Sterility assurance aseptic filling process

SALs obtained from aseptic filling processes have been modelled from theoretical considerations and are probably as good as 10 5 or better. The simulation trial is an insensitive tool that cannot within reasonable experimental dimensions confirm SALs better than 10. It is not to be assumed that an aseptic filling process is under control merely because a series of satisfactory simulation trials with less than one contaminated item in one thousand have been obtained. Adequate assurance of sterility can only be obtained by ensuring that all possible precautions against contamination are in place and that each one is performing in the manner intended. 

Nonaqueous liquids, semi-solids, and dry powders dry heat at 160°C/120 minutes then dry heat under alternative conditions of time and temperature to achieve a sterility assurance level of 10 6 then an alternative to dry heat, e.g., ionizing radiation with a minimum absorbed dose of not less than 25 kGy then a validated alternative irradiation dose (according to ISO 11137) then aseptic filtration and aseptic processing and then the use of presterilized components and aseptic compounding or filling... 

There is no appropriate defined sterility confidence level which can be translated directly into acceptance criteria for broth fill contamination for BFS processes. The most commonly recognized acceptance criterion is a sterility assurance level (SAL) of 10 although modem aseptic filling techniques such as BFS can achieve a higher SAL. This should be reflected by broth fill results and acceptance criteria for this advanced technology. 

This raises a second question of how much confidence must one have to claim sterility The answer to this question, for terminally sterilized products, is that there must be no more than one chance in a million that viable contaminants survive in any one unit. This is called a sterility assurance level (SAL) of 10 . The answer for aseptically filled products is that the SAL must be as close to 10 as is technically possible, with the proviso that thedegree of protection given to the process must afford no more than one chance in a thousand of any one unit becoming contaminated. This is called a contamination rate of 10 , and unlike the SAL it relates only to the protection given to the process and not to the potential for contaminants surviving or proliferating in actual products. ... 

It is not possible to measure levels of sterility assurance (SALs) obtained with commercial systems of achieving sterility. The expected assurance of sterility is too high to be measurable by techniques that rely on detection of nonsterility in sampled items. With processes that involve microbiological inactivation, measurements of subprocess inactivation can be extrapolated to estimate process SALs. This not possible for aseptic filling. 

For critical processes such as sterilisation or aseptic manufacture, even for the earliest human studies, the regulatory authorities will expect the process to be qualified, to attain a high degree of assurance that the end-product will be sterile. If drug availability is an issue, the aseptic processing of sterile products may be validated using media fills to simulate the process. 

Products can be manufactured as sterile by different methods known as aseptic processing and terminal sterilization. Aseptic processing involves passing the ophthalmic solution through a 0.2 pm filter in order to rid the solution of all bacteria. The solution is then filled into sterile ophthalmic containers under sterile conditions. This assures a sterile product. 

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