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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING EBOOK 2021 11 dressed. These data will help inform risk identi- fication and analysis for those instances in which specific detection controls, such as PUPSIT, are necessary for inclusion in the overall filtration con- trol strategy. Ultimately it was found that a typical unit operation or process step entailed an average of 19 individual faults that could ultimately lead to the failure of a filter to sterilize product. Each fault had an average of four redundant risk con- trols (not including sterility testing of sterilized drug product) that served, either to prevent the fault from occurring, or to enable the detection of the fault with sufficient time to correct it before patient safety could be jeopardized. Points-to-consider document The objective of this best practices document was to incorporate practical information from a PUPSIT design and implementation risk assess- ment to offer guidance on decision making crite- ria in specific situations. It could also be used to provide guidance on the design and implemen- tation of PUPSIT, if companies chose to employ this control measure. The document looks at all the requirements for assessing the need for PUPSIT implementation, emphasizing the fact that the method's design and implementation are complex, and not as risk free as users once thought. The document serves as a tool designed to help users make appropriate decisions when an implementation is needed, and to specify which engineering and testing activities require attention. Among the key sections of the document are the integration of PUPSIT into manufacturing opera- tions and the execution of PUPSIT inside isolators and restricted access barrier systems (RABS), as well as discussions of redundant filtration, venting, back pressure and temperature considerations, and change-control issues. In addition, two case stud- ies are provided showing how PUPSIT should be implemented in a hard-piped, highly automated system and in a single-use manual system. Conclusion Debate and discussion over the use of PUPSIT may continue, but the SFQRM's efforts have replaced anecdotes and hearsay with scientific and data- based evidence. Results show that, as with most pharmaceutical processes, solid risk assessments are necessary instead of generic enforcement. In the end, the user must balance any risks con- nected with PUPSIT (e.g., higher filter system complexity and the potential secondary contami- nation resulting from manipulating the sterile fil- trate side of the filter) with the need to ensure that test results will not ref lect masking, for operations that involve a f luid with a high potential to foul and block the filter. Determining whether the risk of implementing PUPSIT is higher than the risk of masking can be accomplished by using specific tests, e.g., during filterability trials, to size the filter for the specific application and/or product bacte- ria challenge test. Process validation and process control are essential. The consortium has published its findings in the PDA Journal and as a PDA Points-to-Consider docu- ment (12–15). Webinars are also being offered on this In the end, the user must balance any risks connected with PUPSIT with the need to ensure that test results will not reflect masking.