生物膜的风险

GMP News
02/11/2016

The Risk of Biofilm

生物膜的风险

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.

由于制药用水里较高的微生物要求，以及与水中微生物污染相关的高风险，制药行业已投入巨大精力防止水系统中的微生物滋生。这样的系统通常由水处理系统和存贮分配系统组成。

The dangers arising from biofilms are hereby often underestimated.

而通常来自生物膜的危险则会被低估。

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.

灭菌措施通常是针对（水性）细菌的。这些细菌进入到高纯度---因而也是没有营养的制药用水中，但仅仅只是微量。由于能力的缘故，来自源水中的低浓度营养物可能会在管道系统的内表面沉积。这些表面也会有地方给细菌安身并迅速繁殖。细菌安身和滋长另一个有利因素是管道表面的水流速较低，甚至在平流中都不存在水流。因此，没有任何机械措施的情况下，不能指望用水流来冲刷细菌。正在形成生物膜的细菌行为方式与自由态时是不同的，它会导致形成多层含有多聚糖的膜，覆盖在生物膜的表面成为保护层。

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.

在此保护层中，细菌特性比起自由态（水性）来变成能非常能耐热、耐消毒剂和脱水反应。这就是为什么生物膜中的细菌可以在灭菌后仍存在的原因。甚至即使膜中所有细菌全部被杀死，细菌多聚糖化合物仍保留在表面，为其它细菌提供理想的营养地，这些细菌可能来自进入水系统的源水。这意味着活的和死的生物膜都显示出对药品的风险。一方面，活菌或生物膜化合物的一部分保持反复依附，因而成为系统中其它部分污染的微生物来源。另一方面，被杀灭的生物膜碎片形成内毒素污染源。

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.

这就是为什么与生物膜做斗争对于制药行业来说一直是一个挑战。为水系统制订恰当的措施（生物膜管理），以及维持一致实施这些措施是非常重要的—例如，热存贮、蒸汽或臭氧灭菌。因此，提前到规划阶段来说，都有必要制订适当的系统设计，应对生物膜生成---例如，防止死管或可能无法排空的低点。还有，系统尽可能按设计方案运行。停机总会带来更高的微生物生长风险。一个不受控的周末就足以导致严重的细菌污染。“保持系统运行”因而成为对设计良好的水系统的最好保护。

来源：Julia

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