PDA Glossary

Term used to describe the state or appearance of the product during 100% or AQL visual in­spection (prior to labeling). As marketed refers to the product in-situ or the form in which it is distributed, for example clear liquid, lyophilized, powder, opalescent liquid, etc. (TR79)

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)

A dose that is unlikely to cause an adverse effect if an individual is exposed, by any route, at or below this dose every day for a lifetime. (TR29)

An amount of a substance consumed on a daily basis that is considered at a safe level. (TR29)

An amount of a substance administered or consumed on a daily basis that is considered a safe level. (TR49)

The quality level that is the worst-tolerable process average when a continuing series of lots are submitted for acceptance sampling. (TR43) (TR 76)

The extent to which, or the limits between which, acceptable variation exists.(TR38)

Numerical limits, ranges, or other suitable measures for acceptance of test results. (TR 14) (TR 29) (TR 38) (TR 64)

Numerical limits, ranges, or other suitable measures for acceptance of test results. Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation. Exceeding the operating range should be documented and explained in the validation report and evaluated for validation study impact. (TR 42)

The pre-defined specifications, standards or ranges that must be met under stated test conditions. (TR 48)

Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical method validation that is satisfied to determine suitability of test method performance.(TR 57) (TR 69) (TR 72) (TR 74)

The criteria that a system or component must satisfy in order to be accepted by a user or other authorized entity. (TR 54-5)

Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures which the drug substance or drug product or materials at other stages of their manufacture should meet (16). Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation and possible batch rejection. (TR60)

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)

A. laidlawii is a mycoplasma in class Mollicutes and order Acholeplasmatales. (TR75)

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 written plan consisting of elements to be accomplished to achieve a specific result. The plan describes responsibility for each element and a target date for completion. (TR22)

Synonym: Drug Substance. (TR14) (TR42)

A substance or mixture of substances that, when delivered in a finished drug product, directly affects the structure or function of the body. (TR54-4)

Any substance or mixture of substance intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. Note: also known as Drug Substance. (TR29) (TR56) (TR41) (TR54-3) (TR60)

Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity o other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. (TR63) (TR70)

Any substance or mixture of substances intended to be used in the manufacture of a drug product, and that when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body. (TR74)

Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of drug, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. (TR60)

Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and when used in the production of a drug, becomes an active ingredient of the drug product (also called “drug substance”). (TR29)

Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body. (TR54-3)

Any substance or mixture of substances intended to be used in the compounding of a drug preparation, thereby becoming the active ingredient in that preparation and furnishing pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans and animals or affecting the structure and function of the body. (TR63)

A raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials normally have defined chemical properties and structures. (TR60)

Systems with active temperature control (e.g., air/sea freight containers, refrigerated trucks/cars). (TR39)

System with active temperature control. It makes use of electricity or fuel for the compressor to maintain temperature. Examples include refrigerated trucks, temperature-controlled ocean containers, and active ULDs. (TR58)

Actively powered system that uses electricity or other fuel source to maintain a temperaturecontrolled environment inside an insulated enclosure under thermostatic regulation (e.g., cold room, refrigerator, temperature-controlled truck, refrigerated ocean or air container). (TR64) (TR72)

(Synonym: Active Temperature Controlled System)

Actively powered system that uses electricity or other fuel source to maintain a temperaturecontrolled environment inside an insulated enclosure under thermostatic regulation (e.g., cold room, refrigerator, temperature-controlled truck, refrigerated ocean or air container). (TR 72) (TR64)

A Unit Load Device (ULD) container used to consolidate cargo on aircraft that contains electrical or battery-powered temperature control systems for transporting temperature-sensitive materials; an RKN type is used in an FMEA example. (TR58)

A unit load device with an active heating and/or cooling system that is typically used in air transportation, usually operated from externally supplied AC or DC power or from internal batteries. (TR64)

A Unit Load Device (ULD) container used to consolidate cargo on aircraft that contains electrical or battery-powered temperature control systems for transporting temperature-sensitive materials; an RKN type is used in an FMEA example. (TR58)

A unit load device with an active heating and/or cooling system that is typically used in air transportation, usually operated from externally supplied AC or DC power or from internal batteries. (TR 64)

Ability of endotoxin (LPS) to initiate the LAL cascade in the compendial bacterial endotoxins test (BET) assay, or the ability to elicit a pyrogenic response in a compendial pyrogen test (2,10). Activity can be measured by other assays such as the monocyte activation test (MAT) or recombinant Factor C tests (rFc), if such tests have been validated, to demonstrate that decisions made from the results are comparable to or superior to the compendial assay. Activity is measured in endotoxin units (EU). In terms of activity, one EU = one IU, regardless of the source. Activity is generally expressed as a concentration, usually EU/mL.(TR82)

Retention of solutes, suspended colloidal particles or microorganisms to fluid contact surfaces, e.g., the surfaces of pores in the filter medium. (May be modified with the following terms: electrokinetic, charge-rated, surface charge, hydrophobic or ionic strength. (TR45)

The retention of solutes, suspended colloidal particles or microorganisms to fluid contact surfaces, e.g., the surfaces of pores in filtration membranes. (TR26)

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)

A device fitted to a BFS machine which provides, at a minimum, a continuous flow of Grade A quality air supply over the filling needles and the point-of-fill. The air shower is also known as a nozzle shroud in shuttle type machines. (TR77)

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)

The air temperature of an environment. (TR58)

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)

A microorganism that does not utilize oxygen as the final electron acceptor during metabolism; microorganism that will grow only in the absence of oxygen. (TR62)(TR22)

A general statistical approach to data analysis (i.e., comparison of means) in which the variation in a method’s results is partitioned among explanatory factors in order to systematically assess factor influence and/or variance components. (TR57)

Substance (usually a residue) for which an analysis is being performed. (TR29) (TR49) (TR70)

A specific chemical moiety being measured, which can be intact drug, biomolecule or its derivative, impurity, and/or excipients in a drug product. [Synonym: measurand] (TR57)

Material used to monitor the performance of a method to assess the integrity and validity of the results. (TR57-2)

The qualification of the analytical instrument(s) used as part of the analytical procedure. (TR57)

Equivalence study that measure the same property of two methods and that shows that replacing one of these methods with the other would not adversely affect the test’s use or results. (TR57-2)

Collection of activities performed to define the intended purpose of the method, select the appropriate technology to implement the method, and identify the critical method variables that need to be controlled to ensure that the method is robust and rugged. (TR57-2)

Collection of activities performed to select an appropriate technique and method conditions to meet the Analytical Target Profile (ATP) requirements. (TR57-2)

Formal or informal study performed to assess initial method performance prior to full ICH Q2(R1) validation; assessment activity that culminates in a scientifically sound method that has an acceptable level of performance, is documented to be suitable for its intended use, and is demonstrated to have “adequate capability … to meet appropriate standards of performance for its purpose” (TR57-2)

Documented process that qualifies a laboratory (receiving unit) to use an analytical test procedure that originates in another laboratory (the transferring unit, also known as the sending unit), thus ensuring that the receiving unit has the knowledge and ability to perform the transferred analytical procedure as intended. (TR57-2)

An analytical method that is used for multiple products and/or types of sample matrix without modification of the procedure. Similar to compendial methods, an APT method may not require full validation for each new product or sample type. (TR57)

That which is performed in order to obtain a reportable result. The procedure should describe in detail the steps necessary to perform the analytical test. This may include but is not limited to: the sample, the reference standard and the reagents preparations, use of the apparatus, generations of the calibration curve, use of the formulae for the calculation [Synonym: Method, Assay] (TR57)

Set of predefined method parameters and performance requirements that help identify the type of method desired relative to method categories (identity, purity, and impurity) defined in ICH Q2(R1) as well as the necessary method performance attributes, such as accuracy, precision, and specificity. (TR57-2)

Additional means used in combination with the basic transportation unit to maintain the required temperature during transport. Examples include active systems and passive systems. (TR39)

Contains in the final raw material or uses in the manufacturing process of the final raw material, any raw material derived directly from bovine or other animal tissues, for example, bovine serum, porcine-derived trypsin, and animal-tissue-de­rived hydrolysates. (TR83)

Non-animal in origin but may be derived from processes that include materials from animal components that come in direct contact with the raw material, for example, a recombinant protein produced in an E. coli fermentation that uses fermentation medium containing tryptone, or a recombinant protein expressed in plants that are exposed to bovine manure fertilizer. (TR83)

Sourced from synthetic components but in­cludes animal-derived components used dur­ing the manufacture of the raw material that do not come in direct contact with the raw mate­rial, for example, polymers or elastomers used in process equipment or plumbing that may contain or may have been exposed to animal-sourced materials such as stearates or slip agents. (TR83)

A membrane in which the pore size and structure differ from one face to the other. These membranes are usually considered “directional” because of the difference in flow characteristics, depending on which surface of the membrane faces the feed stream. (TR15)

Controlled heating process used to remove residual thermal stress from glass containers after glass forming. [Synonym: Lehred] (TR43)

A temperature designed to allow primers to attach to single-stranded DNA or RNA to initiate amplification. The annealing temperature is usually kept a few degrees lower than the melting temperature of the primers to avoid non-specific amplification. See “Melting Temperature”. (TR50)

GMP-mandated evaluation of the standards for each active pharmaceutical ingredient (API), drug product or biologics to determine the need for changes in drug product specifications and/ or manufacturing, control procedures or manu­facturing processes. (TR54-5)

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)

A designated secure area or facility (e.g., cabinet, room, building or computerised system) for the long-term retention of data and metadata for the purposes of verification of the process or activity.(TR80)

The process of protecting records from the possibility of being further altered or deleted, and storing these records under the control of independent data management personnel throughout the required retention period.(TR80)

Measured surface area of a flat projection of a particle.(TR85)

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

The ability to reduce risk. ALARP has two facets: Technical and Economic. Technical practicability refers to the ability to reduce risk regardless of cost. Economic practicability refers to the ability to reduce risk without making the product too costly to produce. (TR54) (TR54-2) (TR54-3)

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)

The length of a particle or fiber divided by its width. (TR85)

Analytical method used to determine the purity or concentration of a specific substance in a mixture. (TR 26)

To evaluate the effects of a manufacturing change on the identity, strength, quality, purity, and potency of a drug product as those factors may relate to the safety or effectiveness of the drug product. (TR38)

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

A physical, chemical, or microbiological property or characteristic of an input or output material. (TR60)

Inspection where either the unit of product is classified as conforming or non-conforming or the number of non-conformities in the unit of products is counted with respect to a given requirement of set of requirements. (TR43)

An output variable or outcome that cannot be directly controlled, but is an indicator that the process performed as expected.(Synonym - Process Performance Parameter) (TR60)

A molecular or product characteristic that is selected for its ability to indicate the quality of the product. Collectively, the quality attributes define identity, purity, potency and stability of the product, and safety with respect to adventitious agents. Specifications measure a selected subset of the quality attributes. (TR60)

Particles that should not be present in excipients, APIs, intermediates, and final oral dosage forms, and their presence should always trigger an investigation. These particles consist of foreign matter that is not intended/designed to be in direct contact with the product/manufacturing process. These particles commonly originate from materials which accidently or unintentionally come into contact with the product or a process stream. (TR78)

A secure, computer-generated, timestamped electronic record that allows for reconstruction of the course of events relating to the creation, modification, or deletion of an electronic record. An audit trail is a chronology of the "who, what, when, and why" of a record.(TR80)

Metadata containing information associated with actions that relate to the creation, modification or deletion of GXP records. An audit trail provides for secure recording of life-cycle details such as creation, additions, deletions or alterations of information in a record, either paper or electronic, without obscuring or overwriting the original record. An audit trail facilitates the reconstruction of the history of such events relating to the record regardless of its medium, including the "who, what, when and why" of the action.(TR80)

The audit trail is a form of metadata that contains information associated with actions that relate to the creation, modification or deletion of GXP records. An audit trail provides for secure recording of life-cycle details such as creation, additions, deletions, or alterations of information in a record, either paper or electronic, without obscuring or overwriting the original record.(TR80)

A tool that can be used to help determine what elements within the audit trail should be reviewed, and the frequency at which the review should take place for each part of the audit trail where a review is required.

