Biomedical Engineering Reference
In-Depth Information
Examples include the “Carcinogenic Potency Database” (CPDB,
http://potency.berkeley.edu/ ) and the U.S. Environmental Protection
Agency's “Distributed Structure-Searchable Toxicity Network”
(DSSTOX, http://www.epa.gov/ncct/dsstox/ ) database. Chances are
that most sponsors will not be able to conduct these studies in-house,
and it is advised to outsource these evaluations.
13. The classes of compounds that extractables include, more particu-
larly, n -nitrosamines, polynuclear aromatics (sometime termed
polyaromatic hydrocarbons , PAH), and 2-mercaptobenzothiozole, along
with biologically active compounds such as bisphenol-A (BPA).
Individual extractable compounds are too numerous to list, but
examples include aromatic antioxidants such as butylated hydroxy-
toluene (BHT), oleamide, bromide, fluoride, chloride, oleic acid, eru-
camide, eicosane, and stearic acid. Databases on extractables are
widely available, such as by PQRI. Comprehensive extractable data
for components can reduce the time and resources needed to qualify
leachables from the systems where they are used. When compar-
ing supplied extractables data for components constructed of similar
materials, end-users should carefully review the methods used to
generate the data. Less rigorous methods may underrepresent the
actual levels and extent of extractables, and a report describing more
extractables may simply come from using more rigorous methods.
14. For determination of leachables in products, it is currently the indus-
try standard to validate analytical methods according to ICH and
USP criteria. This ensures appropriate levels of analytical precision
and accuracy.
15. The overall quantity of extractables or leachables can be estimated
using nonspecific methods such as total organic carbon (TOC) and
nonvolatile residue (NVR) analysis. Such nonspecific quantitation is
especially useful in comparing materials before their final selection
for a process. These analyses can be used individually or collectively
to estimate amounts of extractable material present and to ensure
that targeted methods are not missing a major extractable constitu-
ent. For instance, nonpolar compounds without chromophores can
be identified using Fourier-transform infrared (FTIR) analysis of
nonvolatile residues.
16. Organic extractables will leach into formulations at a higher level if the
products have higher organic content or if surfactants are present.
17. The toxicity of leachables is frequently estimated based on the
amount entering the human body in each dose. Thus, it is often not
the quantity of leachables in a product but how much finds its way
into the human body. This is somewhat analogous to the limits many
regulatory agencies set on residual DNA in a finished product.
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