Closed aseptic procedure

Open the bottom tap, and gently draw into the syringe as much of the saline as possible. Close the tap, remove the syringe, and discard the saline aseptically If necessary, replace the syringe, and repeat this procedure until the bioreactor is as empty as possible. 

Low-fat spreads with 40% fat content and containing protein usually have a shelf life of 8-10 weeks and water-based low-fat spreads of about 4 months based on storage at temperatures below 10°C (50°F) (90) (see Section 5.1). Very low fat spreads with fat contents below 20% and with a water continuous emulsion character require low pH, ultra high temperature processing, and possibly aseptic filling procedures to allow closed shelf lives comparable to conventional low-fat spreads (91). 

A fermentation department attempts to operate its culture lab, seed and main fermenters at 100% aseptic conditions. Good performance is when contamination occurs in 1 % or less of the batches. Naturally, any occurrence of such problems raises the cost of production, and the worst situation is when production is brought to a stop due to contamination. First, it is necessary to have standard operating procedures which are rigidly followed. Second, it is important to have well-trained operators who report back all problems, errors and irregularities, and third, the supervisors and engineer must listen to the operators, and react or explain the information, as the case may be, to close the communication loop and motivate the operators. 

Sterilization in place—Closed systems such as process vessels, dryers, centrifuges, isolators, and other items should be subjected to a validated sterilization procedure, which assures that all internal surfaces have been rendered free of microorganisms. Sterilization-in-place (SIP) procedures reduce the number of aseptic manipulations necessary to ready the equipment for use in the aseptic production processes and as such are considered preferable to aseptic assembly of systems from individually sterilized components (25). The SIP procedure should allow the system to maintain sterility until ready for use without aseptic manipulations. Sterilization-in-place procedures could employ steam, gas, dry heat, radiation, chemical agents, or other validateable sterilization procedure. 

Further risks of the closing procedure are described in the Section 15.2.2. In case of approaches toward ultraclean or aseptic filling, the closures may be disinfected before being transferred to the closing machine. 

The reconstitution of parenteral medicines in the strict sense as well in the extended sense (see Sect. 1.2.1) is very frequently performed in hospital pharmacies. The right performance of this process requires extensive precautions on procedures, premises, validation and control. However these differ considerably, due to working with closed systems, from the generally accepted precautions for aseptic processing from raw materials. The use of the term aseptic handling therefore was felt justified. 

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