Combined Pre- and Post-filtration Testing—Formulation and Fill
Product safety concerns and overall product value are highest during final formulation and dose filling. To address product
quality and reduce waste, pre- and post-filtration integrity testing may be combined during final production stages (Figure
3). To conduct pre-filtration testing, the filter assembly is connected to the sterile hold tank using an aseptic connector.
After it is connected, the filter is wetted using product formulation instead of flush solution to prevent dilution of the
active drug. At this point, pre-filtration testing can be performed.
Figure 3. Combined pre- and post-filtration integrity testing set up
After filter integrity is confirmed, the line to the flush bag is clamped off and the filter assembly is connected to the
vial filling system using an SIP connection, ensuring final product sterility. The flow clamp is then opened for filtration
to begin. After filtration is complete, the filter can be removed from the assembly using aseptic disconnects to maintain
the sterility of the filter until post-filtration integrity testing can be performed. This can be an automated non-destructive
or destructive test such as a bacterial retention test. By conducting both pre- and post-filter integrity tests, operators
are assured that product purity has been maintained in the final drug formulation and is ready for release.
Using single-use systems in filter integrity testing is a cost-effective solution to ensure product purity, increase process
flexibility, and reduce contamination risk. The examples above illustrate the benefits of incorporating appropriate single-use
connection technologies as part of an overall filter integrity testing strategy. As manufacturers seek to maximize every step
in the bioprocess, the integration of single-use components into filter integrity testing protocols will continue to increase.
John Boehm is the bioprocess business unit manager at Colder Products Company, St. Paul, MN, 651.645.0091 firstname.lastname@example.org