Implant Monitoring Bill: A Sign of the Times

If Schoolhouse Rock taught us anything about bills, it's that, "it's a long, long journey to the capitol city; it's a long, long wait while I'm sitting in committee." A similar slow and stalled fate likely awaits a bill introduced in the Senate last week that aims to force medical device manufacturers to monitor implants once they are on the market. But even if the bill doesn't eventually become a law, the proposed legislation serves as quite the kicker to a turbulent year for the medical device market marked by a vaginal mesh uproar, the never-ending metal-on-metal hip implant controversy, and the Institute of Medicine's (IOM) critique of the existing 510 (k) process.

The bipartisan bill--backed by Herb Kohl (D-WI), Richard Blumenthal (D-CT), and Charles E. Grassley (R-IA)--would expand FDA's postmarket authority to include oversight of implants that have been cleared for use via the 510 (k) process. If adopted, the bill would empower the agency to order medical device manufacturers to conduct safety studies of implants after they've hit the market. It would also heighten federal scrutiny of medical device recalls, according to a recent article in the New York Times. In fact, the senators have already been busy trying to gather data on recalls; they sent letters to Medtronic, Johnson & Johnson, Boston Scientific, Zimmer, and C.R. Bard requesting information on how the industry leaders track product safety and recalled medical devices.

"Faulty medical devices, especially those implanted in the body, can have disastrous health impacts on patients," Kohl said in a statement. "This legislation will help ensure that FDA can act quickly and decisively when there's a problem, and that the drive toward getting new technologies to market won't come at the risk of patient safety."

But would it really be that easy? It's unlikely. FDA has the unfortunate position of coming under fire from all sides: Patient advocacy groups point to heavily publicized recalls as proof of a flawed approval system while the medical device industry gripes about the potential to stifle innovation as well as agency inefficiencies. So, to assume that this bill would "ensure that FDA can act quickly and decisively when there's a problem" seems somewhat unrealistic.

The point may be moot, however, as the bill is expected to face serious opposition on Capitol Hill, especially in the face of several bills supported by the medical device industry. "While the bill...most likely faces an uphill fight, it may serve as a negotiating chip in a Congressional debate next year over FDA device regulation," according to the Times.

Regardless of the outcome, the introduction of this bill does seem to signal a rocky road ahead for the medical device industry. The ongoing metal-on-metal hip implant controversy, high-profile FDA warning about vaginal mesh, and IOM report have all added fuel to the already blazing FDA 510 (k) fire. But it's only a matter of time before someone gets burned. --Shana Leonard

Spirol Achieves Nadcap Accreditation

  • Surface Treatment/Passivation – ASTM A 380
  • Surface Treatment/Passivation – ASTM A 967
  • Surface Treatment/Passivation – Other
  • Surface Treatment/Passivation – QQ-P-35
  • Surface Treatment/Passivation– AMS-2700
  • Surface Treatment/Passivation– AMS-QQ-P-35

In addition to the above processing standards, Spirol performs the following tests internally in support of chemical processing in the scope of the audit:

  • B6 Water Immersion/High Humidity Testing
  • Solution Analysis

To maintain Nadcap accreditation, annual audits are conducted by PRI personnel using process-specific Nadcap checklists.

Richard Nass

Fight Diabetes and Obesity without Surgery

Fight Diabetes and Obesity without Surgery

The waistline of the global population continues to grow at an alarming rate. The problem has reached epidemic

“With the successful completion of our IPO, we are well positioned to execute our plans for achieving broader adoption in markets where the EndoBarrier has been launched and expanding into new markets...” --Stuart A. Randle, president and CEO

