Are Sterilizing Filters Reusable?

It depends. However, is this truly what you need? Furthermore, what is the rationale behind it?

While a study demonstrating the filter membrane's capability to sterilize a drug product or process fluid during a single use is informative, it does not reliably predict filter performance after multiple cycles of cleaning, sterilization, and reuse. Therefore, before initiating a potentially challenging and expensive process to reuse your sterilizing filters, it is highly advisable to reflect on the following questions and explore alternative options that could conserve both time and financial resources.

With over 25 years of experience in filter manufacturing and assisting process teams in optimizing their systems, we have identified that the primary motivation for reusing sterilizing filters is the desire to reduce filtration costs. It is important to note that sterilizing the final filters represents the most significant expense in the filtration process. Therefore, it is essential to examine additional cost factors related to filter reuse before determining whether this approach is suitable for your needs.

Are you using the properly sized filter for your application?

If your current filter has a lot of filtration capacity left over after processing a batch, it may be advantageous to consider utilizing a smaller filter to decrease filtration expenses. However, the potential drawbacks of this approach are longer processing times and/or higher pressure drops across the filter. In the extreme, a higher-pressure drop may require some level of re-validation to confirm proper retention at the different process conditions.

Do you have plans to scale up to larger batch sizes?

Increasing the batch size using the same filter will spread the filtration expenses over more of your product, resulting in lower cost-per-volume filtering. If there are intentions to scale up in the near future, it may be more advantageous to allocate resources towards expediting those plans instead of investing in a reuse strategy that could soon be rendered unnecessary.

What is the likelihood of success?

This will depend on what you are filtering, and where in the process the filter is used. In a pharmaceutical process, the further downstream a sterilizing filter is placed, the more critical it is to ensure proper retention. The reuse of any disposable equipment entails inherent risks and hazards that must be effectively managed to ensure the equipment remains safe, effective, and compliant with the manufacturer's specifications and requirements. In a typical drug manufacturing operation, sterilizing filters could be used for:

• Water purification,

• Non-sterile active pharmaceutical ingredients (APIs),

• Final bulk sterile APIs,

• The finished drug component,

• Other ingredients in drug formulation,

• The finished drug.

Water purification and ingredient filtration offer the potential for filter reuse with minimal validation requirements unless it is critical to maintaining batch integrity. For example - if an ingredient is supplied from a bulk container and utilized across several batches of a formulation, the validation demands are less rigorous. However, if the ingredient is used in discrete quantities where it is important to maintain the lot traceability, then there would be more stringent validation requirements.

Reusing sterilizing filters for the other components, ingredients, and final product will require extensive risk assessment and validation efforts as mandated by:

• FDA guidance on sterile filtration strongly suggests that while the reuse of sterilizing filters is generally not encouraged, it may be allowed under specific circumstances, provided there is sufficient justification and comprehensive validation, and that it is important to assess the potential leaching of contaminants or cleaning residues from previously utilized filters prior to their reuse, ensuring that such effects are absent and validated.

• The updated draft of Annex 1, "Manufacture of Sterile Medicinal Products," as part of the EU GMP guidelines, mandates that sterile filters should be disposed of after each use. Reusing filters is typically not allowed unless they have been validated for multiple days of use.

How much are you willing to spend on reusing your filters?

After determining the filter size and batch size, you should calculate the filtration cost (per batch, per volume, etc.) of using your filter(s) once. Subsequently, assess the feasible number of times the filters can be reused and estimate the operational expenses (labor, materials, etc.) required to process the filters for reuse which encompasses cleaning, sterilizing, drying, packaging, storing, etc. This analysis will enable you to determine the potential cost savings derived from filter reuse. Finally, evaluate the budget available for validating filter reuse to ensure a satisfactory return on that investment.

Any perceived economic advantages linked to the reuse of filters must be meticulously balanced against the risks of potential failures, which may include:

• Premature plugging: An inadequate rinsing can result in the formation of biofilm,

• Loss of integrity: membrane degradation may arise under reuse conditions,

• Increased leachable contaminants,

• Filter's capacity to effectively retain bacteria,

• Comprehensive validation efforts,

• Impact on product quality.

How much will it cost to determine if sterilizing filter reuse is the right option?

There will be many steps required to justify and validate the reuse of your sterilizing filters; some of which may pose challenges in accurately estimating the true cost. These include:

• The expenses associated with a comprehensive risk assessment,

• The cost of validating the process,

• The cost of implementing the validated process.

All will involve input from Operations, Engineering, Quality, Regulatory Affairs, etc. The total number of hours dedicated to meetings is uncertain and will vary based on the identified risks and the corresponding mitigation strategies. This validation should consider factors such as pH, viscosity, flow rates, pressure, temperature, chemical compatibility, and the effects of hydraulic shock when setting limits for the multiple reuse of filters. These evaluations must examine the chemical compatibility of the filter with process fluids and the conditions of the reuse cycles, verify the validity of integrity test limits under reuse scenarios, and include a chemical analysis of rinse effluents to identify any potential leaching of bacterial, product, or cleaning agent residues.

