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Cleaning matters

The effective use of cleaning as part of contamination control

By Tim Sandle

Introduction

Cleaning together with disinfection is of great importance within pharmaceutical and healthcare products facilities in order to minimise contamination presence in cleanrooms. Contamination consists of debris, soiling and microorganisms. Conceptually, cleaning and disinfection are two distinct, although interlinked, processes. Cleaning is an important preparatory activity that is always required prior to disinfection, in order to remove any soil or residues that carry the potential to inhibit the effectiveness of the disinfection process to reach, make contact with, and kill microorganisms (1).

 

Cleaning is the process of removing residues and ‘soil’ (such as dirt, grease, protein residues and so on) from surfaces to the extent that they are visually clean. This involves defined methods of application and often the use of a detergent. Importantly, the act of cleaning is necessary prior to the application of a disinfectant for a surface needs to be properly cleaned before the application of a disinfectant in order for the disinfectant to work efficiently, as disinfectants can either be inactivated by organic residues or the soil can create a barrier which prevents the disinfectant from reaching all of the microbial cells. When applying a detergent (or disinfectant) to the target surface, the approaches are either without mechanical action (such as simply directly spraying) and with mechanical action (spray and wiping or soaking and wiping) (2).

Whilst "cleaning" is not "disinfection" the cleaning process can remove or dilute microbial populations. Furthermore, many detergents have chemical additives that can 'disinfect'. However, a cleaning agent will not meet the criteria for disinfection required by the European and United States standards for disinfectant validation in terms of reducing a microbial population of a defined range by the required log reduction.

 

This paper looks at the importance of cleaning, application methods, and the role cleaning should play in validating the cleaning and disinfection process.

How cleaning works

Cleaning means different things in different contexts. Even within pharmaceuticals and healthcare, cleaning can refer to chemical purity (e.g. clean steam) or to cleaning validation, as with equipment processing. For surfaces, cleaning refers to the use of a detergent.

 

Cleaning-Matters1

Figure 1: Simple schematic of a surfactant

A detergent is a chemical used to clean equipment or surfaces by removing unwanted matter (soil). Detergents generally work by penetrating soil and reducing the surface tension (which adhere soil to the surface) to allow its removal (in crude terms, a detergent increases the ‘wettability’ of water). Many detergents are synthetic surfactants (an acronym for Surface Active Agents) or a combination of more than one surfactants (for which hydrotropes are required) in a carrier liquid (normally water). The type of surfactant(s) required will depend on the target type(s) of soil. A good surfactant will address soil affixed to a surface through a variety of mechanisms: emulsifying, lifting, dispersing, sequestering, suspending and decomposing soils.

The active ingredients in surfactants have two sides to their nature. One part is solvent-loving or lyophilic (hydrophilic) and another is solvent-hating or lyophobic (hydrophobic). Surfactants remove particles from surfaces by either capillary effects or electrostatic forces (many detergents contain differently charged ions that can cause microorganisms to repel each other). This repulsion causes the microorganisms to disassociate from the surface and become suspended. Suspended microorganisms are easier to remove from the surface by the rinsing effect of the detergent (or a subsequent water rinse) or to be destroyed by the application of a disinfectant. The relative ease of killing microorganisms in planktonic state compared with killing microorganisms in the sessile state is reflected in the phased approach to disinfectant validation studies (3).

 

An ideal property for a detergent for a surfaces is that it is non-foaming, as this improves drying time and decreases the presence of residues. Detergents should be close to a neutral pH and formulated to be non-ionic solutions. The use of these milder detergents guards against any residues affecting the active ingredient in disinfectants when the disinfectant is subsequently applied. Therefore, for surface cleaning anionic and cationic detergents should be avoided.

Detergents are presented on pre-saturated wipes or mop heads or as solutions to be prepared in deionised or purified water. Further in relation to dilution, the temperature of the water may play a role (based on manufacturer’s instructions). It is preferable to use detergents that do not require the water to be a certain temperature. When preparing detergents, the ‘cloud point’ is important. When this occurs, the cleaning solution becomes cloudy and it is considered to be at optimal detergency and good to use.

 

Through effective cleaning, the effectiveness of disinfection increases because the population of microorganisms will be fewer in number, easier to reach and therefore easier to kill. However, much is dependent upon good application technique.

