CLEANROOM CLEANING AND DISINFECTION

The purpose of cleaning and disinfection is to ensure that a cleanroom meets the required microbial cleanliness level within an appropriate timeframe. Therefore, cleanroom cleaning and disinfection are crucial components of contamination control. The following are eight key steps involved in cleaning and disinfection to ensure a cleanroom's "cleanliness."

1. Proper understanding of cleaning and disinfection

Cleaning and disinfection are two distinct concepts, sometimes confused. Cleaning, primarily, involves the use of detergents and should be performed before disinfection. Detergents clean surfaces, removing surface "oil" (such as dust and grease). Degreasing is a crucial step before disinfection, as the more surface oil remains, the less effective the disinfection will be.

Detergents generally penetrate the oil, reducing its surface strength (the oil clings to the surface) to achieve removal (roughly speaking, detergents increase the cleaning power of water).

Disinfection involves chemical sterilization, which can kill a large number of microbial vegetative forms (some disinfectants are also sporicides).

2. Selecting the most suitable cleaners and disinfectants

Choosing the most suitable cleaners and disinfectants is crucial. Cleanroom managers must ensure the effectiveness of cleaning agents and disinfectants and select the appropriate cleaning agents and disinfectants for each cleanroom type. It's important to note that some cleaning agents and disinfectants cannot be mixed.

When selecting a cleaning agent, the following points are important:

a) The cleaning agent should be neutral and non-ionic.

b) The cleaning agent should be non-foaming.

c) The cleaning agent should be compatible with the disinfectant (i.e., residual cleaning agent should not impair the disinfectant's effectiveness).

When selecting a disinfectant, the following points should be considered:

a) To meet GMP regulations, the two disinfectants should be rotated. Although regulatory authorities require the use of two different disinfectants, scientifically speaking, this is not necessary. To address this, two disinfectants with different efficacy should be selected. It's advisable to select one disinfectant that kills bacterial spores.

b) The disinfectant should have a broad spectrum of activity, meaning it effectively kills a wide range of microbial vegetative forms, including both gram-negative and gram-positive bacteria.

c) Ideally, the disinfectant should be fast-acting. The speed of disinfection depends on the contact time required for the disinfectant to kill a microbial population. This contact time is the length of time the surface to which the disinfectant is applied must remain wet.

d) Organic residues and detergent residues must not affect the effectiveness of the disinfectant.

e) For higher-class cleanrooms (e.g., ISO 14644 Class 5 and 7), disinfectants must be sterile or sterilized by cleanroom operators.

f) The disinfectant must be suitable for use at the cleanroom's operating temperature. If the cleanroom is a refrigerated room, the disinfectant must be verified for effectiveness at that temperature.

g) The disinfectant must not damage the materials being disinfected. If damage is likely, measures must be taken to prevent it. Many disinfectants that kill bacterial spores contain chlorine, which can damage materials such as stainless steel if the residue is not removed promptly after use.

h) The disinfectant must be harmless to operators and comply with local health and safety regulations.

i) The disinfectant should be economical, easy to dilute, and available in suitable containers, such as hand-held spray bottles. 3. Understanding Different types of disinfectants

Disinfectants come in many different types, suitable for different forms of disinfection and exhibiting varying degrees of effectiveness against microorganisms. Disinfectants can act on microbial cells in several different ways, including by targeting the cell wall, the cytoplasmic membrane (where phospholipids and enzymes provide various digestive targets), or the cytoplasm. Understanding the differences between these types of disinfectants is particularly important when choosing between spore-killing and non-spore-killing disinfectants (distinguishing between non-oxidizing and oxidizing chemicals).

Non-oxidizing disinfectants include alcohols, aldehydes, amphoteric surfactants, biguanides, phenols, and quaternary ammonium compounds. Oxidizing disinfectants include halogens and oxidizing agents such as peracetic acid and chlorine dioxide.

4. Validating disinfectants

Validation involves laboratory testing using either AOAC (American) or European standards. Some testing can be performed by the disinfectant manufacturer, while others must be conducted in-house. Disinfectant validation includes challenge testing, which involves testing disinfectant solutions of varying concentrations (as suspensions), testing different surfaces, and testing the disinfection efficacy of different microorganisms, including microorganisms isolated from within the facility.

5. Factors affecting disinfectant effectiveness

In practice, many factors can affect the effectiveness of disinfectants. Understanding these factors is crucial to ensuring the success of disinfection activities. Factors influencing disinfectant effectiveness include:

a) Concentration: It is the choice of concentration that ensures the highest microbial kill rate. The notion that higher disinfectant concentrations kill more bacteria is a myth, as disinfectants are only effective at the right concentration.

b) Duration: The duration of disinfectant application is crucial. Sufficient time is required for the disinfectant to bind to microorganisms, penetrate cell walls, and reach the specific target site.

c) The number and type of microorganisms. Disinfectants are less effective against certain microbial vegetative forms. For example, if a large group of independent microbial spores aggregates, disinfectants that lack the ability to kill bacterial spores will be ineffective. d) Temperature and pH: Each disinfectant has an optimal pH and temperature range for optimal effectiveness. If the temperature and pH are outside these ranges, the disinfectant's effectiveness will be compromised.

6. Cleaning materials

The materials used for disinfection and cleaning must be suitable and capable of evenly applying a thin layer of each detergent and disinfectant. Cleaners and disinfectants used on floors, equipment surfaces, and walls in sterile production areas must be cleanroom-certified and particle-free (e.g., non-woven fabrics, lint-free fleece).

7. Cleaning techniques

Cleaning and disinfection methods are crucial. If detergents and disinfectants are not used correctly, they will not effectively clean the surfaces. Disinfectants cannot penetrate the oily surface layer, leading to elevated microbial contamination levels within the facility. Specified cleaning and disinfection procedures must be in place, such as:

Sweep away dust and debris (if applicable); Wipe with a detergent solution to ensure the detergent has dried; Wipe with a disinfectant solution to keep contact surfaces moist and maintain contact time; Wipe with water for injection or 70% IPA (isopropyl alcohol) to remove any disinfectant residue.

8. Monitoring the effectiveness of cleaning and disinfection

The effectiveness of cleaning and disinfection is primarily assessed through cleanroom environmental monitoring results. This assessment is performed by sampling surfaces for microorganisms using touch plates and swabs. If the results are not within the specified action limits or company internal control standards, there may be issues with the cleaning and disinfection agents, the frequency of cleaning, or the cleaning method. Conversely, if the results meet the standards, cleanroom managers can confidently state that the cleanroom is truly "clean."

Summary

The above lists eight steps for maintaining cleanroom cleanliness using cleaning and disinfection agents. It is recommended that these steps be integrated into standard operating procedures (SOPs) and that training be provided to operators and management personnel. Once the facility has been validated and is under control, the most important thing is to use the correct methods or techniques, the appropriate cleaning agents and disinfectants, and to clean and disinfect the facility continuously at the prescribed intervals. This way, the cleanroom can remain clean.