CCS - CCS in Practice: Is your Cleanroom Cleaning really under Control?

Contract cleaning and cleanrooms - Balancing responsibilities, obligations and costs

In pharmaceutical and biotechnological facilities, especially in cleanrooms operated under GMP requirements, the use of external service providers - for example for cleaning - plays a central role for GMP compliance. According to the EU GMP Guide, in particular the sections on outsourced activities (Chapter 7) and Annex 1, ultimate responsibility always remains with the pharmaceutical manufacturer or marketing authorization holder. Even when service providers are used, the contracting organization must monitor their performance, manage changes and ensure that no unauthorized modifications are made that could adversely affect product quality. Cleaning is an essential element of the Contamination Control Strategy (CCS). Annex 1 requires appropriate cleanliness levels in the "at rest" and "in operation" states as well as environmental monitoring outside the actual production (e.g. after disinfection, before production start, after batch completion or shutdowns) in order to detect contamination events at an early stage and to verify corrective actions.

All persons entering cleanrooms - including cleaning, maintenance and monitoring personnel - require targeted and regular training. This includes basic microbiology and hygiene, cleanroom practice, contamination control, aseptic techniques, and an understanding of the potential impact on the patient if a product is not sterile. The importance of cleaning in the cleanroom is comparable to that of the ventilation system: what the HVAC does to the air, the cleaning staff does to the surfaces. Since cleaning can only be checked on a sampling basis in practice, the underlying system must provide the actual assurance. This includes clearly defined and well-trained cleaning techniques (e.g. "top to bottom", "inside to outside", overlapping wiping strokes, consistently adhering to the higher cleanroom class in airlocks), systematic environmental monitoring as a check of results, and quality oversight (GMP walk-throughs) as process control. Cleaning is therefore not an isolated additional step, but an integral part of the entire process chain.

External or Internal cleaning

When deciding between external cleaning and in-house cleaning, a process-related weighing of the pros and cons is required, embedded in a formal quality risk management process. The benchmark is always the impact on product quality and patient safety. External cleaning often offers the advantage that personnel can focus exclusively on cleaning, has experience with harmonized cleaning systems and components, is familiar with market trends and can therefore make targeted suggestions for optimization. In addition, a defined outcome is purchased, which provides a clear basis for costing and helps to better compensate for resource bottlenecks due to sickness or vacation. On the other hand, external staff often has a more limited understanding of the specific production process and there is an increased risk due to high staff turnover, which necessitates repeated training and cleanroom qualification and makes it more difficult to establish stable routines.

In most cases, in-house cleaning benefits from a better understanding of the production process and from an experienced, stable team that is familiar with the workflows and therefore potentially makes fewer mistakes. However, cleaning by production staff is not always perceived as an activity that is equally critical as the actual production itself, even though it is crucial in the cleanroom for reliably maintaining the required level of cleanliness. In addition, cleaning tasks are often carried out alongside other duties and can therefore come under time pressure. Aspects such as motivation, recognition of the "invisible" cleaning performance (surfaces that already look visually clean), the meaningfulness of precisely defined sampling locations in environmental monitoring, as well as economic considerations (flexibility vs. fixed costing) all feed into this assessment.

Regardless of whether external staff or in-house personnel is used, a solid basic understanding of the overall process is essential: staff must know why they are doing something and how their behavior affects the product and the patient. Training should be practical and illustrative - ideally using the actual equipment employed, in a "safe" environment and with the actual cleanroom garments. Correct execution - for example, ensuring overlapping wiping strokes and complete surface coverage during surface cleaning - must be actively trained. In this way, cleaning is anchored as what it actually is in the GMP environment: a critical, qualified process step that makes a decisive contribution to controlling contamination risks.

Costs of cleaning and more

Cost comparisons are often carried out by administrative functions to decide between in-house cleaning and external cleaning. There is a risk that the efforts mentioned above - e.g. for the entry of personnel and materials, material preparation, training and retraining - are not adequately considered already at the tender stage. This can lead to "apparently" inexpensive offers that ultimately result in cleaning being performed under time and cost pressure, which in turn can cause quality deficiencies and, in the worst case, deviations. The resulting costs can quickly exceed the initial savings many times over.

Further information on external cleaning and on many other current requirements relating to contamination control is provided by both national events, such as the German-language Aseptikon on 6/7 October in Mannheim, Germany, with conferences on aseptic manufacturing, cleanrooms, microbiology and quality oversight, and international trainings, such as the ECA course Contamination Control with an optional additional day on risk assessment, held from 3-6 November in Vienna, Austria.