There are a couple of issues here. The microbiological specifications, themselves, are intended to
establish limits of your product capability. That is, you would be looking at certain stages of the
manufacture – again, I am talking about cell culture and fermentation. You would be looking at
some decision points in fermentation and looking at the culture purity. You would have a decision
point at various points for continuous processing. You would also try to establish these decision
points perhaps after major modifications or perhaps after long-term storage. It is not necessarily a
question for just the suitability for intended use, though there is a component of that. The
microbiological specifications are really there to ensure that your process can handle any
contamination in subsequent steps. Suitability for intended use goes to one of the points – just to
give you an example, there was a topical product that was being used for ulcers and burn
patients. When pseudomonas was detected as one of the organisms that were present, that was
not acceptable because it would have a direct impact on the suitability of the final product
because there were no assurances that it would be removed at subsequent processing steps.
Part of the issue for microbiological specifications, and especially for biologics and biotech
processes, if you have a high level of microbial contamination (including moulds) it is somewhat
difficult to know what impact it’s going to have. Contamination with molds in particular, has been
an issue for some of processes. In particular you need to consider the metabolites of the (mould)
contaminants that could be potentially in your product and how you can assure yourself that you
won’t get something that carries through the entire process and that would be sensitizing. Those
are some examples of issues where, setting the appropriate microbiological specifications are
useful provided that you know that, subsequent processes that could remove contamination and
you can detect contaminants that would have direct impact on API or drug product quality.
