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The recently published Draft Guidance on Rapid Microbiological Methods (RMMs)
for Sterility Testing of Cellular and Gene Therapy Products provides
recommendations on the validation of growth-based RMMs in detail. It is the aim
of the document to facilitate the implementation of an RMM for sterility
testing.
Although this guidance has been designed for Cellular and Gene Therapy Products
it is stated that “Some of the principles of RMM validation discussed in this
guidance might also be applicable to products other than cellular and gene
therapy products that are subject to sterility testing under 21 CFR 610.12.”
Apart from general recommendations on validation aspects (e.g. risk assessment,
limit if detection, specificity, ruggedness, robustness) the document provides a
comprehensive list of different categories of micro-organisms that should be
included in the study:
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Gram-negative bacteria
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Gram-positive bacteria
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aerobic bacteria
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anaerobic bacteria
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yeast
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fungi
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isolates detected in starting materials<
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isolates detected by in-process testing or during preliminary
product testin
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isolates detected by environmental monitoring of your
manufacturing facilit
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isolates from your production areas which represent low
nutrient and high stress environments
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micro-organisms from commercial sources that have continually
been exposed to high nutrient growth media
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slow growing bacteria (such as Proprionobacter acnes)
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fastidious micro-organisms for the RMM
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micro-organisms reported in the scientific literature to be
common isolates from a particular product type
This enumeration enforces the importance of including
micro-organisms which belong to the natural habitat of the production facility
and the product itself.
During the last years the trend towards using isolates for validation studies
has increased significantly.
Furthermore, the document gives some helpful advice on designing a comparison
study. Although the examples mentioned focus on cell-based products similar
questions have to be discussed for other drug products, especially
biopharmaceuticals.
Due to the short dating period of many cell-based products there is no
convincing alternative to implementing RMMs for sterility testing.
Hopefully, this immanent pressure will leverage the use of RMMs also for other
types of pharmaceutical products.
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