A chamber for steam sterilization. (TR45)

Consists of mechanical handling and presenta­tion of product containers combined with auto­mated inspection of the filled containers using image analysis and/or light obscuration. (TR79)

Residual pressure opposing the free flow of liquid or gas at the outlet side of the filter. (TR45)

Pressure applied downstream of a filter or other piece of equipment. (TR26)

Feature that enhances the area to hold the syringe and is usually designed to avoid accidental removal of the plunger from the back. By design, it may also serve as a flange extender to facilitate holding of the syringe during injection. (TR 73)

A true copy of the original data that is maintained securely throughout the records retention period. The backup file should contain the data (which includes associated metadata) and should be in the original format or in a format compatible with the original format.(TR80)

A copy of current (editable) data, metadata and system configuration settings maintained for recovery including disaster recovery.(TR80)

A copy of one or more electronic files created as an alternative in case the original data or system are lost or become unusable. Backup differs from archival in that back-up copies of electronic records are typically only temporarily stored for the purposes of disaster recovery and may be periodically overwritten. Such temporary back-up copies should not be relied upon as an archival mechanism.(TR80)

Single-celled, microscopic organisms typically with a cell wall and characteristic shape (e.g., round, rod-like, spiral or filamentous); lacking a defined nucleus (“prokaryotic”). (TR26)

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)

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

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

A system of physical partitions that affords ISO 5 protection by partially separating its interior from the surrounding environment utilizing airflow. (TR22) (TR62)

A specific quantity of a drug or other material that is intended to have uniform character and quality, within specified acceptance criteria, and is produced according to a single manufacturing order during the same cycle of manufacture (TR38)

In a batch filtration process, the entire volume to be filtered is held in a single feed tank. The retentate stream is recycled back to that single feed tank. (TR15)

A convection oven with a chamber or chambers where items are dry-heat sterilized or depyrogenated as a single load in a discontinuous process. The oven typically uses one or more filters to remove air particles. (TR3)

A process where there are no streams flowing into or out of a controlled volume, as opposed to a continuous process. In a batch filtration process, the feed solution is reduced in volume due to permeation of filtrate through the filter. There is no continuous addition of feed solution to the feed vessel. (TR45)

Review by the quality control unit of the batch manufacturing record for accuracy and completeness and for absence of derivation from the approved manufacturing and testing processes. The batch record is inclusive of all in-process testing and release records for a batch. (TR88)

Homopolymers of glucose connected by (1→3)-β-D- glycosidic linkages. (TR45)

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)

Manufactured biological active substances and medicinal products involving biological process­es and materials, such as cultivation of cells or extraction from living organisms. (TR56)

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)

Analytical sample taken to establish background value for the analytical measurement which may be subtracted from an experimental value to determine the “true” value. (TR29) (TR49)

Basic Local Alignment Search Tool; a bioinformatics algorithm for the comparison of sequence data (e.g., translated amino acids [tBLASTx], proteins [BLASTx], or nucleotides [BLASTn]). (TR 71)

A type of pallet with blocks between the pallet decks or beneath the top deck. These types of pallets usually carry more loads and last longer than stringer and typically 4 way entry. (TR55)

The grouping of related experimental units used in design of experiments (DOE). (TR57)

A thin layer of fluid near the membrane surface in which the tangential velocity changes from zero at the surface to the free stream value away from the surface. (TR15)

Coating of fluid in the immediate vicinity of a bounding surface where the effects of viscosity are significant (TR 69)

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

A scientific approach for defining product/load characteristics (e.g., viscosity, container sizes, container fill volumes, item sizes, loading configurations) that are tested (in a qualification study or validation study) at upper and/or lower limits. (TR1) (TR61)

A validation method that tests the extremes of a process or product. The method assumes the extremes will be representative of all the samples between the extremes. (TR26)

Energy required to initiate plunger movement within the syringe barrel upon injection. (TR 73)

A filtration operation resulting in a significant rise in filtrate turbidity accompanied by a small increase in differential pressure. This occurs when the adsorptive capacity of the filter is reached, resulting in the passage of particles smaller than the pore size of the filter that would normally be removed by adsorption. (TR45)

Small bacteria (0.3–0.4 &;mum in diameter by 0.6–0.1 &;mum long) used to challenge a sterilizing grade filter during validation testing. [Formerly Pseudomonas diminuta](TR45)

The amount of heat (measured in Joules) required to raise the temperature of one pound of water by 1ºF.(TR64)

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

The minimum pressure at which a wetting liquid is pressed out of the pore system of a membrane while forming a steady bubble chain. (TR41)

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)

Consists of solid, liquid, or frozen product in a bulk container configuration such as a bag, tank, or drum. The product may be in these container configurations between process steps or prior to filling into vials, ampoules, cartridges, or syringes. (TR39)

Solids deposited on the upstream side of filter media. (TR15) (TR45) (TR26)

The demonstration that an instrument or device produces results within specified limits when compared to those produced by a reference standard or a standard that is traceable to national or international standards, over an appropriate range of measurements (calibration range). (TR 1) (TR 30) (TR 48) (TR 61) 

The demonstration that a particular instrument or device produces results within specified limits by comparison with those produced by a refer­ence or traceable standard over an appropriate range of measurements. (TR 54-5)

The relationship between measured response values and analytical concentrations of a standard or reference material. (TR57)

In metrology, the maximum permissible range around a specified value that applies to a properly functioning measuring instrument. [Synonym calibration uncertainty, error](TR48)

A series of consecutive production batches manufactured without intervening cleaning and sterilization. (TR13) (TR22) (TR62)

Processing of multiple lots or batches of the same product serially in the same equipment. (TR29) (TR49)

Extending the period of time, or number of cycles a single-use system is operating in a closed process without breaking the sterile barrier processes. The end user is responsible to evaluate and determine if appropriate quality requirements are met for their application. (TR 66)

A self-contained filter device. (TR45)

Compact, self-contained filter assembly. Generally, the whole assembly is disposable. (TR26) (TR41)

A pallet intended for use within the confines of a single facility or system not intended to be exchanged. These are frequently metal or plastic pallets in Good Manufacturing Practices (GMP) manufacturing areas. (TR55)

A solid support upon which the test organism used in biological monitoring is inoculated. (TR51)

A filter device requiring a housing for use. (TR45)

Filter elements encased in a housing. Generally, the filter elements are disposable while the housing units are multi-use. In a few cases, both filter and housings are disposable. (TR26) (TR41)

A tangential flow filtration module containing flat sheet, semipermeable membranes, feed channel and filtrate flow channels. (TR15)

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)

Type of cell population with defined characteristics that originates by serial subculture of a primary cell population that can be banked. (TR83)

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

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

Cells used for production which are at the limit of their invitro cell age. Note Also known as, “End-of-Production-Cells”. (TR56)

The certification by a supplier of the performance of the material tested against a set of specifications, such asidentity, purity, moisture content, pH, color, bioburden, endotoxin, etc. (TR56)

The relationship between the number of colony forming units counted on solid media and the number of genome copies measured using a method suitable for quantitative assessment of genomic DNA. (TR50)

When generated to satisfy a CGMP requirement, all data become a CGMP record. You must document, or save, the data at the time of performance to create a record in compliance with CGMP requirements, including, but not limited to, §§ 211.100(b) and 211.160(a). FDA expects processes to be designed so that quality data is created and maintained and cannot be modified. (TR80)

The concentration in Colony Forming Units/mL of the test microorganism in the challenge fluid. (TR75)

The carrier fluid in which the test microorganism is suspended and delivered to the test filter. (TR75)

The concentration of the test microorganism applied to the test filter (per centimeter squared) or the total number of cells applied to the test filter at the completion of the challenge. (TR75)

The volume of challenge fluid applied to the test filter. (TR75)

The primary component of a sterilizer that contains the items to be sterilized. The chamber is a pressure rated vessel. (TR1) (TR 48)

The primary structural element of a sterilizer that contains the products to be sterilized. The chamber is a pressure (positive and/or negative) rated vessel. (TR30)

The location(s) within the load zone that achieves the lowest process lethality (F₀) and/or the lowest distribution temperatures during the sterilization process. (TR01)

The elapsed time measured from the introduction of steam in the heat-up phase (“steam on”) to the point when the temperature of the heating medium within the chamber reaches the exposure temperature set point. (TR01)

A test conducted to evaluate possible air infiltration to the chamber under vacuum. [Synonym: Vacuum Leak Test] (TR1) (TR48)

A formal program that describes evaluation and actions to be taken if a change is proposed or completed to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and testing of drugs, or a proposed or completed change that may affect the operation of the quality or support systems. (TR22) (TR39) (TR52) (TR58) (TR64) (TR 70)

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

The steps taken for switching multiproduct equipment from the manufacture of one product to the manufacture of a different product. (TR29) (TR49)

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)

The relative stability of filter materials and/or filter assembly components when exposed to process fluids and process parameters. (TR45)

Test system that reveals change in one or more predefined process variables based on a chemical or physical change resulting from exposure to a process. (TR01) (TR30)

A device that is designed to react in a quantitative manner to multiple sterilization variables, (typically, time and temperature and, in some instances, moisture). (TR01) (TR30)

The body of information that defines the technical development, manufacturing facility and support utilities; the process equipment and materials used in manufacturing; the manufacturing process itself; the personnel involved in manufacturing and qual­ity; the chemistry of the product; QC in process and release testing, specifications, and stability of the product; all of the controls, documentation, and training necessary to ensure that all of these listed ac­tivities are properly and effectively carried out. (TR56)

Data recorded during performance of a chromatography unit operation typically includes UV absorption (280 nm), pH, and conductivity, as well as other data (e.g., flow rates or pressure). (TR14)

The passage of a solute (mobile phase) through resin (stationary phase) to achieve purification of substances based on the chemical, physical, and biological properties of the molecules involved. (TR14)

Material used to interact with the process stream in order to purify the target protein. Chromatography resin usually consists of porous particles within a defined particle size range that are insoluble in the process stream (e.g., ceramic beads, agarose). (TR14)

The removal of solid particulates from a liquid through filtration, sedimentation, centrifugation or other means. (TR45)

A situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death. (TR55)

A situation in which use of or exposure to a violative product or may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequence is remote.(TR55)

A situation in which use of or exposure to a violative product is not likely to cause adverse health consequences.(TR55)

Having product residues, process residues, and environmental contaminants removed to an acceptable level. (TR29) (TR49)

The implementation of procedures to render an area, piece of equipment, system, or object free of adulterants and contaminants. (TR 70)

The time from the end of the cleaning process until the equipment is used again (which may be product manufacture, autoclaving, or a steam in place (SIP) cycle). (TR29)

The process of rinsing or washing of process components, as installed without removal, in order to remove or eliminate any contaminants. (TR45)

A baseline filter flow measurement performed with clean water or a buffer, at a specified transmembrane pressure and temperature. (TR15)

The measurement for the level of particulates, microbes, or other extraneous substances on an item or surface. (TR 70)

The process of removing foulants from the membrane structure during normal processing, either through physical or chemical means. (TR13) (TR15)

The removal of adherent visible soil from the surfaces, crevices, serrations, joints, and lumens of instruments, and from devices and equipment, by a manual or mechanical process that prepares the items for safe handling and/or further decontamination. The cleaning process should leave surfaces that are visibly free from foreign material. (TR51)

The solution or solvent used in the washing step of a cleaning process. Examples of cleaning agents are water, organic solvent, commodity chemical diluted in water, and formulated detergent diluted in water. (TR29) (TR70)

The documentation that assures any product and process-related material introduced into equipment as part of the manufacturing process stream is removed and the equipment is adequately stored. (TR29)

A process that is used to remove any product, process-related material and environmental contaminant introduced into equipment as part of the manufacturing stream. (TR29)(TR49)

Documented evidence with a high degree of assurance that a cleaning process will result in products meeting their predetermined quality attributes throughout its life cycle. (TR29)(TR49)

A one-time sampling and testing to ensure that specified equipment has been properly cleaned following a specific cleaning event. (TR29) (TR49)

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)

A document, together with any amendments to it, that describes the objectives, design, methodology, statistical considerations, and organization of a clinical trial. (TR63)

A drug or combination of drugs and/or excipients that are produced with the intent that it be used in a clinical trial, or that is released or otherwise authorized for use in such. This could, subject to appropriate regulatory approval, be an experimental medicine, a product with marketing authorization used in a clinical trial within or beyond the approved indication and/or any placebo articles produced for use in a clinical trial. (TR63)