proportions, and GI Dynamics Inc. (Lexington, MA) is doing something about it. The company has developed a device that mitigates the risks of bariatric surgery and could be more effective than drug therapy. The device isn’t yet approved for sale in the United States but given the growing rate of obesity and type 2 diabetes, it has strong potential in the U.S. market.
The current method of treatment for obese and diabetic patients includes recommendations for lifestyle changes (diet and exercise) and various medications. In more serious situations, patients opt for gastric band or bypass surgery, but both procedures have serious risks and can lead to complications. “We’re focused very much on the patient that has both type 2 diabetes and is obese,” Stuart Randle, president and CEO of GI Dynamics, tells MD+DI. “For those patients today, there are very limited options. Drugs aren’t terribly effective, and the surgical options most of the patients don’t want.”
Enter the EndoBarrier. The device controls glucose levels and helps patients lose weight. It is implanted via an endoscope through the mouth in a nonsurgical procedure that takes about 30 minutes. The device serves as a barrier between food and part of the intestine wall to delay digestion and intervene with the metabolic process. A 60-cm long liner is implanted inside part of the intestine so that food passes through the EndoBarrier without coming into contact with digestive enzymes—this mimics the effects of gastric bypass.
The device improves glucose control within a few days following implantation and can lead to substantial weight loss over a period of time. It can stay in the body for up to 12 months and is removed with an endoscope. Removal of the device takes about 15 minutes.
GI Dynamics is looking to take the EndoBarrier further.  The company brought a chief commercial officer, Mark Twyman, on board in November to help lead the effort. “GI Dynamics is at the forefront of a major change that is occurring in diabetes care and weight management...," said Twyman in a company release. “Based on the study results seen to-date, I am confident that the EndoBarrier is well positioned to have a material impact on people living with type 2 diabetes and obesity, many of whom have few options to improve their disease and overall health.”
Trials are underway to expand the use of the technology, including for retreatment and improving the device’s anchor. The company is developing the EndoBarrier Restrictor, which is intended for cosmetic or short-term weight loss. The device creates a small hole to reduce the rate of gastric emptying and make the patient feel full. The company has completed a 12-week, 10-patient clinical trial of its EndoBarrier Liner with the EndoBarrier Restrictor to create a platform that treats diabetes and leads to weight loss that is greater than using either device on its own.
(left) An obese adult has a body mass index of 30 or higher. This map shows the estimated incidence of obese adults worldwide. Source: WHO, Global Database on Body Mass Index, June 2011. (Right) The incidence of type 1 and type 2 diabetes. Source: International Diabetes Federation 4th edition, 2009.
  • September 2011: Starts trading on the Australian Securities Exchange following $84 million initial public
    GI Dynamics’s first target market is obese patients with type 2 diabetes. Source: GI Dynamics 2011 corporate presentation.
  • offering.
  • October 2010: Receives CE Mark for EndoBarrier for 12 months of treatment.
  • January 2010: Receives strategic investment from Medtronic Inc.
  • June 2009: Presents results of clinical study showing significant weight loss by using the EndoBarrier gastrointestinal liner with its flow restrictor.
Focus Going Forward
  • Continue to expand the capabilities of EndoBarrier.
  • Initiate commercial activity in additional countries.
  • Establish up to 15 centers of excellence in Europe and South America.
  • Build clinical and economic data to support applications for reimbursement.
  • Stuart A. Randle, president and CEO
  • Robert Crane, CFO and corporate secretary
  • Andy Levine, founder and chief technology officer
  • Mark C. Twyman, chief commercial officer
  • Sherrie Coval-Goldsmith, vice president, clinical and regulatory affairs
  • Karl Blohm, PhD, vice president, international

Medtronic Is Playing the Law of Averages Like a Pro

Medtronic and the University of Minnesota's Medical Industry Leadership Institute Student Association (MILIsa) recently sponsored an interdisciplinary competition at the university’s Carlson School of Business. The event, which has been held for four consecutive years, attracts students from a variety of studies to solve problems in the medical device industry.

