Considerations on Re-Use of Sterilizing-Grade Filters

The author examines re-use of hydrophilic- or hydrophobic-membrane sterilizing-grade filters in liquid sterilizing applications.
Oct 31, 2008

Membrane filters designed to sterilize liquids and gases have performed successfully in a broad range of process applications. As economic and market conditions lead pharmaceutical, biotechnology, and vaccine manufacturers to search for ways to improve profitability by decreasing process costs, re-using sterilizing-grade filters may be considered. Although liquid sterilizing-grade filters are generally developed and recommended for single batch or campaign use, there are many applications where they may be subjected to multiple usages (i.e., re-use). This article focuses on the re-use of hydrophilic- or hydrophobic-membrane sterilizing-grade filters applied in liquid-sterilizing applications. The author reviews different approaches that may be defined as re-use, discusses factors to consider when deciding whether to re-use sterilizing-grade filters, and provides a case study that highlights potential risks and considerations for process validation in filter re-use applications.

Suitability of re-use of sterilizing-grade filters in liquid sterilization applications ultimately depends on the requirements of the specific application, the supplier's core filter product-validation studies, and the end user's filtration process validation. This evaluation includes assessments of re-use risk and effects that may compromise the filter's ability to completely retain bacteria and thus sterilize the process fluid.

It is generally accepted that when a nondestructive physical integrity test (e.g., a forward-flow diffusion test or bubble point-type test) of a sterilizing-grade filter is correlated to bacterial retention, re-used filters can be relied on to provide a sterile effluent as long as they continue to demonstrate integrity upon repeated testing. Both forward flow and bubble point-type test methods are highly capable of detecting filter manufacturing defects such as holes in membranes or bypass of membrane cartridge seals due to inadequate installation. It is often overlooked, however, that membrane degradation can occur under incompatible re-use conditions that may compromise the filter's bacterial retention properties. Such cases of membrane degradation are not modeled by filter manufacturers' core validation studies and may not be detectable by common production integrity tests correlated to retention under those model conditions. The case study provided in this article illustrates this point.

The use and re-use of sterilizing grade membrane filters, rated at 0.2 μm and even 0.1 μm, occurs often in nonsterilizing liquid-service applications such as those carried out for bioburden or particle reduction or control. In these applications, the filters may or may not be integrity tested because they are not necessarily expected to remove 100% of incident bacteria with validated assurance (i.e., sterilize) and their filtrates are not claimed to be sterile. They may be used as prefilters or as final filters to control bioburden that may already be very low in the influent fluid. Although such filters have been validated by their manufacturers for quantitative bacteria removal when integral under standard conditions, the risk of marginal, or in some cases, gross failure, carries much less consequence than a risk of nonsterility in the production of a sterile drug or maintenance of a sterile process. Despite the less critical nature of these applications, many of the risks that come with the use of sterilizing-grade filters in sterilizing processes may be applicable and can be used in risk assessment.

Hydrophobic sterilizing-grade membrane filters for air, gas or vent service, typically manufactured with 0.2 μm pore-rated polytetrafluoroethylene (PTFE) or polyvinylidene fluoride (PVDF) membrane, have also traditionally been re-used in multiple batch service with autoclave or in-situ steam (i.e., steam in place, SIP) sterilization between batches or campaigns. Because this article focuses on liquid-sterilizing filtration applications, the re-use of air, gas, and vent filters will not be addressed.