Application technique

For effective cleaning, the application technique is important. Wiping strategy includes the applied pressure force, wiped surface area, the geometry of the mechanical action, the number of passages (4). Each of these is influenced by the presentation. There are five primary means of application:

  • Spray, with no wiping.
    • This method is the least effective. the absence of mechanical action means there is no physical activity to disassociate organisms from the surface and no direct application and hence penetration of the cleaning agent towards the soil.
  • Spray and wipe.
    • Although there is a wiping aspect, the application of the cleaning agent can be difficult to apply leading to either overspray or with some parts of the surface being missed (5).
  • Dip and wipe.
    • The sipping of a wipe into a disinfectant solution is hard to control, especially given the short contact time that the wipe is in contact with the solution for which limits the concentration applied to the wipe and the even distribution of the agent across the wipe (6).
    • With wipes, the surface of the wipe should not be used more than once (as part of the ‘one wipe side, one application, one direction’ strategy) (7). An economy can be introduced by folding the wipe so that four surfaces are available (the four-fold wipe technique). It is important to avoid inappropriate reuse of the towelette as this may promote the accumulation of microorganisms and raise the risk of cross-contamination during the cleaning or disinfection process. With mops, the rinsing of the mop and reapplication enable the mop to be reused for the duration of a cleaning session (8).
  • Soak and wipe.
    • This method is the “bucket method”, where a wipe or mop is soaked into a detergent or disinfectant solution for a recommended time period. The material is then wrung out to remove the excess solution and directly applied to a hard surface. This method allows a relatively long contact time ensuring enough active ingredient load in the towelette before use (9).
    • It is important to understand any possible interactions between wipes and detergent or disinfectant based on a longer soaking time or with any chemical binding of the active ingredient to the wipe which could lead to a decrease in concentration in the bulk solution (10).
    • With the techniques for the cleaning and disinfection of cleanroom floors, either the “two-bucket” or the “three-bucket” technique is recommended. Both of these techniques involve using a bucket of disinfectant and a bucket of water. In the “two-bucket” technique there is a “wringer” (for the mop) over the bucket of water. In the “three-bucket” technique there is a third bucket, empty except for having a wringer mounted over it. To illustrate this, the three-bucket technique involves:
      • Dipping the mop in disinfectant.
      • Mopping the floor.
      • Dipping the mop in the bucket of water.
      • Rinsing the excess water off the mop head into the third (empty) bucket.
      • Dipping the mop in disinfectant.
      • Repeating.
    • Surface wiping or mopping should be carried out from top to bottom, from back to front and from cleanest to dirtiest, changing the wipe at appropriate intervals.
  • Pre-saturated wipes or mop heads.
    • Pre-saturated wipes or mop heads come with the active ingredient pre-soaked into the material (11). It is important to assess whether the supporting efficacy studies from the manufacturer have been based on the material and cleaning solution in tandem and not simply upon the detergent or disinfectant as a separate study. An understand is also required of the amount of liquid released and for how long the pre-saturated material can be used for (12). Care must be taken when opening packets of pre-saturated wipes since remaining wipes will begin to dry out and lose a quantity of the impregnated liquid once the packet is opened, leading to an eventual loss of efficacy at a given time point (13).

The cleaning technique used for cleanrooms should be defined and standardised. It does not matter how effective the cleaning agents selected are if the cleaning technique practised by cleanroom operators is poor.

Rinsing

Some detergents require rinsing prior to the application of the disinfectant because the presence can interfere with the active ingredient of the disinfectant (residues can also tend to render surfaces sticky, which causes operational issues) (14). In other cases, where the residues are low or deemed not to interfere with the disinfectant a suitable period of time must pass (which may simply be the time taken for the floor to dry) prior to the application of the disinfectant. This will depend upon the nature of the detergent and disinfectants, the compatibility between them, and the presence and concentration of residues. The likely presence of residues can be assessed at the time of validation.

Cleaning verification

In terms of verifying cleaning, while there are tests that can be used to assess the presence of residues (such as conductivity probes) or organic materials (through the use of swabs), for the day-to-day practical evaluation when cleaning a cleanroom the assessment is normally to use the right method of application consistently and to assess the area as visually clean prior to the application of a disinfectant.

