Impact on Environmental Monitoring Programs

EU-GMP-annex-1-impage.jpgAuthors: Frank Panofen, PhD, and Daniele Pandolfi

In the Annex 1 draft, most of the relevant principles of the ISO 14644-1:2015 standard are included (Chapter 5.26). The initial number of sampling sites, their even distribution and related sampling volume in critical zones (Grade A and B) rely on this standard.

However, it is clearly stated that these are only the minimum requirements sufficient to classify a cleanroom. All further decisions must be based on process knowledge and risk assessment. Consequently, it will become very difficult in the future to defend why lesser parameters for the qualification were chosen, especially for inspection of manufacturing  environment sampling. This ties deeply with the statement in Chapter 5.28, where “Clean room qualification (including classification) should be clearly differentiated from operational process environmental monitoring”. A clear differentiation needs to be made between each phase of a clean environment's lifetime. 

The classification of a cleanroom, covered in the ISO 14644-1:2015 standard, is based on particle load. There are no microbial limits given for this part of the process, but there has been a major change towards the 2008 version of the guideline: 
In chapter 5.25, particles of the size equal to or bigger than 5 µm have been removed from the
classification and qualification limit table for Grade A, but kept in the recommended limits for
monitoring of the process environment.

The frequency of viable sampling has received an almost revolutionary renewal in the Annex 1 draft, and has become integrated with increasing control over the process by scientifically sound rationale. Chapter 9.25 indicates that sampling must be frequent can be performed using a combination of methods, leaving the decision to the manufacturer as to which sort of methodology and resulting data should be considered as relevant for the sampling point. As always, the reasoning for all decisions must be documented and based on risk assessment and historical/scientific data. Interestingly these strategies also apply to personnel monitoring (Chapter 9.26). At the moment, manufacturers tend to avoid multiple samplings of operators in order to prevent contamination build-up and the subsequent risk to the process and products. A possible solution could be the implementation of more sampling techniques that are not susceptible for residuals, such as the use of swabs instead of contact plates. 

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