with strict conditions. They suggested requiring that women receiving the implants be fully informed about possible complications and be advised to have regular checkups following the surgery.

The panel heard testimony that major studies have found no evidence that implants caused chronic diseases, despite the fact that many women are convinced that they were sickened by silicone leaking from their implants.

Panel member Michael Miller said, “A large amount of latitude needs to be given to people to weigh the benefits and risks. The risks are well-defined and small. The patient can decide.”

After the vote, Inamed CEO Nicholas Teti told the media that the panel's suggestions were “fair” and seemed to reflect proposals advanced by the company. He said Inamed is committed to long-term research after approval, as well as to educating women about possible risks. The panel urged Inamed to follow some of its research subjects for at least 10 years. 

Copyright ©2003 Medical Device & Diagnostic Industry

Medtech Snapshot

Originally Published MDDI December 2003

From manufacturing and business developments to regulatory and reimbursement activities—key developments and events are captured in this year's .

The Editors

The past 12 months were marked by a number of significant events that are shaping the medical device industry's future. The following pages provide a graphic representation of the industry's current state and identify milestones of the past year.

Copyright ©2003 Medical Device & Diagnostic Industry

Nanosprings Could Lead to Biomedical Sensing Applications

Originally Published MDDI December 2003


Eric Swain

Nanosprings could be of use in small-scale sensing and microsystem applications in the future.

A new zinc oxide nanostructure could end up forming the basis for parts of medical microsystem applications. 

Researchers at the Georgia Institute of Technology (Atlanta) have developed a technology called nanosprings. Helical shapes are formed from long single crystals of zinc oxide. Significantly, they have piezoelectric and electrostatic polarization properties that could be of use in small-scale sensing and microsystem applications, perhaps in the medical field.

Nanosprings are similar to “nanobelts,” first reported in 2001, but are smaller. They are up to several millimeters long but are 10–60 nm wide and 5–20 nm thick. 

“These structures . . . are a major step toward a new system of nanostructures,” says Zhong L. Wang, director of Georgia Tech's Center for Nanoscience and Nanotechnology and a professor at its School of Materials Science and Engineering. “Piezoelectric and polar-surface-dominated smart materials based on zinc oxide are important because they could be the transducers and actuators for future generations of nanoscale devices.”

Specifically, he says, “they could be used to measure pressure in biofluid or in other biomedical sensing applications. You could use them to measure nano- or piconewton forces. In micromechanical systems, these structures could provide the coupling between an electrical signal and a mechanical motion.” In addition, fluid flows, airflows, strain forces, and acoustical waves that were previously imperceptible might now be detected.

Also, the structures appear to have a strong electrical charge because of electrostatic polarization. That means they might attract specific molecules, which would make them useful as biosensors to detect single molecules or cells. Thus they might be a fit for in-body biomonitoring applications.

“We would like to use these materials for in situ, real-time, nondestructive monitoring within the body with high levels of sensitivity,” says Wang, who has been collaborating on the research with Xiang Yang Kong. 

It will be a while before applications are found, however. “We can cut this material into specific lengths and manipulate it, but that's only the first step,” Wang says. “We need to know how to integrate this into existing technology. We can generate voltages, but how can we measure them? We must learn to calibrate a system, and quantify the data to know what force is being applied.”

Support for the research came from the National Science Foundation, the NASA Vehicle Systems Program, and the Department of Defense Research and Engineering program.

Copyright ©2003 Medical Device & Diagnostic Industry

Medtech Snapshot

Originally Published MDDI December 2003


FDA-registered medical device establishments, with the number of firms and percentage of U.S. total for each state. Establishments include manufacturers, contract manufacturers, repackagers/relabelers, and rebuilders/refurbishers.
Medical device manufacturing, repackaging, and rebuilding operations, by state. 
Medical device industry market size by specialty (as of October 24, 2003). Source: Dun & Bradstreet.

Copyright ©2003 Medical Device & Diagnostic Industry

Electrical Stimulation Procedure May Aid Stroke Recovery

Originally Published MDDI December 2003


Maureen Kingsley

Robert Levy, MD, PhD

A new surgical procedure involving electrical stimulation may help restore the use of hands and arms to some stroke victims. The procedure involves affixing a tiny electrode onto the brain's protective membrane layer. The electrode, powered by a battery pack and placed into position using an MRI scan, delivers electrical stimulation to parts of the brain responsible for hand or arm function and movement.

The study, sponsored by Northstar Neuroscience Inc. (Seattle), is taking place at Northwestern Memorial Hospital (NMH; Chicago) and four other sites. It will determine whether stroke survivors suffering impaired extremity movement can make greater progress in their recovery when traditional physical rehabilitation is coupled with electrical stimulation of the motor cortex. 

Alan Levy, Northstar's CEO, explains that the procedure used to implant the electrode is designed to be relatively simple and straightforward. The electrode itself is “very flat and thin; I would say postage-stamp sized,” he says. “It sits on the dura mater, the brain's tough covering. It's designed to be very flexible and to go in through as small an opening as possible.”

Robert Levy, MD, PhD, is leading the NMH portion of the study. Levy is professor of neurosurgery and physiology at the Feinberg School of Medicine at Northwestern University. He describes the technology as being “based on devices that physicians have been using for decades—electrodes over the brain and battery packs to drive the electrodes.” Such methods have been in use since the 1960s, he says. 

