I have a question. Which guideline of the U.K. Medicines and Healthcare
Products Regulatory Agency (MHRA) are you talking about concerning
retesting of non-sterile product formulations?
For environmental microbial testing (e.g. air, compressed air and water),
you should not be obtaining OOS test results. By trending your microbial
environmental test data, you should have established microbial alert and
action levels in order to prevent an OOS result. Before obtaining an OOS
for an environmental test sample, you generally find beforehand that there
is an increasing trend in the number of microbial counts. If the microbial
count is at or above the alert level, it tells you that here might be a
problem and more sampling may be required to confirm that there is indeed a
problem. If you have environmental microbial counts that are at or above
the action level for an environmental test sample, it tells you that a
corrective action is required ranging from conducting maintenance and/or
sanitization is required to be performed on air, compressed air and water
systems to return the microbial counts back to normal levels. In general,
a different amount for an environmental test sample is not increased, but
the frequency of conducting microbial testing is increased from what is
normally performed until the system that was OOS had returned is back to
normal or is now in control.
As for conducting retesting of a batch for non-sterile finished product
that is OOS, there is no agreement within the industry in how to proceed. Some
people will say that a retest on a finished product could not be performed
unless there was an investigation to show that there was a laboratory error
that had produced an OOS result.
For non-sterile finished products, I have a different opinion. First, I
would indeed conduct an investigation as to whether there was a laboratory
error that had produced an OOS test result for a batch of a non-sterile
product formulation by examining the sterility test results for the
microbial growth media and microbial count diluents that had been used in
the original test. If the sterility results for these items are found to
be satisfactory, further investigation is required. In addition, I do
recommend that a Gravity Air Settling Plate be used in the same area and
time in which microbial count testing of samples is being performed such as
under a Laminar or Biological Safety Cabinet. If high counts are obtained
that are above a Class 100 or ISO 5 area for your testing cabinet, it may
indicate that there was a laboratory error or the samples themselves were
contaminated by determining whether the same types of organisms were found
in the Gravity Air Settling Plate and the OOS test result for a batch of a
non-sterile product formulation. To determine whether it was the batch
samples, I do recommend that you conduct a microbial analysis on each of
the original test samples that had been tested without compositing them
together. If the retesting of the original retest samples is found to be
OOS, the batch should be rejected. A further investigation in
manufacturing should be conducted to determine if there were errors in
cleaning and sanitization of manufacturing equipment to determine the
reason for the rejection. In addition, I do recommend that a bulk sample
of a batch be taken before filling, but not conduct routine microbial
testing on it unless the finished packaged containers are found to be OOS. If
the bulk is also found to be OOS, its shows that there was an error
somewhere before filling had occurred. It helps to narrow down the area in
manufacturing to where the error had occurred for obtaining an OOS result.
If the retest for each of the original tested samples are found to be in
compliance with the microbial test specifications, I would not release the
batch until retesting of a greater amount of test samples of the batch had
been tested (e.g. greater than twice the number of samples that had been
originally tested). If you are testing beginning, middle and end of a
filling shift or a sample from every hour of a shift for filling a finished
product, I will test twice the amount of sample without compositing them
individually together because microbial contamination in a batch is never
homogeneously distributed. This greater amount of testing will confirm if
the batch is indeed in compliance with the specifications.
A report of this investigation for the original OOS test result should be
completed and on file if the batch is either released or not released..
Donald J. English Microbiological Quality Consulting LLC
Florham Park, New Jersey 07932
On Tue, Oct 29, 2019 at 4:13 PM Selena Rossi <[log in to unmask]> wrote:
> Hi everyone,
> how do you perform the investigation for an microbiological OOS?
> I'm working in non sterile product company and we are revisioning our SOP
> in according MHRA guidance.
> After retest on initial samples (if available) our doubts are on number of
> resamples. 3,6? Statistical decision?
> And when the initial samples are not available (exmple enviromental
> samples) do you perform a new analysis with new sample?
> Any suggestion will be appreciated!
> Thanks in advance and have a great day everyone,
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The PMFList (http://microbiologynetwork.com/pmflist.asp) is operated from
The Microbiology Network (http://microbiologynetwork.com) and supported by
our sponsors as a service to the scientific community.
Please take a second to visit our sponsors' web sites and say thank you for their support of this service.
If your company would be interested in sponsoring this community, please contact [log in to unmask]
Science Advisory Board https://www.scienceboard.net/
Steris - http://www.sterislifesciences.com/
Charles River Laboratories - http://www.criver.com/
Veltek Associates, Inc - http://www.sterile.com
Microbiologics, Inc. - http://www.microbiologics.com
BD Industrial Media - http://www.bd.com/ds/
Boston Analytical http://www.bostonanalytical.com/
Associates of Cape Cod, Inc. - http://www.acciusa.com/
The nature of this service is to provide a medium for communication. The specific statements and endorsements of individuals participating in the discussions are not necessarily those of The Microbiology Network, Inc., the PMF, or the sponsors of the list.