A) Environmental control
Effective environmental control, both physical and biologic is essential but the level achievable is related to the characteristics of the facility. Further rigid standards from plant to plant and from geographic location to another are not appropriate. Allowance also must be made for variation in control associated with the seasonal conditions.
The standards of environmental control vary depending on the area involved (cleanup, packaging, compounding or filling) and type of product being prepared. Unquestionably, the entire area used for the preparation of a product prepared aseptically (without terminal sterilization) must be maintained under the most rigid control that the existing technology permits. If the product is to be terminally sterilized, somewhat less rigid biologic control of the compounding and filling areas may be acceptable. However, rigid standard of cleanliness must be maintained. High standards of cleanliness, excluding daily use of disinfecting procedures are usually acceptable for the cleanup and packaging areas.
B) Traffic control
Carefully designed arrangement to control and minimize traffic, particularly ‘in’ and ‘out’ of the aseptic areas is essential. Access by personnel to the aseptic corridor and aseptic compound and filling rooms will be only possible through an airlock. Pass-through openings and double ended sterilizers are provided to permit controlled passage of supplies from non-aseptic to aseptic area.
Persons should be permitted to enter aseptic areas only after following rigidly prescribed procedures for removing street clothing, washing their hands and putting on gowns, hats, shoes, facemasks, gloves and other prescribed attire. Once they have entered the aseptic area, they should not be permitted to move in and out of the area with out regowning.
Personnel assigned to cleaning and packaging should be restricted to these areas.
Unauthorized personnel should never be permitted to enter the aseptic area.
C) House keeping
All equipment and the surrounding work area must be cleaned thoroughly at the end of the working day. No contaminating residues from the concluded process may remain.
The ceiling, walls, and other structural surfaces must be cleaned with a frequency which is most appropriate. All cleaning equipments should be selected for its effectiveness and freedom from lint-producing tendencies. It should be reserved for use in the aseptic areas only.
D) Surface disinfection
After through cleaning all surfaces should be disinfected, at least in the aseptic areas. An effective liquid disinfectant should be sprayed or wiped on all surfaces. Irradiation from ultraviolet lamps that are located provide adequate radiation intensity on the maximum extent of surfaces in a room and that are maintained free from dust and films further reduces the viable microorganisms present on the surface and in the air.
Ultraviolet rays may be particularly useful to irradiate the inside exposed surfaces of the processing tanks, surfaces under hoods. The surface of the conveyor belts and the similar confined surfaces those are otherwise, difficult to render aseptic. However they cannot reach unexposed surfaces such as pipe connections to tanks, the undersides of conveyors and the inside of containers.
The UV lamps must be kept clean and care must be taken to check for a decrease in effective emission, a natural occurrence due to a change in the glass structure with aging.
E) Air control
In any area occupied by personnel, air must be exchanged at frequent intervals. Fresh outside or recycled air must first be filtered to remove gross particulate matter. A spun glass, cloth, or shredded polyethylene filter may be used for this preliminary cleaning operation.
At times, more than one pre-filter may be used in series, the first one is quite large and the next somewhat smaller pore size to provide a gradation of particle size removal from heavily contaminated air. To remove finer debris down to the submicron range, including microorganism, a high efficiency particulate air (HEPA) filter is used. The HEPA filter has been defined as at least 99.97% efficient in removing particles of 0.3um size and larger and composed of glass fibers and filters or electrostatic precipitators may be employed. Air passing though these units can be considered virtually free from foreign matter. Another air cleaning system washes the air with a disinfectant and controls the humidity at the same time.
Blowers should be installed in the air ventilation system upstream to the filters, so that all the dirt producing devices are ahead of the filter. The clean air is normally distributed to the regulated areas by means of metal (preferably stainless steel) ducts. Since it is practically impossible to keep these ducts as clean as required, it is normally preferred to install HEPA filters at the where the clean air enters the controlled room. Alternatively, the ducts may be replaced with a room (a plenum) usually above the production area, into which clean air is blown and then distributed through opening into each of the process rooms. The entire plenum can be kept clean and aseptic.
The clean and aseptic air is distributed in such a manner that it flows into the maximum security room at the greatest volume flow rate, thereby producing a positive pressure in these areas. This prevents unclean air from rushing into the aseptic area though cracks, temporarily opened doors or other openings. The pressure is reduced successively so that the air follows from the maximum security area to other less critical areas for return to the filtration system. At the intake end of the system, fresh air usually about 2% is continually introduced for the comfort and needs of the personnel. Further, the air is usually conditioned with respect to the temperature and humidity for the comfort of the personnel and sometimes to meet the special requirements of a product.
Horizontal laminar flow hood Vertical laminar flow hood
A relatively new air control system, based on laminar flow principle, has greatly improved the potential for environmental control of aseptic areas. Currently, it is the only means available for achieving a class 100 clean room. A class 100 clean room is defined as a room in which the particle count in the air is not more than 100 per cubic feet of 0.5um and lager in size. The air filtered through HEPA filter is blown evenly out of the entire back or top of the work bench or entire side or from ceiling of a room. The air flow must be uniform in velocity and direction throughout any given cross-section of the area, being exhausted from the opposite side. The air velocity employed should be 100 k 20 ft/min.
Contamination is controlled because it is swept away with the airflow.
Although class 100 work environments are normally specified for the most critical aseptic and or clean operations associated with the parenteral preparations, achieving such levels of cleanliness is expensive and requires effective maintenance and monitoring. It should be recognized that not all operations associates with parenteral medication require such an environment. To such an end other classes are defined. For example, a class 10,000 room is one in which the particle count is not more than 10,000 per cubic feet of 0.5 um and large size. Such a cleanliness level is usually considered suitable for buffer areas around class 100 worksites in which operations such as handling
of pre-cleaned containers, process filtration and aseptic gowning of personnel may be performed. Still less stringent requirements would be applied to laboratories, stock staging areas, and finish packaging where a class 100,000 or similar cleanliness levels would be considered suitable.
Different classes and standards of clean rooms:
The determination of how clean an area is, depends on the classification that it has been designed with different standards. Four different classes are described according to British Standard system 5295 and Federal Standard 209 (FED STD 209).
No comments:
Post a Comment