PDA Glossary

Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. (TR57-2)

The maximum amount of residue allowed in a product, in an analytical sample, or as an amount per surface area. (TR29)

The closeness of the actual test results obtained by the new method to the actual test results obtained by the existing method. (TR33)

An analytical procedure expresses the closeness of agreement between the value that is accepted either as a conventional true value or an accepted reference value and the value found. This is sometimes termed trueness. (TR57)

An established microbial or airborne particle level that, when exceeded, indicates a process is outside of its normal operating range. A response to such an excursion should involve a documented investigation and corrective actions based on the results of that investigation. (TR13)

An established microbial or non-viable particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation. (TR22)

An established microbial or airborne particle level for environmental, water or gas monitoring that, when exceeded, indicates that a facility process is outside of its normal operating range. The response to such an excursion involves a documented investigation and corrective actions based on the results of that investigation. The prescribed action level is often specified in guidance or standards relating to environmental monitoring and water quality. (TR69)

An established microbial or nonviable particle level for environmental, water, or gas monitoring that, when exceeded, indicates a facility or process is outside of its normal operating range. The response to such an excursion may involve a documented investigation and corrective actions based on the results. The prescribed action level is often specified in guidances or standards relating to environmental monitoring and water quality (3-6). (TR88)

An established microbial or non-viable particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation. (TR22)

An internal (in-house) value used to assess the consistency of the process. The cause of the excursion should be investigated and documented and corrective action is generally required. Action limits are not specifications. (TR42)

An established internal (in-house) data-based value which is part of the control strategy and used to assess the consistency of the manufacturing process. An action limit excursion result in an investigation, identification of recovered isolates, root-cause analysis, assessment of a systemic failure and impact on product quality and patient safety. (TR69)

An established internal (in-house) data-based value that is part of the control strategy and used to assess the consistency of the manufacturing process. An action limit excursion result in an investigation, identification of recovered isolates, root-cause analysis, assessment of a systemic failure and impact on product quality and patient safety. (TR74)

A limit that, when exceeded, indicates a process is outside of its normal operating range. A response to such an excursion should involve a documented investigation and corrective actions based on the results of that investigation. (TR60)

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)

A foreign material that is introduced inadvertently; not natural or hereditary (as in microbial, chemical, or biochemical contamination of a purified substance). (TR 69)

An exogenously introduced infectious virus that is unintentionally present in a biological product or its manufacturing process. (TR71) (TR83)

The American Society of Hospital Pharmacists (ASHP) defines a significant ADR as any unexpected, unintended, undesired, or excessive response to a drug that:
(1) Requires discontinuing the drug (therapeutic or diagnostic) Requires changing the drug therapy
(2) Requires modifying the dose (except for minor dosage adjustment)
(3) Necessitates admission to a hospital
(4) Prolongs stay in a healthcare facility
(5) Necessitates supportive treatment
(6) Significantly complicates diagnosis
(7) Negatively affects prognosis
(8) Results in temporary or permanent harm, disability, or death.
The World Health Organization (WHO) defines ADR as any noxious, unintended, and undesired effect of a drug which occurs at doses used for prophylaxis, diagnosis, or therapy, excluding therapeutic failures, intentional and accidental overdose and drug abuse. It does not consider errors in drug administration to be adverse events. (TR55)

An AE report is a communication to the U.S. FDA of an undesirable sign or symptom associated with use of a drug as required and detailed by 21 CFR 314.80. These reports are logged into the U.S. FDA’s Adverse Event Reporting System (AERS). Drug manufacturers are required to report adverse event information to FDA. These reports may also may be voluntarily submitted to the FDA directly by healthcare professionals or the general public at Med Watch. The reports are reviewed, safety issues are monitored, and data are periodically analyzed and assessed by the Center for Drug Evaluation and Research (CDER). (TR55)

A series of alert-level or action-level excursions that indicates the system or areas are not in control and have the potential to affect the product quality. (TR 70)

An increase in the frequency of alert- and action-level excursions or repeated recovery of low levels of microorganisms below the alert level during microbial monitoring or of pharmaceutical ingredient or finished product failure that is indicative of a loss of process control. (TR88)

A microorganism that utilizes oxygen as the final electron acceptor during metabolism; a microorganism that will grow primarily in the presence of oxygen. For the purpose of this report, this definition encompasses facultative anaerobes. (TR22) (TR62)

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 moist heat sterilization process that operates at a controlled pressure greater than saturated steam pressure and typically uses compressed air to bring the chamber to the desired pressure. (TR01) (TR48)

A moist heat sterilization process that operates at a controlled pressure greater than saturated steam pressure and typically uses compressed air to bring the chamber to the desired pressure. (TR01) (TR48)

A test used to evaluate air removal and steam penetration in an empty sterilizer that is used for porous/hard goods load sterilization (e.g., Bowie-Dick Test, DART, Lantor Cube, Browns’ Test). (TR01) (TR 48)

The total number of particles of a specific size per unit volume of air. (TR13)

The total number of particles of a specific size per unit volume of air. (TR13)

A room that controls the airflow between two rooms of different classification. (TR 70)

An established microbial or nonviable particle level giving early warning of potential drift from normal operating conditions; not necessarily grounds for definitive corrective action but typically requires follow-up investigation. (TR13) (TR22) (TR69)

An established level that, when exceeded, is giving an early warning of a potential drift from normal operating conditions; while not necessarily grounds for definitive corrective action, it typically requires follow-up review. (TR 60)

An established microbial or nonviable particle level giving early warning of potential drift from normal operating conditions; not necessarily grounds for definitive corrective action, but typically requires follow-up investigation (3, 4, 7). (TR88)

An established internal (in-house) data-based value giving early warning of potential drift of manufacturing process from normal operating conditions and triggers appropriate follow-up investigations. Alert limits are always lower than action limits. (TR69)

A novel, modern and/or fast microbiological testing method that is different from a classical or traditional growth-based method, such as agar-plate counting or recovery in liquid broth media. The alternative or rapid method may utilize instrumentation and software to manage the testing and resulting data, and may provide quantitative, qualitative and/or microbial identification test results. Automated technologies that utilize classical growth-based methods may also be designated as being novel, modern or rapid, based on their scientific principle and approach to microbial detection. The terms alternative, rapid microbiological method, rapid method and the acronym RMM are used interchangeably within this technical report. (TR33)

A segment of double stranded DNA formed as the product of polymerase chain reaction or other amplification based techniques such as TMA or NASBA. (TR50)

An organism that has the ability to grow in the absence of oxygen. (TR51)

Substance used to destroy or suppress the growth of microorganisms, whether bacteria, fungi, or viruses, on inanimate objects and surfaces. (TR70)

Serves communities of the analytical sciences by providing the tools and processes necessary to develop voluntary consensus standards or technical standards through stakeholder consensus and working groups in which the fit-for-purpose and method performance criteria are established and fully documented. (TR55)

Disinfection of floors, walls, ceilings, and other surfaces. (TR70)

Free from disease-producing microorganisms. (TR28)

Free from disease-producing microorganisms. An operation performed in a controlled environment designed to prevent contamination through the introduction of microorganisms. (TR26)

The part of aseptic processing where a pre- sterilized product is filled and/or packaged into sterile containers and closed. (TR22) (TR28) (TR62) (TR13)

A process in which sterile materials are handled in an environment in which the air supply, materials, equipment and personnel are controlled to prevent microbial and particulate contamination. (TR44) (TR51)

Handling sterile materials in a controlled environment, in which the air supply, facility, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels. (TR28) (TR62) (TR69)

Handling of sterile product, containers, and/ or devices in a controlled environment in which the air supply, materials, equipment, and personnel are regulated to maintain (product) sterility. (TR13)

Controlled environment, consisting of several zones, in which the air supply, facility, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels. (TR22) (TR28) (TR62) (TR70)

A means for establishing the capability of an aseptic process as performed using a growth medium. (TR22) (TR62)

Discrete association of a microorganism with an animate or inanimate surface. (TR69)

A chamber for steam sterilization. (TR45)

Endotoxins are fever producing substances commonly found in the cell wall of certain Gram-negative bacteria. (TR3)

