Cleanroom Qualification

Cleanroom Qualification to EU GMP or DIN EN ISO 14644 standard

The objective of cleanroom qualification is to demonstrate that normative and user-specific requirements have been met during planning, construction and commissioning of the cleanroom. There are two options for it. The first, prospective qualification, is carried out in parallel with planning, implementation and approval.

The second option is retrospective qualification. This is used for cleanrooms already in operation but not previously qualified. The cleanroom’s documentation is updated to provide evidence that the required specifications have been met. A risk analysis is very useful for this. In this way, critical points and potential problems can be identified. Pre-existing data such as production or measurement records are often used for retrospective qualification.

The first step in both types of qualification, prospective and retrospective, is always the preparation of a qualification master plan (QMP).

Design Qualification (DQ)

Relying on the QMP as a framework, design qualification (DQ) is the first step in examining whether the facility meets EU GMP guidelines. The cleanroom shell (walls, ceiling, and floor with their respective fittings), the ventilation system and its control and regulation technology, ducts with installations, as well as all qualifiable systems defined in the QMP are all part of the scope of the DQ. In addition to checking GMP requirements, the DQ also tests whether the facility complies with other regulations such as EN ISO 14644 or VDI 2083 and with the User Requirement Specifications (URS). All resulting requirements should be collected in a checklist as part of the DQ plan.

The checklist is then used to verify the planning documentation. Risk analysis is another component of the DQ, scrutinising the entire system for possible errors or weak points. In working through the checklist and assessing the facility by performing a risk analysis, the DQ report establishes a clear position with regards to the planned facility. Early scrutiny of the planning documentation during DQ will show up deficiencies in planning.

Planning deficiencies discovered during subsequent stages of the project such as the start of construction works, commissioning or acceptance would be far more resource and cost intensive.

Installation Qualification (IQ)

Installation Qualification (IQ) ensures and documents that the facility was installed to normative and user-specific requirements. An IQ is carried out after construction, usually after technical approval of the facility. In a first step, the supplier’s as-built documentation is compared with the planning documentation checked during the DQ. This assessment will establish whether the installed cleanroom facility was built to plan and requirements. During this step, we also check whether the as-built documentation is complete and free from errors. In a second step, we check whether the facility itself was built to as-built specification and whether execution is to EU-GMP guidelines. A risk analysis is useful to evaluate any discrepancies found. Some of the requirements for manufacturing areas that will be tested during IQ are, for example:

  • Inside surfaces should be smooth, free from cracks, damages and open joints
  • Surfaces should not emit particles and be easy to clean and disinfect
  • Surfaces should be impervious to cleaning and disinfecting agents
  • The ventilation system should not have a negative influence on the product and the processes
  • The ventilation system should not produce any particles and should effectively dilute particle concentration or displace particles

Operational Qualification (OQ)

Operational Qualification (OQ) should document that the facility and its components operate as expected in the areas of intended operation.

The OQ plan should contain checklists for functional testing. Among the inspection points are, for example, function and safety check of the ventilation system and the cleanroom (e.g. airlock control and access controls) as well as functional check measurements in an “at rest” state.

For these measurements, EU-GMP guidelines define the two states “at rest” and “in operation”. The “at rest” state is “the condition where the installation is installed and operating, complete with production equipment but with no operating personnel present.” In contrast, the “in operation” state is “the condition where the installation is functioning in the defined operating mode with the specified number of personnel working.” EU-GMP guidelines specify requirements for the classification measurements of air purity in the respective cleanroom classes A to D.

“Only trained personnel” using calibrated measuring systems shall be used for the measurements. As during the previous qualification phases, possible deviations and defects may have to be evaluated in a risk analysis during OQ.

Performance Qualification (PQ)

During Performance Qualification (PQ), the end user verifies whether the facility and its parts, “as connected together, can perform effectively and reproducibly, based on the approved process method and product specification.”

Tests must be done with production materials, qualified substitutes or simulated products. PQ of a cleanroom facility is generally limited to “in operation” testing, checking whether the facility adheres to the specified parameters even at full capacity, that is with the intended number of personnel and with production facilities running.

In addition to particle measurements, microbiological conformity tests are also required. As with all previous phases of qualification, the results of the PQ will be recorded in a report.  Only after successful PQ of the cleanroom facility can process validation begin.

Qualification Report

Once all measures defined for all the qualification phases have been dealt with, the user can conclude the cleanroom facility’s qualification with a final qualification report, summarising the results of all qualification phases (DQ, IQ, OQ, PQ). A short explanation of the reasons is given for any changes (Change Control). Critical deficiencies must be rectified before the final qualification report can be approved, non-critical deficiencies can be rectified later.

However, the company must ensure that the rectification of deficiencies is continued after approval. The final qualification report should also include documentary evidence including all documents prepared during qualification and it should clearly state the qualification status of the cleanroom facility.