Friday, April 15, 2011

Back to Blogging

Back after a month away.  The follwing item appeared todaty that is directly related to the last item we posted here.

FDA's Medical Device Review Scrutinized at Senate Hearing

Recent study suggests that high-risk medical devices were recalled at a rate of 1.4 devices for every one U.S. resident in the first six months of 2010

WASHINGTON - Today, U.S. Senator Herb Kohl, Chairman of the Special Committee on Aging, held a hearing examining the Food & Drug Administration's (FDA) role in protecting patient safety as part of the medical device approval process. The panel featured testimony from Marcia Crosse, Ph.D., Director of the Health Care Team at the Government Accountability Office (GAO). Crosse's testimony outlined the preliminary findings of an ongoing GAO investigation into the FDA's management of medical device review, post-market monitoring and recall processes.

"Concerns persist about the effectiveness of the 510(k) process in general, including its ability to provide adequate assurance that devices are safe and effective," Crosse said in her testimony. "Gaps in FDA's postmarket surveillance show that unsafe and ineffective devices may continue to be used, despite being recalled."

Kohl opened the hearing by emphasizing that "the FDA must constantly strive to maintain a delicate balance between safety and innovation."

"The drive toward getting new technologies to market shouldn't be done at the risk of patient safety," Kohl said. "Faulty medical devices, especially those implanted in the body, can have a disastrous impact on the health of those who use them."

Internal reviews by FDA officials and other outside sources have found troubling lapses in the procedures by which a number of medical devices were approved. The results of these investigations caused procedural and management changes to be implemented at the Center for Devices and Radiological Health in recent months.

The medical device industry is concerned that these management problems have slowed medical device innovation. In his testimony today, David Nexon, Senior Executive Vice President of the Advanced Medical Technology Association, criticized that there are, "inefficiencies at FDA that delay patient access to new treatments and cures and erode U.S. global competitiveness in the development of medical technology."

"I am encouraged by the numerous initiatives that FDA is implementing for more effective medical device approval and post-market surveillance," Kohl said. "Nevertheless, I'm concerned that the agency's oversight of medical products still remains on the GAO's 'high risk' list... and that is unacceptable."

GAO flagged the FDA's management of medical devices with a "high risk" designation in 2009.
The hearing highlighted the story of Ms. Katie Korgaokar, a Denver resident who received a DePuy ASR hip implant to treat a congenital condition called Perthes disease. In 2010, the DePuy hip was recalled and Korgaokar endured a second hip-replacement surgery in early 2011. Korgaokar was one of 96,000 patients affected by the DePuy hip recall.

A recent study, led by Diana Zuckerman, Ph.D. and published in the Archives of Internal Medicine, found that "from 2005 through 2009, the 113 highest-risk device recalls involved 112.6 million recalled products." Zuckerman testified at today's Senate hearing that, "In the first six months of 2010, the FDA recalled more than 437 million additional products because of high risks, including death... in just six months there were 1.4 medical devices recalled for every person living in the U.S."

Kohl said he would be advocating for further reforms at the FDA and urged Dr. William H. Maisel, Chief Scientist at the FDA's Center for Devices and Radiological Health, to push forward with an effort to classify high-risk devices now defaulting through the agency's "fast track" approval system.
"FDA has had over 20 years to tackle these high risk devices," Kohl said. "As we have seen with the Johnson & Johnson hip implant today, it's high time to protect patient safety and correctly classify these devices."

Kohl also suggested that FDA develop a "more robust post-market surveillance program" signaling his interest in addressing this concern in the Medical Device User Fee and Modernization Act reauthorization next year.

A webcast of the hearing is available on the committee webpage:

We'd love to heard your comments.


Friday, February 18, 2011

A recent post about recalls and 510(k) - What's missing? (maybe demoninators)

A recent published article takes the FDA's 510(k) process to task showing that "Most Recalled Medical Devices Went through FDA Fast-Track Process".  A finding of the referenced study is stated that "findings reveal critical flaws in the current FDA device review system..."

Perhaps someone should educate the article authors about the concept of demoninators and a smewhat critical flaw in their analysis as well as the actual numbers.

OK, so in the study 113 devices were recalled from 2005 through 2009.  80 of the 113 (70.1%) were cleared via 510(k)s, 12 (10.6%) were approved via PMAs and 8 (0.07%) were not subject to any review.  ON the surface these numbers suggest that there are 7 times more recalls of 510(k) cleared devices than for OMA approved devices.

