Biomedical Engineering Reference
In-Depth Information
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Surface area:
The surface area exposed to a product stream varies
widely. It is relatively high for filters, in which the internal surface
area is 1,000× the filtration area. Conversely, surface area is relatively
small for O-ring seals.
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Time and temperature:
Longer contact times allow for more poten-
tial leachables to be removed from a material until equilibrium is
reached. Higher temperatures lead to more rapid migration of leach-
ables from materials into a process stream or formulation.
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Pretreatment steps:
Sterilization by steam autoclave and/or gamma
irradiation may cause higher levels of extractables and leachables
depending on the polymer formulation involved in a single-use
component. On the other hand, rinsing may lower the concern for
extractables and leachables (e.g., when filters are flushed before use).
Here are some highlights relating to risk assessment of extractables and
leachables:
1. Regulatory responsibility for overall assessment and understand-
ing of a finished product and process components involved in its
production remains with the product sponsor. This includes evalua-
tions of extractables and leachables. Regulatory agencies do not have
a guideline available yet to help sponsors.
2. All elastomeric and plastic-based materials contain extractables
specific to the formulated and cured materials from which they
are constructed.
3. Contaminants are also found in stainless steel systems in the form
of residues left after cleaning or traces of metals such as iron, nickel,
and chromium salts from the stainless steel itself, so the problem
of contamination from the container is not restricted to disposable
containers.
4. Most polymers without certain additives would not work as mate-
rials of use in disposable processing: this includes stabilizing the
polymer, extruding it, and preventing its oxidation and UV degra-
dation; other additives include antistatic agents, impact modifiers,
catalysts, release agents, colorants, brighteners, bactericides, and
blowing agents. The choice of polymer or method of polymerization
(by heat or chemical means) directly affects the levels and types of
compounds found as extractables.
5. Fluoropolymers offer the best choice as they are typically processed
without additives, stabilizers, or processing aids.
6. A Drug Master File (DMF) or Biological Drug Master File (BMF) for
process-contact equipment is not explicitly required by U.S. regula-
tory authorities. However, it represents a way for vendors to share
