Throughout the industry, there are questions regarding when to integrity test filters in the purification and buffer preparation areas. This includes liquid filters as well as vent and air filters. The requirement to warrant a filter integrity test (FIT) is based on compliance with the validated claim of microbial retention and criticality of the filter performance. Filters with no validated retention claim must be evaluated for integrity testing based on the level of risk to product quality and business risk. An approach for determining risk based on filter criticality and location was developed and adopted in a high-volume biopharmaceutical manufacturing plant. The results showed that certain filters might present a high risk to product quality after failure and warranted integrity testing.
In an ideal world, we would like to integrity test all membrane filters after use, and thereby ensure that each product pool has met proper sanitary standards. But, is this practical or necessary? FIT requires valuable time and resources. If all filters are integrity tested, costs can add up quickly. On average, integrity testing of one filter housing takes two operators approximately two hours. Assuming $75 per hour for an operator's time and about 40 housings for testing (liquid and vent), an average batch costs $6,000 for FIT. A process running once per week would incur $312,000 for resources or the equivalent of two full-time employees for integrity testing alone (cost information is for illustration only). Filters that have been validated for viral or microbial retention require an integrity test. However, those with no validated retention claim may or may not need integrity testing based on the business risk associated with the processing step.
USING FMEA TO ASSESS RISK
A risk-based approach to determine when a filter must be integrity tested can be performed by conducting a failure mode and effects analysis (FMEA). An FMEA may include application categories such as tank-vent filtration, buffer filtration, pre-drug substance (DS) filtration, and DS filtration. Each category is assigned a risk number based on severity, frequency (occurrence), and detectability of filter failure. The combined score from the analysis for each system can be used to determine the relative priority level for performing a FIT.