Filtration Sterilization - Sterilization Methods

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Chapter: Pharmaceutical Microbiology : Sterilization Procedures And Sterility Assurance

The process of filtration is unique among sterilization techniques in that it removes, rather than destroys, microorganisms. Further, it is capable of preventing the passage of both viable and nonviable particles and can thus be used for both the clarification and sterilization of liquids and gases.



The process of filtration is unique among sterilization techniques in that it removes, rather than destroys, microorganisms. Further, it is capable of preventing the passage of both viable and nonviable particles and can thus be used for both the clarification and sterilization of liquids and gases. The principal application of sterilizing grade filters is the treatment of heat-sensitive injections and ophthalmic solutions, biological products and air and other gases for supply to aseptic areas.


Filters may also be required in industrial applications where they become part of venting systems on fermenters, centrifuges, autoclaves and freeze-driers. Certain types of filter (membrane filters) also have an important role in sterility testing, where they can be employed to trap and concentrate contaminating organisms from solutions under test. These filters are then placed on a solid nutrient medium or in a liquid medium and incubated to encourage colony growth or turbidity.


The major mechanisms of filtration are sieving, adsorption and trapping within the matrix of the filter material. Of these, only sieving can be regarded as absolute as it ensures the exclusion of all particles above a defined size. It is generally accepted that synthetic membrane filters, derived from cellulose esters or other polymeric materials, approximate most closely to sieve filters; while fibrous pads, sintered glass and sintered ceramic products can be regarded as depth filters relying principally on mechanisms of adsorption and entrapment. Some of the characteristics of filter media are summarized in Table 21.4. The potential hazard of microbial multiplication within a depth filter and subsequent contamination of the filtrate (microbial grow-through) should be recognized.


a) Filtration Sterilization Of Liquids


In order to compare favourably with other methods of sterilization, the microorganism removal efficiency of filters employed in the processing of liquids must be high. For this reason, membrane filters of 0.2–0.22 μm nominal pore diameter are chiefly used, while sintered filters are used only in restricted circumstances, i.e. for the processing of corrosive liquids, viscous fluids or organic solvents. It may be tempting to assume that the pore size is the major determinant of filtration efficiency and two filters of 0.2 μm pore diameter from different manufacturers will behave similarly. This is not so, because, in addition to the sieving effect, trapping within the filter matrix, adsorption and charge effects all contribute significantly towards the removal of particles. Consequently, the depth of the membrane, its charge and the tortuosity of the channels are all factors which can make the performance of one filter far superior to that of another. The major criterion by which filters should be compared, therefore, is their titre reduction values, i.e. the ratio of the number of organisms challenging a filter under defined conditions to the number penetrating it. In all cases, the filter medium employed must be sterilizable, ideally by steam treatment; in the case of membrane filters this may be for once-only use, or, in the case of larger industrial filters, a small, fixed number of resterilizations; sintered filters may be resterilized many times. Filtration sterilization is an aseptic process and careful monitoring of filter integrity is necessary as well as final product sterility testing.


Membrane filters, in the form of discs, can be assembled into pressure-operated filter holders for syringe mounting and in-line use or vacuum filtration tower devices. Filtration under pressure is generally considered most suitable, as filling at high flow rates directly into the final containers is possible without problems of foaming, solvent evaporation or air leaks. To increase the filtration area, and hence process volumes, several filter discs can be used in parallel in multiple-plate filtration systems or, alternatively, membrane filters can be fabricated into plain or pleated cylinders and installed in cartridges. Membrane filters are often used in combination with a coarse-grade fibre glass depth prefilter to improve their dirt-handling capacity.


b) Filtration Sterilization Of Gases


The principal application for filtration sterilization of gases is in the provision of sterile air to aseptic manufacturing suites, hospital isolation units and some operating theatres. Filters employed generally consist of pleated sheets of glass microfibres separated and supported by an aluminium framework; these are employed in ducts, wall or ceiling panels, overhead canopies, or laminar airflow cabinets. These high-efficiency particulate air (HEPA) filters can remove up to 99.997% of particles more than 0.3 μm in diameter and thus are acting as depth filters. In practice, their microorganism removal efficiency is rather better as the majority of bacteria are found associated with dust particles and only the larger fungal spores are found in the free state. Air is forced through HEPA filters by blower fans, and prefilters are used to remove larger particles to extend the lifetime of the HEPA filter. The operational efficiency and integrity of a HEPA filter can be monitored by pressure differential and airflow rate measurements, and dioctylphthalate smoke particle penetration tests.


Other applications of filters include sterilization of venting or displacement air in tissue and microbiological culture (carbon filters and hydrophobic membrane filters); decontamination of air in mechanical ventilators (glass fibre filters); treatment of exhausted air from microbiological safety cabinets (HEPA filters); and the clarification and sterilization of medical gases (glass wool depth filters and hydrophobic membrane filters).


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