It also requires CMS to work with stakeholders to develop a standard of care for using remote monitoring for those conditions. The bill also provides for a demonstration program to evaluate whether Medicare should cover remote monitoring services for diabetes, epilepsy, and sleep apnea. The bill, sponsored by Reps. Anna Eshoo (D-CA), Charles Pickering (R-MI), John Tanner (D-TN), and Kenny Hulsof (R-MO), drew swift praise from AdvaMed. "What was once only science fiction is now patient care reality. With remote monitoring technologies, a physician can evaluate and manage complex chronic diseases from remote locations and provide real-time care for patients," said AdvaMed President Stephen J. Ubl. "Unfortunately, the adoption and widespread diffusion of such innovations have been stymied by antiquated reimbursement systems." Indeed they have. As patient care moves toward more home-based solutions, the law needs to adapt to reflect this reality.

NEED TO KNOW

The Massachusetts Medical Device Development Center (M2D2)—a partnership between the University of Massachusetts Lowell (www.uml.edu) and the University of Massachusetts Worcester (www.umassmed.edu)—has received a $4 million contribution from the state government of Massachusetts to expand its facility. The goal of M2D2 is to help local medical device companies attract the venture capital needed to deliver new products to market.

Companies—particularly start-ups—often find themselves in a catch-22 when they reach the regulatory approval stage with a new medical device, observes Stephen McCarthy, professor of plastics engineering at UMass Lowell and M2D2 codirector. The companies need investment money to shepherd their concepts through the approval process, but investors hesitate to get involved until a concept is approved. “We call this period the valley of death,” McCarthy says. “The innovations and venture capital are there, but it can be difficult to bring them together.”

M2D2 offers companies various pathways out of the valley of death. Experienced innovators help companies apply for National Institutes of Health and other grants. McCarthy, for instance, holds nine patents and is the cofounder of a nanotechnology-based company. Once funding is in place, M2D2 provides companies with laboratory space for research and building prototypes with the final goal of drawing in venture capital. “Basically, we tell companies how to obtain grant money and then we tell them how to spend it,” McCarthy says.

A new design for orthopedic bone screws and a drug-eluting stent are among the products that have been developed at M2D2 so far. Many more products are expected once the facility expansion is completed. UMass Lowell has already spent about $3 million to convert a 30,000-sq ft campus building into laboratories and equipment for building medical devices. The state’s contribution, along with additional private and federal funding, could allow the new facility to open by the end of the year, McCarthy notes.

The state’s investment is intended to serve as a model for the kinds of contributions that would be made under a proposed $1 billion life-science initiative designed to improve Massachusetts’s economy through growth in the medical sector. Massachusetts has had success in the medical device area recently, including 1378 regulatory approvals between 2002 and 2006, the second most of any state. Nevertheless, Governor Deval Patrick cited stiff competition from California, Minnesota, North Carolina, and China as a driving force behind the state’s contribution to M2D2.

NEED TO KNOW

MicroPep, a recently formed entrepreneurial-driven company, offers completely integrated micromanufacturing and design services.

Combining the capabilities of several service providers, microPep (East Providence, RI; www.micropep.com) claims to be the first completely integrated micromanufacturing firm in the United States. Supported by facilities in Massachusetts, Rhode Island, Illinois, Ohio, Mexico, and China, the company touts itself as a one-stop source for a range of microsized component design and manufacturing services.

Officially launched in January at MD&M West, the company, a subsidiary of Precision Engineered Products Inc., is an entrepreneurial endeavor encompassing five firms with overlapping histories and mutually supporting core competencies. The formation of microPep represents the first time that all of the companies’ capabilities will be united under a single brand name.

“This is a new venture with very solid long-standing companies,” says microPep president John Harker. “If you’re not evolving and changing and trying new things, you can kiss [business] goodbye.”

Armed with the resources to take a project from prototype to production in-house, microPep provides micromanufacturing services that include molding, stamping, and assembly. Specialty plating and single-point diamond turning operations are also offered. The niche service provider’s focus on micron-sized tolerances and very small parts lends itself to such medical applications as implants, minimally invasive surgical instruments, and stent markers. Microfluidic and electronic applications can also benefit from the company’s targeted capabilities.