But the devices being studied in the NMH trial are modified, and the technology to place them correctly in patients with strokes represents advancements in neuroimaging techniques. “For example,” he says, “the study we're doing looks at arms that have been rendered weak by stroke. We have a paradigm whereby patients are told to move their arm and to think about moving their arm while in the MRI scanner, and that area of the brain lights up on the scan. And that's the spot—precisely—where we put the electrode.”

Alan Levy says Northstar plans to do another, larger study of the device within the next year and, assuming all goes well in both studies, apply for FDA approval soon afterward.

Copyright ©2003 Medical Device & Diagnostic Industry

Medtech Snapshot

Originally Published MDDI December 2003


FDA medical device program resources have been reduced in recent years and review performance has begun to decline. User fees provided by MDUFMA are designed to get devices to patients more rapidly and to improve timeliness 
and quality of reviews.

Medical device listings by medical specialty code, with percentage of total listings.
Average review time for original premarket approval (PMA) applications increased from 172 days in 2001 to 213 in 2002. The total average elapsed time to approval of PMAs decreased to 364 days in 2002 as a result of decreases in non-FDA times.

During fiscal year 2002, the median time for review of 510(k)
submissions by Accredited Persons was 77 days after initial receipt—29% faster than reviews performed entirely by FDA. In addition, submissions reviewed by Accredited Persons are not subject to FDA user fees, whereas 510(k)s sent directly to FDA were subject to a fee of $2187 in fiscal year 2003. 

The increase in the number of 510(k) submissions reviewed by third-party organizations can be attributed to the expansion pilot program that now permits third-party review of approximately 460 Class II devices. In 2002, the average total elapsed time from third-party receipt was 70 days for nonpilot 510(k)s and 105 days for expansion pilot 510(k)s. Expansion pilot 510(k)s include Class II devices 
without device-specific guidance that can now be reviewed by 
Accredited Persons.

Spending for healthcare increased to $1.4 trillion in 2001. Total public funding growth exceeded private funding growth. An important source of growth was payment increases to Medicare providers. Medicare expenditures increased to $242 billion, financing one-sixth of overall health care costs. The recession and rising unemployment contributed to increased Medicaid enrollment.

Spending by public agencies, such as the Centers for Medicare and Medicaid Services (CMS) and Veterans Health Administration, accounted for more than one-third of the nation's annual healthcare spending in 2001. 
Summary of FDA decisions on 510(k) submissions, 1998–2002. Source: ODE annual report.

ODE received 4320 original 510(k)s as well as 1780 510(k) supplements. Supplements are responses to hold letters, which restart the 90-day review clock. ODE received 2385 510(k) amendments. These provide additional information while the device is under review. The review clock in not affected. The time it took to review 50% of the 510(k)s fell to 74 days in 2002. 

Copyright ©2003 Medical Device & Diagnostic Industry

Genetic Variations May Affect Radiation Sensitivity

Originally Published MDDI December 2003


Erin Bradford

Nicolaj Andressen, MD

Specific variations in the basic building blocks of DNA may affect a patient's sensitivity to radiotherapy. Researchers in Denmark suggest that it might be possible to develop gene-based, predictive tests to enable doctors to determine the highest dose of radiation a patient could tolerate, thereby improving the efficacy of radiotherapy treatment.

During this year's European Cancer Conference, Nicolaj Andreassen, MD, research fellow in the department of experimental clinical oncology at the University of Aarhus (Aarhus, Denmark), described an analysis that studied variations in five genes known to be involved in the body's response to radiation treatment. He and his colleagues looked at the sequence of the four nucleotides that make up the DNA of each gene, and identified places where the sequence varied from the norm. These variations could influence the amount of radiation a patient can handle, the researchers suggested.

The places on the genes where the variations are found are called single nucleotide polymorphisms (SNPs). SNPs represent sites where a nucleotide varies from the nucleotide that most people have. The occurrence of SNPs means that certain people may have a protein that works differently than the corresponding protein would in a person with a normal nucleotide sequence.

“Our findings indicate that normal tissue radiosensitivity should be regarded as a trait dependent on the combined effect of variation in several genes, and the SNPs could constitute a substantial proportion of such genetic determinants. This means that normal tissue radiosensitivity could potentially be predicted from individual genetic patterns or profiles,” Andreassen explains.

Although the results need confirmation and more work is necessary, Andreassen thinks this discovery could be the first step to developing tests to predict the way individual patients would respond to radiotherapy. “If normal tissue radiosensitivity could be reliably predicted prior to treatment, the radioresistant patients could possibly be offered a higher dose. In many cases, this would increase the chances of cure substantially,” he adds.

At present, radiotherapy doses are often restricted by what the most radiosensitive patients can tolerate. The doses keep the risk of severe normal tissue damage below 5–10%, despite the fact that many patients might be able to tolerate a larger dose without severe tissue reactions.

Andreassen says that, at this stage, it is difficult to predict the implications this study will have for radiation device manufacturers. “The ultimate aim of our research is to establish a gene-based assay that could be used routinely to predict the normal tissue outcome from radiotherapy,” he said. 

Yet he predicts that the years to come will bring an increasing integration between molecular diagnostics and clinical decision making. Until that time, radiation device manufacturers are advised to keep an eye on research such as Andreassen's.

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