So how many devices were on the market in the US from 2005 to 2009.  No telling really, but we can look at the number of devices cleared by FDA in that same time period.  FDAs own database shows that there were:

510(k)s cleared   2005-2009  = 15,733  (There were 127,239 510(k)s cleared since 5/28/1976)
PMAs approved  2005-2009  =  ~150  (There were 1,125 PMAs approved since 5/28/1976, with an average of 32 original PMAs per year over the 35 year history)

Numerator    =        80   510(k) devices recalled that were cleared in 2005-2009 divided by
Denominator = 17,733   510(k) devices cleared in 2005-2009 (CDRH only) = ~0.005%

Numerator    =   12   PMA devices recalled that were cleared in 2005-2009 divided by
Denominator = 160   PMA devices approved estimated for 2005-2009 (CDRH only) =  ~0.075%

By these calculations a device approved by a PMA has approximatley a 15x more likelyhood to have been recalled that a device that was cleared by a 510(k).  Demoninators make all the difference.

NOTE = Most denominators will probably be flawed in several respects. Factors such as the follwing come to mind.
Of the devices recalled, were all of them devices that actually were cleared during 2005-2009?

Were the devices that were cleared since May 28, 1976 to 2005 not included?  Presumabley they were still beign sold and could have been recalled.

What about the devices that did not have to go through any review process (those on the market before May 28, 1976 and those exempt from any FDA submission)?

Some 510(k)s and PMAs are reviewed by CBER (as opposed to CDRH) and these are not reported here.  Were any of the recalled devices CBER reviewed?

etc., etc., etc.

Where is a statistician when you need one?

The article abour the published article.
News and Information about Personal Injury Lawsuits

Most Recalled Medical Devices Went through FDA Fast-Track Process: Study

feature photo
According to new research, 70% of all medical devices recalled since 2005 were approved by the FDA through a controversial “fast-track” process, which only requires the manufacturer to provide minimal data on safety and effectiveness. 

The study was published this week in the Archives of Internal Medicine. Researchers found that there were 113 medical devices recalled from 2005 through 2009 that the FDA decided could cause serious injury or death, however only 21 of those medical devices were approved through the agency’s rigorous premarket approval (PMA) process.

The vast majority (80) of the recalled devices were quickly approved through the FDA’s 510(k) process, which only requires that a medical device be “substantially equivalent” to a device that is already on the market. Another 8 devices were not subject to any oversight at all before they were made available to consumers.

The most commonly recalled medical devices were cardiovascular devices, particularly automated external defibrillators (AEDs), which are used to resuscitate patients suffering cardiac arrest. Most of those devices went through the 510(k) process.

Some researchers estimate that as many as 20% of all AEDs have been recalled by the FDA and AED malfunctions have been linked to hundreds of deaths. Last month the FDA announced that it was considering more stringent requirements for external defibrillators due to the high rate of problems.

The 510(k) process has been under fire from outside and within the FDA for years. The expedited process allows medical devices onto the market with virtually no trials for safety and effectiveness if the manufacturer can show they are substantially equivalent to existing medical devices. However, many critics say that the process is too widely used and that the definition of what is substantially equivalent is too vague and often used to approve devices that are radically different from previous medical devices.

Manufacturers are also frequently allowed to model their new devices and fire them through the process based on old devices that were also approved through the 510(k) process; meaning that some medical devices have gone through as many as three or more generations of improvements, changes and alterations without having to go through PMA requirements.

In June 2009, a study by the Government Accountability Office (GAO) found significant shortcomings in FDA medical device approval procedures, and a heavy reliance on the 510(k) process. The GAO report identified gaps in the FDA reviewing process, deficiencies in the agency’s postmarket surveillance, and also found that FDA has not kept up with regular inspections of medical device manufacturing facilities. Many devices which should be put through the more stringent premarket approval process are put through the premarket notification process instead, the GAO found.

This latest study comes less than a month after the FDA announced that it was streamlining the medical device approval process to make it even easier to get some medical devices onto the market. The announcement came as a shock to some experts, who were expecting the FDA to crack down on 510(k) approvals.

