Aseptic areas

Aseptic areas maintain air cleanliness at no more than 100 particles per cubic foot greater than or equal to 0.5 pm. This is achieved by using HEPA filtration of air over areas where product is exposed to the environment. 

For aseptic air systems, the static pressure of the innermost room of a series of rooms should have pressure higher than the adjacent room leading towards the non-sterile room(s). Air pressure differentials should be monitored on a periodic basis to assure that air from the most critical manufacturing areas is always sufficiently positive and meets predetermined values. 

Personnel must wear garments which shed virtually no fibers or particulate matter and, of course, retain particles shed by the body. Strict procedures must exist for the use of the following sterilized garments and protective coverings  

No cosmetics or jewelry should be worn in the aseptic areas as these are sources of particulate nutter and bacterial contamination. 

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Control of microbial contamination 3.2 Aseptic areas additional requirements... 

Environmental cleanliness and hygiene 3.2.2 Entry to aseptic areas... 

Clean and aseptic areas general requirements 5 Conclusions... 

Internal fltlings snch as cupboards, drawers and shelves must be kept to a minimum. These may be made fiom stainless steel or a laminated plastic, which may be easily cleaned or disinfected bare wood is to be avoided, although painted or otherwise sealed woodwork m be satisfactory. Stainless steel trolleys can be used to transport eqiripmerrt and materials within the clean and aseptic areas but these must remain confined to then-respective units. Equipment should be so designed as to be easily cleaned and sterilized (or disinfected). 

Clean and aseptic areas must be adequately illuminated lights are best housed above transparent panels set in a false ceiling. Electrical switches and sockets should fit flush to the wall. When required, gases should be piped into the area from outside the unit. Pipes and ducts, if they have to be brought into the clean area, must be effechvely sealed through the walls. Additionally they must either be boxed in (which prevents dust accumulation) or readily cleanable. Alternatively, pipes and ducts may be sited above false ceilings. 

Sinks supplied to clean areas should be made of stainless steel and have no overflow, and the water should be of at least potable quahty. Wherever possible, drains in clean areas should be avoided. If installed, however, they should be fitted with effective, easily cleanable traps and with air breaks to prevent backflow. Any floor channels in a clean area should be open, shallow and cleanable and should be connected to drains outside the area. They should be monitored microbiologically. Sinks and drains should be excluded from aseptic areas except where radiopharmaceutical products are being processed when sinks are a requirement. 

Filtered air (Chapter 17) is used to achieve the necessary standards this should be maintained at positive pressure throughout a clean or aseptic area, with the highest... 

The changing procedure for personnel entering an aseptic area is dealt with in section 3.2.2. 

Containers made flxm fibrous materials such as paper, cardboard and sacking, are generally heavily contaminated (especially with moulds and bacterial spores) and should not be taken into clean or aseptic areas where fibres or microorganisms shed flxm them could contaminate the product. Ingredients which must be brought into clean areas must first be transferred to suitable metal or plastic containers. 

Additional requirements for aseptic areas, over and above those discussed in sections 3.1.1 -3.1.8, are considered below. 

Articles which are to he discharged from the clean room (or elsewhere) to the aseptic area must he sterilized. To achieve this they should be transferred via a double-ended sterilizer (i.e. with a door at each end). If it is not possible, or required, that they be discharged directly to the aseptic area, they should be (i) double-wrapped before sterilization (ii) transferred immediately after sterilization to a clean environment until required and (iii) transferred from this clean environment via a double-doored hatch (where the outer wrapping is removed) to the aseptic area (where the inner wrapper is removed at the workbench). Hatchways and sterilizers should be arranged so that only one side of the entry into an aseptic area may be opened at any one time. Solutions manufactured in the clean room may be brought into the aseptic area through a sterile 0.22-/im bacteria-proof membrane filter. 

Under no circumstances should living cultures of microorganisms, whether they be for vaccine preparation (Chapter 16) or for use in monitoring sterilization processes (Chapter 23), be taken into aseptic areas. As already pointed out, separate premises are needed for the aseptic filling of live or of attenuated vaccines. 

The air quality in preparation and aseptic areas can be one of the greatest sources of product contamination. However, this problem can be minimized by use of the equipment currently available to provide clean air essentially free from microorganisms and dirt particles. Depth-type filters, electrostatic filters, and dehumidification systems are used to remove the major... 

At the cross point between nonclassihed and classihed areas, as well as between the different classihed areas, separate airlocks for materials and personnel should be installed. Additionally, airlocks to the clean or to the aseptic areas should be equipped with interlocking doors. Only authorized personnel should be allowed to enter the classihed areas. 

In addition to these investigations with regard to validation requirements, a monitoring program, as described in SOP No. Val. 600.30. Guidelines for area validation aseptic areas should be implemented. 

To describe the procedure for the validation of aseptic area to prevent cross-contamination and demonstrate environmental control... 

The aseptic area validation matrix is summarized in the following table. Table 1 Aseptic Area Validation Matrix... 

Determine the number of air changes per hour in the aseptic area by... 

An oil-free compressed air system is normally used in aseptic areas and often may be involved with product contact. 

All positive control tests in this section use viable challenge microorganisms. These tests should be conducted in a laboratory environment separate from the aseptic area where the product is tested. 

A concurrent intensive monitoring of air, surface, and personnel hygiene should be performed during all validation procedures within the aseptic area. For documentation use Attachment No. 1700.100(A). For template validation/ report refer to Attachment No. 1700.100(B). 

All personnel scheduled to work in the aseptic area must participate in at least one media fill. 

Following the dry-heat cycle, aseptically transfer the units containing endotoxin to an aseptic area for extraction procedures, sampling, and conducting the limulus amebocyte lysate (LAL) test. 

It is easily understood that if the aseptic operation is performed in a separated small space from which personnel have been completely excluded, the necessity for room classification based on particulate and environmental microbiological monitoring requirements may be significantly reduced. In other words, critical operations in an aseptic area should be performed in the smallest space, and intervention by personnel should be minimized by indirect means through the use of protective glove ports and/or half suits. Application of these methods can minimize the chance of contamination. Following are such systems currently in place to reduce the contamination rate in aseptic processing. 

Where firms have introduced unidirectional air systems in preparations and compounding areas for particle control, there is often the temptation to expect these areas to meet the same microbial limits that these locations might attain in the aseptic core. This temptation should be resisted to avoid unnecessary sampling and deviations associated with expecting these environs to meet the conditions of aseptic areas where sanitization frequency, background environment, and most importantly personnel gowning are far superior to that found in the less clean locales [33]. 

Prior to the start of any production activity, materials and components must be transferred from a warehouse environment into a classified environment. For most items this will necessitate removal from boxes or cartons, transfer to a nonwooden pallet, and passage through an air lock which serves as the transfer system between the controlled and uncontrolled environments. Often components are contained within plastic bags within a box or carton, and in some cases there are multiple bag layers to facilitate disinfection and passage through air locks into different zones of operation within the aseptic area. The firm may utilize an external disinfection of the materials in conjunction with this transfer. The concern is for minimization of particles and bioburden on these as yet unprocessed items in order to protect the controlled environment. 

There are items that must be transferred into the aseptic processing area that cannot be treated within a sterilizer/oven. These include portable tanks, electronic equipment, and containers of sterile materials (ready-to-use items, sterile powders, environmental monitoring media, etc.). Air locks, pass-throughs, and similar designs are employed in which the exterior surfaces of the items are disinfected. The disinfection process may be completed by personnel outside and/or inside the aseptic area depending upon the specifics of the design. 

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