Invalid Test
Laboratory test that, as a result of the laboratory (Phase I) investigation, did not meet the test method requirements and whose results would not be deemed valid. This may also apply to a test which was aborted (e.g. breakdown of isolator during sterility testing). (TR88)
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Critical Process (CP)
A process that impacts a critical quality attribute of the intermediate, drug substance or drug product being manufactured and therefore should have established critical process parameters that can be monitored or controlled to ensure that the process produces the desired quality.
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Technically Unavoidable Particles (TUPs)
Particles that are visibly different from the bulk of the material when viewed with the naked eye within the container or against a suitable background (e.g., size, shape, color, number, texture) and are inherent to the manufacturer’s process, product, or raw materials. The unintended presence of a small quantity of particles, stemming from impurities of natural or synthetic ingredients, the manufacturing process, storage, or migration from packaging that is technically unavoidable in good manufacturing practice, and do not pose a risk to patient safety. (TR78)
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Intrinsic Particles
Those particles that arise from sources related to the formulation, packaging, or assembly processes. In each of these cases, the particle material (e.g., glass, stainless steel, rubber, or gasket material) could be identified as a known product-contact material. (TR78)
A particle that comes from within the primary process. These are qualified product contact materials and are often associated with the primary packaging components. They are unplanned but not unexpected.(TR85)
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Zone of Protection/Machine Shroud
A system fitted to a BFS machine to direct a flow of HEPA-filtered air over the Critical Processing Zone of the machine. (TR77)
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Parison
The “tube” of polymer extruded by the BFS machine from which the containers are formed. (TR77)
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Mandrel
Specialized filling needles on certain BFS machines which also act to form the container. (TR77)
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Dynamic (in operation)
BFS machine line fully operational and filling, with the number of allowed operating personnel present as during normal running conditions. (TR77)
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Advanced Aseptic Process
A process in which direct intervention with open product containers or exposed product contact surfaces by operators wearing conventional cleanroom garments is not required and never permitted. (TR77)
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Particulate Load
The total quantity of particles in solution as tested per qualified method. (TR76)
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Particles/Particulate (Intrinsic Particles)
Particles that arise from sources related to the materials of construction of the component. Examples of intrinsic particle materials include elastomeric particles of the same formulation or ingredients from elastomer for elastomeric components. (TR76)
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Particles/Particulate (Inherent Particles)
Particles that are expected from the drug formulation, and therefore not included as a category in this Lexicon.(TR76)
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Particles/Particulate (Extrinsic Particles)
Particles that are not part of the formulation but are foreign and unexpected. Examples of extrinsic particles include fibers (e.g., cellulous), clothing fragments, hair, foreign rubber (including degraded/reverted rubber of the same formulation), metal, plastic, and paint. Materials such as foreign rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a material of construction and therefore not considered part of the rubber formulation.(TR76)
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In-Process Observations
Observations or findings that are found during the processing of a product or products.(TR76)
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Container Closure Integrity (CCI)
The ability of a package to prevent product loss, to block microorganism ingress, and to limit entry of detrimental gases or other substances, thus ensuring that the product meets all necessary safety and quality standards.(TR76)
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Pressure Decay Test
A leak test in which a container or system is pressurized with air to a preset level. After the pressure has stabilized, the decay in pressure over a preset test time is measured and evaluated to determine if a leak (defect) is present. (TR66)
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Probability of a Non-Sterile Unit (PNSU)
The number that expresses the probability of occurrence of a non-sterile unit after exposure to a sterilization process. Within the pharmaceutical industry, a design end point better than or equal to the probability of one non-sterile unit in a million units is expected, i.e., PNSU ≤ 10–6. [Synonym: Steriliy Assurance Level (SAL)] (TR01)
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Primary Contact Surfaces
All process surfaces that have a direct influence on the quality of the drug substance being manufactured, including surfaces processing equipment, storage containers, and of processing aids during manufacturing operations. (TR54-4)
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Process
A series of operations and/or actions used to produce a desired result. (TR38)
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Pressure Hold Test (or Leak Test)
A test for leaks and gross defects in which the system is held at a defined pressure for a defined time. Failure is indicated by the observation of a steady stream of air bubbles downstream of the filter. (TR41)
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Water for Injection (WFI)
Water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms and contains no added substances. (TR45)
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Water for Bacterial Endotoxin Test (BET)
Sterile Water for Injection or other water that shows no reaction with the specific bacterial endotoxin test reagent with which it is to be used, at the limit of sensitivity of such reagent. (TR3)
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Worst-Case Process Condition
A condition or set of conditions encompassing upper and/or lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions (such conditions do not necessarily induce product or process failure). (TR29)