“Our findings reveal critical flaws in the current FDA device review system and its implementation that will require either congressional action or major changes in regulatory policy,” the researchers concluded.
In their conclusion, the study’s researchers recommended that the FDA update how it defines “high-risk” medical devices to include the potential of injury when they fail, enforce existing laws that require all “life-saving and life sustaining” medical devices to the PMA process, and expand its inspection of the manufacturing, post-marketing surveillance, performance standards and guidance to devices approved under the 510(k) process.

FDA Items in the President's Proposed FY 2012 Budget

FDA Law Blog
Hyman, Phelps & McNamara, P.C.

Posted: 15 Feb 2011 10:05 AM PST
By Kurt R. Karst –   
The tome that is the President’s Budget for Fiscal Year 2012 is chock-full of new proposals that, if implemented, would significantly affect both brand-name and generic drug manufacturers. 
What first caught our attention were some statements in an overview of the proposed FY 2012 budget for the Department of Health and Human Services that:

The Administration will accelerate access to more affordable pharmaceuticals that will lead to cost savings for consumers and health programs across the Federal Government.  The President’s Budget includes two proposals to increase availability of generic drugs by providing the Federal Trade Commission [(“FTC”)] authority to stop drug companies from entering into anticompetitive agreements intended to block consumer access to safe and effective generics, and hastening availability of generic biologics while retaining the appropriate incentives for research and development for the innovation of breakthrough products.

Another budget document, titled “Terminations, Reductions, and Savings” provides a little more detail on these proposals.  Both of these issues were topics discussed in President Obama’s 2009 10-year budget proposal.

With respect to patent settlement agreements, which opponents refer to as pay-for-delay agreements, the President’s Budget says that “[t]he Administration proposal would give the [FTC] the authority to prohibit pay-for-delay agreements in order to facilitate access to lower-cost generics.”  This is authority the FTC has craved for years now, and that according to President Obama’s budget proposal would yield savings of $8,790,000,000 between 2012 and 2021.  As we recently reported, in January, Senator Herb Kohl (D-WI), along with several other Senators, introduced S. 27, the Preserve Access to Affordable Generics Act.  The bill, like its predecessor versions introduced, amended, and debated in the 111th Congress, would amend the Federal Trade Commission Act to permit the FTC to “initiate a proceeding to enforce the provisions of [new Sec. 28] against the parties to any agreement resolving or settling, on a final or interim basis, a patent infringement claim, in connection with the sale of a drug product.”  Such agreements, if challenged, would be presumptively anticompetitive and unlawful unless it can be demonstrated “by clear and convincing evidence that the procompetitive benefits of the agreement outweigh the anticompetitive effects of the agreement.” 

With respect to the 12-year period of reference product exclusivity created by the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), President Obama’s FY 2012 says that:

Under current law, innovator brand biologics have 12 years of exclusivity and broad “evergreening” authority, whereby innovator manufacturers are able to make relatively minor changes to the “potency, purity, and safety” of their products to receive an additional 12 years of exclusivity. 

Under the Administration proposal, beginning in 2012, innovator brand biologic manufacturers would have 7 years of exclusivity and would be prohibited from receiving additional exclusivity by “evergreening” their products. 

The Obama Administration estimates that the change in reference product exclusivity  would yield savings of $2,340,000,000 between 2012 and 2021.

The issue of so-called “evergreening,” which is the practice of obtaining additional periods of exclusivity for product modifications, along with the period of reference product exclusivity were hotly debated during consideration of what ultimately became the BPCIA.  According to a December 21, 2010 letter signed by the three principal authors of the BPCIA, evergreening is not a concern because the BPCIA “is clear that no product, under any circumstances, can be granted ‘bonus’ years of data exclusivity for mere improvements on a product.”  The letter goes on to note, however, that “if a ‘next generation’ product is approved by the FDA as a new product (significant changes in safety, purity, or potency) then that new biologic will receive its own 12-year period of data exclusivity.”

The President’s FY 2012 Budget (here beginning on page 227, and here beginning on page 437) also proposes the creation of new user fees. 

The first new fee is the much-ballyhooed generic drug user fee.  Under the President’s proposal, the generic drug user fee charge would be an amount not to exceed $40,122,000 and “would be used to improve review times and reduce the current backlog of applications.”  As we recently reported, the ANDA backlog in FDA’s Office of Generic Drugs (“OGD”) continued to grow unabated in 2010, for a grand total of 2,361 original ANDAs pending at the close of 2010, and with an estimated median approval time of 31 months.  (According to the latest OGD statistics, the ANDA review backlog dipped slightly in January 2011 to 2,356 original ANDAs; however, the number of ANDAs pending more than 180 days continued to grow, from 1,816 ANDAs to 1,836 ANDAs.)