Risk Analysis Recommendations

At a minimum, the risk assessment must consider the following elements (Figure 1):

Figure 1. Risk Analysis

Maintenance of Batch Integrity and Traceability

• Filter dedicated to specific products to prevent cross-contamination.

• Filter flushing and cleaning procedures to prevent batch-to-batch mixing.

• Effect of batch-to-batch mixing and remediation as required.

Cleaning/Sterilization/Drying/Segregating/Storing

• Each step of the reuse process must be evaluated against potential issues, and their possible consequences, and determine preventive measures.

• Choosing the right cleaning method is crucial for ensuring the membrane can be reused effectively. It is important to ensure that the cleaning solution employed is compatible with the membrane material; otherwise, aggressive chemicals could damage the membrane and reduce its performance.

• It is also essential to select an appropriate sterilization technique that aligns with the properties and intended use of the membrane material. Frequently employed sterilization methods encompass high-pressure sterilization, chemical sterilization, and gamma radiation.

Determining the maximum number of uses for the filter

• Does the risk increase with additional filter use?

Understanding if filter reuse will require additional batch testing

• During validation (almost certainly).

• Post validation.

Identifying overall risk and impact associated with specific batch

• Batch rework (if allowable).

• Batch scrapped.

• Accidental release of improperly processed batch.

Assessing endotoxin potential

• Depending on the species of bacteria, endotoxin can be released as they die.

• Potential endotoxin level.

• Impact and mitigation.

Cost

• Each reuse application must undergo an independent evaluation.

Membrane filters designed for the sterilization of liquids and gases have proven to be highly effective in various process applications. Considering economic and market challenges, pharmaceutical, biotechnology, and vaccine manufacturers are increasingly seeking ways to improve profitability by lowering process costs. In this context, the reuse of sterilizing-grade filters stands out as a particularly promising solution. However, it is important to note that membrane degradation can happen if reuse conditions are not appropriate, which may compromise the filter's capacity to retain bacteria. When carefully evaluating the associated risks and the substantial efforts needed to validate the reuse of filters, it becomes evident that the cost of the drug product or process fluid is often considerably higher than that of the filter itself. Furthermore, the potential risk to product quality makes the option of filter reuse less favorable.

Costs of validating the reuse of sterilizing filters

The reuse procedure will necessitate the development of processes and the creation of Standard Operating Procedures (SOPs) at each stage (refer to Figure 2). This effort will involve contributions from various departments, including Operations, Engineering, and Quality, among others. Additionally, it may prove challenging to precisely estimate the amount of work needed for this undertaking.

Figure 2. Reuse procedures

After the reuse procedures and SOPs have been established, each step will require some level of validation. Additionally, the cost of the product consumed during protocol execution must also be considered.

Cost of implementing the reuse of sterilizing filters

In addition to the cost of Process Development and SOPs, there may be new equipment required to implement filter reuse. These must be installed prior to the execution of the validation.

• Sanitization equipment: autoclave, clean-in-place system, etc.

• Drying oven

• Additional integrity testing equipment

• Storage equipment

Is it worth it?

Now that you have a cost estimate to compare against the potential savings of reusing sterilizing filters, you may now consider the following:

• How many reuses are required to generate an adequate return on investment?

• Is this number of reuses achievable?

• What is the financial impact of a batch failure that might result from filter reuse? Depending on the value of the product being filtered, a single batch failure may surpass the savings accrued.

In performing the above analysis, it is important to consider both the base estimated cost as well as to define a range to accommodate any potential unforeseen overruns, by these means ensuring that proceeding with reuse is the right decision.

Each step of the reuse procedure will require Process Development and SOP generation. Here again, this will require resources from multiple departments, including Operations, Engineering and Quality, among others. Consequently, it may be difficult to accurately estimate the level of effort required.

Users must carefully weigh the risks and validation expenses associated with the safe reuse of sterilizing filters against the apparent economic benefits of reuse when designing and qualifying sterilization filtration processes.

Alternatives to reusing sterilizing filters

• Ensure that you are using a filter that is appropriately sized to your batch. As discussed above, changing to a smaller filter would have an immediate impact on cost with minimal validation requirements.

• Consider increasing your batch size. As mentioned above, if this is in your plans, it may be more advantageous to focus on this aspect rather than on reusing your filters.

• Identify and validate an alternate, more economical filter option. This process could prove to be significantly less complex than validating the multiple steps required for reusing a filter and may provide a better return on investment.

Summary and Conclusion

We have discussed that while it may be possible to reuse your sterilizing filters, it will most likely be an expensive and resource-consuming process to arrive at a fully validated and documented process that will satisfy the appropriate regulatory bodies. There are alternative options that, while they may not provide the same level of cost savings as filter reuse, would be simpler and less expensive to implement, yielding a better return on investment.

Need to Optimize your Sterilizing Filtration Cost?

Considering the complexities associated with validating the reuse of filters, it is prudent to consult with Critical Process Filtration’s experienced Applications and Process Support staff before proceeding with the reuse of filters intended for single-use applications. We offer over twenty-five years of experience as a mid-size manufacturer of process filters. We will perform all necessary testing to determine the right sterilizing filters for your process and can assist in risk assessment, process development, and validation as required.