PDA Glossary

Clumping of proteins, viruses, or bacteria that may arise from several mechanisms and may be classified in numerous ways, including soluble/insoluble, covalent/noncovalent, reversible/irreversible, and native/denatured. (TR47)

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)

The total number of microorganisms per unit of material prior to sterilization. (TR13)

Total number of viable microorganisms on or in a health care product prior to sterilization. (TR22)(TR61)(TR62)

A population of viable microorganisms in a fluid prior to sterilizing filtration. (TR26)

A measure of the contaminating organisms found in or on a given amount of material before it undergoes a sterilization process. (TR45) (TR70)

The number of detectable microorganisms (bacteria and fungi) with which an object is contaminated. It is measured in CFU (colony forming units). (TR47)

The number of viable, contaminating microorganisms present on a product immediately prior to decontamination. (TR51)

Viable microbial contaminants associated with personnel manufacturing environments (air and surfaces), equipment, product packaging, raw materials (including water), in-process materials, and finished products. (TR 67) (TR 69)

The host cells that are used to propagate or detect viruses. (TR 47)

Cells used for the manufacture of a biological medicinal product. (TR 71) (TR 83)

The process of creating identical copies of DNA fragments or a homogeneous preparation of cells, viruses or other organisms. (TR47)

A process where cells, viruses or whole tissues are preserved by cooling to low sub-zero temperatures, typically -1960C. (TR47)

Morphological changes induced by viruses in infected cells in invitro culture. They are usually localized around a site of initial infection and vary in appearance based on the virus and the cultured cell. (TR47)

Viruses where infection of cells results in microscopically visible degeneration of the cells or other morphological changes. (TR47)

A technique used to measure the size and size distribution of particles. Particles suspended in a solution will cause scattering of light and the extent of the scattering is related to the size and shape of the particles. (TR47)

A biochemical technique used to detect or measure the presence of an antibody or an antigen in a sample. (TR41) (TR47)

A measure of virus infectively based on formation of a region or “focus”, of infected cells within a monolayer culture that is caused by viruses that do not kill their host, but rather transform them. The number of foci is directly correlated to the number of infectious virus particles. (TR47)

Adherence of red blood cells to virus-specific antigens on the surface of infected cells. In cellbased in vitro assays the reaction is used as an end point for virus detection. (TR47) (TR71)

A clumping together or agglutination of red blood cells. In the context of this Technical Report hemagglutination indicates presence of virus that binds to erythrocytes. (TR47)

The clumping of red blood cells by binding to virus particles. The hemagglutination reaction is used in cell-based in vitro assays as an end point for virus detection. (TR71)

A technique used to determine or confirm the identity of an organism (virus, bacteria, cells). (TR47)

A measure of quantity of infectious virus. An infectious unit does not necessarily reflect the number of virus particles, as virus preparations also contain noninfectious virus particles and, depending on the cellular host, more than one virus particle may be necessary to infect a cell. (TR47)

The capacity of a substance to affect the quantitation of virus in the assay. (TR47)

In the context of this Technical Report the limiting dilution technique is used for virus cloning. The virus suspension is diluted until virus is no longer detectable. The dilution immediately before the dilution where infection of cells is no longer detectable is considered to contain only one virus particle or a very low number of virus particles. (TR47)

A stock of cells or virus used to produce the Working Cell Bank or the Working Virus Bank. Cell/virus banking is used to enhance biological consistency. (TR47)

Small, flexible bacteria that lack a cell wall. Mycoplasma can pass through 0.2 μm and some 0.1 μm rated filters and are unaffected by some antibiotics, such as penicillin. (TR70) (TR47)

An enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. (TR47)

A measure of virus infectively based on formation of a region, or “plaque” of lysed cells within a monolayer culture caused by viruses that kill and disrupt their host cell. The number of plaques is directly correlated to the number of infectious virus particles. (TR47)

The process of extracting virus from a lawn of plaque for growth in cell culture. By performing several rounds of plaque purification a virus clone can be isolated. (TR47)

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)

PCR method in which specialized instruments and reagents are used to measure the amount of amplified DNA present after each round of DNA replication. Analysis of the data allows calculation of the amount of template DNA present in the test sample. The technique can be used to quantify virus or free nucleic acid. (TR47)

RNA viruses containing a virally-encoded reverse transcriptase enzyme able to transcribe the RNA genome into DNA, which can then be incorporated into the host DNA. (TR47)

In the context of this Technical Report, the technique is used for dispersing viruses by use of sound-wave energy. (TR47)

A clumping of fused neighboring cells (syncytia) caused by viral infection when viral fusion proteins are transported to the surface of the infected cells and cause the host cell membrane to fuse with neighboring cells. The number of syncytia is directly correlated to the number of infectious virus particles. (TR47)

Quantal assays for determining the titer of a virus. The 50% tissue culture infective does (TCID50) is the dilution of virus that results in the infection of 50% of cell cultures that have been infected with the same dilution of the virus sample. (TR47)

Subjection of material to an exceedingly high g-force. The technique can be used to band or sediment virus particles. (TR47)

Physical separation of virus particles from the intended product. (TR47) (TR83)

A simple, potentially pathogenic organism composed of a single type of nucleic acid (DNA or RNA) encased in a protein shell (called a capsid) and, in some cases, a lipid membrane (called an envelope). Viruses are incapable of independent replication and therefore must infect a host cell in order to propagate. (TR41)

Obligate, intercellular, replicating, infectious agents that are potentially pathogenic, possessing only a single type of nucleic acid (either RNA or DNA). They use the host cells for propagation as they are unable to grow independently, for example by binary fission, and multiplying their genomic material. (TR47) (TR83)

Unintentionally introduced contaminant viruses. (TR47)

Viral entity whose genome is part of the germ line of the species of origin of the cell line and can be produced in culture by cell lines from these species. (TR47)

A virus used for characterization of viral clearance of the process when the purpose is to characterize the capacity of the manufacturing process to remove and/or inactivate viruses in general, i.e., to characterize the robustness of the purification process. (TR47)

A virus used in process evaluation studies that either is the virus, or of the same species as a virus known to or possible to contaminate the cell substrate or any other reagents or materials used in the production process. (TR47)

Virus that is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties as those of the observed or suspected virus. (TR47)

According to the mode of preparation the following terms are used:
Crude Virus Preparation: A virus preparation that has undergone minimal processing post propagation. The virus is usually separated from cells which are lysed as the result of virus replication or are freezed/thawed in one or several cycles to release the virus from infected cells. The preparation is typically purified from cell debris by low speed centrifugation.
Purified Virus Preparation: A virus that has undergone purification process by one or more techniques, such as density ultracentrifugation, chromatography or membrane adsorber. The purity of the virus preparation varies depending on the purification technique and should be characterized by appropriate analytical methods. (TR47)

A virus preparation that is used directly in a clearance study. It can be crude or purified. Typically a large volume is produced, tested and qualified. This volume is divided into multiple aliquots for individual clearance studies. (TR47)

An initial virus stock produced after a new virus is introduced into a laboratory. Its purpose is to create a Master Virus Bank. (MVB) (TR47)

The maximum volume that can be processed through a filter area. It is the volumetric capacity of the filter for a given process fluid and generally expressed in L/m². (TR41) (TR47)

A stock of cells or virus derived from the MCB/MVB and used to produce production cells, assay cells or virus production lots. (TR 47)