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Z-Value
The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat as the temperature changes during the heating and cooling phases of a sterilization cycle. (TR01) (TR3) The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat over time (i.e., calculation of F0) as the temperature changes in a cycle. (TR61)
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Worst Case Soil
A soil that is the most difficult to clean from production equipment based on knowledge generated from laboratory studies, scientific properties, and/or production experience. (TR29)
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Worst Case Load
The load configuration that is determined to be most difficult to sterilize. This is a function of the cycle control strategy and load item characteristics (e.g., mass, configuration, or air removal challenges). For porous/hard goods loads, this may not necessarily be the minimum or maximum load. (TR01) The load configuration that is determined to be most difficult to sterilize or depyrogenate. This is a function of the process control strategy and load item characteristics (e.g., mass, configuration). (TR3)
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Temperature Probe/Sensor
A generic term used to describe any type of temperature measuring device that works through contact with the material or atmosphere to be measured. [Synonyms: Load Probe, Heat Penetration Probe, Temperature Distribution Probe, Drain Probe] (TR48)
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Temperature Distribution
Temperature measurement of the heating medium (e.g., forced hot air) across the chamber load zone. (TR01) (TR03) (TR30) (TR48)
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Viable
Alive and able to be cultured in the laboratory. (TR69)
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Vapor
The gaseous form of materials that are normally liquids or solids at room temperature and pressure. (TR51)
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Titer Reduction (TR)
A measure of the degree to which a particular filter removes a microorganism under specified test conditions. Calculated as the ratio of the total number of microorganisms used to challenge the filter divided by the total number of microorganisms that passed through the filter. (TR75)
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Unidirectional Air Flow Hood (UAFH)
A cabinet designed to protect materials from operator and environmental contamination. Also referred to as laminar air flow hood. (TR62)
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Vapor Phase Hydrogen Peroxide (VPHP)
A disinfection system in which 35% hydrogen peroxide is changed to a vapor phase and used for bioburden reduction of a chamber or items in a chamber. (TR70)
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Upstream
The influent side of the filter. (TR45) (TR26)
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Viral Removal
Physical separation of virus particles from the intended product. (TR47) (TR83)
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Transmembrane Pressure (TMP)
The pressure difference equal to the average feed-stream pressure minus the average filtrate-stream pressure. TMP = (Pfeed + Pretentate)/2 - Pfiltrate (TR15)
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Thermometric Study
The utilization of independent temperature monitoring devices to determine a temperature profile within the load zone and analysis of the collected data. (TR3)
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Viral Inactivation
Reduction of virus infectivity caused by chemical or physical modification. (TR41) (TR83)
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Thermocouple
A device for measuring temperature in which a pair of wires of different metals are joined and the free ends of the wires are connected to an instrument (such as a voltmeter) that measures the electrical potential difference created at the junction of the two metals. (TR3)
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Transfer Disinfection
A disinfection process conducted on materials and equipment that coats the surface for a validated wetted time to remove bioburden prior to introducing such items into classified areas. (TR70)
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Targeted Species
The range of species for which detection or analysis is aimed for by an assay method. (TR50)
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TCld50 Assay
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)
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Spore
A bacterial dormant form that is highly resistant to adverse conditions. Fungal spores are not highly resistant; their susceptibilities are closer to vegetative microorganisms. (TR13)
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Specified Microorganisms
Microorganisms with limit tests for absence in 1 or 10 g of a drug product, as described in USP <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms and USP <1111> Microbiological Quality of Nonsterile Pharmaceutical Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use. (TR67)
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Sporicidal Vapor Phase Decontamination
The destruction of inactivation of microbial spores using a vapor or gaseous agent. (TR51)
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Single-Use Component (SUC)
An individual part designed to perform a particular function when assembled into a single-use system. (TR66)
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Steam in Place Cycle
A sequence of defined steps and operating parameters (e.g., time, temperature, and pressure) performed in situ on equipment and/or systems to provide a given sterility assurance level (SAL) or defined sanitization level. (TR61)
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Steam: Plant Steam
Steam of undefined chemical or biological quality produced from a boiler, usually containing boiler additives, without further treatment. [Synonym: Factory Steam, House Steam, Industrial Steam] (TR48)
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Sonication
In the context of this Technical Report, the technique is used for dispersing viruses by use of sound-wave energy. (TR47)
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Single-Use System (SUS)
An engineered process equipment solution, most commonly assembled from components made using polymeric materials, which together create a system or unit operation designed for one time or campaign use. (TR66)
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