Nanotech medical device makers seek guidance in uncertain regulatory environment

There is little in the way of regulatory harmonization regarding nanotechnology regulation at this point, which leaves makers of devices and diagnostics with a complicated path to market. Some jurisdictions are farther along than others, but to date, none of them have covered as much ground as the U.S. Food and Drug Administration (FDA).


The view from Europe

Nanotechnology, as defined by The Royal Society, is “The study of phenomena and manipulation of materials at atomic, molecular and macromolecular scales, where properties differ significantly from those at a larger scale.”1 See Figure 1 for a scale that depicts the relative size of nanoscale, microscopic and macroscopic objects.

In the European Union, there is a fairly comprehensive overarching regulatory mechanism for nanotechnology that applies to all products containing nanoscale materials as well as a few regulations that are specific to medical products. As an example of the latter, the European Commission had published a paper in 2014, “Guidance on the Determination of Potential Health Effects of Nanomaterials Used in Medical Devices,” regarding risk assessment for devices bearing nanoscale materials, and much of the document revolves around ISO 10993, which addresses biocompatibility.2 The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) formally adopted the paper the following year.


Figure 1. Nanoscale devices are 100 to 10,000 times smaller than human cells. The depiction displays this scale in size. Source: National Cancer Institute.


The European Commission said in an April 5, 2017, statement that the new medical device regulations present a dedicated classification rule for devices incorporating or consisting of nanomaterials. The commission statement said the critical factor in determining the applicability of the related regulations is whether nanomaterials will be in contact with membranes inside the body. Any devices that present a medium or high risk as a consequence of such contact would fall under the highest risk class and thus be subject to the most stringent conformity assessment procedures, the commission said.

The European Chemicals Agency has as much jurisdiction in this area as perhaps any pan-EU agency. The agency’s REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) went into force in June 2007, and requires that companies follow a given set of procedures for characterization.

These regulations have been revised recently, and manufacturers will have to register their nano-substances if they produce or import one ton or more of the substance in question. The report must include details such as form and size distribution, but the regulations also stipulate that a bulk is a nanoform bulk if 50 percent or more is between 1 and 100 nanometers. There are a number of associated safety testing requirements as well.


Extensive documentation

The take-away message here is that if you are producing or importing bulk nanoscale materials in the EU, you will have to provide extensive documentation as to the type of particle, and the use of nanoscale materials will elevate the risk category of your device or diagnostic if that material comes into contact with the subject or patient.

Among the regulatory agencies of interest is the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), which has had little to say about the matter in the recent past. Generally speaking, MHRA intends to align its medical device regulatory system fairly closely with that of the EU, but that is about all one can say with any certainty. The fact that Brexit is still not an accomplished fact suggests that MHRA has had little time to grapple with the nanotechnology question, and thus the agency may yet attempt to devise at least some regulations for nanotechnology.

The FDA has offered the most specific guidance pertaining to the use of nanotechnology and nanoscale materials, although the agency is not especially prescriptive on a lot of points. In contrast, the EU is focused on demonstrations of material safety and has little to say about the specific application of nanotechnology in health care products.

For those looking beyond the U.S. and Europe, regulators in China announced earlier this year that they intend to address nanotechnology and nanoscale materials in medical devices as part of an expansion of the use of recognized standards. This is a two-year effort, however, and nothing has emerged just yet, although the scope of that proposal seems limited to non-active medical devices.

Still, developers are not without at least some guidelines, thanks to the efforts of the ASTM, formerly known as the American Society for Testing and Materials, and the International Standards Organization, or ISO. In real estate, the saying is “location, location, location,” and one might similarly emphasize standards when it comes to nanotechnology in devices and diagnostics. When facing an uncertain regulatory environment, a demonstration of compliance with those standards is probably your best bet.


This article is adapted from a webinar, “Nanotechnology regulation: Regulatory guidance on using nanotechnology in medical devices,” conducted by the author, Mark McCarty, Regulatory Editor of BioWorld MedTech, and Anette Breindl, Senior Science Editor of BioWorld, both from Clarivate Analytics.

To hear the full presentation, which includes analysis of the increased use of nanotechnology in devices, diagnostics and drugs as well as an in-depth look at how the FDA and other agencies approach nanotechnology regulation, click here.


Watch the on-demand webinar