Sterilizing filtration is now commonplace in pharmaceutical manufacturing and is used in order to prevent microbial contamination from negatively impacting drug quality and, more importantly, to ensure patient safety. A wide range of products and formats are available from multiple vendors that are appropriate for a diverse range of applications.
In extremely simple terms, as described in PDA Technical Report 26, sterilizing filtration is the process of removing microorganisms (not viruses) from a fluid stream without adversely affecting product quality.
The specific technical requirements of sterilizing filtration have evolved over time, ultimately leading to the development of the ASTM F838 standard test method for 0.22µm rated sterilizing-grade membranes, which still applies today.
True requirements for “sterilizing-grade” filtration may be limited. For example, in a continuous bioprocessing environment, where intermediate processes are performed quickly, the only true sterilizing filtration requirement may be around the bioreactor additions and at point of final filling. In these applications, sterilizing-grade filters validated to the ASTM F838 standard such as Parker domnick hunter’s PROPOR SG and PROPOR HC ranges will be a requirement.
In other areas a bioburden reduction filter, such as Parker domnick hunter’s PROPOR BR, may fulfill the application requirements because many stages in a biological manufacturing process (i.e. chromatography and tangential flow filtration steps) are not always themselves sterile.
Although filter vendors typically supply a large volume of supporting data to demonstrate filter performance under standardized test conditions, the responsibility for correctly implementing sterile filtration ultimately falls upon the drug manufacturer.
Simply selecting a suitable type and format of filter is not sufficient; in order to be truly considered “sterilizing-grade”, further process qualification must be performed. This requires an understanding of exactly which filter type to use, and how to successfully implement it.
Therefore it is important for filter users to understand the true requirement of the application in question. Installation of a sterilizing-grade filter module without the appropriate qualification cannot be considered to offer sterilizing-grade performance, and in many cases may be unnecessary.
Filter qualification typically involves demonstrating bacterial retention of the filter under process simulated conditions.Rather than using the standard Brevundimonas diminuta, challenge testing with a specific organism isolated from the manufacturing process may instead be required. In addition, it must be demonstrated that the filter is not adversely affected by the process solution itself, and a suitable non-destructive integrity test regime must also be developed to reliably demonstrate that the filter is fit for purpose prior to and after use.
It is also required that the bioburden upstream of the filter is understood and controlled in order to avoid the risk of non-sterile filtrate due to unusually high microbial loading (in addition to the other risks that would also create). To this end, organisations such as the PDA and EMA state that (unless exceptional circumstances exist) no more than 10cfu per 100mL of solution should be present upstream of the final sterilizing-grade filter.
As a consequence, the support and guidance offered by filtration vendors can be extremely beneficial to drug manufacturers. Vendors can provide initial guidance around appropriate filter selection based on application needs, subsequent optimization of the filtration process though direct technical support, and finally input into the process qualification procedure necessary to ensure repeatable, high-quality manufacturing which satisfies all market and regulatory requirements.
This post was contributed by Andrew Kelly, Filtration Product Manager (Life Sciences), Parker domnick hunter Process Filtration, UK.