29.08.2023 | LOGFILE Feature 32/2023

Contamination Control – Cleanliness Zone Concepts

Contamination Control – Cleanliness Zone Concepts

4 min. reading time | by Harald Flechl

 

According to the new Annex 1, a Contamination Control Strategy (CCS) must be implemented for the entire cleanroom and controlled environment system of the facility.

This must define the cleanliness zone concepts with all critical control points and evaluate the effectiveness of all design, procedural, technical and organisational controls and monitoring measures used to manage the risks associated with contamination.

The CCS and the cleanliness zone concept define the quality and performance characteristics that a pharmaceutical company's cleanroom solutions must meet. This goes far beyond the assignment of air cleanliness classes and should be based not only on empirical values but also on the current state of the art.

The development of a CCS requires detailed technical and process knowledge. Companies without the corresponding expertise and experience can be supported by experienced experts (GMP consultants, planners). However, the responsibility always lies with the manufacturer, who must also contribute the process know-how.

1The ECA Foundation provides a guideline for the creation of a CCS (CCS Guide Download – ECA Foundation (eca-foundation.org) – last accessed 07.02.2023


The starting point for a CCS creation could be, for example, answering the following questions:

  • What can disrupt my process?

  • Which parameters influence product quality and effectiveness?

  • How can I quickly recognise and detect changes?

  • How can I prevent change?

  • What has an impact on patient safety?

In a concise form:

  • What can contaminate the cleanroom (and the product) and how can this be detected and/or prevented as soon as possible?

For example, the following aspects should be considered for the creation of a CCS:

  • Room and process design

  • Premises and equipment

  • Material and personnel flows

  • Media supply and disposal

  • Raw material controls and in-process controls

  • Primary packaging materials and closures

  • Supplier qualification for key components/material

  • Sterilisation process validation

  • Process validation

  • Risk management within the process

  • Maintenance, servicing as part of planned and unplanned interventions without adding risk of contamination

  • Cleaning, disinfection

  • Monitoring in accordance with the state of the art and alternative methods for detecting potential contamination

  • Preventive mechanisms – such as trend analyses, root cause investigations, CAPAs, required resources

  • Continuous improvement based on information derived from the above points


Due diligence must be applied not only to GMP aspects, but also to the protection of personnel and the environment. A good basis for the planning implementation according the requirements laid down in the zone concept is provided by the EN ISO standards on cleanroom technology: the EN ISO 14644 series of standards for cleanroom technology in general and EN 17141 (replaces EN ISO 14698, withdrawn in 2021) concerning biocontamination control.

In Germany, this is supplemented by the VDI-2083 cleanroom technology guideline series, which deals with the specifications of the EN ISO 14644 standard series in greater depth and covers further reaching topics. Some of the VDI guidelines are also applied internationally.

The specifications in these standards are of a general nature, i.e. not purely pharma-specific. Therefore, some points and sections are only to be applied analogously – using ‘common sense’ – or are not to be regarded as relevant. Which points are relevant for the respective process must therefore be determined on a project-specific basis depending on the user requirements. According to current legal standards, the guidelines valid at the time of the system handover are always relevant.

For this reason, a list of the current guidelines is not provided here and reference is made to the relevant sources, e.g. Beuth Verlag, Austrian Standards Institute, etc.

 
Harald Flechl

Author

Harald Flechl
Senior Engineer and Air Conditioning Technician – Clean Room Technology
E-Mail: flechlh@chello.at

 
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