The President’s FY 2012 Budget would also create a new “reinspection fee for medical products” in an amount not to exceed $14,108,000.  According to the proposal, “FDA conducts post-market inspections of manufacturers of human drugs, biologics, animal drugs, and medical devices to assess their compliance with Good Manufacturing Practice and other regulatory requirements. The Budget includes a proposal to enable FDA to assess fees for follow-up reinspections that are required when violations are found during initial inspections.”  President Bush made a similar proposal in his FY 2009 budget request

Finally, the Obama Administration’s budget proposal includes a new “international courier user fee” in an amount not to exceed $5,338,000.  According to the budget proposal, “[t]he volume of imports, predominantly medical products, being brought into the United States by international couriers is growing substantially. To ensure the safety of these FDA regulated products through increased surveillance efforts, the Budget includes a new user charge to international couriers.”

Each of the user fee proposals is contingent upon the enactment of authorizing legislation.  Generic drug user fees, along with generic drug labeling preemption, may be among the most talked about topics at the GPhA Annual Conference taking place in Orlando later this week.

Comments on the FDA Innovation Pathway

Posted: 14 Feb 2011 10:39 PM PST

FDA’s Center for Devices and Radiological Health (“CDRH”) has proposed the “Innovation Pathway Program” for breakthrough medical devices.  CDRH says it will review these products in 150 days or less, which the agency claims is nearly half the review time of most premarket approval (“PMA”) applications.  The first product in the program is from the Defense Advanced Research Projects Agency (“DARPA”).  It is a brain-controlled, upper-extremity prosthetic device, which uses a microchip implanted on the surface of the brain to restore near-natural arm, hand, and finger function to patients suffering from spinal cord injury, stroke, or amputation.
Color us skeptical.  Not about the DARPA product.  We’re talking about the Innovation Pathway Program.
First of all, this program even at its best will affect probably just one or two products each year.  In other words, it is a very narrowly focused program.

Second, for many years, CDRH has had an Expedited Review procedure in place to speed approval of “breakthrough technology.”  Even CDRH has admitted it has not very worked well. 

The Innovation Pathway apparently is intended to improve CDRH’s track record with innovative products.  It would work like this:  CDRH will issue an Innovation Pathway Memorandum with a proposed roadmap and timeline for the development, clinical assessment, and regulatory review of the device.  The product would be assigned a case manager and reviewed by the Center Science Council, which is a new oversight body being developed within CDRH.  The Council will consist of senior managers and experienced scientists. 
As with the Expedited Review program, enrollment in the Innovation Pathway Program would not change the scientific or regulatory standards that CDRH uses to review submissions and authorize products for marketing.
As we said, color us skeptical.  The DARPA brain controlled prosthetic obviously has amazing potential, and FDA likely would have rushed it through in any event.  We’ll know if this new program has any value if additional products actually start speeding down the Innovation Pathway.

It already looks like that won’t happen any time soon.  CDRH said it will now seek comments from the public on this pathway before it is used again.  CDRH will host a public meeting on the Innovation Pathway program on March 15, 2011 at FDA’s White Oak campus.

This public outreach suggests the program announcement has been designed around the single DARPA product, and is not ready for prime time.  There will be a delay just to hold a public meeting and then digest the comments and further revise the program.

All of which suggests that it will be quite some time before another product is so lucky as to be allowed to speed down the Innovation Pathway.

We would prefer that CDRH work on significantly reducing the review times for all products, for both innovative and same-old, same-old technology.  That would be an innovation CDRH could be proud of.

Friday, February 11, 2011

Digital Pathology Blog

An earlier post

January 25, 2011

Standardization and Validation of Digital Pathology in Clinical Laboratories

The following post was submitted by Dr. Holger Lange, CTO of Flagship Biosciences, who is working with a number of pharmaceutical partners on regulatory companion diagnostics development.

Digital Pathology is a new technology, a new industry, where organizations like CLIA, CAP and the FDA provide limited guidance, and the manufacturers still have to learn what it means to provide instruments into a clinical laboratory.

With Digital Pathology now entering the clinical laboratories, it is crucial for physicians and laboratory professionals to understand the regulatory requirements and how to best implement Digital Pathology in their clinical laboratories.

