Credit to Ingram Publishing/the Agency Collection/Getty Images
|
Increased regulatory expectations and the need to mitigate risk have popularised the use of redundant filtration for bulk
and final fill operations. Single-use redundant filtration (SURF) assemblies are an efficient and flexible alternative to
stainless steel systems because they eliminate clean in place (CIP), sterilisation steps and the associated validation protocols.
Preparation time can also be significantly reduced when using single-use assemblies because of their pre-sterilised format
and the ease with which they can be handled. Redundant filtration operations in multi-product facilities can be performed
without spending the extra validation time that is often required for non-disposable systems.
This article identifies a suitable design for redundant filtration operations using single-use technology and standardised
assembly components. The design was finalised with input from a global technical and quality team with consideration given
to international regulatory requirements. The article also demonstrates the capability of the assembly to withstand the high
pressure that is used for integrity testing and drying. Pre-use integrity testing was performed on both filters. Using hydrophilic/hydrophobic
filters on the assembly outlet eliminated flush volume limitations caused by catch bag size. Assembly specifications, such
as leachables and extractables, hold up volume and flushing requirements, were established for a single-use assembly.
Meeting regulatory expectations
As defined in PDA Technical Report 26, redundant filtration is a "type of serial filtration in which a second sterilising-grade
filter is used as a backup in the event of an integrity failure of the primary sterilising filter." The pore size of the sterilising-grade
filters may be the same or tighter than the primary filter (1). Other regulatory bodies (e.g., FDA, EMA and SFDA) have also
issued their own guidelines for sterile filtration. According to the FDA's aseptic processing guidelines published in 2004,
it is recommended that redundant filtration should be considered in many cases where liquid is sterilised by filtration (2).
The EMA's 2008 GMP guidelines state that because of potential risks of sterilisation by filtration, a second filtration step
as close to the filling point as possible is advisable (3).
Designing a redundant filtration system that meets regulations and recommendations is challenging. For stainless steel systems,
the EMA recommends that integrity testing should be performed on sterile filters before use. To do this, filters must be fully
wetted without breaching the sterility on the downstream side of the assembly. Many conventional stainless steel facilities
employ a "catch can" with a sterile vent filter to collect the initial flush liquid from the wetting step. Prior to use, additional
time is required to sterilise, maintain and store the catch can. In addition, use of a catch can constrains the total flush
volume that can be used if the filters need to be rewetted (e.g., in a repeated filter integrity test).
Disposable or single-use redundant filtration (SURF) assemblies offer a flexible solution for this relatively complex operation
(4). These assemblies can be presterilised by the supplier using gamma irradiation and there is no need for cleaning after
use because assemblies are self-contained and entirely disposable.
