The Qualification of cleanrooms

The aim in the Qualification of a cleanroom shall be the proof of the correct planning, construction and commissioning in regards to its normative and user specific requirements.

Two possible solutions:
The first solution herein would be a prospective Qualification. This solution shall be applied in parallel to the planning, realization and acceptance of the cleanroom.

The second solution shall be the retrospective Qualification. This solution shall be applied in the case of cleanrooms that have never been qualified but are already in use. The documentation of the cleanroom facility shall be updated in order to be able to render proof of the fulfillment of the required specifications.

A risk analysis may prove to be useful herein. Possible critical topics and problems may be mitigated hereby. Already existing data such as production protocols or technical measures records often become helpful in the case of retrospective Qualification of cleanroom facilities.

The first step for both types of Qualification, prospective and retrospective, shall always be the creation of a Qualification master plan.

The Design Qualification (DQ)
The Design Qualification (DQ) shall be the first step for audit in order to be able to determine if the cleanroom technical facility accords to the requirements as given in the EU-GMP-Guidelines, following the QMP functioning herein as basis document. The audit scope of the DQ shall include the cleanroom shell (wall, ceiling, floor incl. applicable installations), the ventilation system and sewers incl. installations, the control- and regulation technology of the ventilation systems as well as the in the QMP defined systems pending qualification. In addition to the GMP requirements the DQ shall also audit if the facility accords to further standards such as EN ISO 14644 and VDI 2083 as well as to client specifications (User Requirement Specifications - URS). Any therefrom resulting requirements should be summarized in an audit list in line with the DQ-Plan.

These lists shall be basis for the audit of planning documentation. One further component of the DQ is a risk analysis reviewing the whole system in respect to possible failures or vulnerabilities. A clear opinion regarding the planned facility shall be rendered as part of the DQ report with the processing of the audit list and the assessment of the facility on basis of the risk analysis. An early audit of the plan documentation by the DQ shall assist the early detection of deficiencies within the plan. Should deficiencies in the plan not be detected early on (at the beginning of construction, upon commissioning or acceptance of the project), its correction would engage a higher volume of resources and expenses.

Installation Qualification (IQ)
The Installation Qualification (IQ) shall ensure and document the proper installation of the facility pursuant to normative and user specific requirements. The IQ shall be conducted upon construction of the facility, in the most cases, following the technical acceptance. The status documentation, prepared by the supplier, shall be compared to the in the DQ audited plan documentation in a first step. This audit delivers proof that the installed cleanroom facility has been constructed in line with the plan and requirements. In addition the status documentation is reviewed in regards to its completeness and its accuracy. In a second step it shall be audited if the facility itself has been built within the lines of the status documentation and if the completion was conducted in line with the EU-GMP-guidelines. The application of a risk analysis seems helpful in order to be able to determine discrepancies. Requirements in respect to production facilities, audited within the IQ, are for example:

• Interior surfaces shall be smooth, free of cracks, damages and / or open seams.
• Surfaces shall not emit any particles. In addition they shall be easy to clean and disinfect and resistant against any cleaning- and disinfection agents. 
• The ventilation system should not have a negative effect on the product or the processes. 
• The ventilation system should in addition not produce any particles. It should effectively reduce the particle concentration or respectively eliminate particles.
  
  

The Operational Qualification (OQ)
The Operational Qualification (OQ) shall document that the facility and its elements function as expected in line with the designated operational area. The OQ-Plan should contain audit lists for the functional audits. Elements of the audit shall be e.g. functional and security audits of the ventilation system in the cleanroom (e.g. door pass system control and access control) as well as functional audits determined by measurement techniques when in the status "at rest". The audits determined by measurement techniques shall be defined on basis of the EU-GMP-guidelines in two different status', that is "at rest" and "in operation". The status "at rest" is "the state within which the product equipment shall be installed and is in operation without the presence of the operating personnel". In contrast, the status "in operation" shall be the state within which the facility operates in its intended way with the determined number of personnel". The measurement regarding the classification of air purity shall be determined specifically within the EU-GMP-guidelines pursuant to the applicable clean room classification A to D. The audits regarding the measurement techniques shall be conducted by "trained personnel only" and shall be subject to calibrated measuring systems. As stated earlier, the OQ may require a risk analysis in order to assess certain deficiencies or deviations.

The Performance Qualification (PQ)
In the case of Performance Qualification (PQ) the user verifies if the facility and its parts "as they are connected to each other, function effectively and reproducibly on basis of the approved process method and product specification". Required herein shall be tests with production materials, replacement materials or simulated products. The PQ of cleanroom technical facility shall generally be limited to measurements taken within the status "in operation". Herein it shall be checked if the facility fulfills the specified parameters even if it is running under its full load, that means with the intended maximum of personnel and during running production facilities. Microbiological conformity measurements shall take place in addition to the measurement of particles. The results of the PQ shall be reported upon as any of the afore mentioned qualification phases. The process validation can start only upon a successful PQ of the cleanroom facility.

The Final Qualification Report
The user may finalize the qualification phase of the cleanroom technical facility with a final qualification report upon fulfillment of any and all of the defined actions for the different qualification phases. Herein summarized shall be the results of the different qualification phases (DQ, IQ, OQ, PQ). Any modifications (Change Control) shall be justified briefly. Critical deficiencies shall be cleared prior to the release of the Final Qualification Report, non-critical deficiencies may be processed at a later time. The facility shall follow up on the clearance of the deficiencies even after the release. The Final Qualification Report shall contain documentary records including any and all of the during the qualification phase prepared documents clearly stating the qualification status of the cleanroom technical facility.