More to Be Considered
“There is no one nanotechnology,” Dr. Baker asserted. “Thus nanomaterials, even in the same size range, act very differently. Essentially, they’re just going to have to consider these one-on-one and not make any blanket statements about them.”
Dr. Malinoski of Liquidia added: “One of the critical elements will be, ‘How well can we measure those? How reproducibly? What’s your distribution of particles, and what do different particle sizes do to affect the biological result you’re trying to achieve? How can you distinguish something 10 from something 20, 40, 60, 100 nanometers?”
Also very important, Liquidia chairman Seth Rudnick, M.D., added, is shape. FDA addressed this by saying “manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components.”
Dr. Rudnick remarked, “all of us are trying to define what is a nanostructure that is biologically relevant and important. That probably will be dependent on both size and shape, something we think Liquidia is uniquely positioned to be able to explore but that other companies will be exploring with the agency over the next few years.”
Liquidia is a developer of vaccines based on engineered particles capable of delivering small molecule and biologic therapies to an intended target. Its platform technology is called Particle Replication in Non-Wetting Templates. Those particles can range from tens of nanometers to hundreds of microns.
Liquidia reportedly established a dialogue with agency regulators as it was developing its technologies, starting with lead candidate LIQ001, a seasonal flu vaccine. LIQ001 began Phase I testing last year. “Our first IND was submitted, went through without any regulatory stops, so that we got from concept into the clinic in 18 months,” Dr. Malinoski said. “And part of that was because we saw the need to be proactive and to help educate those reviewers at the agency who were looking at this nanotechnology for the first time.”
FDA hopes other companies follow suit, whether or not they are pursuing required premarket reviews. “Where products applying nanotechnology are not subject to premarket review, the agency urges manufacturers to consult with the agency early in the product development process. In this way, any questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be appropriately and adequately addressed,” the draft guidance advised.
As FDA acknowledges, the draft guidance is just the beginning of its thinking on how to ensure that nanotech-based products are safe and effective. To the extent they address these two qualities, the guidance should provide a valuable roadmap for nanotech-based drug development.
A heavier-than-needed hand by FDA when it comes to regulation, however, creates potential for something else: as Dr. Malinoski put it, “getting so bogged down in guidances that we focus on guidance instead of bringing new products forward.”