Medical Device Daily Washington Editor

WASHINGTON – The development and use of nanoscale materials is hardly new, and nanoscience promises to play a much larger role in devices and drugs in the decades to come. Hence, the Food and Drug Law Institute (FDLI; Washington) last week sponsored its first of what is planned to be an annual symposium on nanotechnology.

While attendees may have expected to hear about different FDA approaches to device and drug applications that incorporate nanomaterials, the consensus among panelists from the agency and the private sector was that the agency has the expertise it needs to review nano-products and requires no new regulatory apparatus to ensure nanotech product safety.

Additionally, the phrase “case-by-case basis” was employed routinely when specific regulatory questions were posed.

Ralph Hall, PhD, of the law firm of Baker and Daniels (Minneapolis), said “one of the key regulatory issues is whether nanotechnology is just another new technology.” Assuming it is new, he said, “the core issue is FDA’s scientific expertise.”

But Hall made the case that nanotechnology “is not new to FDA” because the agency already has reviewed a number of products employing nanoscale materials, including silver nanoparticles, engineered calcium phosphate, liposomes and albumin-bound nanoparticles.

As for the novelty of yet-to-come devices and drugs, Hall said the agency has dealt with novel product lines in the past — such as pacemakers and other high-risk implantable devices — without creating new mechanisms.

“If this is not new, why all the fuss?” Hall asked, adding that despite generic concerns about nanotechnology, the public “has not perceived any issues” with specific products.

“If you want to regulate it, you have to define it,” he said, but that the FDA nanotechnology task force “declined to define it” for what he said were good reasons. Hewing to the definition of objects smaller than 100 nanometers (nm) can be arbitrary because “I may try to design all my products to be 101 nm and get out of your definition.”

Hall said that those who make the case for a new regulatory paradigm run the risk of creating new requirements at considerable expense but no benefit.

“No unique safety issues have emerged” in all these applications, Hall said. He made the case that many FDA scientists are familiar with this scale of matter because most pharmaceuticals “act at their site of action as individual molecules that are in the nanosize range.”

Bernie Liebler, director of technology and regulatory affairs at the Advanced Medical Technology Association (AdvaMed; Washington), discussed the application of nanotechnology to medical devices and hinted at a need to demystify nanotechnology.

Does nanotechnology constitute a new way of making devices?

“It’s a question that constantly comes up and we need to address it,” Liebler said.

“When people think about our industry, they think of” high-risk medical devices, he said, but pointed out that hospital gowns and drapes are also devices, and these “will be affected by nanotech” first.

“We’ll have high-tech coatings on low-tech products,” which “will have a significant impact” on healthcare, he said. “For example, you could probably see anti-friction coatings for catheters, making them easier to get into the body.”

“We are in an era of implants,” Liebler said, such as hip implants. “You’re always looking for longer life in that hip,” and that the durability of implants will improve with the addition of nanoscale materials.

Liebler predicted that FDA will not hire nanotech specialists. “I think we’re going to see specialists in biocompatibility” and other areas with a focus on nanotechnology, he said, adding that “it’s a little hard to foresee someone sitting at a desk as the nanotechnology expert” because of the subject’s breadth.

“The one burning question that has come up before and will come up again: Will the current paradigm work?” Liebler asked.

“Yes it has, and it will continue to,” he said, noting that a pre-market application requires that “you show from ground zero [that the device] is reasonably safe and effective.”

Liebler said if the concern is additional assurances of safety, “there are ways to approach it that require no new regulations or new statutes.” Safety assurance cases, a method for validating the use of products in other industries, “could easily be applied to medical devices.” By adding this technique to risk management, he said, “you would be looking at a way to formally demonstrate” safety in a more rigorous way, should that prove necessary.

Norris Alderson, PhD, associate commissioner for science at FDA and co-chair of the agency’s nanotech task force, said the nanotech report from July 2007 “represents our current thinking” on “nano-engineered materials, not nanotechnology,” calling these different issues. He said that the task force was designed to create a consistent and transparent approach to regulation, acknowledging that “nano-engineered materials may become a part of all the products” regulated by FDA at some point.

FDA discussed the National Nanotechnology Initiative’s definition of nanotechnology, essentially anything between 1 and 100 nm in size, but the agency has concluded: “We don’t need a [fixed] definition because we’re regulating the products, not the technology,” Alderson said. “We’re more concerned about the information that comes available about these materials than about defining” the prefix “nano.”

Alderson indicated that the science suggests that due to the interplay between the construct of materials and scale, “we may have to start thinking about surface area” in order to grapple with the physical/chemical properties of a drug or device, but he also acknowledged that “in many cases, we may not even have standards” for some of the materials that will hit FDA’s reviewers.

“We recognize that in any new technology, we may have to get new expertise ... but our staff is undergoing training on these issues.”

Alderson echoed Liebler’s earlier remarks on competence areas, saying: “we’re not looking for a nano-expert — we’re looking for an expert” with sufficient background in nanomaterials.