LAF cabinet

In pharmacies a laminar flow unit is used to protect the product against microbiological contamination from the operator. With a cross flow LAF cabinet the HEPA filtered air is directed over the working area to the operator. This type of LAF bench thus cannot be used for operations with hazardous substances (hazardous being defined as any substance with a H statement, so with a hazard class higher than one, see Sect. 26.3.1). It can be used for aseptic preparation processes with closed systems, such as aseptic handling, see Chap. 31. 

In general, the air from the production area enters the front of the LAF cabinet in a controlled way, passes at first a set of pre-filters in the cabinet that separates coarse dust. Sometimes more HEPA filters placed in series after the pre-filters act as supplementary pre-filters (in certain types of safety cabinets). After pre-filtration the air is forced via a ventilator box through a set of framed HEPA filters and finally enters the aseptic process area as sterile filtered air in a unidirectional flow. The speed of the unidirectional flow is kept between limits. Finally the exhaust air re-enters the room (crossflow LAF units), or can be exhausted to the outside with or without extra HEPA filtration (safety cabinets). 

With these principles in mind horizontal crossflow LAF cabinets, downflow LAF cabinets, downflow safety cabinets or downflow LAF units with a large area (HEPA filter plenums) are constructed. 

The exact positioning of pre-filters in a LAF cabinet depends on the brand and type of the LAF cabinet and is... 

Electronic balances. They can be used inside the LAF cabinet but give disturbance of the laminar airflow and in return the LAF cabinet might disturb the weighing result. Use only following a risk analysis. 

Commonly two operators are at work in a LAF cabinet. One is the operator, working with the arms and hands inside the cabinet. The second person is standing aside, supporting and controlling the operator, or supporting two operators working simultaneously in two different cabinets. 

LAF cabinets that do not run 24 h a day must be switched on first after 15 min operating at full speed the cabinet must be disinfected and can be used. 

Once or twice a year (depending on the criticality of the processes) the LAF cabinet is inspected, calibrated and qualified. Commonly a contract is signed with a specialised external firm for this. 

In industry an isolator technique is often used for critical aseptic processes. Other techniques with robots and barrier system isolator technology are in use also. Isolators for aseptic manufacturing can be placed in class C or D clean rooms, whereas LAF cabinets should be placed in GMP class B. 

Increased Clothing overalls, daily cleaned. Horizontal LAF cabinet. Separate, limited access No... 

Maximum Clothing overalls, daily cleaned, hair cap, mouth-nose mask, special shoes Hands cleaned and disinfected, sterile single use gloves for each session Horizontal LAF cabinet, safety cabinet or overpressure (positive pressure) isolator In accordance with GMP Grade D smooth surfaces, interlocked changing rorans etc. Grade D... 

LAF cabinets, safety cabinets and isolators should be disinfected from cleanest to less clean areas, e.g. from back to front for a horizontal LAF, in overlapping strokes. The non-shedding cloth (polyester is advisable due to its low particle load) has to be wetted regularly to make sure there is a constant film of liquid on the surface, and this will dry in the airstream. An extension to hold the cloth may be used to disinfect surfaces that are difficult to reach. 

The same goes for cleaning and maintenance of premises, such as the LAF-cabinet or preparation areas. Logbooks must always be present at the place where they are needed, near the device or equipment, or near the workplace, so they can be consulted there during or subsequent to the work. 

Qualification and validation can be outsourced. However, the responsibility remains in-house so the craitract-taker has to be approved according to current GMP requirements for outsourced activities [10]. For example, the following qualification and validation items can be outsourced LAF cabinets, safety cabinets, HVAC-systems, sterilisers, rinsing machines and devices for performing filter integrity testing. When tasks of qualification and validation are outsourced, internal approval of protocols, raw data and reports have to take place according to internal procedures. 

Class II BSC. The Class II BSC (Fig. 9) provides product, personnel, and environmental protection, and is the most common BSC employed in pharmaceutical manufacturing and pharmacy-compounding operations. The Class II BSC has several subclassifications, based upon cabinet ventilation design (Table 1). The Class II BSC (Fig. 8), the most widely used by hospital and home-care pharmacies, features a front access opening with carefully maintained inward airflow for replacement of air exhausted from the cabinet, a HEPA-filtered vertical laminar flow airstream within the entire work area, and HEPA-filtered exhaust air. The vertical laminar flow airstream and front access opening are common to all Class II cabinets, although LAF velocities and patterns, HEPA filter sizes and position, ventilation rates, and cabinet exhaust methods vary considerably in different designs (Fig. 7). 

For aseptic handling in closed systems a cabinet with unidirectional airflow (LAF or safety cabinet) or an isolator can be used (see Sect. 28.3). The requirements for the background room depend on national guidelines and on the types of containment in the cabinets. Adjustments are allowed but must be based on a risk assessment. 

Fume cupboard Moveable exhaust duct Powder exhaust unit LAF unit or booth Safety cabinet Isolator... 

It is advised to require silent, modem ventilators. The expected daily noise of a LAF xmit in operation must be reasonable low and specified in dB. The best solution is to choose a cabinet ventilator with enough spare capacity. In that case the ventilator will not work at the maximum capacity and the noise level in dB will be reasonable or low. 

A laminar flow cabinet will continuously produce heat from the ventilators. If the exhaust airflow from the LAF unit is returned into the room (recirculation), the temperature in the room will rise and more room ventilation and cooling is necessary. Air exhaust to outside the room will give less heating of the room. 

Maximum product protection is the highest of the three levels of product protection. In this case the aseptic activity is carried out within a LAF or safety cabinet or isolator sited within at least an EU Grade D of controlled background in the hospital pharmacy. 

The working area is the immediate environment in which the aseptic handling is performed. It is the working surface (EU Grade A zone) of the LAF or safety cabinet or isolator. 

The background area is the room in which the LAF or safety cabinet, or isolator is housed. In the case of open-fronted cabinets there is a distinction in background requirements between the different guidelines mentioned before. The PIC/S guide [2] and the German ADKA guideline [9] require at least EU Grade C, the Dutch hospital... 

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