PDA Technical Glossary

Synonym: Drug Substance. (TR14) (TR42) A substance or mixture of substances that, when delivered in a finished drug product, directly affects the structure or function of the body. (TR54-4) Any substance or mixture of substance intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. Note: also known as Drug Substance. (TR29) (TR56) (TR41) (TR54-3) (TR60) Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity o other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. (TR63) (TR70) Any substance or mixture of substances intended to be used in the manufacture of a drug product, and that when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body. (TR74)

A bacteriophage is any one of a number of viruses that infect bacteria. The term is commonly used in its shortened form, “phage”. (TR41) (TR 47)

A demonstration of unit operation performance at two different values of a given parameter (e.g., ionic strength, dwell time or temperature), allowing the use any values of that parameter falling within this range. (TR41)

The measured differential gas pressure at which a wetting liquid (e.g., water, alcohol, product) is pushed out of the largest pores of a wetted porous membrane, and a steady stream of gas bubbles or bulk gas flow is detected.(TR15) (TR26) The minimum pressure at which a wetting liquid is pressed out of the pore system of a membrane while forming a steady bubble chain. (TR41)

The ability of a filter to be used with a particular process fluid without a change in the inherent properties of the filter. (TR41)

A test for membrane integrity that involves measuring the rate of gas diffusion through a liquid-wetted membrane.(TR15) An integrity test in which a filter is subjected to differential gas pressures below the bubble point and gas molecule migration through the water-filled pores of a wetted membrane is measured. This behavior follows Fick’s Law of Diffusion (i.e., the gas diffusional flow rate for a filter is proportional to the differential pressure and the total surface area of the filter). (TR41)

In direct flow filtration, all fluid is directed through the membrane in a single pass. (TR41)

Virus-like entity whose genetic material is stably integrated into the germ line of an organism or cell line. Cell lines (notably CHO) may constitutively produce virus-like particles, which are typically noninfectious but still of safety concern. Model retroviruses are generally used as surrogates to measure virus-like particle clearance. (TR41)

A chemical component that is removed from a material by application of an artificial or exaggerated force (e.g., solvent, temperature, time). The term extractable is often erroneously used to describe a leachable. (TR14) (TR15) (TR26) (TR41) (TR45) Chemical substances that can be extracted from components of material process fluid contact surfaces by exertion of an exaggerated force (e.g., organic solvent, extreme elevated temperature, ionic strength, pH, contact time, etc.) Extractables may represent most but not all of the potential leachables that may be seen in process fluids. (TR66) Extractables are organic and inorganic chemical entities that can be released from a pharmaceutical packaging/delivery system, packaging component, or packaging material of construction under laboratory conditions. (TR54-4) Organic or inorganic chemical entity that is forced out of container closure system materials and components under laboratory experimental conditions. (TR73)

The fluid introduced into a process. (TR41)

A process of removing particles from a fluid by passing it through a permeable material, such as a membrane film. (TR41) The process by which particles are removed from a fluid by passing the fluid through a porous material. (TR26)

Best practices in manufacturing of pharmaceuticals or biopharmaceuticals. From a regulatory standpoint, GMPs are regarded as the minimum current good manufacturing practice for methods to be used in, and the facilities or controls to be used for, the manufacture, processing, packaging, or holding of a drug to assure that such drug meets requirements of safety, identity and strength and meets the quality and purity characteristics that it purports or is represented to possess. (TR41) (TR 79)

Particles of uniform size in a dispersed phase. In the case of viruses, this term refers to free virus particles not agglomerated to other viruses or proteins in solution. (TR41)

A filter rating with an arbitrary value, indicating a particulate size range at which the filter manufacturer claims the filter removes some percentage. Nominal ratings vary from manufacturer to manufacturer and may not be suitable to compare filters among manufacturers. Processing conditions, such as operating pressure and concentration of contaminant may have a significant effect on the retention efficiency of the nominally rated filters. (TR41)

A technique widely used in molecular biology in which a DNA polymerase is used to amplify a piece of DNA by in vitro enzymatic replication. As PCR progresses, the DNA thus generated is itself used as a template for replication. This sets in motion a chain reaction in which the DNA template is exponentially amplified. This technique may be used to quantify virus. (TR41) (TR47)

Filtration in which a fluid (feed) stream runs tangential to a membrane. A pressure differential causes some fluid to pass through the membrane. (TR41)

The dilution of virus that results in the probability of infection of 50% in replicate tissue-culture inoculations. (TR41)

The concentration of infectious virus calculated, taking into account the dilution factor. (TR41)

Reduction of virus infectivity caused by chemical or physical modification. (TR41) (TR83)