|
Medical Device Ethylene
Oxide (ETO/EO) Sterilization: Validation and other
challenges
6 Process and equipment
characterization
6.1 General
The purpose of this activity is to define
the entire sterilization process and the equipment
necessary to deliver the sterilization process safely and
reproducibly.
6.2 Process characterization
Process characterization, at a minimum,
shall include:
a) identifying the phases that are
necessary for an EO sterilization process;
b) identifying the process variables for each phase; and
c) documenting the process variables
6.3 Equipment characterization
The specification for the equipment to be
used shall be developed and documented. This specification
shall include:
a) the preconditioning area (if used);
b) the sterilizer; and
c) the aeration area (if used)
9 Validation
9.1 General
The purpose of validation is to demonstrate that the
sterilization process established in the process
definition (see Clause 8) can be delivered effectively and
reproducibly to the product within the sterilization load.
Validation consists of several identified stages:
installation qualification (IQ), operational qualification
(OQ), and performance qualification (PQ). Testing shall
not commence until the procedures and/or protocols have
been approved.
9.2 Installation qualification, IQ
9.3 Operational qualification, OQ
9.4 Performance qualification, PQ – Microbiological &
Physical
9.5 Review and approval of validation
The purpose of this activity is to undertake and document
a review of the validation data to confirm the
acceptability against the approved validation
procedures/protocol for the sterilization process and to
approve the process specification.
10 Routine monitoring and control
The purpose of routine monitoring and control is to
demonstrate that the validated and specified sterilization
process has been delivered to the product.
When validating an EO sterilization process, it is
necessary to perform a mapping of the chamber and monitor
temperature and relative humidity to evaluate the
performance of EO sterilization. Both empty and loaded
chamber tests are required.
It is important that patient safety be addressed by
minimizing exposure to EO and its by-products during
normal product use. ISO 10993 7 specifies limits for EO
and ethylene chlorohydrin (ECH); however, no exposure
limits are set for ethylene glycol (EG) because risk
assessment indicates that when EO residues are controlled,
it is unlikely that biologically significant residues of
EG would be present.
Author’s observations during validation / re-validation
process – challenges:
# Use of wireless data loggers can make validation process
more accurate and easier
# Use of EO concentration monitor probe is recommended.
This is expensive but can be very reassuring for
validation data.
# BI strips used per cycle is substantial in number and
cost of testing post the cycle is substantial, especially
when their results need to be validated from third party
(independent test facility).
These and other time and cost consuming processes make the
validation very assuring for manufacturer, healthcare
person and of course the patient.
Acceptable and beyond Quality of device; assurance of its
safe and effective use should be kept in mind while
carrying out these validations faithfully and diligently.
Some extracts from FDA guidance documents:
How Does the FDA Help Ensure that Medical Devices
Sterilized with Ethylene Oxide Are Safe?
Before most sterile medical devices are on the market, the
FDA reviews premarket submissions to determine if the
sterility information (for example, the method the
manufacturer is choosing to sterilize their device and
validation activities used to show that the device can be
effectively sterilized) is in accordance with
internationally agreed upon voluntary consensus standards
that the FDA recognizes. An important element of our
regulatory framework is a robust standards program. The
FDA encourages medical device manufacturers to use
FDA-recognized voluntary consensus standards in their
submissions, as conformity to relevant standards
streamlines regulatory review and fosters quality. Learn
more about the FDA's Recognized Standards Program.
For ethylene oxide sterilization, voluntary consensus
standards (ANSI AAMI ISO 11135:2014) describe how to
develop, validate, and control ethylene oxide
sterilization processes for medical devices and the
acceptable levels of residual ethylene oxide and ethylene
chlorohydrin left on a device after it has undergone
ethylene oxide sterilization. These standards help ensure
levels of ethylene oxide on medical devices are within
safe limits since long-term and occupational exposure to
ethylene oxide has been linked to cancer. Learn more about
the risks of ethylene oxide on the National Institutes of
Health web page on ethylene oxide. The FDA also inspects
industrial facilities that sterilize medical
devices and medical device manufacturing facilities to
make sure that they have validated sterilization processes
that meet FDA -recognized standards.
EPA's Role in Ethylene Oxide Sterilization
The U.S. Environmental Protection Agency (EPA) reviews and
enforces the Clean Air Act regulations for sterilization
facilities that emit ethylene oxide to ensure that they
protect the public from significant risk. Learn more about
the EPA's Regulations for Ethylene Oxide on EPA's website.
Note: In preparation of this article author acknowledges
he has referred and quoted from ISO 11135 narratives and
FDA guidance documents. He is grateful to them. |
