Medical Device Daily Washington Editor

The history of the FDA — and probably that of most federal regulatory agencies — suggests that pre-emptive regulatory development is the exception rather than the rule.

And even Buckminster Fuller’s molecular buckyball might not be able to provide the exception that proves the rule.

At Tuesday’s nanotechnology meeting hosted by the FDA (Medical Device Daily, Oct. 12, 2006), several called for the agency to write a whole new set of regulations for this class of matter, but the FDA resource crunch and massive number of uncertainties concerning the behavior of tiny matter make it unlikely that the Code of Federal Regulations will be fattened up anytime soon.

Among those who weighed in on the question of whether “nano” regulations are necessary — and presenting a largely minority view — was Matthew Jaffe of the U.S. Council for International Business (New York). He said that “the regulatory process that is in place is significant and adequate to address the [nanomaterials] issues before the FDA.”

Neil Desai, PhD, vice president of R&D at Abraxis Bioscience (Schaumberg, Illinois), seconded this view, arguing that there are “no new or unique toxicities” involved in the use of nanoparticles to deliver drugs and that “we believe FDA has in place adequate regulations” to keep the public safe.

Piotr Grodzinski, PhD, the director of nanotechnology cancer programs at the NCI Alliance for Nanotechnology in Cancer , gave a different read on the prospects for the drug and biologics industries than offered by Desai. He noted that the multifunctional properties of some nanoparticles — those used to deliver both diagnostics and treatments — and the fact that “the level of innovation is very high” in this sector. Both facts, he said, argued for a new regulatory regime.

Kathy Jo Wetter, a researcher with ETC Group (Ottawa, Canada), a clinical trials monitoring group, asserted that nanotechnology has operated in a “regulatory vacuum” and that in 2002 ETC had urged a moratorium on the use of nanomaterials, a proposal she said “received a less than enthusiastic response.” And she urged the audience to “focus on the urgent need to address” the lack of FDA regulations for the nanotechnology products it will regulate.

The production of nanomatter has almost zero history of standards, but in January, ASTM (formerly known as the American Society for Testing and Materials; West Conshohocken, Pennsylvania) released standards for determining the diameter and wall thickness of multi-wall carbon nanotubes using transmission electron microscopy and measuring the length and thickness of nanotubes using atomic force microscopy. However, many other nanoparticles are not yet standardized, leaving the agency with many unanswered questions about the characteristics of nanomatter.

Michael Taylor, who served as the agency’s deputy commissioner for policy from 1991 to 1994 discussed the FDA’s dilemma in a paper for the Woodrow Wilson Center (Washington), noting that the variety of nanomaterials and the range of uses leaves sponsors with “a case-by-case safety assessment” (MDD, Oct. 10, 2006). He said that “it is not clear that existing animal toxicity-testing protocols . . . can be used in their present form,” and that “ratios between the surface area of a nanomaterial and its volume or mass” may have to supercede considerations of “traditional measure of dose.”

Bernie Liebler, the director of technology and regulatory affairs at the Advanced Medical Technology Association (AdvaMed; Washington) is optimistic that device and diagnostics makers will not have to hew to a new set of rules anytime soon.

He told MDD that the quality system regulation for devices “does not really depend on materials properties — it addresses processes. I wouldn’t think you’d need to change the quality system regulations” in order to ensure the safety and efficacy of medical devices.

“The way we view the device regime is that its pretty well understood, but relies on a great deal of interaction” between the agency and the sponsor, he said.

Clearly, reviewers at the Center for Devices and Radiological Health and field investigators have a substantial amount of reading to do to stay abreast of developments in this area.

“There’s a need for a lot of broad education” on the topic at the FDA, Liebler said.

“The reviewers will need some education to understand the new technology” on how nanomatter works and interacts with other components, Leibler noted, and “investigators will need more information” from the company during inspections in order to establish whether process validation, for example, truly validates those processes. As for tests of incoming material, he stated that there are “standard laboratory methods for defining things such as particle size and purity, but there are multiple ways to do that.”

As for the substantial equivalence dilemma that reviewers will soon face, Leibler said that “[t]he agency has a fair bit of discretion . . . and I think this is an area where they’re likely to use it. It would be unfortunate if people expected FDA” to put every nanomaterial-based product through the PMA process.

Leibler echoed other sentiments that credibility is critical in a world that may be wary of nanotech and that the FDA’s role in this pursuit is anything but peripheral. “We’re glad to work with them on public outreach, and we think that’s a valuable role that we as a trade association can play.”

However, “FDA must play a central role in the public outreach” because industry’s claims “don’t resonate” with a skeptical public.