Welcome to our EU GMP Annex 1 questions and answers blog, where Particle Measuring Systems answers commonly asked questions about the latest changes to regulation.
Does the new Annex state any minimum sample volumes (as it has in the past)?
When sampling particles 5 µm or larger, the sample volume calculation using the ISO formula will result in a minimum sample volume of 700 liters per location. There may be importance in sampling specific particle sizes which, even if removed from classification requirements, is still monitored during operation and must be taken into consideration.
Have particle sizes greater than 5.0 microns been removed as a requirement of Grade A or B monitoring?
The limit level for particles equal to or greater than 5.0 µm has been removed from the table. However, this size is still required to be controlled during cleanroom monitoring activities.
Is there any need to use the macro particle descriptor in ISO 14644-1 as we do for the 2008 GMP class limits?
Due to a lack of information pertaining to this assertion in the standard, no, there is no need to use the macro particle descriptor in this way.
The draft includes a table of recommended limits for particle monitoring. Is this against the modern concepts of risk assessment?
The tables are recommended limits for classification and qualification, but not for monitoring. Monitoring must be based on risk assessment (taking the results of the qualification into account), and not based on compendia materials.
How do you interpret the limit of 1 CFU for Grade A environments in Table 2 of the Annex 1 Draft 2017?
Cleanrooms are classified by particle counts, not microbial limits. The limit of 1 CFU should be used for “in operation” cleanroom qualifications. As it is clearly stated to be a limit, every sample with a CFU count must be considered a deviation.
Is microbial active sampling that alternates in frequency for the duration of the process acceptable?
Viable sampling should be frequent and in the case of air monitoring, ideally continuous. A sampling model with frequent but small samplings could be considered a first step towards this requirement, and show your understanding of the regulation. However, a plan on how to meet future requirements should also be presented.
Should all tools for monitoring microbial contamination (i.e., active, settling, contact) be used for each grade?
All methods have their own (limited) value, but using a combination gives a more complete picture. Alternative methods with higher reliability and precision can replace older tools, with an example being the use of long-term active air sampling at a lower flowrate to replace settling plates
Check out our microbial monitors to use with a diverse range of cleanroom grades.