A physician, psychiatrist, etc., who specializes in clinical work as opposed to one engaged in laboratory or experimental studies. (TR58)

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

An isolated system that has no interaction with its external environment, preventing contamination and release of the material contained.(TR28) (TR 66)

A measure of the proportion of the variation of one variable determined by the variation of the other. (TR57)

A temperature- and time-controlled supply chain for products (e.g., refrigerated products typically have a temperature storage range of 2 °C to 8 °C). (TR58)

This concept expands the “normal” definition of cold chain to include all products that need to be stored below 250C and also introduces the ancillary terms “ambient temperatures” and “controlled ambient”. (TR46)

The location within an SIP system that achieves the lowest process lethality (F₀) during a SIP process. Note: When lethality values are not available or not applicable (e.g., a sanitization process operating at less than 100 °C) the cold spot is the location with the lowest temperature profile during the SIP cycle. (TR61)

A mixture with properties between those of a solution and a fine suspension. (TR45)

Growth (division) of adherent microorganisms on a surface (TR 69)

One or more microorganisms that produce a visible, discrete growth entity on a semi-solid, agar-based microbiological medium. (TR22) (TR62)

Visible outcome of growth of microorganisms arising from a single or multiple cells. (TR28)

A single microorganism or an aggregate of many that forms a single discrete colony on solid agar media after suitable incubation. Colony forming units are used for bacterial titer (total bacteria load in a sample) determination on solid media. (TR50) (TR75)

The quantity of mycoplasma contained in the highest dilution of a test article that produces a color change in a pH-sensitive liquid medium (typically containing phenol red) within a specified time of incubation, used for end-point determination of growth. (TR50)

The solute that is passed through the column for separation. (TR14)

Preparation of a column that includes the addition of resin slurry into a column to create a bed suitable for its intended use. Characteristics of a packed column bed include bed height and diameter, backpressure, and number of theoretical plates. (TR14)

A well planned, documented and managed engineering approach to the start-up and transfer of facilities, systems and equipment to the end-user that results in a safe and functional environment that meets established design and user requirement specifications. Commissioning precedes Qualification and includes three phases:
1. Inspection, testing, and regulation
2. Adjustment and setting of work
3. Functional testing (TR 3)

A prescribed number of activities designed to take equipment and systems from a static, substantially complete state to an operable state. (TR 48)

A well planned, documented, managed engineering approach to the start-up and turnover of facilities, systems, and equipment to the end-user, that results in a safe and functional environment that meets established design requirements and stakeholder expectations.(TR 54) (TR 54-5)

Transportation available to the public that does not provide special treatment to any one party and is regulated as to the rates charged, the liability assumed, and the service provided. A common carrier must obtain a certificate of public convenience and necessity from the Federal Trade Commission for interstate traffic. (TR46)

The quality or state of being suitable for comparison. FDA may determine that two products are comparable if the results of the comparability testing demonstrate that a manufacturing change does not affect identity, strength, quality, purity, or potency as they may relate to the safety or effectiveness of the product. (TR38)

A protocol submitted by an applicant under CFR 601.12(e) and 314.70 (g) that describes the specific tests and validation studies and acceptable limits to be achieved to demonstrate the lack of adverse effect for specified types of manufacturing changes on the identity, strength, quality, purity, and potency of the product as they may relate to the safety or effectiveness of the product. Any such protocols, or change to a protocol, shall be submitted as a supplement requiring approval from FDA prior to distribution of the product. The supplement, if approved, may justify a reduced reporting category for the particular change because the use of the protocol for that type of change reduces the potential risk of an adverse effect. (TR38)

An assessment of the similarities between the critical parameters and output results of two or more separate processes or methods. (TR50)

Transfer of a method that involves the analysis of a predetermined number of samples of the same lot by both the sending and the receiving unit. (TR 57-2)

Proof that no adverse interaction between the filter and the process fluid has occurred. (TR26)

A term used in relation to the non-reactivity of filter materials with the substance to be filtered. (TR45)

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

A method that is considered validated as published in one of the recognized compendia. (TR57)

(a) As defined by 21 CFR Part 211.198- Complaint Files. (b) A written record of each complaint shall be maintained in a file designated for drug product complaints. The file regarding such drug product complaints shall be maintained at the establishment where the drug product involved was manufactured, processed, or packed, or such file may be maintained at another facility if the written records in such files are readily available for inspection at that other facility.
1.The written record shall include the following information, where known: the name and strength of the drug product, lot number, name of complainant, nature of complaint, and reply to complainant .
2.Where an investigation under 211.192 is conducted, the written record shall include the findings of the investigation and follow-up. The record or copy of the record of the investigation shall be maintained at the establishment where the investigation occurred in accordance with 211.180. (TR55)

FDA requires complete data in laboratory records, which includes raw data, graphs, charts, and spectra from laboratory instruments and associated metadata. (§§ 211.194(a) and 212.60(g)(3) (2). A complete record of all data secured in the course of each test, including date and time the test was conducted and all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, drug product container, closure, in-process material, or drug product, and lot tested. (TR80)

Element of the assembled prefilled syringe (needle, plunger stopper and tip closure, or adhesive) directly in contact with the drug. (TR 73)

Element of the assembled prefilled syringe (plunger rod, backstop, or safety system) that interacts with the primary components and provides functionality to the delivery system. (TR 73)

A membrane consisting of multiple layers. (TR15)

A process in which a bulk drug substance is combined with one or more excipients and/or another bulk drug substance to produce a drug product. (TR22)

A process wherein bulk drug substance is combined with one or more excipients and/or another bulk drug substance to produce a drug product. (TR62)

The preparation, mixing, assembling, altering, packaging, and labeling of a drug, drug-delivery device, or device in accordance with a licensed practitioner’s prescription, medication order, or initiative based on the practitioner/patient/pharmacist/compounder relationship in the course of professional practice. Compounding includes the following:
• Preparation of drug dosage forms for both human and animal patients
• Preparation of drugs or devices in anticipation of prescription drug orders based on routine, regularly observed prescribing patterns
• Reconstitution or manipulation of commercial products that may require the addition of one or more ingredients
• Preparation of drugs or devices for the purposes of, or as an incident to, research (clinical or academic), teaching, or chemical analysis
• Preparation of drugs and devices for prescriber’s office use where permitted by federal and state law. (TR63)

Components used to pump refrigerant through the active temperature-controlled system. (TR64)

Collective application software, data and hardware platform that provides functionality, control and data to a user or other system. (TR48)

The concentrated feed solution after the removal of filtered liquid through the membrane and into the filtrate. [Synonym: retentate, retentate solution] (TR15)

The ratio of the initial feed volume to the retentate volume. (TR15)

A phenomenon in which the concentration of retained solutes increases in the region adjacent to the membrane surface due to limitations in particle transport back into the bulk solution. (TR15)

Validation that occurs during manufacturing of drug substance for batches that can be released and used in a final drug product for commercial distribution based on thorough monitoring and testing of the drug substance batches (1, 17). (TR60-3)

Validation that occurs during manufacturing of drug substance for batches that can be released and used in a final drug product for commercial distribution based on thorough monitoring and heightened testing of the drug substance batches. (TR42)

Component that removes the heat absorbed by the refrigerant from the compressor and temperature- controlled area. (TR64)

An interval estimate (range of values) of a population parameter, calculated from a random sample of the underlying population. (TR57)

Interval estimate (range of values) of a population parameter calculated from a random sample of the underlying population that represents the likely range in which the true value of the parameter resides. (TR57-2)

Batches prepared to demonstrate when the process operates according to defined ranges of operat­ing parameters and under controlled conditions, meet predetermined quality attributes (sometimes referred to as “validation” batches and demonstra­tion batches). (TR56)

A pre-determined number of production lots, typically three, that represent the process and are evaluated to demonstrate consistency. [Synonyms: validation, consistency, demonstration lots, qualification lots] (TR14) (TR42)

This refers to items (e.g., SUS, storage bags, tubing, filters, diaphragms, flasks, etc.) that form or are a part of process equipment and are used on a per batch basis. (TR66)

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)

A package leak test (either physicochemical or microbiological) that detects the presence of a package breach or gap. Some tests may also be able to identify the magnitude and/or location of the leak (the term container closure integrity test is synonymous with package leak test or package integrity test for the purposes of this TR). (TR86)

The sum of packaging components (primary and secondary) and materials that together contain and protect a product.(TR86)

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)

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 (16). The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API [drug substance] during production [manufacture], sampling, packaging or repackaging, storage or transport (17).

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

Ethnographic research method used to observe and analyze behaviors in actual end-use contexts (actual environments and use scenarios). (TR73)

Recurring activity to increase the ability to fulfill requirements. (TR54)

Assuring that during routine production the process remains in a state of control. (TR60)

US FDA: Assuring that during routine production the process remains in a state of control. ICH: An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (TR60-2)

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)

Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness. (TR88)

At least two process unit operations conducted under predetermined control conditions without process interruptions, where real-time process controls (PATs) may be used to meet the process requirements.

A mechanism by which temperature is regulated and recorded without interruption. It is recommended that if the system is not alarmed, it must be checked at predetermined time intervals. The time intervals should be determined by the facility but should be adequate enough to provide meaningful data of the temperature change over time. (TR46)

A process of data collection in which conditions are monitored continuously throughout the operation. In most U.S. applications, this definition implies “during production.” (TR13)

An alternative approach to process Validation in which manufacturing process performance is continuously monitored and evaluated. (TR60)

Following comprehensive assessments of scientific evidence and risk, quality attributes are ranked according to the degree of criticality. The continuum, as opposed to binary classifications of Critical and Non-Critical, is thought to “more accurately reflect complexity of structure-function relationships and the reality that there is some uncertainty around attribute classification”. (TR60)

A non-discrete scale where parameters or attributes are evaluated relative to their impact on drug substance and drug product quality. (TR60)

Endotoxin preparations other than the international or national reference standards that are traceable in their calibration to the international endotoxin reference standard. A CSE is a secondary or tertiary standard, commonly purified from Escherichia coli, and is usually manufactured and certified by an LAL reagent manufacturer for use with a specific lot of reagent under defined assay conditions.(TR82)

A planned set of controls, derived from current product and process understanding, which ensures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. (TR 54) (TR 60) (TR 54-5) (TR56)

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)

An area that is controlled by regulating temperature. (TR64)

Defined by USP <1079> as the usual and customary working environment of 20 °C to 25 °C (68 - 77 F) that allows for deviations between 15 °C and 30 °C (59 - 86 F) based on stability data. (TR58)

The transfer of heat by the circulation or movement of the heated liquid or gas. (TR3)

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 musty-moldy off-flavor or taste imparted to the wine primarily due to the presence of 2, Combination Products 6-trichloroanisole (2, Combination Products 6-TCA) produced by the fungalo-methylation of 2, Combination Products 6-tricholorophenol (TCP) associated with corks, wooden barrels, and construction materials in wineries. (TR55)

Repair, rework, or adjustment relating to the disposition of an existing deviation. (TR88)

Actions taken to eliminate the cause of an existing (corrective) or potential (preventative) non-conformity to prevent its recurrence. (TR52)

Action to eliminate the cause of a detected non-conformity or other undesirable situation. (TR54)

A response taken to remediate the effect of an excursion or product failure. (TR13)

Action taken to eliminate the causes of an existing deviation or other undesirable situation to prevent recurrence. (TR88)

Action to eliminate the cause of a detected nonconformity or other undesirable situation. NOTE: Corrective action is taken to prevent recurrence, whereas preventive action is taken to prevent occurrence. (TR 52) (TR 54-2) (TR 54-3) (TR 54-5)

A subsystem used to collect and analyze information, identify and investigate product and quality problems, and take appropriate and effective measures to prevent recurrence of the identified problem (8). (TR88)

A measure of covariation, the square root of the coefficient of determination. (TR57)

A thin, stiff material made of pressed paper pulp or pasted sheets of paper and used, for example, for making cartons or fiberpak drums. (TR55)

Errors in computer data that occur during writing, reading, storage, transmission, or processing, which introduce unintended changes to the original data.(TR80)

Personal care product formulations used to enhance an individual’s visual appearance or eliminate odor. This broad definition also applies to any material intended for use as a component of a cosmetic product. Note: The FDA specifically excludes soap from this category. (TR67)

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)

