Studies on airflow visualizations aim at demonstrating, on the one hand, the visual evidence of unidirectional airflows in aseptic structures and, on the other hand, the ability of the system as a whole to protect the product and the critical areas through a constant passage of primary air coming from absolute filters.
Airflow visualization studies must be carried out in “at rest” and “in operation” state and they are particularly suited to throw light on potential sources of physical or biological contamination risk in a production process or in its surrounding environment. The visualization study, more commonly referred to as “smoke test”, takes into account the most common sources of risk that can be provoked by:
- Inappropriate design of critical production areas
- Problematic airflow management of the ventilation system, whether it is centralized or purpose-built through LAFs (Laminar Air Flow) located in the most critical zones of process
- Intervention of the personnel that interrupts the unidirectionality of airflows during aseptic operations
The execution of a good airflow visualization study allows the team to identify areas of potential risk of process and supports in the identification of corrective actions, allowing, therefore, the evaluation of efficacy after the implementation.
REQUIREMENTS: OBSERVATIONS AND WARNING LETTERS
From a regulatory perspective, regulatory agencies have intervened on more occasions through observations and warning letters, reporting the lack of adequate tests that could document an appropriate airflow both in “at rest” and “in operation” state.
|Description||Usable tools||Purpose (sec. A)||Execution (sec. B)|
|Airflows visualization (flow patterns)||Aerosol generator, tracers||Confirm / highlight that the direction and the uniformity of the airflow are compliant to the project and to specific requests||Flows can be visualized by using flexible solid bodies (thin wires) or non-harmful aerosol for cleaning (for example distilled water, alcoholic blends) made visible through adequat4e high intensity lights. Speed measurements in predefined spots can also be carried out, recreating lines with appropriate softwares. For more traditional methods, photos and videos, showing what arised in the tests, must be included in the report|
|Test of the directions of airflows for workspaces subjected to unidirectional airflows.||Hot-film anemometer, three-dimensional ultrasound anemometer, tracers, aerosol generators||Confirm / highlight that the direction and the uniformity of the airflow are compliant to the project and to specific requests||If we assume that the airflow is unidirectional, the measure is reduced to an analysis of the variations of flowrates from filter to filter. Otherwise, airflows can be visualized with the technics illustrated in the previous point.|
The most efficient and rapid method is represented by tracers in the form of visible aerosol diffused by smoke generators. The essential element for the success of the test is the dimension of the micro-droplets. It is essential to minimize gravity and inertia effects which could led to distorted test results. Big and heavy particles fall rapidly without allowing a correct airflows visualization. In the following table we highlighted the sedimentation speed according to the micro-drops diameter.
|Particle diameter (µm):||Sedimentation speed (m/s):||Sedimentation speed (mm/hr)|
FDA 483 OBSERVATION
Inspection agencies generally report an undervaluation of the importance of airflows visualization, observing non-conformities like the followings:
Inadequate Cleanroom Design and Smoke Study Deficiencies:
- Your stopper hopper leans diagonally over the top of the filling line during stopper loading operations, thereby blocking first air over open, exposed sterile vials. In addition to this inadequate design, your smoke studies performed for your ISO 5 areas also lacked simulation of multiple critical interventions that occur during aseptic manufacturing operations.
- Thorough smoke studies are essential to evaluate the effects of such interventions on unidirectional airflow and to ensure design modifications are made wherever necessary.
- The ISO 5 area is critical because sterile product is exposed and therefore vulnerable to contamination. Your aseptic filling process should be designed, and operations executed, to prevent contamination hazards to your sterile product. The flawed design of the filling line and execution of the aseptic operations promote influx of contamination into the critical filling areas.
- During the airflow analysis (smoke study) of aseptic connections on your (b)(4) equipment inside the laminar air flow (LAF) ISO-5 area, our investigator identified air flow disturbances and turbulence. Under dynamic conditions, air did not sufficiently sweep across and away from sterile connections, so the sterility of any product processed under these conditions could be compromised.
- Furthermore, in our review of the smoke study, we identified multiple aseptic technique breaches during aseptic connection of the (b)(4) equipment. Your equipment design and aseptic processing operator competencies appear to contribute to the lack of unidirectionality.