For the past 4-5 years I have worked for a leading Digital Pathology manufacturer. I was responsible for their first product in the clinical market – a digital IHC workflow solution, and their portfolio of FDA clearances. Now I have put together a presentation that summarizes my experience in the clinical market. I hope it will help many physicians and laboratory professionals to quickly get up to speed on how to deal with the implementation of Digital Pathology in their clinical laboratories.

These are the subjects that are covered in the presentation:

Clinical Laboratory Regulations
A discussion on how the CLIA standard and the CAP checklist apply to Digital Pathology. A review of the new ASCO/CAP guidelines for HER2 and ER/PgR for the latest thoughts on standardization and validation in clinical laboratories.

Medical Device Manufacturer Regulations
An overview of the existing US Food and Drug Administration (FDA) clearances for Digital Pathology with an example of a successful study design. A discussion on the FDA advisory panel meeting on Digital Pathology Whole Slide Imaging (WSI) for the latest thoughts on what it takes to validate Digital Pathology systems for primary diagnosis.

Digital Pathology Systems
Practical tips on how to implement a digital pathology system in a clinical laboratory and how digital pathology manufacturers could make it easier. A demo of how a digital pathology system can help with the logistics of its own validation. A discussion on how going digital could be a game changer for the standardization of pathology, looking at the example of the automatic standardization of staining, using standard controls and automatic image analysis.

Go to the Flagship Biosciences product page for digital pathology regulatory products.
You get an 1½ hour video presentation on a DVD and the presentation transcript.
Save yourself many hours of research and reading! Get the insights you need by viewing this video presentation. Get access to material that cannot be found anywhere else.

FDA approves first 3-D mammography imaging system



For Immediate Release: Feb. 11, 2011
Media Inquiries: Erica Jefferson, 301-796-4988,
Consumer Inquiries: 888-INFO-FDA

FDA approves first 3-D mammography imaging system

Selenia Dimensions System may boost accuracy in breast cancer detection, diagnosis

The U.S. Food and Drug Administration today approved the Selenia Dimensions System, the first X-ray mammography device that provides three-dimensional (3-D) images of the breast for breast cancer screening and diagnosis.

A mammogram is a safe, low-dose X-ray of the breast that is the best tool for early detection of breast cancer. However, with the limitations of conventional two-dimensional (2-D) imaging, about 10 percent of women undergo additional testing after the initial screening exam for abnormalities that are later determined to be noncancerous.

The Selenia Dimensions System, an upgrade to Hologic’s existing FDA-approved 2-D system, can provide 2-D and 3-D X-ray images of the breasts. The 3-D images may help physicians more accurately detect and diagnose breast cancer.
“Physicians can now access this unique and innovative 3-D technology that could significantly enhance existing diagnosis and treatment approaches,” said Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

The National Cancer Institute recommends women ages 40 and older have a mammogram every one to two years. Nearly 40 million mammograms are performed each year in the United States.

As part of the approval process, the FDA reviewed results from two studies where board-certified radiologists were asked to review 2-D and 3-D images from more than 300 mammography exams.  In both studies, radiologists viewing both the 2-D and 3-D images obtained a 7 percent improvement in their ability to distinguish between cancerous and non-cancerous cases as compared to viewing 2-D images alone.

While the combination of the Selenia’s 2-D and 3-D images approximately doubled the radiation dose the patient received, it improved the accuracy with which radiologists detected cancers, decreasing the number of women recalled for a diagnostic workup. There is uncertainty for radiation risk estimates; however, the increase in cancer risk from having both a 2-D and 3-D exam is expected to be less than 1.5 percent compared to the natural cancer incidence, and less than 1 percent compared to the risk from conventional 2-D mammography.

The Mammography Quality Standards Act requires that all health care professionals obtain eight hours of training prior to using new mammography technology on patients. The FDA also requires that the manufacturer provide each facility with a manual clearly defining the tests required for initial, periodic, and yearly quality control measures.

According to the NCI, nearly 200,000 women will be diagnosed with breast cancer this year. And 1 in 8 women will be diagnosed with breast cancer during their lifetime. There is a 98 percent survival rate when breast cancer is detected early and still localized to the breast.

The Selenia Dimensions System is marketed by Bedford, Mass.-based Hologic Inc.