Sending and receiving laboratories participate in the AMV study execution. (TR57)

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

Describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the drug substance meets its specification. (TR38)

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)

Critical aspect design elements are components, instruments, and process controls that comprise the critical aspect (e.g., temperature feedback loop). Critical aspect design elements are tested in commissioning and qualification. (TR54-5)

Critical aspects are constituent parts of a system or piece of equipment that provide the ability to control one or more critical process parameter of the associated process (e.g., temperature control­ler of a bioreactor). (TR54-5)

A step at which control can be applied and that is essential to prevent or eliminate a pharmaceutical quality hazard or reduce it to an acceptable level. (TR54-4) (TR61)

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 process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (TR54) (TR54-4) (TR56) (TR54-5) (TR60-2) (TR5 6) (TR 81)

An input process parameter that should be controlled within a meaningful operating range to ensure that drug substance critical quality attributes meet their specifications. Although parameters with wide operating ranges may also impact product quality, they are generally easily controlled and not as likely to result in excursions that impact quality and are therefore low risk of occurrence. (TR60-3)

The location within the aseptic processing area in which product and product contact surfaces are exposed to the environment. The Critical Processing Zone is dependent upon machine design and includes, but is not necessarily limited to, the parison extrusion and cutting area, mold transfer area, air shower, and point-of-fill. (TR77)

A physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. (TR14)(TR54)(TR54-4)(TR57)(TR57-2)(TR60)(TR01)

Product attributes that affect product safety, identity, strength, quality and purity.(TR15)

Attributes that describe a parameter or item that must be controlled within predetermined criteria to ensure that the medicinal product meets its specifications .(TR39)

A defining characteristic of the product, including purity, strength, identity and safety.(TR44)

A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.(TR74)(TR 54-5)(TR81)

A physical, chemical, biological or microbio­logical property or characteristic that should be within an appropriate limit, range, or distribu­tion to ensure the desired product quality, as de­fined in ICH Quality Guidance Q8. (TR56)

A physical, chemical, biological, or microbio­logical property or characteristic that should be within an appropriate limit, range, or distribu­tion to ensure the desired product quality. (TR60-2)

A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. (TR84)

A component of the test method that may have a substantial impact on the consistency and reliability of method performance. Features of critical reagents include: 1. A reagent that requires qualification of each new batch prior to routine use in an analytical procedure, or 2. A material whose method performance characteristics may change over time, during handling, or from lot to lot. 3. An analytical reagent that may be purchased only from a single vendor. Reagent Examples: antibodies or enzymes that require titration prior to use, tissue culture treated plates when only one vendor’s plates give acceptable results for a bioassay, growth factors for bioassay cells, conjugated proteins that require custom preparations, or reference or system suitability standards. (TR57)

Function related: assay reagents that have been shown through development and/or robustness studies to have the potential to generate measurable differences that can significantly affect assay performance, such as sensitivity, specificity, and precision. (TR57-2)

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

A classification of an item (e.g., process, equipment, parameter) that expresses the significance given to the impact of that item, and should therefore be controlled or monitored to ensure product quality, safety or efficacy. (TR54)

A classification of an item (e.g., product, process, equipment, parameter) that expresses the significance given to the impact of that item, and should therefore be controlled or monitored to ensure product quality, safety or efficacy. (TR68)

The International Genetic Standardization System designator for Sprague Dawley (SD) rats. The SD (Crj:CD) is a general multipurpose rat model, used for safety and efficacy testing, aging, nutrition, diet-induced obesity, oncology. (TR55)

See Tangential Flow Filtration. (TR15)

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

An investigatory team, comprising representatives including QCU microbiologists, manufacturing, engineering, and maintenance personnel, and other appropriate SMEs, with the purpose of conducting a manufacturing investigation. (TR88)

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

The nutritional medium which supports the growth of the given microorganism. (TR75)

Practices and systems that are required to be followed for pharmaceutical manufacturing to ensure that the products produced meet specific requirements for identity, strength, quality, and purity. (TR54)

Refers to the Current Good Manufacturing Practice regulations enforced by the FDA and as described in the ICH guidance (ICH Q7 and WHO GMP, for API manufacturing). Current GMP provides for systems that assure proper design, monitoring, and control of manufactur­ing processes and facilities. Adherence to cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. (TR56)

In distribution, the trading partner or reseller, and In direct-to-consumer, the end customer or user (TR46)

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)

A study designed to stress test the product and provide specific information on its ability to withstand transient high and low temperature excursions during distribution and storage. Typically the study conditions are outside of ICH accelerated conditions.(TR53)

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)

The constant of proportionality of the material as defined by Darcy’s Law. (TR45)

Darcy’s Law states that the volumetric flow rate Q of liquid through a specimen of porous material is proportional to the hydrostatic pressure difference ∆p across the specimen, inversely proportional to the length L of the specimen and proportional to the cross-sectional area A. Darcy’s Law is expressed as Q = kA ∆p/L. (TR45)

Facts, figures and statistics collected together for reference or analysis. All original records and true copies of original records, including source data and metadata and all subsequent transformations and reports of these data, that are generated or recorded at the time of the GXP activity and allow full and complete reconstruction and evaluation of the GXP activity.(TR80)

Data means all original records and true copies of original records, including source data and metadata and all subsequent transformations and reports of this data, which are generated or recorded at the time of the GXP activity and allow full and complete reconstruction and evaluation of the GXP activity. Data should be accurately recorded by permanent means at the time of the activity. Data may be contained in paper records (such as worksheets and logbooks), electronic records and audit trails, photographs, microfilm or microfiche, audio- or video-files or any other media whereby information related to GXP activities is recorded.(TR80)

Refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA).(TR80) (TR84)

The degree to which data are complete, consistent, accurate, trustworthy, reliable and that these characteristics of the data are maintained throughout the data life cycle. The data should be collected and maintained in a secure manner, so that they are attributable, legible, contemporaneously recorded, original (or a true copy) and accurate. Assuring data integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices.(TR80) (TR84)

The degree to which data are complete, consistent, accurate, trustworthy and reliable and that these characteristics of the data are maintained throughout the data life cycle. The data should be collected and maintained in a secure manner, such that they are attributable, legible, contemporaneously recorded, original or a true copy and accurate. Assuring data integrity requires appropriate quality and risk management systems, including adherence to sound scientific principles and good documentation practices.(TR80) (TR84)

Controls put in place to either minimize the potential for a data integrity issue to occur or, if an issue does occur, the controls applied to increase the probability of detection.(TR84)

A storage repository that holds, in a structured way, a vast amount of raw data, including metadata, in its native format until it is needed. (TR84)

All phases in the life of the data (including raw data) from initial generation and recording through processing (including transformation or migration), use, data retention, archive/retrieval and destruction.(TR80) (TR84)

All phases of the process by which data is created, processed, reviewed, analyzed and reported, transferred, stored and retrieved and monitored until retirement or disposal. There should be a planned approach to assessing, monitoring and managing the data and the risks to those data in a manner commensurate with potential impact on patient safety, product quality and/or the reliability of the decisions made throughout all phases of the data life cycle. (TR80)(TR84)

A flow map that uses a baseline process flow map and overlays the data flow. (TR84)

An indicator of data’s level of exposure to data integrity failures due to intrinsic weaknesses in manufacturing processes, data-capture technology, and human factors or a combination thereof.(TR84)

For small molecules, the date of manufacture of a drug product is considered to be the initial date that an active ingredient has been added during manufacturing. For biologics the date of manufacture can be determined in multiple ways and should be consistent with internal quality systems and the product license application. (TR53)

Assembly of short reads of a sequence to generate a contiguous sequence (contig). (TR71)

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)

Person(s) with the competence and authority to make appropriate and timely quality risk management decisions.(TR54) (TR54-2)

A planned and orderly removal of a facility, operation or system from use. (TR48)

The process of retiring equipment/systems/facili­ties from production use. (TR54-5)

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

Equipment used exclusively for the manufacture of only one drug product, bulk drug substance, or intermediate. (TR29)

(1) A departure of a quality characteristic from its intended level or state that occurs with a severity sufficient to cause an associated product or service not to satisfy its intended normal or foreseeable usage requirements. (TR51)

(2) The nonfulfillment of intended usage requirements. The departure or absence of one or more quality characteristics from intended usage requirements. (TR43)

A departure of a quality characteristic from its intended level or state that occurs with a severity sufficient to cause an associated product or service not to satisfy its intended normal or foreseeable usage requirements. (TR76)

The nonfulfillment of intended usage requirements. The departure or absence of one or more quality characteristics from intended usage requirements. (TR76)

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)

Activities involving the hands-on steps required to successfully assemble and make a system ready for use for a specific SUS application. (TR66)

A matrix of randomly distributed fibers creating a tortuous path with pores of undefined size and shape. A filter that removes particles by a combination of adsorption and size exclusion within its porous matrix rather than on its frontal surface. (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 method for carrying out carefully planned experiments on a process. Usually, DoE involves a series of experiments that initially involves evaluating many variables and then focuses on a few critical ones. (TR54-4)

A structured, organized method for determining the relationship between factors affecting an assay and output of that assay. (TR57) (TR57-2) (TR74)

A structured, organized method for determining the relationship between factors affecting a process and the output of that process (8). (TR60)

Documented verification that the proposed design of the systems is suitable for the intended purpose. Also establishing confidence that ancillary component systems are capable of consistently operating within established limits and tolerances. (TR39) (TR48) (TR64) (TR 72)

Planned and systematic reviews of specifications, design, and design development and continuous improvement changes performed as appropriate throughout the lifecycle of the manufacturing sys­tem. Design reviews evaluate deliverables against standards and requirements, identify problems, and propose required corrective actions. (TR54-5)

The multidimensional combination and interaction of input variables (e.g., material attributes) and operational parameters that have been demonstrated demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (TR30) (TR60) (TR 57-2)

Controlled documentation that clearly and explic­itly defines the manufacturing system details, codes, and standards to be followed during fabrication and construction to meet associated requirements. (TR54-5)

The arrangement of factors and factor levels. Optimal experimental design minimizes “noise” in data to allow focus on the influence on assay response of critical factors. A factorial experiment (DOE) may minimize experiments required to achieve analytical purpose. (May be modified with complete block, factorial, fractional factorial, full factorial, incomplete block). (TR57)

A method in which a sample cannot be subsequently utilized in any other analytical method or processed to a final product. (TR86)

The ability to discover or determine the existence, presence, or fact of hazard. (TR54) (TR54-5)

The ability to discover or determine the existence, presence, or fact of a hazard (6). For purposes of this technical report, a hazard typically would be a data integrity breach.(TR84)

The ability to discover or determine the existence, presence, or fact of a hazard. (TR54-2) (TR54-3)

The ability to discover or identify a defect or failure. (TR44)

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

A method in which the leakage event being detected or measured is based on phenomena that follow a predictable chain of events. In addition, the measure of leak detection is based on physicochemical technologies that are readily controlled and monitored, yielding objective quantitative data. (TR86)

Documentation and description of work done during the early phases of development. The goal is to document information about the way the process works and to document why key choices were made in selecting the specifics of the process (e.g., flow rate or temperature). These documents can serve as a reference during investigations of discrepancies and during the design of specific Validation and characterization studies.(TR14) (TR 42)

Documentation and description of work done during the early phases of development (Stage 1). The goal is to document information about the way the process works and to document why key choices were made in selecting the specifics of the process (e.g., flow rate or temperature). These documents can serve as a reference during investigations of deviations and during the design of specific validation and process characterization studies.(TR60)

Departure or digression from set parameters. (TR58)

Data or a result outside of the expected range or an unfulfilled requirement; it may be called nonconformity, defect, discrepancy, out-of-specification, out-of-limit, or adverse trend. (TR88)

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)

Complex, branched, high molecular weight polysaccharides made of many glucose molecules joined into chains of varying lengths and branches. (TR41)

The convective elimination of permeable solutes by the addition of fresh solvent to the retentate. (TR15)

A volume equal to the retentate volume to which a diafiltration buffer is added. (TR15)

The difference in pressure between the upstream (feed or influent) and downstream (effluent) sides of the filter. (May be modified with the terms: applied, available differential pressure, clean differential pressure, dirty differential pressure, initial differential pressure, or maximum differential pressure). [Synonym: Delta P (Δ P), PSID, Pressure Drop] (TR45) (TR26)

