Aseptic processing activity

In virtually all aseptic processing activities, operator interventions are required to complete the process. Understanding the types of interventions required and how they are incorporated into the validation program is essential to protocol development. 

Aseptic Assembly. The first interventions performed are those that prepare the equipment for the aseptic process. This entails the removal of sterilized materials and equipment items from the autoclave and transfer to the location where the aseptic processing activities will be performed. This is ordinarily followed by the assembly/preparation of the equipment for the process. Aseptic assembly in which sterilized parts are removed from protective materials, installed and adjusted in preparation for the aseptic process are perhaps the most potentially invasive of all of the activities which must be performed. The operator must be meticulous in their execution of these tasks to prevent the inadvertent contamination of product contact surfaces. Strict adherence to the principles of aseptic technique described earlier is essential. These interventions are a necessary part of every aseptic activity, and it is common to identify the first containers filled as they may be more indicative of potential problems with the aseptic assembly. For this reason, the validation program should include process simulations that include containers filled immediately after the set-up of the equipment. 

Table 1 summarizes the environmental control characteristics for the aseptic processing complex. The areas classihcations are based on activity... 

The manufacture of sterile products is universally acknowledged to be the most difficult of all pharmaceutical production activities to execute. When these products are manufactured using aseptic processing, poorly controlled processes can expose the patient to an unacceptable level of contamination. In rare instances contaminated products can lead to microbial infection resulting from products intended to hasten the patient s recovery. The production of sterile products requires fastidious design, operation, and maintenance of facilities and equipment. It also requires attention to detail in process development and validation to ensure success. This chapter will review the salient elements of sterile manufacturing necessary to provide acceptable levels of risk regarding sterility assurance. 

Aseptic processing in the pharmaceutical industry is almost entirely dependent upon the proficiency of the personnel assigned to this most critical of all activities. The operators must be able to consistently aseptically transfer sterile equipment and materials in a manner that avoids contamination of those materials [1]. This is no mean feat given the contamination continuously released by personnel and the prevailing need for personnel for execution of the process activities. 

Routine Interventions. The execution of the aseptic process ordinarily requires a number of repetitive activities such as product and component replenishment, weight checking, operator breaks, and environmental monitoring. Each of these is a required part of the process, and cannot be eliminated. They should be included in the process simulation and performed... 

As pharmaceutical products contain increasingly potent active constituents and as health, safety, and environmental protection issues increase in importance, isolators have been developed in many shapes and forms to permit thesafe weighing and subdivision of highly active compounds. The most sophisticated applications, such as the subdivision of bulk sterile active compounds, require that the isolator maintain aseptic processing conditions internally at the same time as satisfying the safety requirements. Fig. 2 shows an isolator device designed to allow a keg of potent... 

The concepts of aseptic processing for pharmachemical processing to assure the sterility of the product is no different than classical parental drug production. A sterile facility has a number of fundamental characteristics the first is complete separation and isolation from all other operations. This dictates that people, materials, and even the ventilation be independent of all other activities at the site. First, the HVAC system must be totally independent of the main system, it providing only filtered air, generally through HEPA filters that remove essentially all particulate matter larger than 0.21 pm. 

Preparation of an eye cream (see Sect. 10.6.3) includes the preparation and sterilisation of the aqueous phase in a similar manner to eye drops. The aqueous phase is then incorporated into the sterile ointment base by aseptic processing. Using an oUy solution of the active ingredient instead results in an eye ointment. 

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