Terms for Discussing Filters & Specifications

A membrane in which the pore openings are larger on one side than the other.

A test to determine the integrity and pore size of a filter. The differential pressure at which a steady stream of gas bubbles is emitted from a wetted filter under specific test conditions. The bubble point test measures the largest pore.

A matrix of randomly distributed filters or particles creating a tortuous path of nominally rated size.

The difference in pressure between the upstream and downstream sides of the filter.

A test to determine the integrity of a filter. The test is based upon the transition from diffusional flow to bulk flow, of a gas, through a wetted filter. Either the gas or the downstream liquid, displaced by the gas, may be measured.

The filtrate side of the filter.

A device for carrying out filtration which consists of the filter medium and a suitable holder for constraining and supporting it in the fluid path.

To pass a fluid containing particles through a filter medium whereby particles are removed from the fluid.

The permeable material that removes particles from a fluid being filtered.

The fluid which has passed through a filter.

The process by which particles are removed from a fluid by passing the fluid through a permeable material.

Determines the volume of liquid which will flow through the filter at a fixed pressure and temperature.

Refers to a filter's ability to naturally wet with water. "Water-loving" filter.

Refers to a filter's lack of ability to wet with water. "Water-hating" filter. Ideal for venting applications.

A non-destructive test which is used to predict the functional performance of a filter. The valid use of this test requires that it be correlated to a standardized bacterial retention test. Examples: Bubblepoint test, Diffusion Test, Flow Rate Test.

A membrane in which the pore openings are the same diameter on both sides of the membrane.

A continuous polymeric matrix with channels of defined size.

A filter which after any appropriate pretreatment, such as washing or flushing, will not release fibers into the filtrate of the product that is being filtered.

A discernible mass having an observable length, width, thickness, including particulates and bacteria.

The pore size at which a particle of defined size will be retained with 100% efficiency under specified test conditions. e.g., a 0.02µm sterilizing filter will retain 10 organisms per cm² of Pseudomonas diminuta at 30 psig and ambient temperature.

The pore size at which a particle of defined size will be retained with an efficiency below 100% (typically 90–98%). Rating methods differ widely between manufacturers.

The maximum diameter of a channel through the filter medium.

The percentage of the filter area which is porous.

A non-fiber releasing filter which produces an effluent in which no microorganisms are demonstrable when tested by the method specified in the current edition of the United States Pharmacopeia.

Describes the dirt handling capacity — how long the liquid will continue to flow through the membrane before it clogs. The lower the flow rate and throughput, the longer it takes to complete an analysis. Quality control during manufacturing monitors and determines a membrane's bubblepoint, flow rate, and throughput.

The feed side of the filter.

Retention of gas, liquid, solid or a dissolved substance on a surface due to positive interaction (attraction) between the surface and the molecules of the adsorbed material. The interactive forces can be electrostatic (coulombic) or non-electrostatic (dipole-dipole and hydrophobic). Adsorption to a membrane or filter device can occur in a specific manner (affinity) or non-specifically.

A chamber for sterilizing filters or equipment with saturated steam using constant high temperature and pressure (commonly 121°C, 15 psi). Many materials requiring sterilization (such as cell culture media and injectable drugs) are degraded by the heat of an autoclave and must be sterilized by other means such as filtration.

Defined as the concentration of a ligand that saturates the binding of half of the available binding sites. It is a combination of the available target (receptor) and the affinity of the ligand. Also known as the dissociation constant Kd.

A general term used to categorize tests performed to determine whether the filter's materials of construction are capable of including measurable degrees of systemic toxicity, localized skin irritation, sensitization reaction, or other biological responses. Either in vivo or in vitro test methods may be employed.

The air pressure required to force liquid from the largest wetted pore of a membrane. It serves as an indication of pore size and rates the filter's ability to serve as a particle barrier. The bubble point is dependent on the liquid used to wet the membrane — for a given pore size, the bubble point will be higher in a liquid with a higher surface tension (such as water) than in a liquid with a lower surface tension (such as isopropyl alcohol). Expressed in psi or bar.

A measure of the variation that can occur between samples during a binding assay. Variation can result from liquid transfer, non-specific binding, improper washing, and anomalies with the plate.

Relates to the number of photons detected that are given off by the scintillant counter (radioactivity) or multilabel counter (fluorescent).

A test designed to determine the biological reactivity of mammalian cell cultures following contact with the plastic or membrane with specific extracts prepared from the material under test. The procedure allows for extraction of the material at physiological to non-physiological temperatures for varying intervals.

The difference between the pressure in the system before the fluid reaches the filter (upstream pressure) and the system pressure after the fluid flows through the filter (downstream pressure) in a constant flow situation. As the filter begins to clog, differential pressure increases.

A measure of the efficiency of a filter for the removal of particulate from air, based on retention of 0.3 µm Dioctyl Phthalate (DOP) aerosol droplets, usually expressed as a percentage. A High Efficiency Particulate Air (HEPA) filter must retain at least 99.97% of 0.3 µm DOP droplets.

