What is Sterilizing Filtration and Why is it Important?

What is Sterilizing Filtration and Why is it Important? - Analytical Instrument - Parker domnick hunter Process Filtration DivisionSterilizing 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.

It’s not what you’ve got, it’s what you do with it

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.

The value of experience

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.


Remember to join Parker domnick hunter's webinar Application of QbD Concepts to a Final Sterile FiltrationYou can save your seat here.


This post was contributed by Andrew Kelly, Filtration Product Manager (Life Sciences), Parker domnick hunter Process Filtration, UK.


Parker domnick hunter, specializes in automating and controlling single-use processes. By integrating sensory and automation technology into a process, a manufacturer can control the fluid flow more effectively, ensuring the quality of the final product. Find out more



Related blog posts:

How to Minimize the Risk of Mycoplasma Contamination

Can Process Control Impact the Effectiveness of Mycoplasma Filtration?

7 Tips for Successful QbD Implementation in Biomanufacturing


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Comments for What is Sterilizing Filtration and Why is it Important?

Maik Jornitz
This is a nice, simplistic paper on sterilizing filtration. Although, terms are misused, as end-user sterilizing grade filtration validation is filter process validation and not qualification. Filter qualification is performed by the filter manufacturers within their lab settings. Moreover, PDA is a trade organization and does not endorse the 10cf/100ml bioburden rule. EMA is a regulatory authority. Their CPMP guideline of April 1996 describes the maximum allowable bioburden of 10cf/100ml in the upstream side of a sterilizing grade filter. A debatable topic though.
Andrew Kelly
Many thanks for your feedback Maik. I apologize for any confusion, it was not the intention of the piece to suggest that the PDA endorse a specific bioburden control limit prior to sterilizing grade filtration. I was trying to highlight that such guidance exists and this is referenced in documentation published by each of the PDA and EMA. I do believe that it is good practice for a filtration user to understand the bioburden level which exists within their process. Thank you again for helping us clarify the terminology.

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