Operations aseptic handling

Raw materials Containers Human resources Occupational safety and health Premises Equipment Basic operations Sterilisation methods Aseptic handling Quality requirements and analysis... 

I. Extemporaneous sterile and non-sterile preparations Examples of this kind of preparations are Aseptic handling, i.e. uncomplicated operations with sterile medicines in closed containers after which they get a very short usage period, reconstitution of sterile and non-sterile authorised medicines and extemporaneous non-sterile preparations from raw materials. 

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. 

A safety cabinet is a laminar down flow cabinet, which is constructed specifically for protection of both the sterile product and the operator. It is frequently used in (hospital) pharmacies for aseptic preparation (when products are not fully closed) and for aseptic handling of class 4 or 5 substances (see Sects. 26.5.2 and 26.8). Laminar down flow has the advantage compared to cross flow that the operator does not feel the continuous flow in his direction. Other names for a safety cabinet are biosafety cabinet, biosafety bench, biohazard bench, biohazard cabinet, biological safety cabinet etc. 

Within pharmacy, aseptic handling is carried out in a controlled environment by trained staff. In any hospital, however, aseptic handling also takes place in clinical areas such as wards and operating theatres [4, 5]. This chapter only discusses aseptic handling in pharmacy. Aseptic handling in clinical areas is described in Sect. 13.8. 

A relevant therapeutic group of active substances, handled aseptically, are parenteral antineoplastics. Many are classified as very toxic for the operator, mainly because of carcinogenicity and reprotoxicity [17], see also Sect. 26.3.3. Therefore, if antineoplastics are involved in aseptic handling, requirements are not only to protect the product against contamination of micro-organisms, but also to protect the operator and the environment from the product. The first measure however is a working procedure to minimise exposure to antineoplastics. This involves... 

Although aseptic handling differs significantly from aseptic processing, the principles for microbiological controls, like monitoring and process validation, are the same. As most aseptic work is done manually, the aseptic technique of the operators has to be checked with additional microbiological controls. 

Addition, deletion, or substitution of sterilization steps or procedures for handling sterile materials in an aseptic processing operation. 

Ordinarily, present within the preparation area are localized areas of ISO 5 unidirectional airflow (Class 100) utilized to protect washed components prior to sterilization and/or depyrogenation. These areas are not aseptic and should not be subjected to the more rigorous microbial expectations of aseptic processing. They are designed to reduce/eliminate the potential for particle contamination of unwrapped washed materials. Operators accessing these protective zones wear gloves at all times when handling materials. 

A natural extension from the simple handling of potent compounds is to use barrier technology to provide highly secure mechanisms for processing and more complex manipulation of powders. Isolators of this type and configuration have the objectives of operator and environmental protection as well as the provision of a secure clean and aseptic environment around the process. 

Fig. 5 Facility monitoring and control room (A) and operator interface screen with aseptic area differential pressure readings (B). Features that can be monitored via touch screen from the control room include water status, utility status, outside conditions, air-handling units, and process areas in non-sterile and sterile locations.

When working with in vitro test systems, the operators should make use of good aseptic techniques to avoid any contamination. This includes bacterial/fungi contamination, but also mycoplasma contamination, preferably detected with advanced techniques (such as RT-PCR). Quarantine and handling under strict precautions all incoming cell lines until testing concludes the absence of mycoplasma should be a standard practice in each test facility. Alternatively cell lines can be purchased from cell banks, which certify that the in vitro test systems are mycoplasma-free prior to distribution. 

Staff carrying out special operations, such as working in an aseptic zone or handling hazardous materials, must be given appropriate training. 

Clean and aseptic area clothing should be laundered or cleaned and thereafter handled in such a way that it does not gather contaminants which can later be shed. Separate laundry facilities for such clothing are desirable. It should be noted that some methods of sterilisation may damage fibres and reduce effective garments. Washing and sterilisation operation should follow a dearly displayed written procedure. 

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