To FIT or Not to FIT, That is the Question - A risk-based approach for real-world situations. - BioPharm International


To FIT or Not to FIT, That is the Question
A risk-based approach for real-world situations.

BioPharm International
Volume 22, Issue 11


The decision to perform a pre-use integrity test on filters is based on risk associated with the processing step. This is a business risk rather than a compliance risk. There currently are no regulatory requirements for pre-use integrity testing. In some cases, however, it is recommended to perform a pre-use integrity test to reduce risk and build quality into the process. A pre-use test that identifies a filter breach or an installation issue may help avoid costly re-processing or discard of a valuable drug substance intermediate after post-use integrity failure (e.g., in the case of virus filtration). Pre-use integrity test recommendations must be evaluated on a case-by-case basis to determine if the business risks are high enough to adopt them. If there are resource constraints with performing a pre-use test and the risk is evaluated to be low, a pre-use test may safely be omitted.

Vent filters are one class of filters where a pre-use test may be valuable. Performing a pre-use integrity test will confirm proper installation of the filter. When the filter is left in place and confirmed integral, vendor data (e.g., steam hours) can be used to justify multiple uses if business risk is assessed to be low. Significant cost savings from resource and filter costs could be realized.

Figure 1. A decision tree for determining whether or not a filter integrity test (FIT) is warranted
Figure 1 shows a decision tree for determining whether or not a FIT is warranted. It can be used to assess the necessity of pre- and post-use FIT based on regulatory and quality risk as well as business risk.


A post-use integrity test is required for filters that are validated for microbial or viral retention. However, filters with no validated claim of retention must be evaluated for integrity testing based on risk. Conducting an FMEA is a good first step toward a risk-based approach for determining the need for a FIT. If needed, filters can be further evaluated based on filtration criticality, filter (or vent) location, and the processing step where the filter is being used. If FITs are limited to only those steps, which are validated and those potentially posing high risk to product quality or high business risk, time and resource needs can be dramatically reduced. With the biopharmaceutical manufacturing industry focusing on operational excellence and cost optimization, decreasing nonvalue-added activities such as low-risk filter integrity testing is highly desirable.

Katherine Chaloupka is a senior engineer, Naveen Pathak is a principal engineer, and Sourav Kundu is the director of process engineering, all in the process development department at Amgen, Inc., West Greenwich, RI, 401.392.4391,


1. US Food and Drug Administration. Department of Health and Human Services. Guidance for Industry. Pharmaceutical cGMPs. Sterile drug products produced by aseptic processing—current good manufacturing practice. Rockville, MD; 2004 Sept.


Find more articles on filtration at

  • Letter to the Editor Re: "Diminutive Bacteria Useful for 0.2-μm Filter Studies, FDA's Brorson Says"; October 2009


  • The Proper Use of 47-mm Flat Disc Filters in Filter Sizing Studies; September 2009

Maik W. Jornitz, Theodore H. Meltzer, Wayne Garafola

  • Considerations for Scaling-up Depth Filtration of Harvested Cell Culture Fluid; March 2009

Herb Lutz, Mark Blanchard, Ian Abbott, Ananth Parampalli, George Setiabudi, Vijay Chiruvolu, Megumi Noguchi

  • Improving Tangential Flow Filtration Yield; July 2008

Carlos A. Dominguez, Esteban Rivera, Carlos Escobar, James Weidner

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