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Home Blog When and How to Repeat Your Ethylene Oxide Sterilization Validation

When and How to Repeat Your Ethylene Oxide

Sterilization Validation
Posted by Rob Packard on March 30, 2015
This article reviews some of the factors to consider when you are evaluating the
need to repeat your ethylene oxide sterilization validation.

ISO 11135-1:2014 is the international standard for sterilization validation for Ethylene
Oxide (EO or EtO) sterilizers. The standard full validation is required for initial
qualification of your EO sterilization process. Full validation consists of the following:
1. Process Challenge Device (PCD) validation

2. Bioburden measurement
3. EO residual measurement (as per ISO 10993-7:2008/R2012)
4. Fractional Cycle (at least one)
5. 3x Half Cycle
6. 3x Full Cycle
In addition to the full validation, you might also validate partial loads and/or resterilization of product in the case of rework.
Ethylene oxide sterilization is typically outsourced to a contract sterilizer due to the
environmental and safety requirements of working with EO. Typically the contract
sterilizer will provide a standard validation protocol for full validation that is compliant
with ISO 11135-1. However, the ISO 11135-1 standard requires that manufacturers
perform annual process reviews to evaluate the need for re-validation of the
sterilization process. Assuming there have been no problems, and no changes to the
product or process, then re-validation is not required at the end of the first year.
However, most companies are expected to re-validate the process after two years.
So why do some companies perform re-validation after three years or more?
Longer Re-Validation Cycles
If there have been not changes to the sterilization process, the product or the
biological indicators, then the manufacturer can use this as a justification for waiting
until two years have elapsed before re-validating the ethylene oxide sterilization
process. In addition, there should be no evidence of sterilization failures or other
problems with the validated process. However, that alone is not necessarily enough
to justify extending the duration between validations beyond two years. Companies
that are able to justify intervals of three or more years have multiple products that are
using the same sterilization process.
In this case, the manufacturer may alternate annually between three, four or even
five different product families that are using the same sterilization process. In this
case, one of the product families is being re-validated each year or every two years,
but the interval between validations for any one product family is longer. If the
products are made of similar materials and using the same sterilization process, then
this approach is valid. If you only have one product, then you need to re-validate the
sterilization process once every two years to verify the process remains effective.

Minimum Re-Validation Requirements

When you determine that it is time to re-validate your ethylene oxide sterilization
process, you need to perform the following tests in order to meet the minimum
requirements of ISO 11135-1:
1. Bioburden measurement
2. EO residual measurement
3. One Fractional Cycle
4. 3x Half Cycle
5. One Full Cycle
The purpose of #1 is to verify that bioburden levels have not changed. In practice,
most companies monitor bioburden on a quarterly basis and therefore this step
should be routine. Step 2, EO residual measurement, should be performed in order
to verify that there have not been minor changes to the product or process that would
increase the concentration of EO, Ethylene Chlorohydrin (ECH) or Ethylene Glycol
(EG) beyond the Tolerable Contact Limit (TCL). The purpose of this second test is to
prevent localized irritation caused by residual chemicals from the ethylene oxide
sterilization process.
Step 3 of the re-validation is intended to verify that a full injection of EO is more than
required to kill the bioburden present for the number of injections required for a halfcycle. Therefore, if required minimum concentration of EO is 2 for two injections, two
injections of a 3.6 EO concentration may be used for a half-cycle. Ideally, the
Process Challenge Devices (PCDs) will be non-sterile after a fractional cycle, while
the internal biological indicators will be sterile. After a half-cycle, all biological
indicators, including the PCDs, should be sterile.
The final step is to perform a full cycle. Product from the full cycle is typically used for
the EO residual testing. Any product from the full cycle that is not used for testing can
be sold after sterility testing is complete.
Partial Loads & Rework
If you occasionally sterilize loads that are less than full loads, then you need to
ensure that you have validated a minimum load or a specific partial load (e.g., halfpallet, instead of a full pallet). In the case of a partial or minimum load, you may

identify different locations in your load that are considered worst-case. These are
the locations that had PCDs that were not sterile in a fractional cycle.
Most companies do not have concerns about the cost of the actual sterilization runs
during re-validation, and biological indicators are typically less expensive than boxes
of product. The primary cost concern for re-validation is any product that must be
scrapped. Therefore, many companies will accumulate dunnage (i.e., empty
packaging or scrap product) over time in order to fill a sterilizer. This dunnage may
be used to ensure that every load is a full load, or it may be only used for revalidation.
Another alternative to using dunnage for re-validation is to validate a rework process.
Any product that is exposed to a fractional cycle or half-cycle can be resterilized in a
full cycle. In order to justify the commercial use of that product, a company needs to
validate that the product will not be damaged by exposure to two full cycles. One of
the key acceptance criteria for rework is the EO residual levels in the product.
However, the manufacturer also needs to determine if there has been any
deterioration of the product by a second exposure to EO that would affect
performance.
Other Considerations
Many companies do a poor job of reviewing the potential impact of changes to
product, packaging and biological indicators. Ideally, initial validation involves
different lots of product, packaging and biological indicators to assess lot-to-lot
variability. However, many times, the packaging and biological indicators consist of
only one lot during validation. Minor changes to the tolerances may reduce the
amount of ethylene oxide that is absorbed by the product or change the resistance o
the biological indicator to the sterilization process. Therefore, these minor
changes should trigger a re-validation.
Changes in suppliers with the same specification can also be difficult to evaluate. If a
component is made of a material that absorbs EO, then it may be recommended to
re-validate sterilization for any changes to suppliers of those components. Revalidation in these cases may consist of only a fractional cycle or only a full-cycle to
evaluate risks associated with the change.
Who Should Be Making Evaluations
The evaluation of need for re-validation should include input of three types: 1)
microbiological, 2) materials, and 3) performance. In order to make these

assessments, typically a cross-functional team is needed. Someone with

responsibility for design and development can assess performance impact of
changes. A materials engineer is typically needed for assessment of interaction
between components and EO. Finally, a microbiologist is needed to confirm that
there is no impact related to biological indicators or bioburden.

Medical Device Academy also

released a new webinar recording on the topic of Bioburden Failure Analysis last
week - Read More
If you need assistance with sterilization validation or bioburden failure analysis,
please contact me by email at rob@13485cert.com or call me at +1.802.281.4381
+1.802.281.4381 FREE.

Tags: ethylene oxide, ethylene oxide sterilization validation

Posted in: Process Validation
Leave a Comment (1)
1 Comment

1.
Jayasheel HegdeApril 5, 2015
A very good article. It is very important to conduct a re-validation whenever a product
packaging is modified or changed. You have made it very clear in this article.

reply

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