Working with microscale parts requires a different mindset from the manufacture of standard components in terms of materials and metrologies, according to Donna Bibber, microPep technical partner. “MicroPep was put together so that it could service a very different industry [segment] than conventional-size parts,” she says. “This makes sense for the medical industry.”

In late March Covidien recalled orefilled syringes which contained heparin. We may not have seen the last of the recalls.

The ACLA renewed its call for Congress to repeal the project. What does this have to do with medical device manufacturers? Medicare has other competitive-bidding projects underway, including one on durable medical equipment. Perhaps the judge's ruling will eventually have an impact on those as well. Also, if smaller clinical labs did go out of business, that could harm sales of diagnostics-equipment manufacturers.

BREAKTHROUGHS

A manufacturer claims that its FOP-F125, shown above on a 0.02-in. needle, is the smallest fiber-optic pressure sensor yet developed.

Constructed with a diameter of 125 µm, a fiber-optic pressure sensor is the smallest of its kind, according to its manufacturer, Fiso Technologies Inc. The FOP-F125 sensor was developed to extend the reach of pressure-monitoring systems without sacrificing accuracy. Its small profile enables the sensor to be directly mounted at the tip of a fiber-optic cable, thus allowing the sensor to be positioned inside of the body at the exact point of measurement—potentially yielding a more accurate model than traditional pressure-monitoring systems. In addition, the sensor could be embedded in next-generation devices capable of accessing previously unreachable areas of the body.

Lumen pressure sensors can fail to provide the up-to-the-second accuracy needed to safely execute various surgical procedures, says Éric Pinet, principal scientist at Fiso. “With this new technology, the miniature sensor can be directly mounted at the catheter tip, so the real in situ pressure is being measured at all times,” he says. “With traditional systems, pressure measured through fluid-filled catheters can be inaccurate because it’s influenced by fluid friction, catheter compliance, or by the presence of tiny bubbles, which all create damping effects that distort fast-changing waveforms.”

Bulky pressure sensors can’t be mounted at the tip of catheters because the space is needed for other monitoring sensors or instruments. But the FOP-F125 is small enough that it does not present an impediment to other potential components. The company has developed a production process specifically to allow large-scale manufacturing of the sensor directly at the tip of glass optical fiber without using adhesive.

The main obstacle to achieving miniaturization was maintaining sensor accuracy, Pinet says. “Sensitivity of a pressure sensor is proportional to the diaphragm’s diameter to the power of four, so reducing the sensor’s diameter drastically decreases its sensitivity,” he explains. “Our advance was to replace the silicon diaphragm of our current generation of pressure sensor with a more flexible glass diaphragm and to reduce the thickness of the membrane so that the sensor could be both small and sufficiently sensitive.”

The sensor’s optical design makes it immune to the electromagnetic field and radio-frequency interferences often encountered in operating room settings and in close proximity to imaging systems. It also provides clear definition of complex pressure waveforms, such as human arterial blood pressure variations generated by heart valve closure. Suitable for invasive devices such as intracranial, intravascular, and intrauterine monitoring systems, the sensor’s responsiveness is also useful in determining pressure-curve characteristics at faster paces.

Fiso Technologies Inc., Quebec City, QC, Canada
www.fiso.com

These include not being prepared, not asking FDA who will be attending the meeting, making poor use of time, making rash committments, and leaving the table without a clear plan of action. The speakers also discussed how difficult it can be to understand FDA's position in the process, because as stated above, the agency is an enforcer, not a consultant. "You have to respect FDA's role," Cassens said, "but also realize that we are people too." Johnson advised not to bring a lawyer to such meetings, especially ones with the district office. "It's not that you can't bring a lawyer; in Washington, everyone does," he said. "But in district offices it will palpably change the flavor of a meeting, putting FDA on guard." If that happens, he explained, a firm might get less advice on what to do. It's a tightrope walk, he admitted. "FDA is not objective, no matter how much they try to be," he said. Once it has formed an opinion, OEMs will find it difficult to change, he explained. "It's not fair, but FDA is doing its job." A PDF of the presentation, "Top 10 Mistakes Not to Make when Meeting with FDA," can be found on the RAPS Web site. -- Heather Thompson

