PRE-USE INTEGRITY TESTING
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
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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.
CONCLUSIONS AND RECOMMENDATIONS
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,
klankeri@amgen.com
REFERENCES
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.
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