TECHNICAL BULLETIN

SELECTION OF EXTERNAL PROCESS CHALLENGE DEVICE

(EPCD) FOR ETHYLENE OXIDE STERILIZATION PROCESSES

Background
Biological indicators are an integral element of process definition for the validation and routine monitoring of
Ethylene Oxide (EO) sterilization processes. Section 8.6 of ISO11135 outlines the requirements for biological
indicators which may be used in process definition with 8.6.c specifically stating:
If a PCD is used for process definition, validation or routine monitoring and control, the appropriateness of the
PCD shall be determined. The PCD shall be equivalent or more challenging to the process than the most
difficult-to-sterilize part of the product.
ISO11135-2 - Guidance on the application of ISO 11135-1, gives further clarification of how to meet this
requirement in section 8.6, with the last paragraph in the guidance outlining the criteria for comparing one
PCD with another, i.e. internal PCD versus external PCD.
There may be instances when it is desirable to compare the resistance of one PCD to another without
comparing both to the resistance of the product. This is typically used when an internal PCD has been proven to
be appropriate and an external PCD is being introduced. In this case, a method of demonstrating the
appropriateness of the PCD is to demonstrate that the external PCD has equal or greater resistance when
compared to the internal PCD. If the relative resistance of the external PCD is less than the relative resistance
of the internal PCD (not more than 20 %), the PCDs may be considered equivalent.
The relative resistance of a BI / PCD to a sterilization process is defined by its D-value (time to achieve a 1 log
reduction in the initial population). There are three methods for calculation of D-value outlined in Annex A of
ISO1135-1,;
1. Direct Enumeration,
2. Fractional negative using the Holcolm-Spearman-Karber Procedure (HSKP)
3. Fractional negative using the Strumbo-Murphy-Cocoran Procedure (SMKP)
While the first two methods require multiple fractional cycles to be run in order to calculate the D-value, the
SMCP requires only one cycle to be in the quantal zone to calculate an estimated D-Value. For this reason the
SMCP is a useful means of comparing the relevant resistance of a selection of PCDs run on the same fractional
cycle. The formula for calculation of D-value using SMCP is outlined below.

Formula Ref - C.3.3.3.1 of ISO14161

Where
t= Dwell time (minutes)
No = Population of Biological Indicator
n= Number of replicates
r= Number showing no growth

Note: If the SMCP is being used to calculate a process D-value for subsequent calculation of the routine
processing time as outlined in B.1.2.b of ISO11135-1, the D-value should be calculated as an average of
at least three factional cycles to confirm reproducibility.
Interpretation of Sub-Lethal Cycles Results
It is important when selecting an EPCD for routine processing to find the right balance between demonstrating
that it is equivalent or more challenging than an IPCD and making sure that the EPCD can be fully inactivated
with the desired cycle parameters. If an EPCD is selected that is a significantly greater challenge than the IPCD,
it may result in the cycle time being extended to achieve full kill on the EPCD. This may result in unwanted
product attributes such as functionality issues and elevated EO residual levels, resulting in longer aeration
times.

Page 1 of 2 Applied Sterilisation Technologies.

 TECHNICAL BULLETIN
SELECTION OF EXTERNAL PROCESS CHALLENGE DEVICE
(EPCD) FOR ETHYLENE OXIDE STERILIZATION PROCESSES
It is also important to understand that results from sub-lethal cycles may be inconclusive. Where this is the
case, it is important to repeat the cycle with parameters altered to look to get growth results in the quantal
range so that adequate comparison of resistance can be made.
Below are some worked scenarios of potential results from sub-lethal cycles and how they may be
interpreted.
# BIs per set : 50 BI Population : 1,000,000 EO Dwell Time : 20 Minutes
IPCD EPCD
Scenario Growth D-Value Growth D-Value Comment
# (Mins) (Mins)

1 0 <2.6* 0 <2.6* No growth in either IPCD or EPCD so cannot make comparison. Repeat
the cycle with reduced lethality to get result in quantal range

2 50 >3.7** 50 >3.7** All growth in both IPCD or EPCD so cannot make comparison. Repeat the
cycle with increased lethality to get result in quantal range

3 0 <2.6* 50 >3.7** EPCD may be too great a challenge and may result in longer routine cycle
time. Best course of action would be to repeat sublethal with reduced
lethality and other less challenging EPCDs to identify and less
challenging EPCD.

4 50 >3.7** 0 <2.6* EPCD not appropriate as less of a challenge than the IPCD.
Repeat sub-lethal cycle with increased lethality and selection of more
challenging EPCDs to identify a suitable EPCD.

5 0 <2.6 20 3.18 EPCD more challenging but still appropriate.

6 20 3.18 30 3.31 EPCD equivalent / slightly more challenging so appropriate.

7 30 3.31 20 3.18 Relative resistance of EPCD is only 3.9% lower than that of IPCD and can
be deemed to be equivalent based on guidance offered in section 8.6 of
ISO11135-2.

* Where there are no positive BIs it is not possible to calculate an actual D-value. All that can be established is that the D value is less
than the value calculated based on a single BI being positive.
** Where there is full growth on all BIs then it is not possible to calculate an actual D-Value. All that can be established is that the
D-Value is greater than the value calculated.

Conclusion
When selecting an EPCD it is important to select one that is appropriate in relation to its relationship
with an IPCD but not so challenging that it results in unnecessary extension of cycle length and/or EO
concentration to deliver the required level of lethality to the chosen EPCD.
The SMKP is a useful means of comparing the relative resistance of a selection of PCDs from a single
fractional cycle.
In order to make an appropriate decision in relation to the selection of an EPCD, the growth recovery
needs to be in the quantal region so that comparison of relative resistance can be made.
If the relative resistance of the external PCD is less than the relative resistance of the internal PCD
(not more than 20 %), the PCDs may be considered equivalent

Page 2 of 2 Applied Sterilisation Technologies.