- Aseptic processing equipment should provide for appropriate ergonomics that enable operators to reproducibly conduct aseptic manipulations. In addition, it is critical that your aseptic processing operators have the knowledge and skills to practice strict aseptic techniques. Even operations that have been successfully qualified can be compromised by poor operational, maintenance, or personnel practices.
Other observations report that:
- Operators interrupt the unidirectionality of airflows, creating a turbulent air motion
- The angle of the room does not allow a correct airflows visualization
- The reagent source is not effectively positioned
- Smoke tests in ISO 5 hoods have not been carried out during “in operation” state
- No evaluation study of the airflow model has been carried out during aseptic operations
- No evaluation of the airflow configuration has been carried out in order to determine if personnel activities or manual transfers of materials between ISO 8 and ISO 7 negatively influence the air movement and the cascade of air
- Smoke studies have not been adequately documented
- Video of airflow model does not include data to appropriately evaluate the potential impact of the product on turbulence by observing vortexes in the middle of ISO 5 hoods during “in operation” state
SUCCESSFUL ASPECTS OF SMOKE TESTS
As resulting from FDA observations, there are some fundamental elements that must be studied during a correct visualization test:
- In the preliminary stage it is fundamental to accurately study the environment layout and the instruments it contains. It is very important to have a precise picture of operations that are carried out during “in operation” state from operators during work cycles.
- Determine in advance the video-operator’s movements according to the specifications described above: taking into account the potential obstacles or the possibility to keep the camera at a right distance from the flow, it is essential that video shots are studied in advance and, in case, designed from different angles according to the specific needs.
- Type of smoke generator and type of reagent
In order for a study on airflow visualization to give a concrete benefit to the process for which it is designed, it is fundamental that its execution and technical and qualification documentation is organized in a clear and objective way. All phases submitted to the test must be clear, in particular those concerning test conditions and investigated process phases. The evidences provided must be organized by giving particular attention to the integrity of raw data collected during the study and on which final conclusions are based.
Smoke tests trigger a sort of domino effect, in which an airflow control becomes the motor behind subsequent and consequent controls and verifications. Operators’ behaviour inside the cleanroom, their exact adhesion to SOPs, their education and process quality become verifiable thanks to the visualization of smoke flows. Inspection agencies, indeed, have often questioned tests that did not contemplate those phases which are not directly related to airflows, such as transfer of materials between different zones.
AN ADDED VALUE: MYFOG
An important consideration: from the Quality point of view it is evident the importance of smoke tests routine that goes beyond specific events like changes in environments and in operative procedures.
An airflows visualization study is useful, indeed, in the definition of operative procedures and in the training of operators in terms of behaviours to follow inside an aseptic environments.
MYFOG IS A UNIQUE AND INNOVATIVE INSTRUMENT!
- Works with WFI (Water For Injection)
- Single operator
- Remote control
- Dense, quality smoke
- viewing of the speed and direction of air flows in all classified environments
- balancing of pressures between rooms via visual indicator
- detecting air stagnation areas
- remote control (fan speed, fog density, pause mode)
- 8” TfT touch screen
- water level viewing and diagnostics with status colour guide
- temperature monitoring and diagnostics with graphic visualisation
- automatic optimisation of the life cycle of transducers, switched on selectively depending on the hours of operation
- fog density adjustment
- fan rotation speed adjustment (fog diffusion speed)
- fast Start/Stop function
- monitoring of operation times, emission, and use of every single piezoelectric transducer
- piezoelectric transducer malfunctioning diagnostics
- explicit alarm diagnostics indicator
- diagnostics menu in Operator mode (viewing only) protected by password
- diagnostics menu in Supervisor mode (changes allowed) protected by password
- pause function with storing of current generation settings
- cycle resumption with stored settings upon exit from pause or after power cut
- variable acoustic signal depending on the function
- transducer lifecycle alarm
The success of a smoke test requires essential accessories to ease operational difficulties. MyFog comes complete with “intelligent” accessories:
- additional tube extension joints
- perforated nozzle for fog curtains
- telescopic handle
- case with casters for transport
- “follow me” tube