When the nature of the product or package lim­its the ability to perform a thorough inspection for particles. (TR79)

A test to determine the integrity of a filter. The test is based on the measurement of the diffusive (diffusional) flow of a gas through a wetted filter, along with any bulk flow of gas through open (unwetted) pores. Either the gas flow or the downstream liquid, displaced by the gas flow, may be measured. [Synonym: Forward Flow Test] (TR45)

A test for membrane integrity that involves measuring the rate of gas diffusion through a liquid-wetted membrane.(TR15)

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

The movement of a dissolved gas across a liquidwetted membrane based on the concentration (e.g., gas pressure) differential. (TR26)

A test to determine the integrity of a filter. [Synonym: diffusive flow test, forward flow test.] (TR26)

The product conforms to the required drawing dimensions. (TR43)(TR76)

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

Particles with diameters larger than the filter pore diameter that are prevented from passing through the filter. (TR26)

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)

Transport of a medicinal product from a drug manufacturer’s warehouse/storage facility to distribution centers, commercial customers, or clinical facilities. Subsequent distribution may also occur. (TR39)

Movement of product within a designated supply chain, including activities that range from preparation for shipment to receipt of the product at the final destination.(TR58)

The temperature range, supported by stability studies, within which a medicinal product can be transported for a short duration of time without adverse effect on quality parameters. (TR39)

Qualification of packaging components for physical distribution integrity like shock, vibration, and drop tests. (TR58)

Device placed in the interior of the controlled environment space (CES) to measure air temperature but is not placed in the product (see penetration thermocouple). (TR64)

See Development Reports , Process Characterization Report , Process Validation Protocol, or Process Validation Report (TR14) (TR42)

Refers to the demand side of the supply chain. Downstream consists of one or more companies or individuals who participate in the flow of goods and services moving from the manufacturer to the final user or consumer. This is the opposite of upstream. (TR46)

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

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

A general term used to define the entire process of bringing a new drug to the Market. It includes drug discovery, process and product development, pre-clinical research (microorganisms/cell culture/animals) and Clinical trials (on humans). (TR56)

A pharmaceutical product type that contains a drug substance, generally, in association with excipients. [Synonym: Dosage Form; Finished Product] (TR57)(TR14)(TR42)

A finished dosage form (e.g., tablet, capsule, or solution) that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.(TR38) (TR67) (TR88)

The dosage form in the final immediate packaging intended for marketing.(TR60)(TR82)

A document that provides a structured action plan to proactively prevent drug shortages and also respond to a shortage in the event that one occurs. (TR68)

A single source of information on risks that can result in drug shortages, associated risk levels, risk control actions with owners, status, due dates and residual risk after appropriate risk control actions have been taken. (TR68)

The active ingredient that is subsequently formulated with excipients to produce the drug product. It can be composed of the desired product, product-related substances, and product- and process-related impurities. It may also contain excipients, including buffers and other components. [Synonyms: bulk drug substance, bulk material, active pharmaceutical ingredient (API)] (TR14) (TR57) (TR74) (TR60)

Active pharmaceutical ingredient in a drug product that is responsible for that product’s therapeutic activity.(TR67) (TR82) (TR88)

See Active Pharmaceutical Ingredient (API). (TR56)

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)

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

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)

The record format allows interaction between the user and the record content.(TR80)

An electronic record which the user reviewer can interact with.(TR80)

Records, such as electronic records, that allow for an interactive relationship between the user and the record content.(TR80)

Generally used to indicate Phase 1 and A clinical studies.(TR 56)

Generally used to indicate the following clinical study activities: Microdosing Studies, Phase 1 Trials, Phase 2 Trials, and Phase 3 Trials. See any of the following studies for more information. (TR56)

Studies designed to speed up the development of promising drugs by establishing very early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. May include the administration of single sub therapeutic doses of the study drug to a small number of subjects (10 to 15) to gather preliminary data on the agent’s pharmacokinetics (how the body processes the drug) and pharmacodynamics (how the drug works in the body). A microdosing study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. (TR56)

Phase 1 trials are the first stage of testing in human subjects. Often, a small (20-100) group of healthy volunteers will be selected. For life-threatening indications such as oncology, these can be patients that have the target disease but may not yet be the ideal target population. This Phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. (TR56)

Once the initial safety of the study drug has been confirmed in Phase 1 trials, Phase 2 trials are performed on larger groups (20-300) are designed to assess efficacy, as well as to continue safety assessments in a large group of volunteers and patients. Phase 2a is specifically designed to assess dosing requirements (how much drug should be given). Phase 2b trials are specifically designed to study efficacy (how well the drug works at the prescribed dose(s). (TR56)

Final clinical stage Phase 3 trials are designed to demonstrate the potential advantages of the new therapy over other therapies already on the market; safety and efficacy of the new therapy are studies over a long period of time and many more patients (1,000-3,000) are enrolled into the study with less restrictive eligibility criteria; phase 3 studies are intended to help scientists identify rarer side effects of treatment and prepare for a broader application of the product; phase 3 trials enroll patients to verify efficacy and monitor adverse reactions during longer-term use. (TR56)

The fraudulent, intentional substitution or addition of a substance in a product for the purpose of increasing the apparent value of the product or reducing the cost of its production (i.e., for economic gain). (TR54-3)

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

The total surface area of the filter available to the process fluid. (TR26)

The liquid flowing out of a column. (TR14)

Fluid that flows out of a process step. (TR26)

Thermoplastic material formulation (that may or may not contain rubber/natural latex) derived from elastic polymer; often used interchangeably with the term “rubber.” (TR73)

An array of electronic sensors designed to selectively identify chemicals responsible for odors. The zNose™ system is one example that is commercially available and consists of a vapor pre-concentrator, a direct-heated high-speed chromatography column, a solid-state sensor and a programmable gate array microprocessor system. (TR55)

A record used for GMP purposes or for regulatory submission that is stored electronically for the purposes of reproduction, retrieval or archival. (TR48)

Solution (effluent) that flows out of the chromatographic column containing the drug substance. [Synonym: collected product fractions] (TR14)

Desorption of a drug substance from a chromatographic column. (TR14)

The emissivity of the surface of a material is its effectiveness in emitting energy as thermal radiation. This is measured between 0 (zero) and 1 (one); 0 having the ability to reflect all energy, and 1 allowing all energy to pass through it. Glass, for example, has emissivity of 0.91 (smooth, uncoated); aluminium foil has emissivity of 0.03. (TR72)

A dispersed colloidal system consisting of two immiscible liquid phases generally stabilized with one or more suitable agents. Injectable emulsions are sterile liquid dosage forms of drug substances dissolved or dispersed in a suitable emulsion me­dium. Injectable emulsions are for parenteral ad­ministration of poorly water-soluble drugs. (TR79)

A tool or process which provides the means to achieve an objective (ICH Q10). (TR54)

Cells cultured (under conditions comparable to those used in production) from the MCB or WCB to a passage level or population doubling level comparable to or beyond the highest level reached in production. Note: The ICH term is: “Cells at Limit of invitro Cell Age Used for Production”.
Note: The term as defined in ICH Guidance Q5 D is “Cells at Limit of in vitro Cell Age Used for Production”; also abbreviated as EPC. (TR56)

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)

Column washing with a solution or buffer(s) in preparation for the column load. (TR14)

The period that elapses between the attainment of the minimum exposure temperature at the reference measurement point (typically the drain) and the attainment of the sterilization temperature at all points within the load. This period is an indication of the ability to properly remove air and heat the load items; consequently, it is typically only evaluated by placing heat penetration probes in porous/hard goods loads. (TR01) (TR48)

The moisture content of wood below the fiber saturation point is a function of both the relative humidity and the temperature of surrounding air. The equilibrium moisture content (EMC) is the moisture content at which the wood is neither gaining nor losing moisture; this however, is a dynamic equilibrium and changes with relative humidity and temperature. (TR55)

Automated or non-automated, mechanical or non-mechanical equipment used to produce the drug product, including equipment used to package the drug product. (TR38)

The sequence of equipment through which a product is produced or processed. (TR29) (TR49)

See Comparability. (TR38)

A comparison with the primary objective of showing that the results from two methods differ by an amount which has negligible impact on fitness for use. This is usually demonstrated by showing that the true difference is likely to lie between a lower and an upper equivalence margin of acceptance differences. (TR57)

The largest difference between the results from two methods that is considered as being scientifically and statistically acceptable. (TR57)

Test of conformance to interval-based target acceptance criteria; differs from most common statistical tests in the nature of the statistical hypothesis. In equivalence testing, the alternative hypothesis is that the difference is sufficiently small that no important difference exists. A common statistical procedure used for equivalence testing is the two one-sided T-test. (TR57-2)

A measure of how similar the test results are when compared with the existing method. (TR33)

Deviation from expected value. Error may be random or systematic. (TR57)

A self-evident documented mistake that will bring the validity of a laboratory test into question. (TR88)

A self-evident documented mistake that will bring the manufacturing process into question. (TR88)

Component that transfers heat out of or into the CES (to control the area temperature). (TR64)

A systematic technique that employs forward logic to construct a graphical representation of consequences from an initiating event. (TR54)

A component of a drug formulation that has no active pharmacologic function. Excipients are commonly used in drug formulations as modulators of pH or osmolality for parenteral administration and as stabilizers for APIs. (TR54-4)

An ingredient added intentionally to the drug substance that should not have pharmacological properties in the quantity used. (TR57)

Inactive pharmaceutical ingredients in a product formulation that are responsible for the product’s manufacturability and physicochemical attributes. (TR67) (TR88)

The capacity of an assay not to detect microorganisms closely related to a target microorganism. (TR33)

A temperature or humidity deviation from conditions such as those specified by product labeling or shipping specifications. (TR53)

Measurement that exceeds an alert, concern, or action level/limit by either a discreet value or an increasing/decreasing trend. (TR69)

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)

A type of compounding whereby a drug or combination of drugs and/or excipients is prepared under the supervision of a pharmacist to create a customized medication dosage form in accordance with a clinical protocol. (TR63)

Refers to a legislative requirement that packaging manufacturers “take back” their packaging, or otherwise ensure (through a tax) that it is collected and properly disposed of. (TR46)

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)

A chemical component that is removed from a material by application of an artificial or exaggerated force (e.g., solvent, temperature, time). The term extractable is often erroneously used to describe a leachable. (TR14) (TR15) (TR26) (TR41) (TR45)

Chemical substances that can be extracted from components of material process fluid contact surfaces by exertion of an exaggerated force (e.g., organic solvent, extreme elevated temperature, ionic strength, pH, contact time, etc.) Extractables may represent most but not all of the potential leachables that may be seen in process fluids. (TR66)

Extractables are organic and inorganic chemical entities that can be released from a pharmaceutical packaging/delivery system, packaging component, or packaging material of construction under laboratory conditions. (TR54-4)

Organic or inorganic chemical entity that is forced out of container closure system materials and components under laboratory experimental conditions. (TR73)

A known test article processed with a nucleic acid extraction procedure in order to ensure the proper extraction of nucleic acid. (TR50)

The efficiency of extraction of target analyte from a test matrix. It is usually measured as ratio (percentage) of analyte amount extracted from the matrix to that originally present in the matrix before extraction. (TR50)

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)

Filled syringe delivery force (that does not include break-loose force) quantified as the highest non-break-loose force to complete the injection stroke. (TR73)

<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>

Independent QRM expert who facilitates risk assessment; guides documentation, risk control, and risk review; and helps present risk assessment results and risk control proposals. (TR54-2) (TR54-5)

A physical building with a defined building number or name. (TR38)

Independent variables that may influence assay outcome. (May be modified with confounded, crossed, fixed, interaction, level, modifying, nested, random). (TR57) (TR57-2)

A test typically conducted by the sterilizer manufacturer after the system has been assembled and before the system is shipped to the installation site. (TR48) (TR54-5)

The condition or fact of not achieving expected results; a cessation of proper functioning or performance. (TR44)

An impact on customer requirements. Generally, failure effect has an external customer focus, but it can also include downstream processes. (TR58)

A method of assessing and evaluating risk. (TR44)

A systematic method for identifying, analyzing, prioritizing and documenting potential failure modes, their effects on system, product and process performance, and the possible causes of failure in order to prevent defects from occurring. (TR54) (TR54-2) (TR54-3) (TR54-4) (TR74) (TR54-5)

A tool for analyzing processes or systems to evaluate all operating steps in order to identify and assess the risk associated with any potential failures. (TR65)

An analytical technique that results in a rankordered list of concerns to take action on. (TR72)

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)

The FAO’s mandate is to raise levels of nutrition, improve agricultural productivity, better the lives of rural populations, and contribute to the growth of the world economy. (TR55)

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

A deductive technique used to analyze the causes of faults (defects). The technique visually models how logical relationships between failures, human errors, and external events can combine to cause specific faults. (TR54) (TR54-2) (TR54-3) (TR54-5)

Inspectional observation sheet used by FDA investigators to document their findings. (TR67)

A modification of the batch filtration process in which a separate (typically larger) reservoir feeds a smaller recycle tank. The retentate stream is returned to the recycle tank. (TR15)

The starting solution prior to filtration. (TR15)

The fluid introduced into a process. (TR41)

The pressure measured at the inlet of the tangential flow filter device. (TR15)

Feret Min is the minimum distance between parallel tangents at opposing particle borders. Feret Max is the maximum distance between parallel tangents at opposing particle borders.

