Laminar flow clean rooms

Figure 9.29 shows a typical arrangement of a laminar-flow clean room. The flow may be vertical through a perforated ceiling and floor. 

Intuitively, GSD can be considered to be inversely related to the efficacy of installed engineering controls. A GSD of 1.0 means that all exposures are identical, a condition nearly realized in some laminar flow clean rooms. When GSD > 2.5, as may be the case for some kinds of maintenance work, it is likely that there are no functioning engineering controls. The exposure variability for most American workers is characterized by a GSD lying between 1.2 and 2.5 (3). 

Cleanrooms should be effectively flushed with air supplied under positive pressure and delivered through filters, of appropriate efficiency, located where the air enters the processing environment Air inlets should be remote from air outlets in order to achieve effective flushing of the room space and to aHow critical operations to be located in the least contaminated stream of air. Air outlets should be at a low level. Except for laminar-flow clean rooms, the dangers of re-entrained room air entering the work zone should be taken into account when designing the suite and the layout of equipment... 

Vertical laminar flow clean benches also are not BSCs. They may be useful, for example, in hospital pharmacies when a clean area is needed. Although these units generally have a sash, the air is usually discharged into the room under the sash, resulting in the same potential problems as the horizontal laminar flow clean benches. 

For Cd, laminar flow clean benches or clean rooms were recommended to avoid contamination. Acids used should be further purified by sub-boiling point distillation. If all precautions to reduce blanks are not followed too high results will be observed. 

All operations (cleaning, filtration, acidification and sample handling) were carried out in a specially designed Class 100 room, either fitted in a standard 20 ft transport container which was fully equipped as a chemical laboratory or in a room transformed as such on board of the research ship. All operations with the sample were performed in a closed system, except for the sample acidification and the filling of the bottles, which were performed in a laminar flow clean bench inside the clean room. All personnel working in the clean area used polythene gloves, dust-free garments and shoe-covers. 

In the early days of laminar flow, the idea of entire rooms being protected by laminar flow was greeted with enthusiasm. They are now rarely found in connection with aseptic filling. They arc far more expensive to construct than conventional turbulent flow clean rooms, because of the need for more filters and greater engineering capabilities to move a lot of air at high velocity. Moreover, a horizontal laminar flow wall provides unidirectional air flow only as far as the first work station. Thereafter it is no different from a conventional clean... 

In general, the CL is operated as a mixed-flow clean-room facility, meaning that the Class-lOO/ISO Class 5 areas are the workbenches and fiime cupboards in the various rooms, rather than the entire room. A laminar flow of clean air falls from high-performance particulate (HEPA) filters in the suspended ceiling of the room and is directed to the work area by plastic curtains. Certain clean laboratories in the network employ full laminar flow in the rooms at US Class lO/ISO Class 4 cleanliness conditions. The most sensitive measure of effectiveness is the blank levels of U and Pu that can be achieved, rather than the chosen cleanliness class. Blanks consist of the following types ... 

Possible contamination due to atmospheric dust and particle emission attributable to laboratory staff activities (smoking, use of cosmetics, etc.) can be avoided in trace analytical determinations at the pg/kg, pg/L, and pg/m ranges by working under clean-room conditions. A laminar-flow clean bench ensures that particles with a diameter >0.1 pm will be removed with an efficiency of 99.9% through high-efficiency, sub-... 

The arrangement shown in Fig. 9.28 is used in industrial halls or auditoriums. Clean rooms have complex systems using laminar flow to ensure that the room IS fully ventilated. 

Filtered air may be used to purge a complete room, or it m be confined to a specific area and incorporate the principle of laminar flow, which permits operations to be carried out in a gentle current of sterile air. The direction of the airflow may be horizontal or vertical, depending upon the type of equipment being nsed, the type of operation and the material being handled. It is important that there is no obstruction between the air supply and the exposed product, since this may resnlt in the deflection of microorganisms or particulate matter fiom a non-sterile surface and canse contamination. Airflow gauges are essential to monitor that the correct flow rate is obtained in laminar flow units and in complete suites to ensure that a positive pressure fiom clean to less clean areas is always maintained. 

