Abstract
Aseptic processing is a widely used methodology in the health care industry for the preparation of sterile materials. The term aseptic processing as it is applied in the pharmaceutical industry refers to the assembly of sterilized components and product in a specialized clean environment. The clean environment may be a conventional human scale classified clean rooms or an environment engineered to further reduce the likelihood of contamination by reducing (or as much as is possible eliminating) direct human contact with the product and components being assembled “aseptically.” The idea of sterile products manufactured aseptically is inherently contradictory, a demonstrably sterile product cannot be produced aseptically using even the most advanced technology available today. Nevertheless, on any given day millions of putatively sterile dosage form units are produced using aseptic techniques that in the literal sense are inadequate to achieve sterility. A sterile product is one that is free from all living organisms, whether in a vegetative or spore state. This is an absolute condition, something cannot be partially or nearly sterile, the presence of a single viable organism represents a failure of the product, and the systems (environment, equipment, and procedures) used to produce it. Asepsis, that state in which all aseptically filled sterile products are manufactured, cannot be established as “sterile.” Asepsis is commonly defined as a condition in which living pathogenic organisms are absent.
Putting aside the classical definitions, one must consider the real difficulty in establishing an aseptic environment, let alone a sterile one. The practitioner is left with a insurmountable task, to somehow create an environment free of any organisms, but also one (with the exception of isolators) in which personnel must be present to perform critical functions. The problem is further compounded if it recalled that personnel are considered the single greatest source of microbial contamination in aseptic processing. Recent experiments have shown that personnel clothed in new, sterile clean room garments slough viable contamination at a rate of roughly one viable particulate to 10,000 non-viable particles. During slow deliberate movements with the best possible clothing, operators will slough particulate and viable organisms. Therefore, the probability of human borne microbial contamination being released in the conventional clean room is one over the course of any reasonably long operational shift. With this fact in mind, how then is one to accomplish a truly sterile or even aseptic environment? Especially when we must consider that many organisms that are normally non-pathogenic, can under certain circumstances become opportunistically pathogenic. Among those circumstances are a debilitated condition of general health in the patient, or, as is increasingly common, immunological insufficiency due to age or pre-existing condition.
Other than the obvious considerations of proper facility design, sterilization validation, and sanitization procedures (all of which are discussed elsewhere in this encyclopedia), the focus of attention must be on the personnel and the activities which they must perform. These actions are broadly termed, aseptic technique, and like any other human activity they can be accomplished in a variety of ways. In order to better understand aseptic technique, some general guidance and examples of good and bad technique can be used to delineate what should and should not be permitted.
The fundamental concept behind every aseptic processing activity is that non-sterile objects must never touch sterile objects. This is often accomplished by the establishment of a “sterile field” in which the core activities are performed. All of the surfaces of the gowned human operator must be always considered non-sterile. Non-sterile objects including the operators hands must never be placed between the source of the air and a sterile object. The operators' hands and arms must always be kept at a level beneath that of open product containers. Sterile components should under no circumstances be touched directly with gloved hands, a sterilized tool should always used for this purpose. Since gloved hands and arms will enter the sterile field they must never touch walls, floors, doors, etc. Strenuous lifting and moving of tanks, trolleys, etc. must not be done by operators assigned to work within or near the sterile field, because the more strenuous the activity the higher the level of particle generation, and at least some of the particulate released by the operator will surely by viable microorganisms.
Some of the techniques to avoid include: reaching over exposed sterile objects to make adjustments beyond them; correcting a stopper feed problem with a gloved hand; touching face, eye shield, or any other non-sterile object with gloves; taking an air sample directly over open containers; continuously standing inside flexible partitions that mark the boundary of the sterile field; breaking up clumps of components with gloved hands. Each of these actions exposes the sterile objects to undue risk of contamination from the personnel. Certainly there are more ways to contaminate the “sterile field” than we can imagine. For this reason, the procedures used in and around the “sterile field” must be carefully defined and followed closely by all personnel. These procedures should follow the general principles outlined above and are evaluated in a media fill simulation and performed in an identical fashion during aseptic processing. It is beneficial to define in writing how each procedure is to be performed and train the operators in these exact procedures. View Section:
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Putting aside the classical definitions, one must consider the real difficulty in establishing an aseptic environment, let alone a sterile one. The practitioner is left with a insurmountable task, to somehow create an environment free of any organisms, but also one (with the exception of isolators) in which personnel must be present to perform critical functions. The problem is further compounded if it recalled that personnel are considered the single greatest source of microbial contamination in aseptic processing. Recent experiments have shown that personnel clothed in new, sterile clean room garments slough viable contamination at a rate of roughly one viable particulate to 10,000 non-viable particles. During slow deliberate movements with the best possible clothing, operators will slough particulate and viable organisms. Therefore, the probability of human borne microbial contamination being released in the conventional clean room is one over the course of any reasonably long operational shift. With this fact in mind, how then is one to accomplish a truly sterile or even aseptic environment? Especially when we must consider that many organisms that are normally non-pathogenic, can under certain circumstances become opportunistically pathogenic. Among those circumstances are a debilitated condition of general health in the patient, or, as is increasingly common, immunological insufficiency due to age or pre-existing condition.
Other than the obvious considerations of proper facility design, sterilization validation, and sanitization procedures (all of which are discussed elsewhere in this encyclopedia), the focus of attention must be on the personnel and the activities which they must perform. These actions are broadly termed, aseptic technique, and like any other human activity they can be accomplished in a variety of ways. In order to better understand aseptic technique, some general guidance and examples of good and bad technique can be used to delineate what should and should not be permitted.
The fundamental concept behind every aseptic processing activity is that non-sterile objects must never touch sterile objects. This is often accomplished by the establishment of a “sterile field” in which the core activities are performed. All of the surfaces of the gowned human operator must be always considered non-sterile. Non-sterile objects including the operators hands must never be placed between the source of the air and a sterile object. The operators' hands and arms must always be kept at a level beneath that of open product containers. Sterile components should under no circumstances be touched directly with gloved hands, a sterilized tool should always used for this purpose. Since gloved hands and arms will enter the sterile field they must never touch walls, floors, doors, etc. Strenuous lifting and moving of tanks, trolleys, etc. must not be done by operators assigned to work within or near the sterile field, because the more strenuous the activity the higher the level of particle generation, and at least some of the particulate released by the operator will surely by viable microorganisms.
Some of the techniques to avoid include: reaching over exposed sterile objects to make adjustments beyond them; correcting a stopper feed problem with a gloved hand; touching face, eye shield, or any other non-sterile object with gloves; taking an air sample directly over open containers; continuously standing inside flexible partitions that mark the boundary of the sterile field; breaking up clumps of components with gloved hands. Each of these actions exposes the sterile objects to undue risk of contamination from the personnel. Certainly there are more ways to contaminate the “sterile field” than we can imagine. For this reason, the procedures used in and around the “sterile field” must be carefully defined and followed closely by all personnel. These procedures should follow the general principles outlined above and are evaluated in a media fill simulation and performed in an identical fashion during aseptic processing. It is beneficial to define in writing how each procedure is to be performed and train the operators in these exact procedures. View Section:
