Jump to content

Worth knowing from the area of cleanroom qualification

The knowledge area cleanroom qualification answers questions about the cleanroom classes and the tests within the scope of a cleanroom qualification. You will also receive an overview of the specifications from DIN EN ISO 14644-3:2020-08.

Which cleanroom classes are there?

In DIN EN ISO 14644-1, the various cleanroom classes (ISO 1-9) are classified on the basis of the maximum permissible particle concentration (in particles per cubic metre of air). In the EU GMP guidelines, the cleanroom classes are assigned the letters A to D, with an additional distinction being made between dormante state and manufacturing.

Limit values for particles (permanent monitoring) in Annex 1 as of 08/2022:
EU Guidelines to Good Manufacturing Practice, Annex 1, 08/2022

Limit values classification (qualification) in Annex 1 as of 08/2022:
EU Guidelines to Good Manufacturing Practice, Annex 1, 08/2022

Classification of air purity based on particle concentrations in accordance with DIN EN ISO 14644-1:2016:

Which tests/measurements are carried out during a cleanroom qualification?

The following measurements are typically performed during a cleanroom qualification:

  • Climate measurements
  • Pressure measurements
  • Flow measurements
  • Determination of the particulate purity class
  • Filter integrity tests and measurement of recovery times
  • Microbiological monitoring

Cleanroom qualification

What innovations does DIN EN ISO 14644-3:2020-08 bring with it regarding the performance of leak tests on HEPA filters?

Performing the filter leak test has not become any easier. There is additional formalism (e.g., derivation of Dp) and continued heavy fare in leakage definition via Na. The conformity statement for filters H13/H14 has become more stringent by a factor of 5. This has an impact on the feasibility (more re-measurements) and especially on the aerosol load of the HEPA filters. The concentrations increase several times compared to the previous version. The acceptance criterion of an in-situ test was formulated more strictly than the local transmittance in EN 1822-1. Further aggravation comes from the unnecessary definition of Na/Np. By choosing such a small value for counting events, there will be many counting events.

Leakage test on HEPA filters

What changes result from the August 2022 revision of Annex 1 of the EU GMP Guidance for the qualification of cleanrooms?

Despite some changes in the August 2022 version of Annex 1 of the EU GMP Guidance, the basic concept has remained the same. Thus, there are no significant changes for the recovery time definition as well as for the measurement of air velocities in the TAV area and the microbial status. Basically, however, the creation and implementation of a contamination control strategy, CCS for short, is now required as a central element of the quality assurance measures. In addition, there are now dedicated requirements for minimum efforts and intervals for qualification measurements and an explicit distinction is made between measurements in the different operating states "at rest" and "in operation". With a harmonisation of limit values for particle concentration in the determination of the particulate cleanliness class with DIN EN ISO 14644-1:2016, a discrepancy arises between the now different measures of qualification and monitoring.

Establishment of a GMP monitoring concept in the pharmaceutical manufacturing sector