Biomedical Engineering Reference
In-Depth Information
nanomaterials(s) or otherwise involve the application of nanotechnology that might require addition
data or special steps to address potential safety or quality issues.”
*
The CVM procedure addresses the investigational stage, as well as the post-clinical stage. At
the early phase, the reviewer is to note whether the applicant has addressed any unique safety con-
cerns related to the use of nanomaterials in the formulation and how the applicant has attempted
to characterize those hazards. The reviewer is to address the issue of whether additional separate
safety studies of the measurement of additional safety parameters in the margin of safety studies
are needed. The review catalog also addresses a review of formulation bridging studies, human food
safety reviews, toxicology, residue chemistry, microbial food safety, and the CMC. The CVM docu-
ment is useful because it not only lists the technical information to include, but what those studies
and data should address. This effort is a good example of the FDA using its guidances to attempt to
generate meaningful scientific information regarding a product.
There is an interesting article by Dr. Jan Simak
†
at the Biologics Research Projects link on the
Center for Biologics Evaluation and Research (CBER) website. Dr. Simak describes the purpose of
his research as a study of nanomaterials made of carbon atoms:
Because of their unique and useful properties, carbon nanomaterials are under investigation for vari-
ous applications in biomedical nanotechnologies, usually as structures called carbon fullerenes and
carbon nanotubes (CNTs). The superior mechanical characteristics of CNTs make them very attractive
materials for making devices for collecting, processing, and storing blood transfusion products, diag-
nostic biosensors (devices that use biological material such as enzymes, cells, or antibodies to detect
a substance), drug delivery systems, and imaging devices for use inside blood vessels. Several studies,
however, are raising safety concerns by showing toxic effects of fullerenes and CNTs. Therefore, one
part of our research is focused on determining the mechanism of toxicity in these studies, by evaluating
whether these nanomaterials are toxic to blood vessels and blood cells.
One important class of nanomaterials is made of carbon atoms. Because of their unique and use-
ful properties, carbon nanomaterials are under investigation for various applications in biomedical
nanotechnologies, usually as structures called carbon fullerenes and CNTs.
The paper goes on to describe how the CBER staff will explore the potential toxic effects of the
nanotubes and other materials, and the paper gives clues to a potential applicant on what CBER
deems important in studying the toxicity of nanomaterials:
Thus the investigation of effects of fullerenes and CNTs on blood cells, platelets and endothelial cells is
a critical safety issue. The results of our Critical Path research project on blood and vascular biocompat-
ibility of carbon nanomaterials will help FDA to create regulatory policy for evaluating the safety and
effectiveness of different biomedical nanomaterials.
Our investigation is focused on effects of various commercially available carbon nanomaterials and
their structural and chemical derivatives on plasma membranes of cultured endothelial cells, blood
cells, and platelets isolated from blood. We use a variety of cell biology assays to study
in vitro
cyto-
toxicity of these materials, such as apoptosis, necrosis, autophagy, effects on the cell cycle, cell surface
activation markers, and intracellular calcium concentration.
‡
In a particular guidance section, issued about when to file a 510(k) for changes to an existing
device, another center, the Center for Devices and Radiological Health (CDRH) stated that:
Important Note on 510(k) Devices that Contain Nanomaterials or Otherwise Involve the Application
of Nanotechnology:
Nanotechnology is a new and evolving field for both the medical device industry
*
Id.
at 1.
†
Simak, J. 2011. Investigation of potential toxic effects of engineered nanoparticles and biologic microparticles in blood and
their biomarker applications. http://www.fda.gov/BiologicsBloodVaccines/ScienceResearch/BiologicsResearchAreas/
ucm127045.htm.
‡
Id.
