The Risk of Biofilm

Recommendation

17-19 September 2024

Granulation & Tableting - Live Online Training
GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

Because of the high microbiological requirements on water for pharmaceutical use and the high risks linked to a microbiological water contamination, enormous efforts are taken in the pharmaceutical industry to prevent from bacterial growth in water systems. Such systems are normally composed of the water treatment as well as the storage and distribution system.

The dangers arising from biofilms are hereby often underestimated.

Sanitisation measures are often directed to (aquatic) bacteria. Those bacteria reach the high-purity - and thus nutrient-poor - waters of the pharmaceutical industry, but only to an insignificant extent. For energy reasons, a small concentration of nutrients coming from the feed water can form deposits on the inner surfaces of piping system for example. Those surfaces are also a promising location for bacteria to settle and proliferate. An additional favourable factor for that settlement and proliferation of bacteria is the low flow rate on the surfaces of the pipes, which even tends to be inexistent in laminar flows. Therefore, without any mechanical action, a flow washing of the bacteria can't be expected. Bacteria in formatting biofilms behave differently than in a free state. This leads to the formation of layers containing polysaccharide which overlie the bacteria of the biofilm as a protector.

Within this protection layer, the bacteria are characterised by a very much higher tolerance to heat, disinfectants and dehydration than in a free (aquatic) state. This is a reason why bacteria in biofilms can survive sanitisation measures. Even if all cells within a film are killed, the cell-polysaccharide-compound remaining on the surface offers an ideal breeding ground for other bacteria which may come isolated from the feed water into the water system. This means that both living and dead biofilms present a risk for the pharmaceutical finished product. On the one hand, living bacteria or parts of the biofilm compound keep on detaching again and again and thus present a microbiological source of contamination for other parts of the system.  On the other hand, killed-off biofilm fragments constitute a source of contamination with endotoxins.

That's why the fight against biofilms is and remains a challenge for the pharmaceutical industry. It is essential to set appropriate measures for the water system (biofilm management) and to implement them consistently - for example hot storage, sanitisation with steam or ozone. Therefore, as early as the planning phase it is necessary to establish an appropriate design of the system counteracting the formation of biofilms - e.g. preventing from dead-legs or low points that cannot be emptied. Yet, the system operating is as essential as the design. Downtimes always present a higher risk of microbial growth. An uncontrolled weekend is already sufficient to lead to a significant bacterial contamination. "Keep the system running" is thus the best protection of a well-designed water system.