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PROCESS SIMULATIONS
Growth promotion testing must be undertaken on the
growth medium used for process simulations. There is
some confusing guidance as to when to perform this.
The FDA Guidance document does not make
specification on the timing of the test and the EU Annex
1 document does not even ask for a growth promotion
test. However, both the PICS (Pharmaceutical
Inspectorate Cooperation) and ISO documents ask that
growth promotion testing is performed upon conclusion
of the incubation period (usually 14 days). Whilst the
latter initially seems to be the more sensible option, it
also increases the holding time prior to release, as
product is waiting for the growth promotion tests to be
incubated and analysed.
Many pharmaceutical manufacturers prefer to run
growth promotion testing in parallel with the media
fill samples. Randomly removing samples from the
process simulation run has little basis for detecting
contamination. Contamination of the filling line being
challenged is a random event, and such samples are
unlikely to show all of the contamination present. In
order to meet the various regulatory guidance half-way,
a compromise would be to fill additional units at the end
of the process simulation, and use these for the growth
promotion test. These are then incubated under identical
conditions as the process simulation samples. This
approach both ensures that the process simulation units
and growth promotion test units are separated, and the
overall time of the process simulation project is reduced.
Any units that are incubated should be inspected
prior to incubation. Any defects that compromise the
container closure or non-integral units are rejected. All
rejections should be documented, with reasons for
rejection and the number of units rejected. Incubation is
then performed for 14 days at 20-350C (+/-2.50C). These
parameters have been accepted by the global regulatory
authorities and should allow the growth of bacteria,
yeast and moulds. Units are incubated in an inverted
position for the first half of the incubation period,
and then returned to an upright position for the
remainder. Also, isolates that are seen in the firms
environmental monitoring programme need to be
picked up by a media fill run, and data confirming this
should be made available.
Through the thorough design and execution of a
rugged process simulation, and the use of a high quality
growth promotion medium, meticulous challenge of the
aseptic process is achieved.
The author can be contacted at phil.smith@oxoid.com
Innovations in Pharmaceutical Technology