Is it possible to remove a Biofilm in pharmaceutical Water Systems?

Typical for a biofilm in the water system are repeated but irregularly occurring OOS values in the microbiology of routinely taken water samples. This leads to deviation tests, a large number of new water samples and quick, initial sanitization measures, which usually achieve little lasting improvement. But is it possible to permanently remove a biofilm in a pharmaceutical water system?

Definition of a biofilm?

A biofilm consists of a microbial community that adheres to surfaces and is enclosed in a self-produced matrix of extracellular polymeric substances (EPS). Biofilms can form on almost any surface in humid environments, including the inner walls of pipes, forgotten hoses or membrane valves such as those used in pharmaceutical water systems. They are problematic as they show increased resistance to antimicrobial agents and affect the quality of pharmaceutical water by releasing bacteria.

Challenges in the removal of biofilms

The removal of biofilms from pharmaceutical water systems is challenging because they:
1. form a physical barrier against sanitization measures due to the EPS matrix.
2. are able to regenerate quickly after incomplete removal attempts.
3. can cling to hard-to-reach areas, which also makes them difficult to remove completely.

Methods for removing biofilm

Mechanical cleaning: Mechanical methods such as brushing or pigging the internal surfaces of pipelines tend not to be used in pharmaceutical environments.
Chemical sanitization: Chemical disinfectants are the most common method of combating biofilms in pharmaceutical water systems. Common chemicals include:

• Oxidizing agents such as ozone, hypochlorite solution, hydrogen peroxide, peracetic acid
• Alkalis, such as sodium hydroxide solution

Oxidative chemicals can kill microorganisms very well. However, these agents reach their limits with a massive biofilm, which is protected by an EPS layer as described. Caustic soda is more effective here, as the hydroxide ions can break down organic bonds. All chemical agents must be dosed carefully to avoid damaging the material and must be removed completely. The rule of thumb when using caustic soda is: pH 13, exposure time 3 hours, temperature 30 °C. It may be advisable to change the seals afterwards.
Thermal sanitization: In thermal sanitization, high temperatures are used to eliminate biofilms. The advantage is that the increased temperature also reaches areas that are difficult to access, such as branch pipes, if the duration of the thermal sanitization is long enough. Temperatures of 70-80 °C are common. Hot systems are therefore self-sanitizing.

Conclusion

The removal of biofilms from pharmaceutical water systems is difficult. Therefore, the measure should not be the removal of a biofilm, but the prevention of such a biofilm. An appropriate system design is essential for this (no dead leg, stub lines, cold spots, etc.). Ozonization of the system is very helpful in preventing biofilm. Regular heating of the entire system is also a good prevention strategy. The most important aspect, however, is to avoid stagnant water. This applies to the entire system as well as to individual components, which should be able to be drained. The water system should therefore not be left standing over the weekend, but should rather be producing water in the design. The motto is: "keep it running!"