Biomedical Engineering Reference
In-Depth Information
18. The component used for an extractables study should be the same
one that will be used in a process, and it should have the same pre-
treatment steps as is intended for that process. For instance, if a pro-
cess uses gamma irradiation for sterilization, then the component
used for extractables testing should be sterilized by this method.
Often, a vendor will provide simulated data based on similar prod-
ucts by extrapolating the data from other components; this would
not be acceptable.
19. The solvents used for leachables studies should include water and a
low-molecular-weight alcohol such as ethanol or
n
-propanol. Where
appropriate, an organic solvent with the appropriate solubility
parameters will help identify additional extractables. Extractions
should be performed at relatively extreme time and temperature
conditions. However, the solvents or extraction conditions should
not be so extreme as to degrade materials to a point at which they are
not mechanically functional (e.g., melting or dissolving). Extreme
conditions used should be relative to those under which a material
is normally used. For example, one normally used at room tempera-
ture might be extracted at an elevated temperature of 50°C or 70°C.
20. Analytical methods should include HPLC and GC-MS methods to
detect and identify specific, individual, extractable compounds.
HPLC with an ultraviolet (HPLC-UV) or mass spectrometer (LC-MS)
detector and GC-MS are the most scientifically robust methods for
this purpose. When metals are a concern, inductively coupled plasma
analysis is widely used, both with and without mass-spectrometric
detection (ICP and ICP-MS).
21. While it is desirable to identify each extractable, for some extract-
ables, such as siloxanes and oligomers of base polymers, precise
identification is not feasible because of the large number of closely
related isomers and oligomers. In such cases, a general classification
can be used. Quantitation of identified extractables is informative,
but it does not need to be performed at a high level of precision. This
is different from recommendations for evaluating extractables for
final containers or closures, for which analytical and toxicological
limits should be set based on a measured level of extractables.
22. User-specific components, such as filters, connecters, tubing and
bags, etc., may be built by using subcomponents from different ven-
dors. It is unlikely that the composite system would have complete
data on extractables from the vendor assembling the component.
Individual data for each subcomponent can be pooled, but it may be
easier for the sponsor to conduct the study on the entire component
at one time. It is therefore advisable that sponsors use off-the-shelf
products where possible.