Assay for measuring active endotoxin by combining a liquid test sample with Limulus amebocyte lysate (LAL) reagent and measuring the resulting proportional reaction via visual, turbidimetric, chromogenic, or other validated means of detection. (TR3)

Small glass beads (spheres) obtainable in a range of sizes, used in the recovery of spores from paper carriers. (TR51)

A systematic difference in a method that manifests itself as a deviation of the method mean from an expected value. (TR57)

Total systematic error, in contrast to random error. Measurement centered on the true result is said to be unbiased or have no systematic error. The distance between the center of a large (infinite) number of measurements and the correct value is the bias. (TR 57-2)

A method used to assess the presence of analytes (chemical or biological) in biological samples (e.g., serum, plasma, etc.). (TR57)

Analysis (as of a drug) to quantify the biological activity(ies) of one or more components by determining its capacity for producing an expected biological activity. (TR57)

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)

Chemical substance that has been proven to kill specific microorganisms common in the pharmaceutical manufacturing environment. (TR 69)

Microbially derived sessile community characterized by cells that are irreversibly attached to a substratum, interface, or each other; are embedded in a matrix of extracellular polymeric substances (EPSs) that they produce; and exhibit an altered phenotype with respect to growth rate and gene transcription. (TR 69)

Accumulation and subsequent deleterious effects of biological contaminants on engineered products or processes (TR 69)

Property that describes the specific ability or capacity of a product to achieve a defined biological effect. (TR57)

An inoculated carrier contained within its primary pack ready for use and providing a defined resistance to the specified sterilization process. (TR51)

A test system containing viable microorganisms of a pure and specified strain providing a defined resistance to a specified sterilization process (TR1)(TR3) (TR30) (TR61)

A product (therapeutic or prophylactic) for human use that has been manufactured in or from a biological source. Examples include recombinant therapeutic proteins or vaccines. Biological medicinal products are also referred to as: biological medicines, biological products, biologics and biologic drugs. (TR 71)

A component of performance qualification that demonstrates, by use of biological indicators, that the required lethality (F_BIO) is achieved consistently throughout the load. (TR1) (TR3) (TR30)

A component of performance qualification that demonstrates, by use of biological indicators, that the required lethality (F_BIO) or spore log reduction (SLR) is achieved consistently throughout the sterilized or sanitized portion of the SIP system. (TR61)

An enclosed, ventilated workspace with engineering controls designed to remove or minimize exposure to hazardous biological materials. A BSC is a principle device to provide containment of infectious splashes or aerosols generated by many microbiological procedures. BSCs are designed to provide personnel, environmental and product protection when appropriate practices and procedures are followed. A cabinet that is designed to protect the operator and the environment from the hazards of handling infected material and other dangerous biological. (TR62)

Biological tests include animal, cell culture, or biochemical based testing that measures a biological, biochemical, or physiological response. (TR38)

An application, filed with the US Food and Drug Administration (FDA), which contains specific information on the manufacturing processes, chemistry, pharmacology, clinical pharmacology and the medical effects of the biologic product (similar function as the Marketing Authorization Application in Europe). (TR56)

The enzyme chlorophenol o-methyltransferase responsible for fungal methylation has been isolated in cell-free extracts. Biomethylation, in this context, may be seen as a detoxification mechanism, although it plays a role in the production of mycotoxins by secondary metabolism. Slightly xerophilic fungi frequently associated halophenol biomethylation include Trichoderma longibrachiatum, Trichoderma virgatum, Aspergillus sydowii, and Penicillium islandicum. (TR55)

A test to indicate the maximum pore size of a filter. The differential gas pressure at which a liquid (usually water) is pushed out of the largest pores and a steady stream of gas bubbles is detected from a previously wetted filter under specific test conditions. Used to test filter integrity with specific, validated, pressure values, wetting liquids and temperatures for specific pore-size (and type of ) filters. (TR26)

The CE marking is a key indicator of a product’s compliance with EU legislation and enables the free movement of products within the European market. (TR58)

A systematic approach to proposing, evaluating, approving, implementing, and reviewing changes. (TR 51) (TR 54-5)

Scientifically sound method of a generally complex nature that is used for nonroutine assessment of specific biochemical, chemical, physicochemical, immunochemical, microbiological, and biological characteristics or inherent properties of a compound. (TR 57-2)

A series of tests designed to increase process knowledge by examining proposed operational ranges and their individual and/or combined impact on the chromatography process. (TR14)

A late-stage study that evaluates the process to increase process knowledge and examines proposed operational ranges and their individual and/or combined impact on target protein quality. (TR42)

A room designed, maintained, and controlled to prevent particle and microbiological contamination of a drug product or medical device. A cleanroom is assigned and reproducibly meets an appropriate air cleanliness classification. (TR13)

The minimum amount of time that a sanitizer, disinfectant, or sporicide must be left in complete (wet) contact with the surface to be treated in order to be effective. (TR70)

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)

The location within a sealed liquid container that achieves the lowest process lethality (F₀) during a sterilization process. (TR01)

Any adventitiously or externally introduced material(s) (e.g., chemical, biochemical, or microbial species) not intended to be part of the process. (TR14) (TR15) (TR70)

An undesired impurity of a chemical or microbiological nature that is introduced into a raw material, intermediate, or API (drug substance) during manufacture. (TR14) (TR15)

Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not intended to be part of the manufacturing process of the drug substance or drug product. (TR69) (TR74)

Any adventitiously introduced material (e.g., chemi­cal, biochemical) or microorganisms including viruses not intended to be included in the manufacturing process of the drug substance or drug product. (TR83)

The percentage of units filled in a process simulation that are positive for microbial growth after incubation. (TR22)

A convection oven with a conveyor belt that transports articles through several temperature zones that are supplied with heated forced HEPA filtered air. The pre-heat/loading zone warms articles prior to the heat zone, the heat zone heats articles to sterilization or depyrogenation temperature and the cool zone cools articles prior to conveyance out of the unit. [Synonym: Tunnel Sterilizer] (TR3)

A device that modulates the flow of fluid (e.g., gas, steam, water) in a conduit in response to a signal from a process measurement control system. (TR48)

An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination (an air supply approximating to Grade D may be appropriate), and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure positive to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. (TR13)

The phase of a sterilization cycle that occurs after completion of the exposure phase. Parameters of a cool-down phase are typically defined in order to meet applicable user requirements for load cooling and drying. (TR01)

The phase of a sterilization cycle that occurs after completion of the exposure phase. [Synonym: post-conditioning phase, slow exhaust phase, drying phase, equalization phase] (TR48)

The phase of an SIP cycle that occurs after completion of the exposure phase. Parameters (e.g., time, temperature, pressure) of a cool-down phase are typically defined in order to meet applicable user requirements for system cooling and drying. (TR61)

A small, generally flat portion of a defined material of construction (such as stainless steel or PTFE) and of a defined surface finish, typically used for laboratory cleaning evaluations and/or for laboratory sampling recovery studies. (TR29) (TR49)

The appropriate distribution of a chemical agent needed on the equipment surface to be effective. (TR70)

An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas. (TR13) (TR22) (TR44) (TR62)

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.

A surface within a critical area that may come in direct contact with sterilized products, containers, or closures. (TR13)

See Tangential Flow Filtration. (TR15)

Volumetric rate of fluid flow parallel to the membrane surface. (TR15)

A series of activities performed for the purpose of defining or confirming the cycle parameters (e.g., time, temperature, pressure) necessary to ensure sanitization or sterilization. (TR61)

A discrete series of sterilizer process steps (such as, heat-up, exposure and cool-down) performed sequentially that represent a complete sterilization cycle. (TR48)

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)

Area of entrapment in a vessel or piping run that could lead to contamination of the product. (TR69)

An area of entrapment in the vessel or piping run that could lead to contamination of the product due to insufficient exposure to moist heat. (TR61)

A process that is designed to remove soil (including microorganisms) and may consist of cleaning and/or disinfection. (TR51)

The breakdown (usually chemical) of material during manufacture, including during and after the cleaning process. (TR49) (TR70)

Molecular variants resulting from changes in the desired product or product-related substance brought about over time and/or by the action of light, temperature, pH, water, etc., or by reaction with an excipient and/or the immediate container/ closure system. Such changes may occur because of manufacture and/or storage (e.g., deamidation, oxidation, aggregation, proteolysis). Degradation products may be either product-related substance or product-related impurities. (TR57)

Water treated by passing through both cation- and anion-exchange resin beds, or a mixed-resin bed to remove both positive and negative ions. (TR45)

The destruction and/or removal of bacterial endotoxins. A depyrogenation process should demonstrate at least 99.9% or a 3-log endotoxin reduction. (TR3)

Removal or destruction of pyrogens. (TR70)

A synthetic wetting agent and emulsifier that can be added to a solvent to improve its cleaning efficiency. (TR70)

The temperature at which a vapor or vapors become saturated. (TR51)

The temperature to which a given parcel of humid air must be cooled, at constant barometric pressure, for water vapor to condense into water. The condensed water is called dew. The dew point is a saturation temperature. The dew point is associated with Relative Humidity (RH). A high RH indicates that the dew point is closer to the current air temperature. RH of 100% indicates the dew point is equal to the current temperature and the air is maximally saturated with water. When the dew point remains constant and temperature increases, RH will decrease. (TR55)

The time from the end of product manufacturing until the beginning of the cleaning process (also called “soiled hold time”). (TR29)

A device designed for on/off operation; fully opened or fully closed. (TR48)

A chemical or physical agent that reduces, destroys, or eliminates vegetative forms of harmful microorganisms but not spores. (TR70)

The destruction of pathogenic and other kinds of microorganisms by thermal or chemical means. (TR51) (TR70)

Process of eliminating nearly all recognized pathogenic microorganisms but not necessarily all microbial forms (e.g., bacterial spores) on inanimate objects. (TR69)

The chemical or physical inactivation of a bioburden on inanimate surfaces. Typically this requires a minimum three-log (3-log) reduction of vegetative microorganisms and two-log (2-log) reduction for bacterial spore be achieved in validation. (TR13)

The effluent side of the process step (filter). (TR45)

The filtrate or outlet side of the filter. (TR26)

No visible water in the equipment or line when viewed under appropriate lighting conditions. (TR29) No visible water pool evident in the equipment or line when viewed under appropriate lighting conditions. (TR49)

An absolute measure of the actual latent heat of a sample of steam relative to the theoretical latent heat of saturated steam. (TR01) (TR48)

A dimensionless test quantity developed to approximate the dryness fraction. (TR01)

The time in minutes required for a onelogarithm, or 90%, reduction of the population of microorganisms used as a biological indicator under specified lethal conditions. For steam sterilization, the D-value should always be specified with a reference temperature, DT . For example, a BI system with a D121°C = 1.4 minutes requires 1.4 minutes at 121°C to reduce the population by one logarithm.(TR1) (TR61)

The time in minutes required for a one-logarithm, or 90%, reduction of the population of microorganisms used as a biological indicator under specified lethal conditions. For dry-heat sterilization, the D-value should always be specified with a reference temperature, DT. For example, a biological indicator (BI) challenge system with a D 160°C=1.9 minutes, requires 1.9 minutes at 160°C to reduce the population by one logarithm. (TR3)

The time in minutes at a specific temperature required to reduce the population of a specific microorganism by 90% [or one (1) log] in defined conditions [e.g., method of sterilization (dry heat versus

steam), solute, or carrier]. (TR13)

The time in minutes required for a one-logarithm, or 90%, reduction of the population of microorganisms used as a biological indicator under specified lethal conditions. (TR51)

The period that items are subjected to a given processing condition. [Synonym: Residence Time] (TR3)

BFS machine line fully operational and filling, with the number of allowed operating personnel present as during normal running conditions. (TR77)

Monitoring of an environment during normal operations, that is, when the usual equipment is operating and personnel are present, and the process or simulated process is ongoing. Per the EU and ISO documents this is synonymous with operational condition (including the equipment operating and personnel present). (TR13)

A device that produces vacuum by means of the Venturi effect. [Synonym: Aspirator, ejector pump] (TR48)

A virus that pre-exists in the genome of the cell substrate. (TR71)

A virus that integrates into the genome of the cell substrate. (TR83)

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 type of spore formed intracellularly by some bacterial genera. (TR51)

Lipopolysaccharides from the cell walls of bacteria, the most potent of which derive from Gram-negative organisms. When injected, they are known to cause a febrile, or fever-producing reaction that can cause severe patient reactions, and on occasion, can be fatal. (TR26) (TR44)

Pyrogenic lipopolysaccharide component of Gram-negative bacterial cell walls. (TR69)

An article challenged with a vial of endotoxin (or a carrier spiked with endotoxin) designed for use in depyrogenation studies. The endotoxin (a purified lipopolysaccaride) is validated for use in or on an endotoxin indicator. The carrier is made from a material appropriate for the intended depyrogenation processes to which it will be subjected. The endotoxin on a carrier is added at a concentration sufficient to allow recovery of a minimum of 1000 USP endotoxin units/carrier. The endotoxin indicator would allow for accurate indication of at least a 3-log reduction in USP endotoxin units during depyrogenation process challenges. (TR3)

A classical PCR method based on repeated cycling of the reaction mixture between two or three temperatures (denaturing, annealing, and extension) with detection of the amplified product after reaction completion (e.g., by agarose gel electrophoresis). (TR50)

Conditions and corresponding measurements as associated with facilities and equipment used in the control of a manufacturing area that may impact the identity, strength, quality, or purity of a product. Among such parameters are airflow rates and patterns, pressure differentials, materials and personnel flow, temperature and relative humidity, as well as nonviable and viable particulates. (TR13)

Microorganisms associated with a processing environment. (TR22)

Describes the processes and activities that need to take place to characterize and monitor the quality of the environment. (TR70)

Monitoring for nonviable particulates and/or microorganisms where the result meets or exceeds the alert and/or action level or limit. (TR88)

Defined documented program which describes the routine particulate and microbiological monitoring of processing and manufacturing areas, and includes a corrective action plan when action levels are exceeded. It includes assessment of environmental air, surfaces and personnel. (TR22) (TR28) (TR62)

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

Lipopolysaccharides from the cell walls of bacteria, the most potent of which derive from Gram-negative organisms. When injected, they are known to cause a febrile, or fever-producing reaction that can cause severe patient reactions, and on occasion, can be fatal. (TR26) (TR44)

Pyrogenic lipopolysaccharide component of Gram-negative bacterial cell walls.(TR69)

The major constituent of the outer membrane of Gram-negative bacteria is composed of lipid A, the core polysaccharide, and the O-antigen polysaccharide; endotoxin is also known as lipopolysaccharide (LPS).(TR82)

The phase of the sterilization cycle in which the appropriate parameters are maintained within defined ranges for the time (exposure time or dwell period) and temperature determined to be necessary to achieve the desired lethality. (TR1) (TR3) (TR30) (TR48) (TR61)

Product of microbial growth, particularly in biofilms, composed of polysaccharides, lipids, proteins, and nucleic acids; produced by bacteria and fungi; is an important mediator of microbial attachment to surfaces and biofilm formation. (TR69)

Those particles that are not part of the formulation, package, or assembly process but rather are foreign and unexpected. Materials such as rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a product-contact material. (TR78)

Foreign material that comes from outside the primary process.  Often these are from the manufacturing environment or incomplete cleaning of components. They are uncontrolled. (TR85)

<p>A term used when the specific reference conditions of T_ref- = 121.1&deg;C and z = 10&deg;C are used to calculate the equivalent lethality. For example, when the z-value of the BI is 10&deg;C, a cycle with an F(T=121.1&deg;C, z=10&deg;C), or F₀, equal to 8 minutes is equivalent (in terms of delivered lethality) to a square wave cycle of 8 minutes at 121.1&deg;C. A square wave cycle that provided an exposure of 25.9 minutes at 116&deg;C would also yield an F₀ of 8 minutes.   Note: The reference temperature used in calculating F₀ is 121.1&deg;C, which is the approximate mathematical equivalent of 250°F. (TR01) (TR30) (TR48) (TR61)</p>

A test result that is erroneously classified in a negative category (e.g., the absence of a viable microbial detection result when viable microorganisms are present). (TR33)

A test result that is erroneously classified in a positive category (e.g., a viable microbial detection result when viable microorganisms are not present). (TR33)

A population of microorganisms having complex nutritional requirements and thus difficult to cultivate. (TR50)

The fluid and all constituents in a fermentation vessel prior to separation. (TR45)

A device used to remove particles from a fluid process stream that consists of a porous medium and a support structure. Porous material through which a liquid or gas is passed to remove viable and non-viable particles.(TR26)

This term refers to items such as drug substances, drug products, finished product held in bulk before final packaging, and clinical trial materials that are likely to be stored for significant periods of time and are also subject to the risks of distribution. (TR53)

Refers to the air exiting at the face of HEPA filters. Based on the airflow through HEPA filters and its unidirectional air flow the air exiting at the filter face is for the purposed of aseptic processing free of particulate contamination (both viable and non-viable). (TR70)

The work location first in the path of HEPA filtered air. (TR62)

A flexible-wall container designed with 2 sides (two dimensional or “pillow” shape) or 6 sides (three dimensional cuboid shape) designed to hold process fluids or product. (TR66)

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)

Fraction-negative methods use the starting population of a biological indicator (N₀) and data in the quantal range to create a two-point line from which the DT-value can be determined. The quantal range is the exposure period over which a set of replicate test units exhibit a dichotomous response – some are positive for growth and the rest are negative for growth. (TR01)

Microorganisms responsible for infection in healthy individuals (i.e., individuals with normal operative and functional host defense mechanisms) that may be acquired from exposure to other infected people or animals, environmental reservoirs (exogenous) or the individual’s normal (endogenous) microbial flora. (TR67)

No visible water pool in the equipment or line when viewed under appropriate lighting conditions (but may contain water droplets). (TR29)

A process of collecting data in which conditions are monitored at a defined frequency not exceeding sixty minutes during operation. In most U.S. applications, this means “during production.” (TR13)

A measurement of sterilization effectiveness, the F-value is the calculated equivalent lethality (using a specified z-value), in terms of minutes at a reference temperature (T_ref), delivered by a sterilization cycle. (TR1) (TR3) (TR30) (TR48) (TR61)

A term used to describe the delivered lethality, measured in terms of actual kill of microorganisms on or in a BI challenge system. The FBiological-value is calculated as DT × LR, where DT is the D-value of the BI system at the reference temperature (T) and LR is the actual logarithmic reduction (log N₀ – log N_F) of the BI population achieved during the cycle. (TR1)

A term used when the specific reference conditions of T_ref = 121.1°C and z = 10°C are used to calculate the equivalent lethality. For example, when the z-value of the BI is 10°C a cycle with an F(T=121.1°C, z=10°C), or F₀, equal to 8 minutes is equivalent (in terms of delivered lethality) to a square wave cycle of 8 minutes at 121.1°C. A square wave cycle that provided an exposure of 25.9 minutes at 160deg;C would also yield an F₀ of 8 minutes. (TR1)

A term used to describe the delivered lethality calculated based on the physical parameters of the cycle. The FPhysical-value is the integration of the lethal rate (L) over time. The lethal rate is calculated for a reference temperature (T_ref-) and z-value using the equation: L = 10(T-T_ref- )/z. (TR1)

The term F-value may also be used in dryheat depyrogenation processes to calculate the time in minutes equivalent to a lethality or endotoxin destruction effect delivered by dry heat at 250°C. The F-value reference temperature is set at 250°C and the z-value minimum is set at 46.4°C. (TR3)

A term used when the specific reference conditions of T_ref = 160°C and z=20°C are used to calculate the equivalent lethality. For example, when the z-value of the BI is 20°C a process with an F_{(T=160°C, z=20°C)}, or F_H, equal to 8 minutes is equivalent (in terms of delivered lethality) to a square wave process of 8 minutes at 160°C. A square wave process that provided an exposure of 45.2 minutes at 145°C would also yield an F_H of 8 minutes. (TR3)

The process by which a material is rendered sterile by exposing the material to a radioactive source, such as Cobalt 60. (TR70)

Ionizing radiation that can be used to sterilize a material. (TR26)

A gene or DNA sequence within a chromosome which can be used for discrimination of one mycoplasma species or strain from another. (TR50)

An amount of nucleic acid equivalent to the genetic complement present in the genome of a single microorganism. (TR50)

Relating to those characters that reside in the genetic complement of a specific strain of a specific organism. (TR51)

A compound that destroys all vegetative microorganisms. (TR70)

An organism that retains the Gram stain. (TR51)

A sterilization process based on the principle that cold air within the chamber is heavier than the steam entering and will sink to the bottom of the chamber. As steam enters the chamber, air is pushed out the bottom drain and exits, with the condensate, through a steam trap. (TR01) (TR48) (TR61)

A process of dividing areas of equivalent classifications into grids for the purpose of uniformly assessing contamination characteristics in that area.This process is usually confined to the validation of new facilities and not routine monitoring. (TR13)

A strategy for establishing similar cleaning processes, usually based on similar products or similar equipment, and to validate the cleaning process based primarily on validation data for a representative of the group. (TR29) (TR49)

Test performed to demonstrate that media will support microbial growth. (TR22) (TR28)

Energy that is transferred as a result of a temperature difference between an object and its surrounding. (TR01) (TR3)

Heat penetration testing is a temperature measurement that is used to evaluate the amount of energy that has been transferred to the materials that are to be sterilized within the load. For measurements of heat penetration, the probes should be placed on or in the load items being evaluated. (TR01) (TR3) (TR30) (TR48)

Energy that is transferred as a result of a temperature difference between an object and its surroundings. (TR48)

The phase of a sterilization cycle that occurs prior to the exposure phase. Process parameters are developed for this phase in order to meet applicable user requirements for load conditioning (e.g., air removal and preheating.) (TR01) (TR3) (TR48) (TR61)

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 type of air filter that must satisfy certain standards of efficiency such as those set by the United States Department of Energy (DOE). The air filter must remove 99.97% of all particles greater than 0.3 micrometer from the air that passes through it. (TR62) (TR70)

The formation of a double-stranded complex of complementary strands of nucleic acids (e.g., a primer and single-stranded DNA or RNA) (TR50)

The ability of an assay to detect a target microorganism. (TR33)

Cell lines that are used in in vitro assays to detect the presence of viral agents. (TR71)

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)

Tests that provide data that are collected without pre-established acceptance criteria to further evaluate the process. (TR42)

A carrier upon which a defined number of test organisms have been deposited. (TR51)

Checks performed during production to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or API (drug substance) conforms to its specifications and/or other defined quality criteria (e.g., limits for bioburden and endotoxin). [Synonym: process control] (TR14) (TR74)

Checks performed during production to monitor and, if appropriate, to adjust the process and/or to ensure that the intermediate or drug substance conforms to its specifications (17) and/or other defined quality criteria (e.g., limits for bioburden and endotoxin). (TR60)

Checks performed during production to monitor and, if appropriate, adjust the process to ensure that the intermediate or active pharmaceutical ingredient conforms to its specifications. (TR57-2)

Observations or findings that are found during the processing of a product or products.(TR76)

An inspection where either a unit of product is classified as conforming or nonconforming or the number of nonconformities in the unit of products is counted with respect to a given requirement or set of requirements (TR76)

Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements. (TR14) (TR42) (TR48) (TR61) (TR64)

The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manu­facturer’s recommendations. (TR54-5)

Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements (17). (TR60)

Test to determine the functional performance of a membrane filter or container/closure system. (TR22)

A nondestructive test used to predict the functional performance of a filter. (TR45)

A nondestructive physical test that can be correlated to the bacterial retention capability of a filter/filter assembly. (TR26)

A method of determining if a membrane or filter is physically intact and free from gross defects. (TR15)

Use for which a product, process or service is intended according to the specifications, instructions and information provided by the manufacturer. (TR54)

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

An aseptic manipulation or activity performed by personnel that occurs within the critical area. (TR22) (TR44) (TR62)

An intervention that is performed to correct or adjust an aseptic process during its execution. Examples include such activities as: clearing component misfeed, adjusting sensors, and replacing equipment components. (TR22) (TR62)

An intervention that is an integral part of the aseptic process and is required for set-up or routine operation and/or monitoring, e.g., aseptic assembly, container replenishment, environmental sampling, etc. Inherent interventions are required by batch record, procedure, or work instruction for the proper conduct of the aseptic process. (TR22) (TR62)

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)

A field study that validates the effectiveness of a disinfecting agent, the trained operators, and the approved operating procedures. (TR70)

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)

A pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial. (TR29)

The process by which an item is exposed to ionizing radiation (typically gamma) to reduce or eliminate bioburden. (TR41)

Environmental operating conditions defined in ISO 14644-1, “Cleanrooms and associated controlled environments”. (Note: For total particulates, ISO 5 approximates the Class 100 description from the now obsolete U.S. Federal Standard 2009 and is roughly comparable to Grade A as defined in European GMP Annex 1 – “Manufacture of Sterile Medicinal Products.”) (TR22) (TR62)

Environmental operating conditions defined in ISO 14644-1, “Cleanrooms and associated controlled environments.” Note: For total particulates, ISO 7 approximates Class 10,000 from the now obsolete Federal Standard 209. (TR62)

Environmental operating conditions defined in ISO 14644-1, “Cleanrooms and associated controlled environments.” Note: For total particulates, ISO 8 approximates Class 100,000 from the now obsolete Federal Standard 209. (TR62)

International Organization for Standardization/International Electrotechnical Commision. (TR52)

Microorganisms that are recovered from a facility. (TR70)

An industry-specific separative enclosure. (TR51)

A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous, isolation of its interior from the surrounding environment. Any air exchange with the surrounding environment takes place only through microbially retentive filters. (TR22) (TR62) (TR13)

A decontaminated unit meeting ISO 5 conditions that provides uncompromised, continuous, isolation of its interior from the surrounding environment. It may transfer air directly to the surrounding environment through openings (e.g., “mouse holes”) that preclude the ingress of microbial contamination. (TR13) (TR22) (TR62)

Type of fluid (gas or liquid) movement in which the fluid travels smoothly (in a nonturbulent way) or in regular paths. The velocity, pressure, and other flow properties at each point in the fluid remain constant. (TR69)

Maximum daily dose of the next product to be produced in the equipment train. (TR70)

Latency is the ability of a virus to be dormant (latent) within a cell (for example, genetic episomes; provirus). Under certain conditions the virus may become active and produce particles. (TR71)

Leak rate is the quantity of air leakage over time into the sterilizer chamber obtained while performing a chamber leak test. The leak rate should not exceed a level that will inhibit the sterilization process during air removal or vacuum drying stages. (TR03)

See System Integrity Test. (TR61)

A filter made up of a series of biconvex cells that are stacked on top of one another with rings between them to prevent bypass between the cells. End-caps are then placed at the top and bottom of the assembly and are held in place with a central core. [Synonyms: Lenticular Cartridge, Modules, Filter Elements, Filter Devices] (TR45)

A value for a residue above which a cleaning process would not be acceptable. (TR29) A value for a residue above which a cleaning validation protocol would fail. (TR49)

The lowest concentration of microorganisms in a test sample that can be detected, but not necessarily quantified, under the stated experimental conditions. (TR33)

The lowest amount of analyte in a sample that can be distinguished from the absence of analyte. (TR41)

The lowest concentration of analyte that can be unambiguously detected in a sample. For qualitative and for quantitative NAT methods, this value is conventionally expressed as a 95% positive cut-off value, representing the target concentration detected in 95% of repeated tests using a certain assay. (TR50)

The lowest number of microorganisms in a test sample that can be enumerated with acceptable accuracy and precision under the stated experimental conditions. (TR33)

An actual physical unit that is agreed to between the drug manufacturer and the glass manufacturer that defines the approximate maximum degree of acceptability for a specified non-conformance. Creation of limit samples between the user and the manufacturer is optional. (TR43)

A quantitative test designed to give a positive/negative response. Ideally, a limit test has a high degree of specificity and a low limit of detection. (TR50).

The lowest amount of analyte in a sample that can be detected but not necessarily quantitated as an exact value by an individual analytical procedure. [Synonym: Limit of detection (LOD)] (TR57)

The lowest amount of analyte is a sample that can be quantitatively determined with suitable precision and accuracy by an individual analytical procedure. [Synonym: Limit of quantitation (LOQ)] (TR57)

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)

Endotoxin detection and quantitation can be accomplished at high sensitivity and specificity using reagents manufactured from Limulus Amebocyte Lysate, a biological reagent prepared from horseshoe crabs and offered in a variety of formulations. (TR45)

A biologically based assay for the detection and quantitation of bacterial endotoxin. (TR69)

The ability to elicit results that are proportional to the concentration of microorganisms present in the sample within a given range, where accuracy and precision are demonstrated. (TR33)

The linearity of an analytical procedure is its ability (within a given range) to obtain test results that are directly proportional to the concentration (amount) of analyte in the sample. (TR57)

A component of the cell wall of Gram-negative bacteria.(TR3)

Component of the outer cell wall of Gram-negative bacteria that is pyrogenic. (TR69)(TR82)

A load consisting of closed containers of aqueous liquids. The sterilization of the container contents is achieved through transfer of energy through the container into the aqueous liquid. (TR01) (TR30) (TR48)

A chemical, physical or biological indicator that provides an indication that a load was exposed to moist heat processing conditions. Note: In the United States, the load monitor must consist of a device in the form of a chemical, physical or biological indicator that is capable of direct measurement, or if appropriate, an indirect measurement of physical lethality delivered to the load. (TR30)

Area within the sterilization chamber where materials to be sterilized may be placed. (TR01) (TR3) (TR48)

Log reduction is defined as the first log being 90%, the second log being 9% and the third log being 0.09% of the original inoculums. (TR70)

The logarithm to the base 10 of the ratio of organisms in the feed to organisms in the filtrate. (i.e., Log10(109/2) = 9.7). [Synonym: Log Titer Reduction] (TR45)

Titer Reduction (TR) expressed as a base 10 logarithm. (TR75)

The virus reduction factor of an individual purification or inactivation step is defined as the log10 of the ratio of the virus titer or total load in the prepurification material and the virus titer or load in the post-purification material which is ready for use in the next step of the process. (TR41)

A purification method based on sequence-specific hybridization of labeled nucleic acid probes with targeted regions of test article nucleic acids, followed by magnetic bead capture. (TR50)

Specialized filling needles on certain BFS machines which also act to form the container. (TR77)

A cleaning procedure requiring operator-performed critical steps (e.g., scrubbing with a brush or rinsing with a hose). (TR70)

Component of a product or a cleaning agent used as an analyte to quantitate the total amount of product or cleaning agent present. (TR29)

An internal control in which an amplifiable amount of nucleic acid is added to a test article to determine inhibition of the PCR. This addition is usually performed pre-extraction and should provide a weak signal 100% of the time. Also known as “interference control”. (TR50)

The maximum quantity or mass of items permitted in a sterilizer load. (TR01) The maximum quantity or mass of items permitted in a depyrogenation or sterilization load. (TR3) The maximum quantity or mass of products permitted in a validated sterilizer load. (TR30)The maximum quantity or mass of items permitted in a sterilizer load. (TR48)

The part of the filter through which fluid passes that retains particles during filtration. (TR45)

See Aseptic Processing Simulation. (TR22)

A finely porous structure having lateral dimensions much greater than its thickness, through which mass transfer may occur by the application of driving forces like pressure or electro-osmotic. (TR15)

The effective surface area of a membrane device that is available for filtration. (TR15)

An analytical procedure that yields numerical results compared to quantitative specification(s). (TR57)

Organic compounds produced by microorganisms during metabolism and released into the bulk-phase environment. (TR69)

The description of microorganisms based on their cellular morphology, Gram reaction, and key diagnostic tests (e.g., Gram-positive coagulase-negative cocci). (TR13)

The arrangement of microorganisms into taxonomic groups based on their similarities and relationships. (TR13)

A test performed to quantify the number of microorganisms present in a sample of material. Standard microbial methods are utilized to estimate the number of colony forming units (CFU) per unit mass or volume. (TR28)

Compendial test for microbial counts using the plate-count, membrane-filtration or most probable number methods described in USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumerations Tests. (TR67)

The determination of the genus, and species when possible, to which a laboratory or manufacturing isolate belongs. (TR13)

The compendial tests for microbial enumeration and absence of specified microorganisms as found in USP <61> Microbiological Examination of Nonsterile Products: Microbial Enumerations Tests and USP <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms. (TR67)

Biochemical characterization of isolated colonies to determine the isolate genus and, where feasible and appropriate, the species. (TR22)

The formation of very fine layers of condensation often invisible to the naked eye. (TR51)

Pressure-driven, membrane-based separation process in which particles and dissolved macromolecules (typically 0.1 &;mum or larger) are retained. (TR15)

A microbe; a free-living organism too small to be seen by the naked eye. (TR45) (TR26)

A bacterium, yeast, or mold that, due to it prominence in product recalls, infection outbreaks, nosocomial infections, and the clinical literature, results in a multifactor risk assessment to determine whether the microorganism is objectionable if it is present in a specific nonsterile product. (TR67)

The minimum cycle conditions (in terms of delivered minimum lethality or minimum time and temperature) that would be considered acceptable. (TR01) (TR61)

The minimum quantity or mass of items permitted in a validated depyrogenation or sterilization load. (TR01) (TR3) (TR30) (TR48)

A load that contains multiple item item types representing various sterilization challenges. For example, some load items may have air removal challenges, while others pose a challenge due to their mass. (TR01)

A soil which is used in place of the manufactured product during a cleaning validation protocol (also called a “surrogate” soil). (TR29)

A process of soiling the equipment for a cleaning validation protocol in which soil is applied to the equipment surfaces to simulate the condition of the soil on those surfaces following typical product manufacturing. (TR29)

An individual unit consisting of multiple membranes in any format within a frame structure containing integral channels and ports for feed, retentate, filtrate and air connections. (TR15)

Filter element that is incorporated into a cartridge or capsule. (TR26)

Steam, steam-air mixtures, and superheated water used for sterilization. (TR01)

Equipment (e.g., a pressure-rated vessel and associated controls) used to achieve sterilization through time, temperature and pressure. [Synonym: Autoclave, Steam Sterilizer] (TR48)

A class of bacteria which lack a cell wall. Mollicutes are small, typically about 0.1-0.5 &;mum in size, and vary in form (trivial name: mycoplasma) (TR50)

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 statistical method of estimating the number of viable organisms suspended in a liquid. (TR51)

The average number of infectious units added per cell in an infection. (TR41)

An engineered process equipment solution for process management and unit operations designed for repeated use. (TR66)

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)

A sterilizing grade filter that also provides a log reduction value (or a titer reduction value) for a specified test mycoplasma according to the PDA Mycoplasma Consensus Method. (TR75)

A test article used to assess the performance of an assay in the known absence of a targeted microorganism or nucleic acid. Negative controls are used to minimize a risk of false positive results, which could occur due to non-specific signals. (TR50)

A manufacturer’s measure of an ultrafiltration membrane based on a defined solute-retention coefficient. (TR15)

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)

Air and other gases that will not condense to liquid state, thereby not releasing latent heat under the conditions of sterilization. (TR01)

Nonfiber-releasing filter means any filter, which after any appropriate pretreatment, such as washing or flushing, will not release fibers into the component or drug product that is being filtered. All filters composed of asbestos are deemed to be fiber-releasing filters. (TR45)

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 general viral clearance capacity of the purification process.) (TR41)

A term used in reference to particulates that are not capable of living, growing, or developing and functioning successfully (“unable to divide” or “not capable of reproducing”). (TR13)

According to 21 CFR 211.113 objectionable microorganisms can be: product related or recipient related. Please see glossary for "product related" or "recipient related" for additional information. (TR67)

A cell culture contamination not immediately apparent by visual inspection or other obvious indicators. (TR50)

(See system, open) (TR28)

Microorganisms responsible for infection in injured, invasively treated or immune-suppressed individuals that typically do not cause infection in healthy individuals, unlike frank pathogens. (TR67)

A sterilization design approach where minimal information is required about the product bioburden. A worst-case bioburden assumption is used to determine the delivered lethality needed to achieve a PNSU of 10^-6 on or in the items being sterilized. When using this approach, the qualification program must demonstrate that both the F_BIO and F_PHYS are greater than 12 minutes. The required lethality may vary regionally. (Note: For typical SIP systems, the F_PHYS will need to be greater than the FBIO.) (TR01) (TR3) (TR30) (TR61)

Procurement of a product such as liquid or powder format culture media or buffer and that has been supplied in single-use technology. (TR66)

A sterility release system based upon effective control, monitoring, documentation, and batch records review of a validated sterilization process cycle in lieu of release procedures based upon end-product sterility testing. (TR01) (TR3) (TR13)

A sterility release program based on effective control, monitoring and documentation of a validated sterile-product manufacturing process where sterility release is based on demonstrated achievement of critical operational parameters and performance attributes in lieu of end-product sterility testing. (TR30)

The “tube” of polymer extruded by the BFS machine from which the containers are formed. (TR77)

A qualification method that uses less than the full exposure time to demonstrate sterilization or sanitization cycle efficacy. [Synonym: fractional cycle.] (TR61)

Any discrete unit of material structure; a discernible mass having an observable length, width, thickness, size and shape. (TR45) (TR26)

Foreign material which is unintended and either removable from the surface of a primary packaging component or freely moving within a filled and sealed pharmaceutical dosage form. The term particle is used interchangeably with “particulate” and “particulate matter” without any intended difference in meaning. (TR85)

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)

Particles that are expected from the drug formulation, and therefore not included as a category in this Lexicon.(TR76)

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)

Relating to, or occurring in the form of particles. (TR45) (TR26)

The total quantity of particles in solution as tested per qualified method. (TR76)

Propogation of a seed stock by serial sub-culturing. (TR51)

The length of time that the temperature remains within the acceptable range when power is lost. (TR64)

Any microorganism which by direct interaction with (i.e., infection of) another organism causes disease in the organism (by convention, a multi-cellular organism). (TR51)

A probe placed in contact with the load item or inside a container of liquid to measure the temperature of the load item or liquid. (TR01)

A thermocouple placed in contact with the load item to measure the temperature of the load item. (TR3)

A thermocouple that is placed in or against the material/product to measure the material/product temperature. (TR64)

A small, ceramic carrier surface used to hold cultures of microorganisms. Used in antimicrobial effectiveness testing procedures. (TR70)

Measured length of the outer edges of a particle.

The degree to which a fluid will pass through a permeable substance under specified pressure and temperature conditions. (TR41) (TR26)

The fluid which passes through a membrane. (see also filtrate) (TR41)

A component of performance qualification that demonstrates that predetermined physical requirements, including temperature distribution and heat penetration, are achieved consistently throughout the load. (TR01)(TR03)

The manufacturing of a drug substance by a procedure fully representative of and simulating that to be applied to a production-scale batch. (TR38)

A schematic diagram that shows the relational arrangement of piping, components, instruments, and equipment connections of the system. It also illustrates the control and functional relationship. (TR48)

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)

An extra-chromosomal DNA molecule in bacteria which is capable of replicating independently of the host chromosomal DNA. Plasmids are often used as positive controls for NAT assays. (TR50)

A membrane-module geometry, utilizing flat sheet membranes, in which membranes are stacked between supporting plates. (TR15) A device used to support filter sheets and provide inlet- and outlet-flow channels. It is composed of a series of filters sheets separated by alternating plates (outlets) and frames (inlets) that are compressed between two end-plates (heads) by either hydraulic or mechanical means. (TR45)

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)

The channel(s)/path(s) in a membrane through which a fluid or a gas may pass. (TR41) (TR26)

The size of the channel passages through the filter media. (TR41)

The range of pore sizes in a filter used to determine the filter’s average pore size. (TR15)

An analytical technique used to determine various quantifiable aspects of a material’s porous nature, such as pore diameter, total pore volume, surface area, and bulk and absolute densities. (TR41)

The percentage of a membrane’s volume that is occupied by pores. (TR15)

A porous/hard goods load consists of items in which the bioburden is inactivated through direct contact with saturated steam. Porous/ hard goods load items include: filters, stoppers, tubing (hoses), mops, garments, stoppers, cleaning equipment, or machine change parts. (TR01)

A control filter membrane with a larger pore size rating than the test filter and used to demonstrate the penetrative ability of the test microorganism. Penetration of this filter by at least one CFU is required to validate a test. (TR75)

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)

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)

Number of viable organisms present on or in product prior to exposure to the sterilization process. (TR30)

A sterilization process in which air is removed from the chamber using a vacuum pump or other mechanical system before the exposure phase begins. This method is particularly suited to load items that can trap air such as tubing, filters and filling machine assemblies. (TR01)

A process in which air is removed by applying a vacuum (i.e., negative pressure) or pulses of vacuum to precondition the system prior to the exposure phase. (TR61)

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)

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)

A series of operations and/or actions used to produce a desired result. (TR38)

Conditions and corresponding measurements associated with the manufacturing process that may affect the identity, strength, quality, potency, and purity of a product. Examples of parameters of concern include bioburden, process rate, weight, volume, temperature, and pressure. (TR13)

Procedural steps taken for switching from the manufacturing of one product to another product. (TR29)

A device that is designed for precise positioning and continuous movement, typically in response to a varying analog signal. [Synonym: Modulating Valve] (TR48)

A class of UV photoactivated chemicals able to covalently modify nucleic acids. Psoralens may be used to reduce contaminating nucleic acid in NAT reagents. (TR50)

Any substance capable of eliciting a febrile (or fever) response upon injection or infection (as in endotoxin released in vivo by Gram-negative bacteria. (TR3)

Fever-producing substance (TR69)

A material that elicits a pyrogenic response (fever). (TR70)

A synthetic, chemically-labeled single-stranded nucleic acid complementary to a selected sequence within a DNA sequence to be amplified using forward and reverse primers in a Q-PCR reaction. A probe is typically labeled with both a fluorophor and quencher. The latter inhibits fluorescence until the quencher and fluorophore are separated by the exonuclease activity of DNA polymerase. (TR50)

Technologies that allow users to obtain microbiology test results more quickly than traditional microbiological methods, which are usually culture/ growth based. (TR69)

Prepared for loading with the pharmaceutical product. (TR73)

Washed components supplied in a package suitable for sterilization prior to use with sterile injectable products. (TR85)

A marketing term often used to describe the benefits of single-use technology or SUS. This designation has no regulatory or scientific basis supporting suitability for use and the end user is responsible to evaluate and determine if appropriate quality requirements are met for their application. (TR66)

Washed and sterilized components supplied in a package suitable for transfer into an aseptic processing area and used with sterile injectable products without further processing. (TR85)

The ability of a filter to exclude solutes or particulate matter from passing through. (TR45)

Chemical or microbiological material remaining on equipment surfaces after a cleaning process. (TR29)

RABS are aseptic processing systems (ISO 5) intended to substantially reduce human borne contamination within the aseptic environment where sterile product, containers, closures and equipment are exposed by the use of separative devices and defined mechanical features and operating procedures. (TR22) (TR62)

Aseptic processing systems (ISO 5) intended to substantially reduce human-borne contamination within the aseptic environment where sterile product, containers, closures, and equipment are exposed by the use of separative devices and defined mechanical features and operating procedures. (TR13)

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)

A membrane-based filtration process in which the membrane rejects salt from solution. Pore size is not entirely meaningful for reverse-osmosis membranes, as pores are often not observable by microscopic methods. Reverse osmosis is used to desalinate water. (TR15)

Parameters that are specified for ongoing sterilization operations. The operational cycle is typically controlled to produce additional lethality over the qualified minimum acceptable cycle in order to provide increased sterility assurance. (TR01) (TR61)

Reduction of microbial contaminants to safe levels as judged by public health requirements for the specific country. (TR13)

A significant reduction in bioburden, achieved in chromatography by the use of bactericidal agents, such as sodium hydroxide (NaOH), hydrochloric acid (HCl), ethanol (EtOH), and isopropanol (IPA). (TR14)

The process of reducing microbial levels by treatment at less than defined sterilizing conditions. Typically water at 80 °C or a chemical treatment is used to perform sanitization of process components. (TR45)

A process that reduces the number of viable microorganisms to a defined level. (TR61) (TR69)

To make physically clean and to remove and destroy, to the maximum degree that is practical, agents injurious to health. (TR70)

A compound that will reduce the number of vegetative microorganisms to a safe level as determined by public health requirements. Normally a reduction of 10³ in vegetative microorganisms is obtained. (TR70)

Steam that is at a temperature and pressure that corresponds to the vaporization curve of water. It is in a state of equilibrium between being a liquid and a gas, with no entrained liquid water. [Synonym: Dry Saturated Steam] (TR01) (TR48) (TR61)

A sterilization process, typically used for porous/hard goods loads, where the sterilizing medium is saturated steam. (TR01)

Studies used to select a particular type and grade of filter media. (TR45)

Device using constructional and dynamic means to create assured levels of separation between the inside and outside of a defined volume. [Synonym: Separative Device] (TR51)

Microorganisms that are attached to animate or inanimate surfaces, as opposed to planktonic organisms. (TR69)

Relative motion between adjacent layers of a moving liquid. (TR69)

The velocity gradient in a flowing fluid. This value is proportional to the average linear velocity and is inversely proportional to the channel height or diameter when the recirculation is in the laminar flow regime (most TFF applications). (TR15)

Size-exclusion filtration occurs when a particle is too large to pass through the filter medium and is retained on the surface or within the depth of the filter. (TR45)

The ratio of the filtrate concentration of component i (Ci,f) to the bulk or feed concentration of component i (Ci,b) as in the following equation: S = Ci,f/Ci,b Where S = 1 for a freely passing solute, typically a low molecular weight solute S = 0 for a solute that is fully retained by the membrane [Synonym: transmission; product transmission] (TR15)

An individual part designed to perform a particular function when assembled into a single-use system. (TR66)

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)

The chemical or microbiological materials left on process equipment after completion of process manufacturing, but before initiation of the cleaning process. (TR29)

To use sound energy to agitate particles; generally used to accomplish mixing or cleaning. (TR70)

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

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)

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)

The number of log reductions (10-fold changes) of spores from the initial population. For the overkill sterilization method, one targets a spore log reduction of 12 to achieve 1 x 10^-6 probability of a survivor when using a biological indicator having a population of 1 x 10⁶. (TR61)

A process that destroys or inactivates microbial spores. (TR51)

The destruction of inactivation of microbial spores using a vapor or gaseous agent. (TR51)

A compound that destroys all vegetative microorganisms and bacterial and fungal spores. (TR70)

The formation of a spore. (TR51)

Monitoring of the environment in the absence of normal operations. This includes having the equipment installed and operational when no personnel are present. Per the EU and ISO standards, this is synonymous with “at rest.” (TR13)

A sterilization process in which the heating medium used to heat the load is in a mixture of air and steam that is typically used for liquid loads. This addition of air results in an air overpressure condition. (TR01)

Pallets in which the wood has been heated to achieve a minimum core temperature of 56 °C (132.8 °F) for at least 30 min. Pallets treated via this method bear the initials HT (heat treated) near the International Plant Protection Convention (IPPC) logo. This is one of the methods required for international shipment. (TR55)

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)

A specifically sized hole (e.g., 1/32 or 1/

Supply Chain inch diameter) to allow condensate or steam to pass through. [Synonyms: flow orifice, steam bleed.] (TR60)

Sterilization by flowing saturated steam through a vented vessel or system. (TR45)

A self-actuating, automatic device that removes condensate and air from the system. (TR61)

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)

Process steam is similar to plant steam, except the steam is generated using a controlled feed water source to which no volatile additives (amines or hydrazines) have been introduced. Process steam may be appropriate for moist heat sterilization of liquid loads where the containers are filled and sealed prior to sterilization. (TR48)

Collected condensate that complies with the Compendial requirements for Water for Injecton (WFI). [Synonyms: clean steam, high quality steam] (TR01) (TR61) (TR48)

The process of applying clean pressurized steam to a stationary piece of equipment in order to sterilize it. (TR41)

Absence of life; usually refers to absence of viable microorganisms. Note: In practice, no such absolute statement regarding the absence of microorganisms can be proven. (TR22) (TR62)

The absence of viable microorganisms. (TR44) (TR70)

The sterile boundary is the demarcation in a system between the portion of the system that requires sterile contact surfaces (e.g., sterile side of filters and downstream piping) and the rest of the system (e.g., upstream side of filters, condensate drain lines). (TR61)

The probability or likelihood that something is sterile. (TR44)

Probability that a batch of product is sterile. (TR28)

Probability of a single viable microorganism occurring on or in an item after sterilization. Note: The term SAL takes a quantitative value, generally 10^-6. When applying this quantitative value to assurance of sterility, an SAL of 10^-6 has a lower value but provides a greater assurance of sterility than an SAL of 10^-3. (TR3) (TR61)

Test performed to determine if viable microorganisms are present. (TR28) (TR62)

A process used to render a product free of viable organisms with a specified probability. (TR01) (TR30) (TR69)

A process by which something is rendered sterile (i.e., moist heat, dry heat, chemical, irradiation); normally validated at 10⁶ organism reduction. (TR70)

Validated process used to render product free from viable microorganisms (TR13) (TR26)

A sequence of defined operating parameters (e.g., time, temperature and pressure) and conditions required to render an item sterile. (TR01) (TR30) (TR48)

A sequence of defined operating parameters (e.g., time and temperature) required to render an item sterile. (TR3)

A process used to render a product free of viable organisms with a specified probability. (TR3)

Execution of a sterilization cycle. (TR01)

Documents that define sterilizer system attributes and how they should be met. (TR48)

A set of specifications and information related to the installation features including equipment, hardware and software) of the system that will ensure the realization of the user requirements. [Synonym: Detailed Design Specification (DDS] (TR48)

A description of functional attributes and operational characteristics of the system that will ensure fulfillment of the user requirements. [Synonym: Functional Requirement Specification, Functional Design Specification] (TR48)

A description of features and performance requirements of a system that will fulfill the needs of the end user. (TR48)

Physical evaluations (e.g., chamber integrity or air removal) conducted on a scheduled frequency to demonstrate ongoing control of the sterilizer system. (TR30)

A filter intended for terminal processing of sterile liquids that has been tested under worst-case actual processing conditions for the ability to retain a minimum challenge of 10⁷ cells of Brevundimonas diminuta per cm² of filter area. (TR41)

A filter that reproducibly removes all test microorganisms from the process stream, producing a sterile effluent. (TR75)

A filter that reproducibly removes test microorganisms from the process stream, producing a sterile filtrate. (TR26)

A surrogate for tangential flow filtration where shear is achieved by rapidly stirring the solution immediately adjacent to the membrane. Typically the stirring is accomplished by mechanical means, such as through the use of a stir bar or impeller. (TR15)

A specific isolate of a species that is maintained in pure culture and is serotypically, genotypically, or chemotaxonomically characterized to differentiate it from other strains of the same species. The strain is representative of the species and provides a reference for the species based on its historic isolation, characterization, and deposition in recognized culture collections. (TR13)

Primary construction material of a surface to be cleaned or disinfected. (TR70)

Steam that is at a higher temperature than that indicated by the equilibration curve for the vaporization of water (at a given pressure).(TR01) (TR61)

Water in a liquid phase at a tempe- rature above 100°C requiring overpressure to maintain this state. (TR01)

A sterilization process in which the heating medium is superheated water that is continuously circulated with air overpressure. This process requires air overpressure to keep the water in a liquid state. [Synonyms: water cascade, water spray process, water immersion process, water submersion process, raining water process, steam-air-water process] (TR01)

A soluble compound that reduces the surface tension of a liquid or reduces interfacial tension between two liquids (causing formation or micelles) or between a liquid and a solid. [Synonym:Wetting Agent] (TR45) (TR26)

Functionally equivalent substitution of an alternative SUS, for an existing SUS design providing a contingency or process improvement with equivalent process performance and product quality. The end user is responsible to evaluate and determine if appropriate quality requirements are met for their application. (TR66)

D-value of a BI when measured in a specified gas generator/separative enclosure combination operating within a defined sporicidal vapor-phase decontamination cycle. (TR51)

Any test designed to detect leaks or other breaches in system integrity that might compromise operator safety or system sterility (or sanitary status). [Synonym: leak test.] (TR61)

A system integrity test that measures the mass flow needed to maintain a given pressure. (TR61)

A system integrity test in which the system is pressurized to a predetermined level with filter sterilized compressed air or other compressed gas, after which the system is isolated and the amount of pressure loss over time is measured. (TR61)

A system integrity test in which the system under test is evacuated to a predetermined setpoint and the system is isolated from the external environment. The decay in vacuum level over time is measured. (TR61)

Physical evaluations (e.g., chamber integrity or air removal) conducted on a scheduled frequency to demonstrate ongoing control of the sterilizer system. (TR01)

A “closed” system is sterilized-in-place or sterilized while closed prior to using a validated procedure, is pressure and/or vacuum tight to some pre-defined leak rate maintained through the length of the campaign, can be utilized for its intended purpose without breach to the integrity of the system, can be adapted for fluid transfers in and/or out while maintaining asepsis, is connectable to other closed systems while maintaining integrity of all closed systems (e.g., Rapid Transfer Port, steamed connection, etc.), is safe guarded from any loss of integrity by scheduled preventative maintenance and utilizes sterilizing filters for sterilization of process streams which are integrity tested and traceable to each product lot. (TR28)

A system which fails to meet one or more of the criteria which define a closed system. (TR28)

Deviation from first-order death kinetics in a microbial population observed when the logarithm of the number of survivors is plotted against time. The “tail” of the survivor curve represents organisms surviving for times in excess of those that would be predicted from first-order kinetics. (TR51)

The range of species for which detection or analysis is aimed for by an assay method. (TR50)

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)

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)

Temperature is the measure of thermal energy. (TR01)

Temperature measurement of the heating medium (e.g., forced hot air) across the chamber load zone. (TR01) (TR03) (TR30) (TR48)

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)

A process whereby product is sterilized within its sterile barrier system. (TR01

The application of a lethal agent to sealed, finished drug products for the purpose of achieving a predetermined sterility assurance level (SAL) of usually less than 10^-6 (i.e., a probability of a nonsterile unit of less than one in a million). A process where the material is sterilized in its final packaged configuration. (TR13)

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)

The utilization of independent temperature monitoring devices to determine a temperature profile within the load zone and analysis of the collected data. (TR3)

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)

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)

The pressure difference equal to the average feed-stream pressure minus the average filtrate-stream pressure. TMP = (P_feed + P_retentate)/2 - P_filtrate (TR15)

A cabinet designed to protect materials from operator and environmental contamination. Also referred to as laminar air flow hood. (TR62)

Lack of sterility assurance or an unacceptable level of endotoxin that could result in harm to the patient. (TR44)

The influent side of the filter. (TR45) (TR26)

The gaseous form of materials that are normally liquids or solids at room temperature and pressure. (TR51)

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)

Cells in an actively growing state. Some microorganisms can only be vegetative, while others are sporeformers and can be in a vegetative or spore (dormant) state. (TR13)

Alive and able to be cultured in the laboratory. (TR69)

Unable to be cultured in the prevailing test conditions but nonetheless capable of cell division and carrying out metabolic functions (TR69)

Elimination of a target virus by removal of viral particles or by inactivation of viral infectivity. (TR41)

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

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

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)

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)

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)

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)

A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, which pose the greatest chance of process or product failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure. (TR28)

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)

A system fitted to a BFS machine to direct a flow of HEPA-filtered air over the Critical Processing Zone of the machine. (TR77)

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)