Medtronic also has a similar-minded initiative known as Medtronic Eureka that attempts to bring physicians and inventors together to come up with ideas for new medical technologies.
A reader wrote in to share his perspective on the news. “I know Medtronic well enough to know that they have their own agenda, but I applaud them for thinking outside the box and tapping as many minds as possible,” he writes. “The law of averages tells us that one in 1000 people will come up with a good idea. One in 1,000,000 will come up with a great idea. And one in 1,000,000,000 will come up with a revolutionary idea,” he adds. “They are playing the law of averages like a pro by tapping as many minds as possible.” By getting input from people outside of their circle of influence, the “one in a million” idea is just around the corner. “All they have to do is keep ‘tapping.’”
—Brian Buntz

Related Content:
'Economist' Casts Medtronic CEO Ishrak as Savior of Device Industry

Make Sure You Really Know Who You Are Doing Business With When Outsourcing to China or India

Niedelman gave me a preview of his talk (more information is available on the MD&M website) and shared some advice for medtech companies that outsource to destinations such as China and India. 

Many companies don't really know the companies they do business with. "I can’t tell you how many manufacturers never even visit their supplier in China or India because they claim it is too costly."

Instead, many companies rely on photos on websites, which often look nothing like the real facilities. "The bottom line is, if you were to physically see some of these sites, you wouldn’t even step foot in them," he says. He explains that  Pew Charitable Trust published a white paper on heparin the provides an example of this. 

Many of these companies put up a bogus "nice photo" on their website and "bank on you not coming" to inspect the manufacturing facilities. 

It's often a more successful strategy to partner with a U.S. firm that has facilities in low-cost countries, he recommended.

—Brian Buntz

Hydrogel Scaffolds Allow Complete Skin Regeneration in Burn Wound Healing

A new component in a wound treatment method could greatly help heal third-degree burn victims, promoting new blood vessel and skin formation. A specially-designed hydrogel developed by researchers at Johns Hopkins University (Baltimore, MD) can be used in an inexpensive burn dressing to regenerate skin without use of drugs. Though the hydrogel hasn't been tested on humans yet, on studies with mouse tissue have shown that it can promote the development of new blood vessels and regenerate complex layers of skin, including oil-producing glands and hair follicles.

For the last three years, postdoctoral fellow and lead author Guoming Sun has been working with hydrogels for growing new blood vessels, a process called angiogenisis, intending to load the gel with stem cells to trigger tissue development. But after testing the gel alone, Sun's team was surprised to see such promising results. Since the hydrogel doesn't contain biological components or drugs, it would be classified as a device by the FDA when going through the approval process.

The hydrogel is made mainly from water and a dissolved polysaccharide called dextran, and the researchers aren't exactly sure how it works. Inflammatory cells penetrate the hydrogel, degrading it and enabling blood vessels to fill in and grow new tissue. One theory is that the hydrogel may draw in bone marrow tem cells circulating in the blood, giving them a cue to become new blood vessels and skin. The quicker the regeneration process happens for tissue, the smaller the chance of scarring. After 21 days, all of the harmless hydrogel is absorbed, and the tissue continues to heal.

Beyond burns, this hydrogel could also help treat other skin conditions like foot ulcers of diabetic patients, and it could be manufactured easily on a large scale. More testing is required on animals before human testing could begin, but the researchers hope that the hydrogel could be approved for clinical use in just a few years. The research was published in the Dec. 12-16 online Early Edition of Proceedings of the National Academy of Sciences.

How to Deal with a Supply Chain that Is Growing Ever More Complex and Global

At present, there is a lot of FDA, congressional, and consumer interest in the supplier control initiative, explains Steve Niedelman, lead quality system and compliance consultant, King & Spalding LLP (Washington, DC) who is chairing a session on the topic at MD&M West in February 2012. Niedelman was formerly the deputy associate commissioner for regulatory operations for FDA.
Steven NiedelmanAs evidence of agency concern regarding the global supply chain and the issues that accompany the globalization of the medical device industry, Niedelman points to the recently appointed and created position for deputy commissioner for global regulatory operations.
There have also been Senate hearings addressing the issue, Niedelman points out. “The most recent [hearing] focused on heparin, which people think of only as a drug,” he explains. “But in fact, as an outcome of the heparin situation of three years ago, there were more device recalls that resulted from it than any pharmaceutical recall.” The issue goes far beyond what many people simplistically think of as heparin as a blood thinner for dialysis, he says. Heparin is used as a flush for medical devices as well as a lubricant for many devices such as syringes. In all, the heparin issue has affected millions of devices.
Another topic of interest is that medical devices are becoming global commodities. “It is really difficult to blur the distinction between domestic product and imported product because so many of the components, parts, subassemblies are imported,” Niedelman says. “FDA sees 24,000,000 lines of imported products per year of which now 25% are medical devices,” he says. “That is a huge shift over a decade ago when 90% of all FDA imported products were foods,” he adds. “The volume of products of FDA imports has quadrupled in the past decade and tripled in the past five years alone.”
As a result of these changes, it is the manufacturer’s responsibility to ensure that a robust supplier quality program is in place to assure the quality of the products that they are distributing to their patients. “FDA has made it clear to manufacturers that it is their responsibility to stay abreast of who their suppliers are per the quality system regulation,” Niedelman says.

Why Outsourcing?

Device companies outsource for a number of reasons: Typical projects to outsource include part assemblies, components, finished devices, packaging, labelling, sterilization services, design services, consulting, cleaning, and IT support.
As for the reason behind outsouring, that also varies. “A company may not have in-house capacity of capability,” Niedelman says. “They may not have the space to handle these issues within house. The volume of product, perhaps, has grown so exponentially they can’t keep abreast of it and need to outsource. Or conversely, it is so small an infrequent, it doesn’t pay for them to do it themselves.”

To fill a gap. For many companies, outside technology and expertise is needed to assure that finished products are being manufactured correctly. Niedelman points to the growing numbers of virtual companies in the United States that are also contributing to increased demand for outsourcing. There are fewer and fewer brick and mortar firms, he says. "These virtual companies depend entirely on outsourcing for everything they do." 

Cost benefits. The financial benefits of outsourcing is perhaps one of its most obvious benefits. "Suppliers in low cost countries make things very enticing in the device industry," Niedelaman acknowledges. "But  people need to factor in several issues when doing business in low-cost countries." Potential savings must weighed against increased cost of surveillance. "You can’t solely rely on third-party audits," he says. "They are really not held liable at the end of the day if they fail."

Advice when Doing Business in Low-Cost Countries

"I can’t tell you how many manufacturers never even visit their supplier in China or India..."

Because such low-cost suppliers are remotely located, it will require greater oversight on the manufacturer’s part. "You really need to know your sources," Niedelman says. "I can’t tell you how many manufacturers never even visit their supplier in China or India because they claim it is too costly." Instead, they depend upon photos on websites that are unreliable predictor of the actual conditions of the factory. "The bottom line is, if you were to physically see some of these sites, you wouldn’t even step foot in them," he adds.
"Actually, the Pew Charitable Trust did a white paper on heparin that just published this past summer. And in there, there are some photographs that were taken by an auditor in China showing what the physical site looks like. It is disgusting," he says. "But anybody can put any nice photo on a website and they bank on you not coming. Or they have show and shadow setups, which is a model factory set up. You go over, you see that site. It looks great but your product is not manufactured there."

It is important that manufacturers have tight supplier quality agreements, Niedelman stresses. "They should have very specific no-change clauses. [Manufacturers] are at very high risk if they contract out design control and intellectual property."

Niedelman suggests, when doing business in low-cost countries, to look "for a U.S. company with a wholly owned low-cost third-world operation." That way, you can hold somebody in the United States accountable. This approach seems to be much more successful, he adds.
There really is a risk-based approach to managing outsourcing that requires six elements:

  1. Initial supplier selection.
  2. Contractual quality agreements.
  3. Risk management stratification.
  4. Identifying the highest risk (and low- and medium-risk).
  5. Subsuppliers (suppliers to your suppliers)
  6. Using a risk-based audit program.

Other Advice

"Not having an adequate supplier quality program does increase your risk of FDA oversight."

It is always a good idea to have some corrective action planning and follow up, Niedelman says.

Take responsibility for your product. "Manufacturers may hem and haw with the supplier over time but [FDA] is going to look to them to make sure there product is properly taken care of once it is in the market," he adds.

