Biofilms as the Cause of OOS/OOT Results

GMP News No. 899: Biofilms as the Cause of OOS/OOT Results

GMP News
8 March 2007

Biofilms as the Cause of OOS/OOT Results

Even in well-maintained water systems, time and again OOS/OOT results in microbiological monitoring will occur suddenly and only for a short period. If the organisms found are typical water germs, in most cases biofilms in the plant are the cause.

Due to the strict microbiological requirements on water for pharmaceutical use and the high risks represented by the microbial contamination of water, the pharmaceutical industry makes great efforts to prevent microbial growth in water systems.

In this context the danger involved in biofilms is often underestimated. Sanitisation measures are often aimed at single mobile bacteria. These can be found in the high-purity and thus scarcely nourishing waters of the pharmaceutical industry, like water for injection - however, in very small numbers. For energetic reasons, the low-concentrated nutrients, which come from the feed water, adhere to the surfaces e.g. of water pipes. This is also where the bacteria can attach themselves and proliferate. Another promotive effect is the low flow velocity on the pipe surfaces, which even tends towards zero in laminar flow and can hardly rinse the microbes off the pipes.

In the growing biofilm, the germs show a different behaviour than when floating free. They produce a polysaccharide, which both forms a protective layer over the bacteria in the biofilm and serves to "catch" further nutrients from the water. Within this protective layer, the germs are characterised by a markedly elevated resistance against heat, disinfectants and dehydration than in the free state. This is why bacteria in biofilms can survive sanitisation measures. But even if all cells within the film are killed, the amalgamation of cells and polysaccharide remaining on the surface offer an ideal medium to further bacteria entering the water system sporadically with the feed water. Both living and dead biofilms represent a danger to the pharmaceutical end product. On the one hand, living bacteria or parts of the biofilm compound come off the surface from time to time and are thus a microbiological contamination source. On the other hand, dead biofilm fragments, too, represent a contamination source of endotoxins.

The battle against biofilms still remains a major challenge to the pharmaceutical industry. It is crucial to find suitable measures for the water system in question and to implement them consequently, e.g. hot storage, sanitisation with steam and ozone. In addition, as early as in the design stage, taking account of an appropriate surface treatment and a sufficiently turbulent flow can help to prevent the creation of biofilm during the operation of the water system.

Dr Robert Eicher
On behalf of the European Compliance Academy (ECA)

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