Is a separate and distinct cleaning step always needed before disinfection? STERIS' Walid El Azab explains the scientific approach for choosing the appropriate method for cleanrooms and non-contact product surfaces
The draft European Good Manufacturing Practice (EU GMP) Annex 1 is the focus of a great deal of discussion. In many ways, this is good as it builds interest, engagement, and inclusion. The downside of this debate, however, is the potential to spread misinformation. It would be prudent for pharmaceutical manufacturers to practice due diligence before changing any procedures.
Let's not forget that the goal of regulatory guidance is to provide standards for basic requirements, not to define procedures. This allows manufacturers to develop and implement procedures that are tailored to their facilities and processes. The procedures must be designed according to each manufacturer’s unique processes, rather than merely adhering to the minimum regulatory standard, as this may or may not be appropriate and can result in misaligned methods. An effective procedure is one that is designed based on a scientific approach and is aligned with the regulatory requirements.
The objective of this article is to clarify when a one or a two-step cleaning and disinfection procedure for cleanrooms and non-contact product surfaces should be implemented. In other words, is a separate and distinct cleaning step always needed before disinfection?
“Clean before disinfect” is the golden rule that everyone knows and a legacy from the healthcare and food industry. This principle often relies on bleach, which cannot handle large amounts of soil load and has limited stability. Furthermore, food industry processes can generate high amounts of organic and inorganic residue, which can rapidly deplete products that are not designed to handle such soil. In these cases, the cleaning step aims to remove visible soils from the surfaces, before disinfection, to avoid interference with the disinfectant’s effectiveness. Therefore, a cleaning stage before disinfection is necessary for a manufacturing process that generates a high visible amount of residue.
High levels of residue may be generated in the production of API’s (active pharmaceutical ingredients), tablets or liquid-dose manufacturing cleanrooms where the containment systems may be inadequately designed. In this instance, it is not possible to avoid the accumulation of residues on surfaces.
However, cleanrooms designed with proper containment systems, such as closed manufacturing or hood systems, help to reduce or prevent the build-up of visible residues. Additionally, numerous manufacturing processes generate very low levels of residue. In such cases, is a one-step cleaning and disinfection procedure possible?
The amount of residue generated should not be the only parameter that dictates a cleaning and disinfection programme. The source and nature of the residue should be considered as well. In particular, organic material, for example from a media spill, may present more of a challenge to a formulated disinfectant than light soil from personnel motion (e.g. walking) in highly restricted areas.
It is evident that different parameters must be considered before implementing a cleaning and disinfection procedure. These parameters include:
The manufacturer should analyse the different parameters examined earlier. The outcome of the evaluation should help to draw a scientific justification for deciding whether a one or two step cleaning and disinfection procedure is required.
The following are two approaches manufacturers may use to determine if a one or two-step cleaning and disinfection process is needed:
FIGURE 1: DECISION TREE TO JUSTIFY A ONE OR TWO-STEP CLEANING AND DISINFECTION PROCEDURE
* The amount of residue should be assessed based on visual observation of the cleanroom surfaces. Note that external partner with cleanroom expertise may help to define low, moderate or high amount residue.
** If the disinfectant efficacy test on isolate is less than 15 minutes wet contact time, a one-step cleaning and disinfection may be justified. However, if the wet contact time is higher than 15 minutes, it is advised to use a two-step cleaning and disinfection procedure.
*** Assuming the condition of the area is excellent and no damaged of the areas is visible where product spillage, cleaner or disinfectant may pool.
Below is an example of a simple assessment approach, which may help justify a one or two-step cleaning and disinfection procedure: For the sake of simplification, the risk classification used is 1 (low risk), 2 (medium risk) and 3 (high risk) (see table 1).
TABLE 1: ASSESSMENT TO JUSTIFY A ONE OR TWO-STEP CLEANING AND DISINFECTION PROCEDURE
* The amount of residue should be assessed based on visual observation of the cleanroom surfaces.
** If the disinfectant efficacy testing has been performed at the expected surface temperature during application, and depending on the wet contact time, the risk number may be reduced or maintained. If the area condition is not optimal, then another factor may be added such as:
Level 3: bad condition of the area (i.e. presence of a crack, colour change), level 2: satisfying condition (minor) and level 1: excellent area condition.
*** The surface being cleaned with a high-liquid volume in an attempt to wet the area would play a role in disinfectant residue emergence.
In this case, the risk priority number (RPN) is equal to the sum of the value of each parameter: lowest RPN equal to 5, a medium RPN equal to 8, and a highest RPN equal to 15. Note that based on historical data and observations, the manufacturer should be able to set up the RPN threshold value. In this example a threshold value is 8:
The complete set of factors that affect cleaning and disinfection effectiveness should be identified and considered. An analysis with “in the field” observation is necessary to understand the different factors that impact the effectiveness of the cleaning and disinfection programme.
A thorough analysis of the manufacturer’s surface cleanroom “cleanness”, the technique to apply the disinfectant, the disinfectant composition, and the environment where the disinfectant is used, is crucial to support scientific justification of a one or two-step cleaning and disinfection procedure.
N.B. This article is featured in the March 2019 issue of Cleanroom Technology. The digital edition is available online.