Diagnostics & Imaging Week Washington Editor
GAITHERSBURG, Maryland – Some say that no news is good news, but sometimes no news is just no news, which was the case with the Monday session covering devices and diagnostics at FDA's nanotechnology gathering.
Several members of the agency attempted to get the crowd involved, but an informal poll of the audience showed only few firms in attendance that are working on nanotech-based products and most of those were there to keep tabs on regulatory developments. The low number of attendees saying they are involved with development of products belies the fact that, while the sector is still in the fledgling stage, literally hundreds of nanotech products are known to be in various stages of development.
Subhas Malghan, PhD, deputy director office of science and engineering at CDRH, said the history of the manipulation of materials at the nanomatter level was not full of rousing successes. He said that many efforts "failed at the engineering stage" because the science did not adequately characterize the underlying material technology.
He also acknowledged "we [still] do not have all the tools we need at this stage" to adequately characterize some of the nanomaterials that are available to manufacturers.
Malghan said FDA had sponsored the session "to seek your input." He said, "One of the recommendations of the 2007 task force" was to develop guidances and "we're seeking your input on what kinds of guidances" industry needs.
He said there are "two factors we are concerned about" — namely what kinds of information and data are needed to demonstrate safety and efficacy, and "the circumstances in which a product's regulatory status might change due to the presence of nanoscale materials," a reference to the possibility that a device might move from a 510(k) standing back to a PMA classification.
Malghan observed, "at times, I think we use the word 'nano' in a very loose sense," noting that a difference in scale can affect both chemistry and physics. The first question for FDA, he said, is "what characteristics of nanoscale materials should be identified and evaluated to ensure safety and efficacy?"
The second question is what assessment tools are available to evaluate nanoscale materials. he said "size is the first area ... but size varies" by quite a bit, and development of measurement standards is not as readily put together as might be thought.
Malghan said particle sizes that fall within the traditionally defined range of nanomaterials is wide – a nanometer is a billionth of a meter and anything between 1 and 100 nanometers is generally deemed "nano" – so the equipment needed to detect them is not the cheapest.
A web search for scanning electron microscopes backs Malghan's remarks. According to the web site for one manufacturer, lower-end units start at $100,000 and can pick up matter only as small as 100 nanometers, suggesting a bigger budget might be required.
One of the big issues that FDA expects to pop up in the years ahead is whether the manufacturing process for nanoscale materials is different from that of conventional materials.
Mel Stratmeyer, PhD, of FDA's Office of Science and Technology, said "one of the things we've run into in our lab is that we get different size samples that are not always uniform" as well as dead bacteria in samples that "still cause biological effects" despite being dead.
Perhaps the biggest question of all in terms of the number of products affected is that of how the introduction of nanoscale matter might make turn a 510(k) into a PMA. One member of the agency's staff said the agency will tend to assume that a change of technology that is not well characterized will tend to push reviewers to see a device with a predicate as a PMA despite the existence of that functional predecessor.
George Wong, PhD, a reviewer at FDA with a background in biomedical engineering, offered the example of a biological paste used to treat spinal problems. He said a change from a micron size to nanosize matter in the product's formulation "is a significant change to me," largely because of the permeability of a cell membrane to nano-sized particles. "For me, that would be a PMA" rather than a 510(k).
On the other hand, Liz Mansfield, MD, a policy advisor at FDA, said "I don't think a difference in technology would necessarily take a product out of the 510(k) category," at least not for a diagnostic that operates outside the human body and incurs no direct contact.
Regarding combination products, John Weiner, assistant director of policy for combination products at the Office of Combination Products, reminded the audience that OCP has "only 60 days to think about" how to classify a product, so feedback from industry is vital to build an approach that will make sense.
There was little interest in the question of how to classify a combination product, but one member of the audience said the primary mode of action as the primary determinant was still appropriate, hence "the general approach to classification is still applicable."
On the other hand, Malghan pointed out that a particle of sufficiently small size might blur the line between mechanical and chemical effects, which might invalidate the first step in the classification process.
Bernie Liebler, director of technology and regulatory affairs at the Advanced Medical Technology Association (Washington) told Diagnostics & Imaging Week "the way the system is currently structured is adequate" to establish safety and efficacy of devices that contain nanoscale materials.