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

A porous medium used for the separation of components in a fluid stream.(TR15)

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)

To pass a fluid through a porous medium whereby bacteria or other particles are removed from the fluid. (TR26)

The effective surface area of a filter that is available for filtration; not the internal pore surface area, but rather the surface of one side of a filter. (TR45)

A measurement of how well a filter retains particles. It is usually expressed as the percentage, or ratio, of the retention of particles of a specific size by a filter. (TR26)

The basic filter unit from which cartridges or capsules are assembled. (TR26)

A numerical rating of filter performance based on the ability of the filter to retain an appropriate model microorganism under given test conditions. (TR75)

A test to determine the suitability and sizing of a filter with a given fluid. (TR26)

Fluid that has been passed through a process step (filter). [Synonym: Permeate] (TR15) (TR26)

The pressure measured at the outlet side of the tangential flow filter device containing filtered material. [Synonym: permeate pressure] (TR15)

A process of removing particles from a fluid by passing it through a permeable material, such as a membrane film. (TR41)

The process by which particles are removed from a fluid by passing the fluid through a porous material. (TR26)

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 method of controlling inventory to ensure that the material with the shortest remaining shelf-life is distributed first. (TR52)

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)

Decrease in flow rate at constant pressure as a result of filter fouling. (TR45)

An experiment to determine flow rate and throughput of a filter type or combination of filters on a specific liquid, usually by using a small area filter, to determine the sizing of a filter system by extrapolation. (TR45)

The volumetric rate of flow of a solution, expressed in units of volume per time (e.g., L/min or gal/day). (TR15) (TR26)

Effluent that may contain the product that is not retained by chromatography resin during column loading. (TR14)

The rate of transfer of fluid through a cross-sectional area often applied to filtrate flow rate; expressed in units of volume per time per unit area (e.g., LMH: liters per square meter per hour). (TR15)

The rate of filtrate flow divided by the membrane area. (TR26)

Instantaneous or current flux relative to initial or buffer flux. (TR41)

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)

A structured, organized method for determining the relationship between factors affecting a process and the output of that process. (TR60)

Observed actual or simulated use of early prototypes to help reliably identify product conceptspecific, use-related hazards that may have been missed by other methods. (TR73)

A listing of the ingredients and composition of the dosage form. (TR38) The percent composition of ingredients in a product. (TR67)

Solute or suspended solid that interacts with the membrane causing a decrease in performance (see Fouling). (TR15)

Adsorption or interaction with components in the feed stream resulting in a decrease in membrane performance. Generally, fouling can be reversed by cleaning the membrane. (TR15)

The result of solutes blinding or blocking membrane pores. It is observed as a decrease in the flux (at constant pressure) or an increase in the filtration differential pressure (at constant flux). (TR26)

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 study designed to determine the effect of repeated freezing (typically to -20 °C), and thawing back to labeled storage conditions (typically +5 °C for refrigerated products, and +25 °C for temperature products). Freeze-thaw studies are designed to evaluate the impact of short-term excursions where product may be exposed to sub-zero temperatures, followed by standard shipping conditions. (TR53)

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 porous sieve or screen installed at the top and bottom of a column used to retain chromatography resin particles and allow passage of the process stream. [Synonym: sinter] (TR14)

A calibration process that includes all measurement system components, from sensor to measurement value (e.g., temperature calibration of a data logger and attached thermocouple wires). (TR64)

The currently approved International Standards for Phytosanitary Measures (ISPM) fumigation method is methyl bromide (MB) fumigation and is one of the two approved phytosanitary measures in ISPM 15 (treatment and marking of wood packaging materials [WPM] that is required for international shipment. The use of methyl bromide is not permitted in some IPPC countries (e.g. the EU), and the latest ISPM 15 standard has a recommendation to reduce its use. Note: Steam heat treatment is the other ISPM 15 approved method. (TR55)

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)

The pressure measured by a pressure gauge. Typically expressed in units of psig, bar or kilopascal. (TR45)

Gauge pressure is the difference between a given fluid pressure and that of the atmosphere. (TR26)

Gels (sometimes called jellies) are semisolid sys­tems consisting either of suspensions of small inorganic particles or of organic molecules inter­penetrated by a liquid. Gels can be classed either as single-phase or two-phase systems. (TR79)

A method of walking through and personally observing processes. (TR84)

A generator unit that is used to provide electrical power to maintain the temperature in a container/ trailer in transit and is not attached to a stationary power source. Gensets consist of a diesel or electrically powered engine that produces the required voltage to operate the temperature control unit (TCU; reefer) on the container/trailer. (TR64)

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)

Force in Newtons (N) required for plunger movement within an empty syringe. (TR73)

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

Defined as that part of quality assurance that ensures that the quality of the pharmaceutical product is maintained by means of adequate control of numerous activities which occur during the distribution process. (TR55)

(commonly abbreviated GDP, or as GDocP to distinguish from “Good Distribution Practice”) Describes standards by which documents are cre­ated and maintained. (TR56)

Documented proven and accepted engineering methods and practices that applied throughout the project life-cycle to deliver solutions that are cost effective, are compliant with regulations and meet the requirements of the user. (TR48)

Those established engineering methods and standards that are applied throughout the lifecycle to deliver appropriate and cost-effective solutions. (TR60) (TR54-5)

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)

Acronym for the good practice guides governing the preclinical, clinical, manufacturing, testing, storage, distribution and postmarket activities for regulated pharmaceuticals, biologicals, and medical devices, such as good laboratory practices, good clinical practices, good manufacturing practices, good pharmacovigilance practices and good distribution practices.(TR80)

A qualification method that uses fifty percent of the exposure time to demonstrate sterilization cycle efficacy. The physical and biological lethality values achieved in the half-cycle exposure time are doubled to project the lethality that will be achieved by the full cycle.(TR01)

Damage to health, including damage occurring from loss of product quality or availability. (TR44) (TR54) (TR54-2) (TR54-4) (TR68)

The screening of a biopharmaceutical bulk cell culture harvest for any adventitious contaminants, including mycoplasma, before further processing. (TR50)

The potential source of harm. (TR44) (TR54) (TR54-2) (TR58) (TR61)

A systematic, proactive, and preventative tool for assuring product quality, reliability, and safety (TR54-3) (TR54)

A management system in which potential hazards are addressed through the identification and control of key risk factors (critical control points) of the biological, chemical, and physical hazards from raw material production, procurement and handling, to manufacturing, distribution and consumption of the finished product. (TR55)

A structured, systematic and qualitative technique for examination of a planned or existing process or operation in order to identify and evaluate problems that may represent risks to personnel or equipment, or prevent efficient operation. (TR54)

Circumstances in which people, property, or the environment is exposed to a hazard. (TR54-2)

A tool for classifying a voluntary recall by a firm. The HHE guides the US FDA in determining the risk to the public from the defective product and appropriate actions for the firm and the FDA to take to protect public health. (TR55)

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)

Refers to technology of indoor and automated environmental control. (TR70)

Two types of methods to include kiln drying versus steam heat. (TR55)

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)

Henry’s law can be put into mathematical terms (at constant temperature) as p=k_H x c, where p is the partial pressure of the solute, i.e.. TBA in the gas above the solution, c is the concentration of the solute and k_H is a constant with the dimensions of pressure divided by concentration. The constant, known as Henry’s law constant, depends on the solute, the solvent and the temperature. (TR55)

A measurement of column packing efficiency or integrity, calculated from the column height divided by the number of theoretical plates. (TR14)

A linear polymer, HDPE is prepared from ethylene by a catalytic process. The absence of branching results in a more closely packed structure with a higher density and somewhat higher chemical resistance than low-density polyethylene (LDPE). (TR55)

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)

A drug active that can cause serious adverse effects at typical doses. Those adverse effects are generally not related to the main therapeutic activity of the drug, and includes effects such as carcinogenicity, mutagenicity, genotoxicity, reproductive hazards, allergenicity, and cytotoxicity. (TR29)

A type of database designed to archive automation and process data. (TR84)

For purposes of this guidance, data on impurities or physical attributes from three or more consecutive, representative pre-modification batches. (TR38)

Amount of fluid remaining in the syringe when the plunger has reached the end of travel within the barrel. (TR73)

A non-transfected cell substrate that is gener­ally well-characterized and banked. It can be manipulated to generate a cell substrate for production of a biological medicinal product. (TR83)

A science discipline that examines human psychological, social, physical, and biological characteristics to evaluate the design, operation, or use of products or systems for optimizing human performance, health, safety, and/or habitability. [Synonym: Ergonomics] (TR62)(TR80)

The use of a computerized system in which there is a combination of original electronic records and paper records that comprise the total record set that should be reviewed and retained.(TR80)

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

Pressure that results from forcing liquid through an orifice, pipe or other channel. (TR45)

See definition for Pressure Shock. (TR45)

Literally “water loving.” A filter that will wet with aqueous solutions to allow flow at a low pressure differential. (TR26)

Literally “water fearing.” A filter that repels aqueous and other high-surface tension fluids and therefore cannot be wetted unless subjected to a high pressure differential. When prewetted with low surface tension fluid, such as alcohol, the membrane will allow water flow at a low pressure differential. (TR26)

An international organization that seeks to promote the peaceful use of nuclear energy and to inhibit its use for any military purpose, including nuclear weapons. (TR55)

Use of an analytical procedure to determine the chemical and biochemical identity of a material. (TR57)

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

Determination of how a product failure may extend an investigation “to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy” (10). (TR88)

Implants are long-acting dosage forms that provide continuous release of an API for periods of months to years. They are administered by the parenteral route. For systemic delivery, they may be placed subcutaneously or, for local delivery, they can be placed in a specific region in the body. (TR79)

Any component present in the drug substance or drug product that is not the desired product, a product-related substance, or excipient including buffer components. It may be either processor product-related. (TR14) (TR57) (TR74)

Any component present in the drug substance or drug product which is not the desired product, a product-related substance, or excipient. It may be either process- or product-related (17). (TR60)

A description of the identified and unidentified impurities present in a drug substance (ICH A3A). (TR38)

Any event that occurs during the shelf life of a product that may have an adverse effect on quality (e.g., temperature excursion, missing temperature monitor when required, shipment time in excess of qualified packout duration, wet/ crushed packaging). (TR58)

Part of the Quality Management System that handles incidents, deviations, excursions, and exceptions in the supply chain. (TR58)

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

A preventative program where parts or products are subjected to evaluation upon receipt.(TR43)

A program where, upon receipt, parts or products are subjected to measuring, examining, testing, or gauging one or more characteristics of a product or service, and comparing the results with specified requirements in order to establish whether conformity is achieved for each characteristic.(TR 76)

International commerce terms. These are a series of international sales terms, published by the International Chamber of Commerce (ICC), and widely used in international commercial transactions. (TR58)

Two or more measurements or observations that are generated from independently prepared samples and do not affect each other. (TR57)

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)

Fluid that flows into a process step. [Synonym: feed.] (TR26)

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

The applied pressure entering the upstream side of the filter. [Synonym: influent, upstream or line pressure] (TR26)

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)

Chemicals substances that are leached, from product-contact or non-product-contact materials under typical process conditions and could be cleared or sufficiently diluted by downstream processes so as to be undetected as leachables in the final dosage. Alternate Terms: Transient Leachables, Migrant Leachable. (TR66)

