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10 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING EBOOK 2021 P h a r mTe c h . c o m Manufacturing outcomes. In addition, some have raised concerns about the level of control that filter manufactur- ers and users have over their respective processes, as a way to justify concern about the risk of filter defects that could result in masking. To address this issue, the consortium working group set out to perform a set of unbiased QRM- based assessments to assess the risks associated with the manufacture, handling, and use of steril- izing filters; determine the effectiveness of controls addressing those risks; and provide guidance for how these assessments could be used by industry to evaluate their processes. The objective of the risk assessments was to define a robust QRM approach that could be employed by filter manufacturers and users to determine risks of sterile filter failure and define a control strategy to provide improve filter integrity and sterility assur- ance, including both preventive and detection (e.g., PUPSIT) controls as appropriate, based on scientific understanding and associated risk. This work used a systematic approach to assess the end-to-end risk to the sterile filtration process in several generic process examples: • Identifying existing and potential controls to prevent filter failure. • Assessing mechanisms for detecting failures that cannot be prevented (including, but not limited to, PUPSIT). • Providing a QRM framework for two core user groups: o Filter manufacturers, to help improve as- surance of filter integrity by defining the risks associated with the design, production, storage, handling, and shipping of steriliz- ing filters and associated preventive and detection controls o Biopharmaceutical manufacturers, to help improve assurance of the sterile filtration process by defining risks associated with the receipt, handling, storage, installation, and use of sterilizing filters and associated preventive and detection controls, includ- ing but not limited to PUPSIT. • The QRM approach was designed to: o Employ the best available data, information, and scientific knowledge in the identifica- tion and estimation of risk o Preserve the assessment's objectivity o Enable a holistic review of the sterile filtra- tion value stream o Be objective as to the outcome of the QRM effort o Enable the development of an effective con- trol strategy, including both preventive and detection controls, as appropriate. The risk assessment involved close collabora- tion between filter manufacturers and end users. It determined not only the robust quality control systems implemented by the filter manufacturers, but also showed potential risks at end-user sites. Results of this work strengthened the support for both the filter supplier and the end user. Fault tree analysis With failure modes identified, the fault tree analy- sis (FTA) risk assessment could then be used. This approach is designed to help filter manufacturers and users determine, implement, and evaluate con- trols to reduce the risk of filter f laws that could produce binding conditions. Data will continue to be incorporated into the filter use FTA, as needed, to ensure that all risks and their relative magnitudes are adequately ad-