Medical Treatment, Out of Reach - NY Times article

Received this article by e-mail and am passing it on.

Brendan Benner
Vice President of Public Affairs
Medical Device Manufacturers Association (MDMA)

 I wanted to make sure you saw the front page story in yesterday’s New York Times' Business section detailing the challenges patients and innovators are having with FDA.

MDMA and others have been working on this story for several weeks, and we believe this story turned out well to show the real-world impact of unnecessary delays.

This is a very compelling piece and has received widespread attention in Congress and Washington media.

I would encourage you to pass this along to the local business and health care reporters in your community to ensure this important topic gets more exposure.

In addition, if your company utilizes social media, this would also be a great item to post and increase its visibility.

All the best,

Medical Treatment, Out of Reach

Late last year, Biosensors International, a medical device company, shut down its operation in Southern California, which had once housed 90 people, including the company’s top executives and researchers.

The reason, executives say, was that it would take too long to get its new cardiac stent approved by the Food and Drug Administration.

“It’s available all over the world, including Mexico and Canada, but not in the United States,” said the chief executive, Jeffrey B. Jump, an American who runs the company from Switzerland. “We decided, let’s spend our money in China, Brazil, India, Europe.”

Medical device industry executives and investors are complaining vociferously these days that the industry’s competitive edge in the United States and overseas is being jeopardized by a heightened regulatory scrutiny.

The F.D.A., they and others say, appears to be reacting to criticism that its approvals for some products had been lax, leading to a spate of recalls of some unsafe medical devices, like implanted defibrillators and hip replacements.

Now, executives of device companies say the F.D.A. has gone too far in flexing its regulatory muscle, and they worry that a slower, tougher approval process in a weakened economy could chill investments and cripple innovation.

In addition, they say that American patients are being deprived of the latest technology because companies routinely seek approval for new devices in Europe first. For instance, heart valves that can be installed through a catheter instead of open-heart surgery have been available in Europe since 2007 but will not be available in the United States until late this year at the earliest.

“Ten years from now, we’ll all get on planes and fly somewhere to get treated,” said Jonathan MacQuitty, a Silicon Valley venture capitalist with Abingworth Management.

Marti Conger, a business consultant in Benicia, Calif., already has. She went to England in October 2009 to get an implant of a new artificial disk for her spine developed by Spinal Kinetics of Sunnyvale, Calif.

“Sunnyvale is 40 miles south of my house,” said Ms. Conger, who has become an advocate for faster device approvals in the United States. “I had to go to England to get my surgery.”

Stenum Spine Hospital in Germany has performed disk surgery on 1,000 Americans over the last eight years, said Jim Rider, the hospital’s American marketing agent.

Acknowledging industry concerns, the F.D.A. on Tuesday proposed creating an “innovation pathway” aimed at speeding regulatory reviews of a small number of groundbreaking devices. And last month the agency announced measures it said would make the regulatory process more predictable for the vast majority of devices.

“A consistent and predictable review process will stimulate investment here at home and keep jobs from going overseas,” Dr. Jeffery Shuren, the director of the agency’s medical device division, told reporters.

But Dr. Shuren said the F.D.A. would not relax its standards, arguing that Europe’s system might be too lax. He said that a breast implant, a lung sealant and an implant for elbow fractures were approved in Europe but not in the United States, and then had to be taken off the market in Europe for safety reasons.

“We don’t use our people as guinea pigs in the U.S.,” he said

Medical device executives said they welcomed the steps, but continued to express concerns. Consumer advocates, like Dr. Sidney Wolfe of Public Citizen, however, said that device regulation was already much less stringent than for drugs and that the F.D.A. was caving in to industry demands rather than ensuring consumer safety.

Dr. Charles Rosen, a spine surgeon who is also president of the Association for Medical Ethics, said that the newest devices were not always best. He said he had at least 50 patients who had suffered serious problems from an older artificial disk. Many of those patients, he said, had gone to Europe to get them before they were available in the United States.

Just since November, three reports — two sponsored by device industry trade groups and one conducted by the consulting firm PricewaterhouseCoopers — have raised concerns about the F.D.A. approval process. One report found that the rate of recalls in Europe was similar to that in the United States, suggesting faster approvals overseas were not hurting patients.

The complaints are driven in part by financial pressures. Venture capitalists, because of the financial crisis and their own poor returns, have less money and need quicker returns on their investments from the companies they back.