Any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product (21 CFR 210.3(b)). (TR38)

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)

A material produced during steps of the processing of a drug substance that undergoes further molecular change or purification before it becomes a drug substance. (TR14) (TR74)

A material produced during steps of the processing of a drug substance that undergoes further molecular change or purification before it becomes a drug substance (17). (TR60)

A material produced during the steps of the processing of an API that undergo further molecular change or purification before it becomes an API. Intermediates may or may not be isolated. (TR60)

The chemical mixture that may or may not have completed the chemistry steps, and thus is not in its final chemical and physical/conformational state, and has not been through final process steps to final drug substance.
Examples in the small molecule world include isolated intermediates, intermediates, and final intermediates.
Examples in the large molecule world include crude protein mixtures (pre-transformation, conversion, or folding) and purified protein prior to any final polishing steps. (TR38)

The precision within the same laboratory using different analysts, equipment, reagents and/or on different days. (TR33)

A shipping container used to ship cargo through more than one of the four traditional modes of transportation (road, air, ocean, and rail). (TR64)

A reaction performed to provide confirmation of adequate performance of the NAT assay including preparation of nucleic acid, its amplification using appropriate amplification technology, and analysis of amplified products. An example is the amplification of a housekeeping gene from the production cell line which provides a positive signal even in the absence of contaminant DNA. (TR50)

ISO containers are shipping containers manufactured according to specifications from the International Standards Organization. They may also be referred to as “sea containers” or “inter-modal” containers. (TR46)

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)

Term defines when a chemical is administered through the peritoneal cavity (area that contains the abdominal organs). (TR55)

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)

In the hands of the end user who can be the health professional or the patient. In-Use refers to the time period where product is in the custody of the end user or health care professional. (TR53)

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

Laboratory test result confirmed to be invalid as determined by a laboratory investigation. (TR88)

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)

A clinician scientist taking part in a clinical trial having direct and immediate clinical responsibility for the subject or patient and their treatment with the clinical trial material. (TR63)

A RNA copy synthesized using a double-stranded DNA as template. The RNA polymerases of bacteriophage T7 or SP6 are usually used to perform the in-vitro transcription. (TR50)

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)

An intermediate that is obtained as the product after workup of a purification step in the process scheme for the drug substance. The isolation or purification procedure should be part of the validated process. An aliquot of a product that is worked up and/or purified for purposes of characterization does not constitute an isolated intermediate. (TR38)

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)

World-wide organization that supports its membership in designing and developing effective pre-shipment packaging performance standards, guides, and best practices for product distribution. (TR39)

Reports containing scientific data and expert professional judgment to substantiate decisions. (TR38)

A subset of the characteristics of the drug which are determined to be most important to quality. (TR63)

A process of drying lumber in a dry kiln to a specified moisture content using the correct drying schedule (combination of dry- and wet-bulb temperature settings). Kiln-drying suffices as a heat treatment. This type of treatment is not ISPM certified and would not necessarily have an HT (heat-treated) stamp. However, this is a normal process for drying of lumber. (TR55)

The International System of Units derived unit of pressure. (TR75)

Systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components (ICH Q10). (TR54) (TR68) (TR54-5)

The process by which a label is affixed to a packaging component. (TR85)

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)

Median lethal dose or median lethal concentration, of a toxin, radiation, or pathogen is the dose required to kill half the members of a tested population after specified test duration. LD50 figures are frequently used as a general indicator of a substance’s acute toxicity. (TR55)

A chemical component that migrates from a contact surface into a drug product or process fluid during storage or normal use conditions. The term leachable is often erroneously used to describe an extractable. (TR14) (TR26)

Leachables are organic and inorganic chemical entities that migrate from a packaging/delivery system, packaging component, or packaging material of construction into an associated drug product under normal conditions of storage and use or during accelerated drug product stability studies. Leachables are typically a subset of extractables or are derived from extractables. (TR54-4)

Chemical substances that are leached, from product-contact or non-product-contact materials, under typical process conditions and detected in final dosage. Leachables may be a subset of extractables, and can include their reaction or breakdown products. (TR66)

Organic or inorganic chemical entity that migrates from pharmaceutical container closure system components into a drug product formulation. (TR73)

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)

The measure of the distance along its longest axis. Light obscuration (LO). Analytical technique measuring the size and quantity of subvisible particles. (TR85)

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)

Life supporting or life sustaining is used to describe a product that is essential to, or that yields information that is essential to, the restoration or continuation of a bodily function that is important to the continuation of human life. (TR68)

All phases in the life of a product from the initial development through marketing until the product’s discontinuation. (TR54) (TR60)

All phases in the life of a product, from the initial development through marketing until the prod­uct is discontinued. (TR60-2)

A functional molecule (small molecule or protein) coupled to the chromatography resin that selectively interacts with the target protein, impurities, or other molecules from the process stream. (TR14)

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)

The amount of target molecules per volume of resin (e.g., gram protein per milliliter resin). (TR14)

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)

Thickness of an air-filled insulation material. (TR72)

The partition coefficient is a ratio of concentrations of un-ionized compound between the two solutions usually water and octanol. To measure the partition coefficient of ionizable solutes, the pH of the aqueous phase is adjusted such that the predominant form of the compound is un-ionized. The logarithm of the ratio of the concentration of the un-ionized solute in the solvents is called log P; The log P values is also known as a measure of lipophilicity. (TR55)

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)

Freight forwarders and brokers that assist in moving the product, but may not physically touch the product. (TR52)

An electronic system with limited storage capacity that overwrites older data when it reaches that capacity. (TR84)

A day on which an employee does not work because of injury in a work-related accident. (TR52)

A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits.(TR76)

The inability to recover ≥50% activity over time when known amount of endotoxin is added to an undiluted product. LER cannot be overcome by dilution.(TR82)

Freeze-dried product typically in the form of a solid plug or cake in the container. (TR79)

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)

Data generated from visual inspection of a blind­ed set of seeded test containers that demonstrates the detection capability of human inspection. The test set is sometimes referred to as a “particle size threshold set,” where various foreign particu­late types in a gradation of sizes are examined to yield a statistically significant probability of de­tection percentage for each unit. This allows the determination of what types and sizes of particu­lates can be reproducibly detected in a specific product/container system. (TR79)

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

Consists of manual handling and presentation of filled containers under controlled conditions of lighting and background to allow for human visual inspection. (TR79)

Process used by a person to modify the integration of peak area by modifying the baseline, splitting peaks, or dropping a baseline as assigned by the chromatography software to overrule the pre-established integration parameters within the chromatographic software.(TR80)

The production, packing, testing, storage, release and distribution of drugs or medical devices for use in humans or animals where the manufacturing is indented to produce doses, typically in significant numbers, for an undefined population of future patients or clinical trial subjects. (TR63)

All operations including purchasing and receipt of materials to production, packaging, labelling, quality control, release, storage, distribution of components and the related controls. (TR 76)

The term system or systems represents equipment, facility, critical utilities, instruments, and other entities which perform the process or provide the conditions under which the process is performed. (TR54-5)

All phases in the life of a manufacturing system from the initial development until the manufac­turing system retirement, including specification design, fabrication, installation, commissioning, qualification, operation, maintenance, change, decommissioning and retirement. (TR54-5)

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

Voluntary withdrawal, recall or notification to patients, consumers or physicians of marketed pharmaceutical or consumer healthcare products for compliance or safety reasons. (TR55)

The package presentation intended for the end user (e.g., bottle + cap liner + screw cap + label + dose cup + carton; may contain multiple units of product), but not including packaging used solely for transportation (e.g., corrugated boxes or insulated containers). (TR39)

An application submitted by a sponsor to the European Medicines Agency (EMA) for approval to market a new drug for human use in Europe. The MAA is similar in purpose to the Biologic License Application (BLA) or New Drug Application (NDA) in the United States. (TR56)

A type of interference that may result in low endotoxin recovery.(TR82)

An analytical test method for identifying the chemical composition of a sample by separating its gaseous component ions according to their mass and charge. (TR26)

The MCB represents a collection of cells of uniform composition derived from a single source prepared under defined culture conditions. (TR 54-4)

The MCB represents a collection of cells of uni­form composition derived from a single source pre­pared under defined culture conditions, aliquoted into multiple vials, cryopreserved and stored in the vapor phase of liquid nitrogen. (TR 83)

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

Reference culture of a microorganism derived from an authenticated source such as American Type Culture Collection (ATCC) and used to produce working seed lots. (TR51)

Information provided with chemicals and other materials intended to provide workers and emergency personnel with procedures for handling or working with that substance in a safe manner. Includes information such as physical data (melting point, boiling point, flash point, etc.), toxicity, health effects, first aid, reactivity, storage, disposal, protective equipment, and spill-handling procedures. (TR65)

Polymers or other materials that make up the components of the filter. (TR26)

The combination of materials (e.g., excipients, stabilizer components, etc.) which are components together with the measured analyte. (TR57)

The direct or indirect alteration or interference in response due to the presence of additional sample components due to sample preparation (for analysis) or other interfering substances in the sample (product related excipients or residuals). (TR57) (TR57-2)

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 greatest gap or leak rate that does not put product quality at risk (2). (TR86)

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 highest dose of an agent that can be administered without unacceptable toxicity. (TR55)

The single calculated temperature at which the total amount of degradation over a particular period is equal to the sum of the individual degradations that would occur at various temperatures. Thus, MKT may be considered as an isothermal storage temperature that simulates the nonisothermal effects of storage temperature variation. It is not a simple arithmetic mean. (TR46) (TR58)

A meaningful disruption is a change in production that is reasonably likely to lead to a reduction in the supply of a drug by a manufacturer that is more than negligible and affects the ability of the manufacturer to fill orders or meet expected demand for its product. A meaningful disruption is not an interruption in manufacturing due to matters such as routine maintenance and does not include insignificant changes in manufacturing so long as the manufacturer expects to resume operations in a short period of time. (TR68)

Those values where activity is confirmed by interpolation from a reference standard curve.(TR82)

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

See Aseptic Processing Simulation. (TR22)

Any drug product used to diagnose, treat, or prevent a serious disease or medical condition for which no other drug is judged to be an appropriate substitute or there is an inadequate supply of an acceptable alternative as determined by the relevant health authority. (TR68)

Any product intended for the diagnosis, treatment, or prevention of disease. (TR39)

In filtration, the porous material which retains particles as a fluid passes through during the process of filtration (TR26)

The calculated or observed temperature for a primer/nucleic acid mixture at which 50% of primer-binding sites are in single strand form. (TR50)

A thin, microporous medium used to remove particles and microorganisms from a fluid stream under pressure. (TR26)

Analytical technique to collect particles from a liquid sample on a membrane filter followed by manual examination (sizing and counting) with a microscope. (TR85)

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)

A substance that is either the result of metabolism or a requirement for a metabolic process. (TR70)

The contextual information required to understand data. A data value is by itself meaningless without additional information about the data. Metadata is often described as data about data. Metadata is structured information that describes, explains, or otherwise makes it easier to retrieve, use, or manage data.(TR80)

Metadata is data that describe the attributes of other data and provide context and meaning. Typically, these are data that describe the structure, data elements, inter-relationships and other characteristics of data. It also permits data to be attributable to an individual (or if automatically generated, to the original data source).(TR80)

Metadata are data about data that provide the contextual information required to understand those data. These include structural and descriptive metadata. Such data describe the structure, data elements, interrelationships and other characteristics of data. They also permit data to be attributable to an individual.(TR80)

The resulting acceptable uncertainty of results to achieve the required capability to detect, quantify, and/or discriminate the analyte at levels that is relevant to the intended use. (TR57)

The demonstration of analytical method comparability (AMC) for method replacements. A study to demonstrate that a modification to an existing method either improves or does not significantly change the analytical procedure’s characteristics relative to the methods’ validation and intended use. (TR57)

A process that involves the selection, optimization, and qualification of a physical/chemical, biological, molecular, or microbiological test procedure. (TR57)

All stages in the life of a method, from the initial development through marketing, until the method’s discontinuation. (TR57-2)

Proven acceptable ranges of a method based on knowledge of the effects of critical instrument and procedural parameters on method performance within the design space. (TR57-2)

Any factor or method operational step that can be varied continuously (e.g., flow rate) or specified at controllable unique levels (e.g., Gas Chromatograph liner type).

Formal or informal study performed to assess initial method performance prior to full ICH Q2 (R1) validation; assessment activity that cul­minates in a scientifically sound method that has an acceptable level of performance and is docu­mented to be suitable for its intended use. (TR56)

Experimental studies performed to confirm the inherent performance capabilities of a test method for the material being analyzed and the intended use of the method. Method qualification can be performed during early development phases, prior to method validation. Specific method qualification characteristics (e.g., accuracy, specificity) should be confirmed based on the intended use of the analytical method and the relevant risk(s). (TR57)

A formal, archived demonstration of the analyti­cal capacity of an assay that provides justification for use of the assay for an intended purpose. (TR56)

A formal, archived demonstration of the analytical capacity of an assay that provides justification for use of the assay for an intended purpose. Validations are conducted prospectively according to a written, approved plan that states acceptance criteria. (TR57) (TR57-2)

An analytical procedure, based on the characteristics of a material that yields results that are not amenable to reliable enumeration. (TR57)

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

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)

A microbial test result that deviates from approved specifications or in-process limits. (TR88)

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)

Studies designed to speed up the development of promising drugs by establishing early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. May in­clude the administration of single subtherapeutic doses of the study drug to a small number of sub­jects (10 to 15) to gather preliminary data on the agent’s pharmacokinetics and pharmacodynam­ics. A Microdosing study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. (TR56)

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)

One of the five major components of a TCU, the unit interfaces with temperature sensors in the discharge and return air and adjusts the output rate of active cooling or heating to achieve the setpoint temperature. (TR64)

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)

Systematic steps taken or in place to reduce or limit the identified risk. (TR84)

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)

The moisture content of wood is calculated by the following formula: Moisture content = (Mg-Mod)/Mod. Where Mg is the green mass of the wood and Mod is its oven-dry mass (the attainment of constant mass generally after drying in an oven set at 103 ± 2 °C for 24h). The equation can also be expressed as a fraction of the mass of the water and the mass of the oven-dry wood rather than a percentage. For example, 0.59 kg/kg (oven-dry basis) expresses the same moisture content as 59% (oven-dry basis). (TR55)

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)

Endotoxin prepared from Gram-negative bacteria produced under defined conditions and with minimal nonchemical processing, e.g., centrifugation and filtration.(TR82)

A thin, hollow, metal tube commonly used with a syringe to inject substances into the body. (TR73)

Rigid or flexible polymeric substance used to seal and protect the needle. (TR73)

A safety feature or mechanism that effectively reduces the risk of an exposure incident (e.g., accidental needlestick). (TR73)

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)

Rigid plastic support placed into a tub to keep syringes upright with sufficient separation to allow for easy manipulation by manual or automated fill-line systems. (TR73)

An application filed with the FDA used for the regulation and control of new drugs in the Unit­ed States; the goal is to provide enough infor­mation to permit the FDA reviewer to reach the following key decisions: whether the drug is safe and effective in its proposed use(s), and wheth­er the benefits of the drug outweigh the risks; whether the drugs proposed labeling (package insert) is appropriate, and what it should con­tain; whether the methods used in manufactur­ing the drug, and the controls used to maintain the drug’s quality are adequate to preserve the drug’s identity, strength, quality, and purity. (TR56)

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)

The assumed activity of an endotoxin preparation, dilution, or "spike"; based on label-claim information.(TR82)

For this report, nonclinical laboratory study means in vivo or in vitro experiments, in which test arti­cles are studied prospectively in test systems under laboratory conditions in order to determine their safety. The definition does not include: studies us­ing human subjects or clinical studies, field trials in animals, or any basic exploratory studies carried out to determine whether a test article has any po­tential utility or to determine physical or chemical characteristics as described in ICH S6 and 21 CFR Part 58 (GLP).
Note: Also referred to as Preclinical, Toxicity or “Tox” studies. (TR56)

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

A departure of a quality characteristic from its intended level or state that occurs with severity sufficient to cause an associated product or service not to meet a specification requirement. [Synonym: Defect] (TR43)(TR76)

A condition of any product or component in which one or more characteristics do not conform to requirements. Includes failures, deficiencies, defects, and malfunctions. [Synonym: Defect](TR43)(TR76)

Critical: A Nonconformity that is likely to result in personal injury or potential hazard to the patient. This classification includes any nonconformity that compromises the integrity of the container, and risks microbiological contamination of a sterile product.
Major A: A Nonconformity leading to serious impairments, for example, a malfunction that makes the packaging unusable.
Major B: A Nonconformity leading to impairments of a lesser degree, for example, reduced efficiency in production.
Minor: A Nonconformity that does not impact product quality or process capability.
N/A: An imperfection classification that is less than the size, magnitude and impact of a nonconformity is considered not applicable. Therefore an imperfection that is considered to be non-applicable is acceptable.(TR43)

Critical: A nonconformity that risks personal injury or potential hazard to the patient. Any nonconformity that risks container closure in¬tegrity is assigned to this classification.
Major A: A nonconformity leading to serious container impairments, e.g., a malfunction making packaging unusable.
Major B: A nonconformity leading to contain¬er impairments of a lesser degree, e.g., reduced efficiency in production.
Minor: A nonconformity that does not impact product quality or process capability.
N/A: Imperfections that are considered to be nonapplicable or nondefects and are therefore acceptable.(TR 76)

A method in which a passing sample can subsequently be utilized in additional analytical methods or processed to a final product. (TR86)

Refers to a filter that does not shed fibers into the filtrate. (TR26)

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 comparison with the primary objective of showing that the result from one method is not inferior to the method being compared. This is usually demonstrated by showing that the true difference is likely to lie above the lower equivalence margin. (TR57)

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)

The therapeutic dose of a product as given on the approved product labeling. (TR29) (TR49)

A defined range, within (or equal to) the Proven Acceptable Range, specified in the manufacturing instructions as the target and range at which a process parameter is controlled, while producing unit operation material or final product meeting release criteria and CQAs. (TR60) (TR60-2)

An infection acquired in a hospital or other healthcare institution that was not present at the time of admission; the most common sites of infection are the urinary tract, surgical wound and lower respiratory tract and bloodstream. The vast majority of nosocomial infections are associated with use of invasive medical devices (e.g., urinary tract catheters, ventilators and central venous catheters). (TR67)

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

A method for detection, and in some cases, quantification of target organisms via detection of organism specific nucleic acid. PCR or polymerase chain reaction is a common NAT method that is based on amplification of targeted sequences using primers and specialized DNA polymerases. (TR50)

An isothermal amplification method targeting RNA in which amplifications of RNA occurs via DNA intermediates. Each of the DNA templates can make 100 to 1000 copies of RNA amplicons, potentially resulting in the production of greater than a billion amplicons. (TR50)

A sample with a precisely measured content of specific nucleic acid. A nucleic acid standard can be serially diluted to assess the limit of detection of an NAT assay or to create a standard curve for Q-PCR to determine the concentration of target nucleic acid. (TR50)

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)

The likelihood that the cause of the failure will happen, resulting in harm to the patient. The likelihood that a unit operation that could potentially cause a failure, happens in such a way that does cause the failure. The FMEA rating scale that defines the frequency of a failure mode. (TR44)

Probability that an event that leads to harm will occur. (TR54-2) (TR54-3)

Odors are perceived through stimulation of receptor cells and nerve endings of the trigeminal nerve in the olfactory epithelium, which lie in a small area in the upper reaches of the nasal cavity. Odors are perceived directly through the nose (orthonasal) or during gestation when volatile odorous organaohalogens reach the olfactory centers through the nasopharyneal passage (retonasal). (TR55)

The lowest concentration of a compound detectable to 50% of the people tested. (TR55)

A formal plan to assure the process remains in its validated state during routine (post-PPQ) production and the process remains in a state of control (2, 3). (TR60-3)

Observations or findings that are found during the processing of a product or products. (TR43)

(See system, open) (TR28)

The operating characteristic curve shows the probability of acceptance (Pa) for any level of lot quality. (TR43)

Values (e.g., time, temperature, pressure) that are controlled and/or measured that collectively define each phase of a sterilization cycle (e.g., heat-up, exposure, cool-down). (TR01) (TR3) (TR48) (TR61)

An input variable (e.g., time, temperature, pressure) or condition of the manufacturing process that can be directly controlled. (Synonym: process parameter) (TR30) (TR51)

Values that are controlled and/or measured and are linked to safety and efficacy of a product or the process. Failure to meet a critical parameter should result in rejection of the load. (TR01) (TR3) (TR48) (TR51)

Values that are controlled and/or measured and are used to assure the ongoing “state of control” and consistency of runs. Failure to meet a key process parameter should result in an investigation with a documented rationale for the disposition of the load. (TR01) (TR3) (TR51) (TR48)

Values that are controlled and/or measured and are used to assure the ongoing “state of control” of steam in place cycles. Failure to meet a key process parameter should result in an investigation. (TR61)

Rules or concepts governing the operation of the system. (TR38)

Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR14) (TR61) (TR64) (TR72)

The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR54-5)

Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges (17). (TR60-3)

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)

This is defined as the value of the next-best choice available when choosing between several mutually exclusive choices (e.g., the decision to expand a facility may result in losing the opportunity to invest the maintenance funds in the financial markets). Opportunity costs are often excluded from estimates of fixed operation costs because they can be difficult for comparative analyses in the overall decision process. (TR66)

A unitless measure of the absorption of light of a given wavelength in media of a given path length. (TR41)

The major organohalogens or organic compounds containing chlorine, bromine or iodine of interest are halophenols and haloanisoles, especially 2,4,6 tricholorophenol (TCP), 2, 4, 6 tribromophenols (TBPs), 2, 4, 6 trichloroanisole (TCA), and 2, 4, 6 tribromoanisole (TBA). (TR55)

The first or source capture of data or information, e.g., original paper record of manual observation or electronic raw data file from a computerised system, and all subsequent data required to fully reconstruct the conduct of the GXP activity. Original records can be static or dynamic.(TR80)

The pressure exiting the downstream side of the filter. [Synonym: effluent or downstream pressure] (TR26)

Any unexplained deviation or result that failed to meet set levels for environmental monitoring and other utilities. (TR88)

Any unexplained deviation or the failure of a pharmaceutical ingredient, drug substance, or drug product batch to meet any of its regulatory-release and shelf-life specifications. (TR88)

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)

Drug products sold in drug stores directly to customers without a physician’s prescription. (TR67)

Is the measure of the ability of the package to prevent product loss or maintain product sterility and the ability to maintain the internal environment (2). (TR86)

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

Insulated container that uses refrigerant to keep a product within a specified temperature and time range; see passive system. (TR58)

Pallets are flat transportation structures that are used in the efficient shipping, warehousing and in-plant distribution of goods. A loaded pallet may be moved using a fork lift or pallet jack. They are usually 48 x 40 inches in dimension. They are most commonly constructed of wood but may be plastic, metal or even paper. (TR55)

(TR14)

An input process parameter that should be controlled within a meaningful, narrow operating range to ensure that API quality attributes meet their specifications. Although parameters with wide operating ranges may also impact product quality, they are generally easily controlled and not as likely to result in excursions that affect quality and are therefore low risk. [Synonym: critical process parameter (CPP)] (TR14)

A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (TR60)

A process parameter whose variability has an impact on critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (TR74)

An input process parameter that should be carefully controlled within a narrow range and is essential for process performance. A key operational parameter does not affect critical product quality attributes. If the acceptable range is exceeded it may affect the process (e.g., yield, duration) but not product quality. (TR14)

An input process parameter that should be carefully controlled within a narrow range and is essential for process performance. A key process parameter does not affect product quality attributes. If the acceptable range is exceeded, it may affect the process (e.g. yield, duration) but not product quality. (TR60)

All input process parameters that fall outside the definition for critical operational parameter are non-critical. Non-critical operational parameters are divided into key and non-key operational parameters. [For further explanation, see Sub-section 3.3.6 (TR14)

An input process parameter that has been demonstrated to be easily controlled or has a wide acceptable limit. Non-key operational parameters may have an impact on drug substance quality or process performance if acceptable limits are exceeded. (TR14)

An input parameter that has been demonstrated to be easily controlled or has a wide acceptable limit. Non-key operational parameters may have an impact on quality or process performance if acceptable limits are exceeded. (TR60)