The filter area that is available for filtration. For a given membrane, the larger the filter area, the higher the flow rate at a given initial differential pressure. Filter media and devices are available in a wide range of sizes with different EFAs.

A complex molecule (lipopolysaccharide) which forms an integral part of gram-negative bacterial cell walls and is released when the integrity of the wall is disturbed (i.e., cell division, growth, and death). Endotoxins may be released during biosynthesis of a recombinant DNA product, necessitating purification steps to ensure their removal.

Substances present in the composition of the filter media or the filter manufacturing process that may be leached into the fluid as it is filtered, thereby affecting its purity. May include manufacturing debris, surfactants, and adhesives. Extractable components can be minimized with sufficient preflushing.

Measurement of the percentage of particles which are removed from the fluid by the filter. In liquid filtration, filter efficiency is given on the basis of particles at or above a certain diameter in size. Efficiency can be calculated from a beta value as follows: % Efficiency = (B-1/B) × 100

A measure of how long a filter will last before requiring replacement or cleaning, stated in time or volume of fluid filtered. A filter's actual life depends on the particulates and conditions it is exposed to in actual usage. Typically, useful life can be determined by a two-to-four fold increase of differential pressure in a constant flow system or a drop in flow rate of 50–80% in a constant pressure system.

Light emitted from a fluorophore (fluorescent molecule) as a result of excitation. The excitation wavelength is different from the emission wavelength — the difference between these wavelengths is known as the Stokes shift. Most fluorophores give a sample emission approximately 1 picosecond after excitation; in time-resolved fluorescence, the emission occurs after a microsecond lag.

Regulations promulgated by the Food and Drug Administration governing the manufacture of drugs (21 CFR 210 and 211), medical devices (21 CFR 820), and Large Volume Parenterals (21 CFR 212 proposed). cGMPs are the current accepted standards of operation in a regulated industry.

Volume of fluid retained in a filter and/or housing after purging the assembly with air or a suitable gas. Hold-up volume is usually considered to be lost volume.

A test to ensure that a sterilizing-grade filter is intact and will function as intended. Recommended integrity tests include the Forward Flow test, Bubble Point test, and the Pressure Hold test. Integrity tests on sterilizing-grade filters are correlated with bacterial challenge data.

An LAL gel clot test prescribed by the United States Pharmacopeia (USP) to detect and determine the level of bacterial endotoxins in a substance. The reagent is made from the circulating blood cells (amoebocytes) of Limulus polyphemus, the horseshoe crab.

The emission and detection of light produced by chemical reactions or bioluminescence. These enzymes can be used as labels to trace a molecule of interest. It does not require laser excitation like fluorescence because it is a result of a chemical reaction. Luminescence reactions can be carried out on membranes (blots), in a plate, or in a solution.

Normal rating system for ultrafiltration and nanofiltration membranes. MWCO is defined as the molecular weight of solute of which the membrane retains 90%. Often defined by the molecular weight of dextran particles retained.

Minimum and maximum parameters set for validation and processing pressures and temperatures.

The degree to which a fluid will pass through a permeable substance under specified conditions. The space or void volume between molecules allowing fluid flow.

A value describing the acidity or alkalinity of an aqueous solution. pH is the negative logarithm (base 10) of the concentration of hydrogen ions (equivalents per liter). A pH of 7 is neutral; below 7 is acidic; above 7 (up to 14) is basic.

The tendency of a substance to raise body temperature when injected into the body. Filtration materials that come in contact with injectable liquids must meet pyrogenicity standards and be classified as non-pyrogenic. Pyrogenicity can be determined by tests such as the Limulus Amoebocyte Lysate (LAL) test.

Ability of a filter to retain bacteria, DNA, or other biomolecules from a solution. The percentage of a chemical or organism population that can be recovered after processing.

Ability of a filter to retain particles (total number or those of a specific size) suspended in a gas or liquid. In ultrafiltration, refers to the ability to concentrate molecules in solution. Expressed as a percentage of particles or molecules originally present.

To make clean by removing dirt and other extraneous materials with soap and general disinfectant so as to reduce the possibility of growth and spread of pathogenic organisms. Common sanitization agents include 70% ethanol and bleach.

To make or be free of any viable microorganisms. Demonstrated by testing to show the absence of growth of microorganisms. Note: if a high bioburden level was present prior to sterilization, pyrogens may still be present afterward.

Typically measured with a micrometer and usually expressed as microns or mils. A micron is one millionth of a meter; a mil is one thousandth of an inch (0.0254 mm).

The amount of solution that will pass through a filter prior to clogging.

Tests to indicate adverse reactions or lethality to drugs or drug components, also used to assess the biosafety of filters. Tests include appropriate combinations of direct injection, extraction, and implantation. Generally known as the USP Biological Reactivity Test.

Depression of pressure below atmospheric pressure. The maximum vacuum possible is approximately 63.5 cm (25 in.) of Hg.

The amount of pressure required to transmit water through the largest pore of a dry hydrophobic filter. It serves as an indication of pore size for a hydrophobic membrane and rates a filter's ability to serve as an aqueous barrier. The larger the pore size, the less pressure required. Expressed in psi or bar.