Cleaning to reduce biofilm likelihood

Biofilms form more easily where there are residues, especially residues of organic material. Regularly cleaning is important to ensure the prospects for biofilm formation are reduced. Where biofilm communities take hold, the microorganisms contained within the community are far more difficult to kill due to the presence of organic material and as a consequence of the protective sim-like matrices excreted by the microbial community (15).

Validation

As per the draft EU GMP Annex 1, the cleaning process should be validated. This is normally through the execution of a field trail. The objectives of such an activity are to:

  • Demonstrate that any residue or debris that would detrimentally impact the effectiveness of the disinfecting agent used have been removed or minimised.
  • Demonstrate that the cleaning and disinfection process can minimise chemical, microbial and particulate contamination. This is normally assessed through environmental monitoring, showing that the process can consistently achieve microbial contamination levels below the maximal values for the grade of cleanroom and that the presence of resistant strains is minimised and that such organisms do not show any recurrence. By resistance, this is in reference to organisms resistant to the disinfection regime currently in use and to the phenomenon of innate resistance, where some microorganisms are more resistant (such as due to a factor of their cell wall, for example) to a given disinfectant. This is usually overcome by rotating between two disinfectants with different active ingredients in order to increase the spectrum of kill. The validation activity will help to establish the frequency between agents and the frequency of disinfectant application overall.

Validation studies relate to the specific manner in which disinfectants are use (by this there will be differences between sprays, sprays followed by wiping, and pre-saturated wipes, for example). Furthermore, validation needs to be extended to the in-use expiry periods of prepared solution.

Cleaning procedures

Cleaning procedures must specify key elements of the cleaning procedure. Cleaning procedures must clearly state the important activities to be performed by personnel doing the cleaning as a series of steps. Through this, the variation inherent in a manual cleaning process can be minimised. Cleaning procedures should also state the most important process parameters (16):

  • The objectives of cleaning.
  • The frequency of cleaning.
  • The type of detergent.
  • The cleaning agent concentration.
  • The type of water.
  • The temperatures of use (if applicable).
  • Method of application.
  • Rinsing requirements.

An important focus is with reducing operator variation in the cleaning process. This means that operators must be carefully trained against cleaning procedures. This requires actual performance under the supervision of area experts for training cannot be by “read and
sign.” Training should be reviewed through periodic auditing by the quality unit and requiring operators to undergone periodic refresher training is a good practice.

Summary

This paper has looked at the important role cleaning plays as a pre-step prior to disinfecting surfaces within cleanrooms and controlled environments. The paper has discussed the importance of good detergent selection and with the use of different application techniques. With methods, the use of mechanical action is very important to disassociate and remove organic soils to leave microorganisms remaining on the surface vulnerable to the target disinfectant.

References
  1. Vin a, P., Rubio, S. and Sandle, T. (2011): ‘Selection and Validation of Disinfectants’, in Saghee, M.R., Sandle, T. and Tidswell, E.C. (Eds.) (2011): Microbiology and Sterility Assurance in Pharmaceuticals and Medical Devices, New Delhi: Business Horizons, pp219-236
  2. Tebbutt, G.M. (1991) An assessment of cleaning and sampling methods for food-contact surfaces in premises preparing and selling high-risk foods. Epidemiol Infect 106, 319– 327
  3. Sandle, T. (2012). ‘Cleaning and Disinfection’. In Sandle, T. (2012). The CDC Handbook: A Guide to Cleaning and Disinfecting Cleanrooms, Grosvenor House Publishing: Surrey, UK, pp1-31
  4. West AM, Nkemngong CA, Voorn MG, Wu T, Li X, Teska PJ, et al. Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes. Antimicrob Resist Infect Control. 2018;7:1–8
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  12. West AM, Nkemngong CA, Voorn MG, Wu T, Li X, Teska PJ, et al. Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes. Antimicrob Resist Infect Control. 2018;7:1–8
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  15. String, G., Domini, M., Mirindi, P. et al. Efficacy of locally-available cleaning methods in removing biofilms from taps and surfaces of household water storage containers. npj Clean Water 3, 13 (2020). https://doi.org/10.1038/s41545-020-0061-y
  16. Sandle, T. Putting disinfectant to the test: Designing a field trial, Cleanroom Technology, 2020 at: https://cleanroomtechnology.com/news/article_page/Putting_disinfectant_to_the_test_Designing_a_field_trial/166799