Pharmacy Courses

Sterilization Processes and Sterility Assurance

Microorganisms represent a potential threat to human health in various settings. The presence of some microorganisms in foods, pharmaceuticals and even the environment can cause illness and even death. 

In the pharmaceutical and medical device industries, sterile products are produced using two primary methods: terminal sterilization or aseptic processing. Terminal sterilization provides for the clean assembly of the product as a final package, which is then subjected to a lethal process. Aseptic processing rearranges the steps: the product components are individually sterilized and then assembled in an extremely clean environment.

In addition to the therapeutic goal of all medical products there is a safety requirement; a major component of which in the context of sterile pharmaceuticals and medical devices is “sterility”. Sterility, which has been defined as the absence of life (or inability to reproduce), is an absolute concept.

The determination of a suitable process (cycle) for sterilization must first consider the expected effect of the process on the materials. Certainly there is no value in defining a process that, while effective in destruction of microorganisms, has substantial adverse quality and/or reliability impact on the items being processed. A balance must often be struck between an extreme process that provides substantial microbial kill and less aggressive conditions that preserve the material’s essential quality attributes. With the exception of stainless steel and glass (and even these can be impacted in some instances), the material effects have to be taken into account in cycle development. If the adverse material effects are excessive, a different sterilization process should be selected.

Qualification of sterilization equipment and its associated utility systems must be performed prior to beginning performance qualification. The reproducibility of sterilization cycles is largely dependent on the controls, utilities, and mechanics of the sterilizer and its ability to consistently operate according to expectations. The essential elements of the sterilizer and its supply services should be verified as properly installed and set to their specifications as part of the initial qualification and is often termed the installation qualification. 

The most widely used sterilization medium is moist heat, which is utilized for in-process sterilization of stainless steel, glass, and elastomeric materials (Dry Goods Sterilization); liquids in sealed containers (Liquid Good Sterilization); and for sterilization of large processing systems (Sterilization-in-Place). 

Sterilization processes using moist heat entail the exposure of microorganisms to liquid water at elevated temperatures, which is believed to irreversibly denature cell wall proteins. In the absence of liquid water, the destructive process occurs much more slowly (see dry heat sterilization below). Steam sterilization is thus best accomplished in the presence of saturation conditions where both gas (steam) and liquid (condensate) are present.

A seemingly similar process is used for the sterilization of containers filled with aqueous liquids. The outward similarity with parts sterilization is actually misleading. In these processes sterilization of the fluid is accomplished by heating of the container exterior, conduction through the container, and heating of the contents. 

Depyrogenation tunnels are continuous processing units used for use for primary glass containers, typically installed following a washing operation and providing in-feed directly to an aseptic filling operation. An advantage of the continuous process is that each container sees essentially the same process. Units using wide feed belts do have some variation across the belt, but this is small compared to the typically wider temperature distribution experience with batch ovens.