Abstract

The administration of parenteral drugs is associated with an expectation for sterility of the materials involved. In actuality, the real desire is for safety, as we also expect these products to be properly formulated, without toxic components, and essentially free of particles. It should be acknowledged that proving the absence of anything absolutely is a Sisyphean task, one that is bound to go unsatisfied. Sterility demonstration is a comparable activity, and it can never be proven. Absolute sterility, which means complete absence of any microorganism, must be understood as an unattainable goal. No amount of environmental monitoring, sterility testing, or media fill execution can hope to demonstrate that any container is, in fact, sterile. The methods and the metrics conventionally utilized such as action/alert levels, sampling of intervention related containers, and restrictive acceptance criteria cannot provide direct evidence of sterility. There may have been a time when the means for aseptic processing were so limited that the assessment tools could provide some measure of confidence. The sterility test was introduced in the 1930’s long before high-efficiency particulate air (HEPA) filters, sterile gloves, and validation of sterilization, and it may have served some useful purpose. In today’s world of automation, restricted access barrier system (RABS), and isolators, the detection of any contamination has become a rare occurrence, and while the performance expectations have become increasing restrictive, they are no longer adequate for the control of the modern-day aseptic processing. The everyday performance of most modern aseptic filling operations, even those relying on gowned operators is such that predominant assessment tools are no longer adequate.