"Our goal is to bring regulatory bodies together, not make them exactly the same," he said during the RAPS Horizons conference, held in late March in San Francisco. Brooks and Michael Gropp, global regulatory strategist for Medtronic, spoke to attendees about the global regulatory environment and how harmonized regulations are being adopted -- or better yet, adapted. "The idea [among manufacturers] is that harmonization is a big bang theory. In reality, verbatim adoption is unlikely," said Gropp. He explained that a convergence model is more likely as countries implement standards such as ISO 13485, and then apply local preferences over that standard. Part of the difficulty is that countries with established regulations do not have flexibility. "It's hard to retroactively harmonize," Gropp said. "Consider how difficult it is to change a law in the United States." Even so, harmonization efforts have had an enormous effect on the regulatory climate and will continue to do so, especially for countries with immature regulatory structures. Countries without prior medical device regulations are likely to apply the standards as they are written, Gropp said. For example, India will soon have a regulatory mechanism in place for manufacturers of medical devices in that country. It is likely that ISO 13485 and other standards will play prominent roles, Brooks said. Ultimately, it is up to an OEM's regulatory staff to understand the regulatory idiosyncracies of each country, Gropp said. They are responsible for understanding and interpreting the directives. A PDF and MP3 of the presentation, "Implications of Global Regulatory Changes," is available on the RAPS Web site. -- Heather Thompson 

She spoke in March at the PharmaMedDevice conference held in Philadelphia. A draft guidance published in 2004 offers some advice, but it is still up to the manufacturer to sort out which parts of the QSR apply and which parts of the drug GMPs apply, Alexander said. "You must justify what you choose to follow, especially in areas where they conflict," she said. She said device manufacturers who may not have experience with the drug GMPs will need to keep the following provisions in mind, as they differ quite a bit from what's in the QSR: * 21 CFR 211.84: Testing and approval or rejection of components, containers, and closures. Identity tests (preferably United States Pharmacopoeia) must be performed on all components, containers, and closures that come in. They cannot be used until they have been tested and released for use by the quality control department. * 21 CFR 211.103: Calculation of Yield. Manufacturers must specify or estimate expected yields, and state them in the batch record. A firm must designate one person to calculate them and another to verify them. Any deviation must be corrected to prevent recurrence. * 21 CFR 211.137: Expiration Dating. Drug products must bear an expiration date determined by stability testing (for more on stability testing, see below). It must appear on the labeling. * 21 CFR 211.165: Testing and Release for Distribution. Tests to determine the identity and strength of each active ingredient must be performed on each batch. Tests to ensure the drug is free of objectionable microorganisms must also be performed on each batch. The accuracy, sensitivity, specificity, and reproducibility of test methods must be established and documented. * 21 CFR 211.166: Stability testing. "It's kind of like shelf-life testing, but not," Alexander said. One crucial difference is that accelerated-aging tests may not be used in lieu of real-time tests. Accelerated-aging tests can only be used to support tentative expiration dates, pending the outcome of the real-time studies. The tests must be performed using the same package that will be used on the marketed product. * 21 CFR 211.167: Special Testing Requirements. Drug products purported to be sterile or pyrogen-free must undergo tests to prove that. This section also has provisions relating to ophthalmic ointments and controlled-release dosages. * 21 CFR 211.170: Reserve Samples. Manufacturers must retain a sample of product that is representative of each lot. The amount of samples kept must be at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its established specifications, except for sterility and pyrogen testing. The purpose is to help diagnose a cause in case of a recall. The problem is that an individual medical device is usually much more expensive than an individual package of drugs, so the reserve-sample requirement can be quite burdensome for combination-device manufacturers. "It could mean holding onto millions of dollars worth of product if you're dealing with something like a drug-eluting stent," said Alexander. "That does not make any sense. Especially since what they're really looking for is the degradation of the drug." Michael Gross, prinicpal consultant of Chimera Consulting and a member of the Combination Products Coalition, said the issue is "totally unresolved," and FDA appears to be dealing with it on a case-by-case basis. -- Erik Swain