MANUFACTURING IS KEY
At its September public meeting, the FDA heard comments from industry representatives and scientists on what manufacturing
and product characterization issues should be considered in crafting guidance for developing safe and effective products containing
nanoscale materials. Of particular interest to the FDA is whether using nanomaterials changes the manufacturing process for
drugs and biologics, what added parameters should be measured, if nanoscale materials raise new issues in production scale-up,
and how such materials might alter product standards and specifications. The bottom line is to determine to what extent the
size, shape, and surface charge of a nanoscale material affects the quality, safety, and effectiveness of an excipient or
drug formulated with such ingredients.
Characterization of nanomaterials in medicines also poses new challenges. There is a need for appropriate tools to assess
product chemistry and unique characteristics, including primary particle size; aggregation and agglomeration state; two- and
three-dimensional distribution; and particle size distribution. Chemical composition should consider element distribution,
crystal form, surface composition, and reactivity. Full product characterization may require enhanced quality control measures
and evidence that a manufacturer can produce consistent formulations with low batch-to-batch variability.
David Hobson of nanoTox, Inc. (Austin, TX) explained that because nanomaterials have a much higher surface-area-to-weight
ratio than conventional materials, this can affect mechanisms of action, biodistribution, and pharmacokinetics. Whereas stability
testing for nanomaterials should follow international guidelines, more extensive stability assessment may be necessary because
nanomaterials can change under different storage and handling conditions.
A goal for manufacturers and the FDA is to avoid regulatory requirements likely to block development of new products incorporating
nanomaterials. Researchers are developing new cancer therapies that are more soluble and targeted and less toxic: anti-cancer
drugs from CytImmune Sciences (Rockville, MD) use colloidal gold nanoparticles, and Elan (Dublin, Ireland) finds that nanocrystal
technology can produce highly soluble ingredients. Nanomaterials are being tested as possible vectors for delivering gene
therapies to patients, and nano tissue engineering combines stem cells and nano-lattices. Researchers at the University of
Michigan recently announced progress in developing a nanoemulsion hepatitis B vaccine that doesn't need sterile syringes,
refrigeration, or repeated booster shots.
Nanotech drugs, moreover, may be less vulnerable to enzymatic and chemical degradation and provide enhanced bioavailability.
Another benefit may be the ability of nanoparticles to serve as effective platforms or carriers for insoluble or poorly soluble
drugs and as scaffolding to attach chemical moieties in ways to increase solubility or decrease clearance. Reformulation of
old or obsolete compounds to incorporate nanomaterials may also allow manufacturers to extend the life of existing drugs and
enhance patent protection.
The emergence of nanotech drugs fits the broader shift to personalized medicine. Nanotech diagnostics able to quantify disease-related
biomarkers may identify precise medicines to fit patient needs. The hope is that more targeted drugs may require less frequent
dosing, enhance safety profiles, and improve patient compliance.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, firstname.lastname@example.org