Are You Using the Right Filter? Bioburden Reduction vs. Sterile Filtration

Biopharmaceutical processes necessitate stringent microbial control to guarantee product quality and safety. These processes must be carefully designed and operated to minimize the introduction of microorganisms into the process and to ensure the sterility of the final product. The utilization of appropriate filters at each stage of these processes plays a pivotal role in achieving this objective. However, the identification of the most suitable filters for a given process presents a challenge.

Initially, it may be advisable to implement sterilizing filters in areas where there is a potential for microbial contamination. This approach would ensure the necessary protection, but it may not be the most cost-effective option. Sterilizing filters are expensive, and their cost can accumulate rapidly if a large number are required. One strategy to optimize overall filtration costs is to identify potential applications for bioburden reduction filters instead of sterilizing filters.

What’s the difference?

Sterilizing filters undergo rigorous manufacturing, testing, and validation processes to effectively remove virtually all microorganisms from a specified fluid. The pore size required for filtration is contingent upon the targeted organism. Bacteria removal typically utilize filters with a pore size of 0.22 or 0.1 micron. Conversely, mycoplasma removal requires filters rated for a pore size of 0.1 or 0.03 micron. These filters undergo comprehensive 100% integrity testing, typically conducted through forward flow diffusion at pressures slightly below the membrane bubble point. The diffusion results are subsequently validated for microbial retention adherence to ASTM F838 protocols.

Bioburden reduction filters can reduce or eliminate microbial contamination, but they are not tested to the same standard and are not validated to provide sterile effluent. Depending on the intended use, they may have the same pore size as sterilizing filters if used as prefilters to reduce the biological load on final sterilizing filters, or possibly a slightly larger pore size where particulate retention with some biological reduction is required.

How do I know which one to use?

This requires careful analysis of the process to determine where absolute sterility is required, and where it might not be. For example:

• Raw materials entering a bioreactor should ideally be as close to sterile as practical, as the bioreactor offers an optimal environment for growth with an extended residence time. In this scenario, a sterilizing filter can be used, preceded by a particulate/bio-reduction prefilter. The sterilizing filter safeguards the bioreactor, while the prefilter extends the lifespan of the costly sterilizing filter.

• Material feeding a chromatography or other purification step with limited residence time and less favorable conditions for growth could potentially benefit from the use of a bioburden reduction filter to safeguard the process against particulates and thereby mitigate the bioburden.

• The selection of a tank vent filter would be contingent upon the environmental conditions surrounding the tank. In a clean room setting, a bioburden reduction filter is likely to be adequate. Conversely, in an area prone to contamination, a sterilizing filter would be a more prudent choice to ensure safety.

• Gas filters require the same analysis as liquid filters. Is the gas entering an environment that require sterility, or am I primarily concerned about particulate contamination?

• Final filtration will almost always require the use of a sterilizing filter. In instances where endotoxin contamination is a concern, this can be accomplished using a positively charged sterilizing filter, which will effectively eliminate both bacteria and endotoxin.

After analyzing the process to determine the appropriate filter type, a comprehensive risk assessment is necessary to identify potential risks associated with substituting a bioburden reduction filter for a sterilizing filter. Furthermore, it is essential to evaluate whether these risks can be effectively mitigated prior to implementation.

Upstream vs Downstream Sterilizing and Bioburden Reduction Filtration

Figure 1: Upstream Sterilizing and Bioburden Reduction Filtration

Figure 2: Downstream Sterilizing and Bioburden Reduction Filtration

Note that the above figures show Sterilizing Filters as the best option. Based on proper risk assessment of filtration requirements, some systems may utilize Bioburden Reduction Filters instead.

See our Application Summary to Learn More: Sterilizing and Bioburden in Biopharm

How can this reduce filtration expenses?

By utilizing appropriate filters and prefilters, it is possible to substantially decrease overall filtration expenses. Sterilizing filters incur significant costs. Utilizing less expensive prefilters that extend the lifespan of sterilizing filters offers an advantage. Additionally, replacing sterilizing filters with a less expensive bioburden reduction filter will yield substantial financial benefits.

Summary

Biopharmaceutical processes require a series of steps, each of which presents a potential entry point for bacteria. The installation of appropriate Prefilter, Bioburden Reduction, and Sterilizing Filters ensures product sterility, thereby guaranteeing product quality and patient safety. Critical Process Filtration offers a comprehensive range of filter materials and configurations, enabling the optimization of your filtration process while simultaneously minimizing filtration expenses.

Critical Process Filtration Products:

Sterilizing Options (liquid)

• PPS (Dual layer PES membrane)
• DPPS (PES membrane with bioburden prefilter)
• SPS (Single layer PES membrane)
• HPPS (PES membrane with high capacity PES prefilter)
• PNM (Nylon 6,6 membrane)

Sterilizing Options (gas)

• PTM / PTR (PTFE membrane)

Bioburden Reduction Options (liquid)

• BPS (PES membrane; High capacity PES prefilter layer optional)
• BNM (Nylon 6,6 membrane)
• BPVWL (PVDF membrane)

Bioburden Reduction Options (gas)

• BTM (PTFE membrane)
• BPVWB (Hydrophobic PVDF membrane)

Prefilter Options

• PPD (polypropylene depth filter)
• PGD (fiberglass depth filter)
• BCWPS (high capacity PES)
  

Validations

• 22 micron membrane filters are validated for > 7-log reduction of Brevundimonas diminuta
• 1 micron membrane filters are validated for > 7-log reduction of Brevundimonas diminuta and reduction of Acholeplasma laidlawii (mycoplasma)
• 1M membrane filters are validated for > 7-log reduction of Acholeplasma laidlawii (mycoplasma)

For more information, please contact the Critical Process Filtration Technical Service team at Technicalservices@criticalprocess.com.