GMP-Compliant Sanitisation of Pharmaceutical Water Systems

GMP News
13 June 2007
 

GMP-Compliant Sanitisation of Pharmaceutical Water Systems

 
Sanitisation of pharmaceutical water systems is still an important issue within the pharmaceutical industry. One reason is, of course, the huge amount of water used: as a solvent or washing agent during processing or as an ingredient in the final product. The second reason lies within the nature of water, which is characterised and identified by its by-products (WFI and drinking water are distinguished only by their contamination). These quality attributes cannot all be measured online or before use. This is the case for microbiological contamination, which takes several days to be determined. During this time the water is used, the product is manufactured, and costs arise. To prevent products from having to be recalled or destroyed because of microbiological contamination, an effective sanitisation is essential.

There are three different sanitisation techniques used today:

Thermal method: Using heat (periodically or continuously: 75 - 80 °C at the coldest point in the system) is still the preferred method in the pharmaceutical industry. It is limited to heat-insensitive systems, but very effective in the reduction of microbiological species. Another advantage of this method is that it is easy to validate. It has to be stated, however, that heat does not remove existing biofilms, which are a source of nutrition and a contact surface for further aquatic micro-organisms as well as a source of endotoxins in the water system, of course. On the other hand none of the methods listed is capable of removing biofilms.

Chemical method: Peracetic acid and hydrogen peroxide are used for chemical sanitisation for example. According to the "added substances rule" USP every added substance has to be removed with appropriate means. The preferred chemical agent is ozone. Although the FDA discouraged from its use some years ago, it is accepted nowadays and increasingly used. The advantage of ozone is its effectiveness: a reduction of log 6 can be achieved with a concentration of 0.01 - 0.02 mg/L with exposure of 5 minutes. Besides the reduction of living micro-organisms, it oxidises and therefore reduces TOC, i. e. nutrients for further micro-organisms. The disadvantage is its toxic potential (risk for production personnel) and the oxygenation of the water, which could be harmful to oxygen-sensitive products. The discussion whether ozone is an added substance and whether there is a potential for the formation of harmful side-products by the oxidation of organic material is still ongoing. Ozone has to be destroyed with UV light before pharmaceutical use, and this has to be validated of course.

Physical method: Using UV light at a wavelength of 254 nm is another possibility of reducing the number of colony-forming units in the water system as UV light inhibits the reproduction of micro-organisms by alteration of the genome of the cells. As this method is not very effective, it is recommended only in combination with another sanitisation method. It can be used in periodically heated systems during cold cycles, in chemically sanitised systems, and it is needed for removal of ozone anyway.

As none of these methods is capable of removing existing biofilms, it is essential to follow the basic rules for avoiding the formation of biofilms in pharmaceutical water systems:

  • The water system should be operated continuously, and dead legs should be avoided.
  • The system should be periodically or permanently sanitised.
  • The system should be thoroughly monitored.

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

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