"Not having an adequate supplier quality program does increase your risk of FDA oversight," he says. "It is becoming increasingly commonplace that the agency is looking at supplier quality. It is now within the top ten reasons for a warning letter. It is also in the top ten for FDA 483 cites," he adds.

"At the end of the day, it is just in everybody’s best interest to have an effective supplier quality program to reduce your liabilities, risks, and to ensure that your product is safe and effective."

CDRH Report: The Barriers to Quality

A CDRH report says greater visibility on the agency’s expectations of device quality and properly aligning its regulatory approach are needed to improve device quality and reduce adverse events. The report, Understanding Barriers to Medical Device Quality, says FDA “should consider a comprehensive program centered on three parallel and overlapping agendas: (1) aligning compliance focus to address industry quality gaps; (2) enhancing transparency and visibility of performance to drive quality; and (3) increasing industry engagement.”

On transparency, the report says better quality can be achieved if more information about companies’ quality performance became available. It says FDA should “construct and routinely report industry-wide and product-category wide quality and patient outcome information,” along with publishing “a synthesis of causes and trends of adverse events and product recalls overall and by product class.”

Additionally, the report said for guidance, FDA could look to what agencies that regulate other technological indus-tries, like the Federal Aviation Administration and the Nuclear Regulatory Commission, are doing. The report says that “there exist opportunities to adopt best practices around how these agencies deal with the industry to promote and maintain a high level of safety and quality.”

Consumers Union Seeks Stronger Device Law

The Consumers Union (CU) is getting involved in the debate over the medical device approval process, asking Congress to bolster FDA’s standards for allowing a device on the market. The consumer advocacy group wants the agency to take a much stricter approach with regard to “all implantable and life-sustaining medical devices,” and to strengthen its postmarket surveillance system.

“Lax medical device approval standards are putting patient lives at risk,” Lisa McGiffert, manager of CU’s Safe Patient Project, said in the release. “The current system has allowed FDA to fast-track approval of more than 90% of new medical devices based on whether they are similar to other devices already on the market and without clinical trials that show the devices are safe and effective. It’s time to strengthen the federal law on medical devices, not scale back oversight at the expense of patient safety.”

The group sent a letter to Congress in November in which it suggested that the legislative body could implement stricter standards during the MDUFA reauthorization process. It seemed to be responding to efforts by industry to paint the current framework as a prohibitive burden, dismissing concerns about “onerous regulation.” 

The CU wants devices to go through an approval process similar to that which pharmaceuticals face. Device makers currently have to provide a “reasonable assurance” of safety, but the CU would like to see the standards changed so that a company must provide “substantial evidence” of safety. It wants the 510(k) program taken off the table when it comes to implantables or life-sustaining devices, arguing that such devices should only go through the full premarket approval (PMA) process, and wants recalled devices to no longer be allowed to be used as predicates for the approval of other devices.

The group also listed some steps that Congress could take to improve FDA’s regulation of devices postmarket, including requiring the implementation of a unique identifier system, funding programs like MedWatch, MAUDE, and the Sentinel initiative, and supporting the agency’s efforts to effectively manage recalls and postmarket studies. Finally, the CU wants Congress to “retain current conflict-of-interest standards for federal advisory committees.”

As the CU was taking this step, members of the bipartisan, bicameral Congressional medtech caucus sent their own letter to FDA commissioner Margaret Hamburg, asking her to preserve the industry and protect innovation by making changes to the agency’s approval process. The legislators cautioned that “unless we make significant improvements to the predictability and transparency of the regulatory process, we will lose the industry, the jobs that go with it, and the innovation to transform our healthcare system.”

The caucus members write that they “share [FDA’s] commitment to ensuring safe and effective medical devices are available to patients,” but “are very concerned about recent declines in FDA performance,” including ”increased review times, inconsistent expectations, and poor communication.”

They urge Hamburg to “recognize and correct the disparity between ‘FDA time’ and real time when tracking device approvals,” consider “benefits of harmonization with international testing standards,” address “the unintended consequences of advisory panel conflict-of-interest rules,” and create “a transparent tracking and review system for applications and clearness decisions.”