Bigger device companies also complain about the F.D.A., but not as much as struggling start-ups. “The F.D.A. is asking for larger trials, more thoughtful trials, all in the interest of the American public,” said Dr. Stephen N. Oesterle, senior vice president for medicine and technology at Medtronic.

To be sure, the United States remains the clear world leader in medical device innovation, according to the report by PricewaterhouseCoopers. Some 32 of the 46 medical technology companies with annual sales exceeding $1 billion are based in the United States, the report said.

Still, the report said the United States’ lead was slipping.

Device companies have been seeking early approval in Europe for years because it is easier. In Europe, a device must be shown to be safe, while in the United States it must also be shown to be effective in treating a disease or condition. And European approvals are handled by third parties, not a powerful central agency like the F.D.A.

But numerous device executives and venture capitalists said the F.D.A. has tightened regulatory oversight in the last couple of years. Not only does it take longer to get approval but it can take months or years to even begin a clinical trial necessary to gain approval.

Disc Dynamics made seven proposals over three years but could not get clearance from the F.D.A. to conduct a trial of its gel for spine repair, said David Stassen, managing partner of Split Rock Partners, a venture firm that backed the company. “It got to the point where the company just ran out of cash,” Mr. Stassen said. Disc Dynamics was shut down last year after an investment of about $65 million.

Dr. Shuren of the F.D.A. said the agency had concerns from preliminary studies that the material in the gel could cause cancer and that the gel would come out of the disk, requiring a new operation.

Some companies and investors are even contemplating forgoing the American market completely.

“We never intend to spend a nickel in the United States for clinical trials,” said William Starling, a venture capitalist who also runs Synecor, a device company incubator in North Carolina.

Mr. Starling is an investor in Spinal Kinetics, whose artificial disk was implanted in Ms. Conger in England.

The company began working with both the F.D.A. and European regulators in early 2005. It won approval in Europe in 2007 after testing its device in 30 patients and spending $4 million. Since then, thousands of the disks have been implanted.

Only last May did it receive approval for a final trial for F.D.A. approval that would involve about 250 patients. But hard-pressed investors are not willing for now to put up the $50 million or so the trial would cost, Mr. Starling said.

In the meantime, Spinal Kinetics is moving its manufacturing to Germany and has already laid off 20 people in Silicon Valley. One reason for the move, Mr. Starling said, was that some countries in Asia and Latin America allowed use of devices that have been approved in the country in which they are made. So moving manufacturing out of the United States opens up those markets.

Totally forsaking the lucrative American market could be difficult. While approval in Europe is easier, health care systems there tend to spend less on medical devices. Even if a device were approved, doctors in Europe might not use it if there was not enough data proving it really works.

Some companies, however, are trying to generate some sales in Europe in an effort to be acquired by a bigger company, which could then afford to deal with the F.D.A.

Dr. Shuren of the F.D.A. said in an interview that there had been “no conscious effort” to make device approvals tougher. “We are dealing with increasingly more complex devices coming to market,” he said.

But numerous executives say agency reviewers seem to be more cautious as Congress and others criticize the agency for being too lenient. Critics cited two recent examples: the DePuy hip implant recalled last year and an instance in which top agency officials approved a knee repair implant, made by ReGen Biologics, over the strenuous objections of their scientific reviewers.

Pharmaceutical executives are also complaining about how tough the F.D.A. has become. But they are not forsaking the American market, in part because there is not a big disparity in the regulatory system for drugs between the United States and Europe.

Some figures bear out a toughening in devices. The F.D.A. last year granted 19 premarket approvals — the type of clearance required for the most highly regulated devices — down from 48 in 2000.

The average time to win an approval through the less stringent 510(k) pathway, which is used for most devices, rose to 116 days in fiscal year 2008 from 97 days in fiscal year 2002. Agency figures show there have been increases in the proportion of applications sent back for questioning.

Investment by American venture capitalists in the medical device sector has fallen 37 percent since 2007 to $2.3 billion last year, according to the MoneyTree survey from PwC, the National Venture Capital Association and Thomson Reuters. That is steeper than the 27 percent drop for all venture capital investing.

Last year, total venture capital investing increased 19 percent while investment in medical devices fell 9 percent.

Brendan Benner
Vice President of Public Affairs
Medical Device Manufacturers Association
1350 I St, Suite 540
Washington, DC 20005