The greatest risk of contamination of a pharmaceutical product comes from its immediate environment. Additional protection from particulate and microbial contamination is therefore essential in both the filling area of the clean room and in the aseptic unit. This can be provided by a protective work station supplied with a unidirectional flow of filtered sterile air. Such a facility is known as a laminar airflow unit in which the displacement of air is either horizontal (i.e. from back to front) or vertical (i.e. from top to bottom) with a minimum homogenous airflow rate of 0.45 ms" at the working position. Thus, airborne contamination is not added to the work space and any generated by manipulations within that area is swept away by the laminar air currents. 

Regardless of the methods used to obtain a clean air environment, unless the parenteral operator is made completely aware of the limits of laminar flow, uses careful, planned movements, and is wearing proper clothing, he or she can be a source of product contamination. Operator movement within aseptic rooms should be minimized. The rooms must be disinfected regularly and thoroughly before setting up for aseptic operation. 

Figure 3.1. Diagrammatic illustration of the flow pattern of HEPA-filtered air through a t5 pical clean room. Air is pumped into the room through HEPA filters (see text) located in the ceiling, and exits via extract units, normally located at floor level. Although the air flow is non-unidirectional (i.e. not true laminar flow), it generates a constant downward sweeping motion, which helps remove air-borne particulate matter from the room...

Downstream processing is normally undertaken under clean room conditions, with the final steps (e.g. sterile filtration and aseptic filling into final product containers) being undertaken under Grade A laminar flow conditions (Figure 3.18). 

All finished products are tested for sterility in a controlled-access clean room environment in a laminar flow hood, which provides no greater level of a microbial challenge than that encountered in the fill environment. The testing environment consists of a gowning room and sterility test suite that meets the same air quality standards as the hlling suite. 

On a broader scale, pharmaceutical manufacturers were beginning to utilize absolute filtration as a primary engineering control in the maintenance of large, carefully controlled clean spaces in the batch production of quality-controlled parenteral products. In this application, LAF was supplied directly to production lines and extended critical worksurfaces within defined, non-turbulent entrance and exit planes as parallel or columnated airflow (misnamed laminar flow ). This highly controlled laminar airstream was supplied to the critical worksurface, in addition to conventionally supplied turbulent airflow to the general space, provided through terminal diffusers for filtration of the balance of room air. In this manner, the stepped control of all critical, as well as support areas was achieved. 

Airborne particles are one important source of sample contamination. Therefore, the laboratory must enable samples to be treated and measurements to be carried out in a satisfactorily dust-free environment. Improvements in existing laboratories can be obtained by installing a laminar flow hood, but optimal improvement involves the design of clean rooms in which air is pumped through a dust-stop prefilter and then forced by a blower through an absolute filter inside the working... 

Figure 5.3). This laboratory is subdivided into two parts the first is equipped as a general chemical laboratory, contains the sampling bottles stand and constitutes the pre-room for the second part this last is the internal clean area equipped with two laminar flow hoods class 100 (US Federal Standard 209D) (89). 

Particles settle by gravity on to settle plates. Large and heavy particles tend to settle out due to gravitational forces with increasing air movement only the very heaviest particles settle out. This limits the value of the method in laminar flow protected areas or other clean rooms where still air is not intended. Of course it can be argued that dead air is the main coiKcra in clean rooms, and... 

Class B Work rooms of Class form the background rooms for a critical place A. A laminar air flow chamber which is used to attain the air quality of class A must be installed in a work room with an air quality as described under clean room B. ... 

C. In the case of filling of liquids for injection, filling must be performed in clean rooms C with special precautions, such as the use of a laminar air flow chamber. 

Laminar Airflow Air flowing in a single pass in a single direction, through a clean room or dean room area with uniform velocity along parallel flow-lines. Laminar air flow systems should provide a homogeneous air speed of O.dOm/s for vertical flow and 0.45m/s for horizontal flow. 

Exploration of /rg/kg or ng/kg levels of Cr requires many precautions (Versieck and Cornells, 1989). One of the primary concerns is that for clean room conditions. Belgian atmospheric aerosols contain 37 mg /kg Cr particulate matter, with a range of 8.8 - 150 mg/kg. Good analytical practice requires a fall-out below 1 / g/m. day in the working area. The use of a laminar flow hood, if possible a class 100 one, may offer an adequate solution at a modest price. 

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