The Difference Between Fluid Sterilization and Endotoxin Retention
Most Commonly Asked Filtration Question Series
You’ve sanitized your system. You have sterilizing grade filters installed at key points in your process. Your bioburden measurements are low but you still have endotoxin issues. What’s going on?
For more than 20 years we’ve been configuring, testing and manufacturing filters that target specific performance requirements for our customers. Understanding endotoxin filtration is critical when processing pharmaceutical/biopharmaceutical fluids, so we’ve added this topic to our most commonly asked questions. If you have any questions after you're done reading this article, call us at (603) 880-4420 or complete the form below.
How is Endotoxin Created?
Preventing bacteria contamination is a key objective for your filtration system. Use of validated sterilizing filters will prevent bacteria from passing downstream. But, when you sanitize your system, many of the bacteria that may be present are killed. As these bacteria die, the cells decompose and break up into cell fragments.
Depending on the bacteria type, these cell fragments may release endotoxins into your process stream. These cell fragments are typically smaller than 0.01 micron, and will not be removed by a 0.22 or even a 0.10 micron sterilizing filter.
How is Endotoxin Removed from the Process Stream?
Removal based strictly on size exclusion could be done using a tight Ultra Filtration (UF) process step. The very small pore size needed will require an elevated pressure and potentially large surface area filters to meet the required process flow. This would involve modifying the process plumbing to incorporate the UF filter step, and installation of a larger pump to generate the required pressure. This will increase both capital and operating costs of your system.
Fortunately, there is a simpler solution. The endotoxin has an inherent negative charge, which allows a positively charged filter to remove the endotoxin by absorption rather than relying solely on size exclusion. A positively charged sterilizing grade filter can even perform double duty - removing both bacteria and endotoxin from the system. Implementing this technology will require fewer (if any) changes to your process, and will be a far more economical solution. Critical Process Filtration's PPC Filter removes both bacteria and endotoxins.
Selecting the Right Filters
Several factors must be considered when selecting Sterilizing and Endotoxin removal filters:
Process flow rate
The required process flow rate will determine the number of filter elements and housing size required.
Potential bacteria load in the process stream
The potential for bacteria contamination is a consideration in whether or not an in-line sterilization process (UV, etc.) is required. If a high load is anticipated, the in-line process will help reduce the load on the sterilizing filters. If the anticipated load is low, then the filters alone could be sufficient.
Potential endotoxin load in the process stream
If the potential for endotoxin contamination is low, a positively charged sterilizing filter could be an option. If the expected load is high, implementation of separate sterilizing and endotoxin removal filters would allow for replacement of only the endotoxin filter as the charge is depleted.
Acceptable endotoxin concentration
Most systems target < 0.25 EU/ml (the limit for Water for Injection). Some system limits may be even more stringent. The specified limit will help determine the appropriate endotoxin filter. For most applications, a positively charge 0.22 micron filter will be sufficient. For the stricter applications, a dual layer 0.22 or even 0.10 micron charged filter might be a better option.Testing frequency
How often the process will be tested for bacteria and endotoxin will play a role in filter selection. If testing will be infrequent, then the filters selected will need to have a high assurance of performance - perhaps a 0.10 micron rating instead of 0.22 micron. This may also require some level of validation. If testing is conducted frequently, then you will have ongoing evidence that the filters are performing as expected.
Expected filter life
How long you expect your filters to last will have an impact on the size of your filter process. This will also be affected by the expected levels bacteria and endotoxin contamination.Filter change-out strategy
Do you test your process frequently and change filters based on performance? Or do you expect the filters to last a certain time and change them proactively based on a schedule? Here again this can impact which filters to use and how many will be required in your system.
Where to Place Filters
In a recirculating system, it is usually advisable to install separate sterilizing and endotoxin removal filters. The sterilizing filter will remove bacteria and other contaminants that might affect the performance of the endotoxin removal filter. This also allows placement of the filters where they will do the most good, and allows for replacement of the individual filters as needed. For example, in a system utilizing a tank for recirculation, the sterilizing filter could be placed on the inlet side of the tank. The endotoxin removal filter would be better placed toward the outlet side of the recirculating loop, after any in-line sterilization steps (UV, etc.). Critical Process Filtration's GPC filter will remove endotoxins in a stand alone position.
When considering a point-of-use filter, a positively charged sterilizing grade filter would be a good choice. This will remove any unintended contamination of both bacteria and endotoxin and provide added insurance for process and product safety.
In a non-recirculating system, the decision to use separate or combined sterilizing and endotoxin removal filters would depend on potential bacteria and endotoxin load, where in the process it is critical to prevent contamination, and where any in-line sterilization steps are installed.
Does Your Application Call for Endotoxin Removal?
If so, let us help you configure the best solution. We have an experienced Applications and Process Support staff that will identify the appropriate sterilizing and/or endotoxin removal filters for your process while optimizing the cost of your filters. And we deliver fast - products ship in weeks, not months!
From presales consulting, to testing and analysis, to full validation services, Critical Process Filtration delivers quality products and support that meet your filtration performance requirements.
Contact us today at (603) 880-4420 or send us your endotoxin filtration questions here.