PDA Glossary

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)

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)

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

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 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)

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)

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)

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

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

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

Free from disease-producing microorganisms. (TR28)

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A 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)

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)

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)

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

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 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)

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

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

A 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)

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 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)

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)

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)

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)

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)

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)

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)

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

The ability of a package to prevent product loss, to block microorganism ingress, and to limit entry of detrimental gases or other substances, thus ensuring that the product meets all necessary safety and quality standards.(TR76)

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

Any adventitiously 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).

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)

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)

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)

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 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)

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 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)

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)

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 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)

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)

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

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

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

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

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)

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)

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

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

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

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)

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

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)

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)

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)

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

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

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

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

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

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

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

The 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)

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)

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)

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)

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

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

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 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)

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)

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)

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)

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)

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)

<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 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)

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)

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)

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)

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

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

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)

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)

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 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)

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)

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 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)

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)

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

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)

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)

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

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)

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)

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

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)

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

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

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

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

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

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

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

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

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)

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 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)

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)

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

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

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)

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 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)

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 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)

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)

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

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)

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)

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)

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 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)

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

See Aseptic Processing Simulation. (TR22)

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 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)

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)

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)

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

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

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

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

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

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

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

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

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

A 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)

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)

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)

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 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)

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)

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)

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)

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)

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

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)

(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)

An input variable or condition of the manufacturing process that can be directly controlled in the process. Typically, these parameters are physical or chemical (e.g., temperature, process time, column flow rate, column wash volume, reagent concentration, or buffer pH). [Synonym: process parameter] (TR14)

An output variable or outcome that cannot be directly controlled but is an indicator that the process performed as expected. [Synonym: performance attributes] (TR14)

An input variable or condition of the manufacturing process that can be directly controlled in the process. Typically, these parameters are physical or chemical (e.g. temperature, process time, column flow rate, column wash volume, reagent concentration, or buffer pH). (TR60)

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

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

1 part in 1 x 1⁰⁹ total parts. Can be measured in mass/mass (e.g., 1 nanogram/gram) or in volume/volume (e.g, 1 nanoliter/liter). (TR55)

1 part in 1 x 10¹² total parts. Can be measured in mass/mass (e.g., 1 picogram/gram) or in volume/volume (e.g, 1 picoliter/liter). (TR55)

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

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

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

A mathematical measure in a chromatogram of the HETP peak shape that is determined by measuring the front and back halves of a peak and is reflective of column efficiency. The ideal chromatogram contains a peak of perfect symmetry. (TR14)

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

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

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

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

An output variable or outcome that cannot be directly controlled but is a measurable indicator that the process performed as expected (e.g., bioburden, load monitor). [Synonym: performance parameter] (TR30)

Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications. (TR3) (TR14) (TR45) (TR42) (TR48) (TR61) (TR64)

Transport tests of product or representative product that is conducted during actual transportation or distribution. (TR39)

Documented evidence that provides a high de­gree of assurance that the equipment and/or system functions accurately and consistently according to predetermined specifications in its operating environment. (TR54-5)

Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications (17). (TR60-3)

Re-execution of qualification studies performed on a periodic basis to verify that systems and pro­cesses remain able to produce a result that con­sistently meets predetermined acceptance criteria through execution of a lab or field study. (TR54-5)

A documented review of pertinent data as appro­priate (for example, manufacturing performance trend data, change history, deviation history) to confirm that a process/method/system continues to consistently produce a result meeting prede­termined acceptance criteria. (TR54-5)

How the drug works in the body, the biochemical and physiological effects of drug and its mecha­nisms of their actions. (TR56)

How the body processes the drug; the study of the movement of drugs in the body, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. (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)

Final clinical stage Phase 3 trials are designed to demonstrate the potential advantages of the new therapy; safety and efficacy of the new therapy are studied over a longer period of time, and more patients (1,000-3,000) are enrolled in 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 long term use. (TR56)

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

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

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

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

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

Development of a production strategy for a new drug starting from manufacturing processes similar to those used to manufacture other drugs of the same type (the production for which there already exists considerable experience). (TR60)

Existing method based on the same basic principles and steps as a new method that is required and defined in the design/strategy phase; applies to multiple sample types and requires minimal changes or refinements based on specific product requirements. (TR57-2)

A test article used to assess the performance of an assay in the known presence of a targeted microorganism or nucleic acid. A positive control is used to monitor the performance of assay routinely and during validation. For culture-based assays, a live mycoplasma preparation must be used to show that the assay was run properly. NAT positive controls use a nucleic acid with the target sequence of interest. (TR50)

Unit filled in an aseptic processing simulation that exhibits detectable microbial growth after incubation. (TR22) (TR62)

Inspection of glass containers after product filling. (TR43)

The measure of the biological activity using a suitably quantitative biological assay, based on the attribute of the product that is linked to the relevant biological properties. (TR57)

An expression of the activity of a secondary calibration standard to relate units of weight (ng/ vial or ng/mL) to units of activity (EU/ng) in a preparation.(TR82)

The degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of the same suspension of microorganisms and using different suspensions across the range of the test. Also known as repeatability. (TR33)

The closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision, and reproducibility. It is usually expressed as the variance, standard deviation, or coefficient of variation of a series of measurements. (TR57)

The closeness of agreement between a series of measurements obtained within laboratory variations (e.g., different days, different analysts, different equipment). (TR57)

The closeness of agreement between a series of measurements obtained under ideal conditions (e.g., same day, analyst, and instrument). (TR57)

The closeness of agreement between a series of measurements for the same sample obtained among different laboratories. (TR57)

A tool of analysis based on applying prior experience or knowledge of a hazard or failure to identify future hazards, hazardous situations and events that might cause harm, as well as to estimate their probability of occurrence for a given activity, facility, product or system. (TR54-5)

Force applied per unit area, usually expressed as psi, mbar, kPa or kg/cm². (TR45) (TR26)

A leak test in which a container or system is pressurized with air to a preset level. After the pressure has stabilized, the decay in pressure over a preset test time is measured and evaluated to determine if a leak (defect) is present. (TR66)

A test for leaks and gross defects in which the system is held at a defined pressure for a defined time. Failure is indicated by the observation of a steady stream of air bubbles downstream of the filter. (TR41)

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

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

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

Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. NOTE: Preventative action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. (TR54)

Substance shown by extensive analytical testing to be authentic, representative material; can be
1) obtained from an officially recognized source,
2) prepared by independent synthesis,
3) obtained from existing production material, or
4) prepared by further purification of existing product material; is representative of the production process, so distinct reference materials for product-related substances, product-related impurities, and process-related impurities may need to be established. (TR57-2)

The number that expresses the probability of occurrence of a non-sterile unit after exposure to a sterilization process. Within the pharmaceutical industry, a design end point better than or equal to the probability of one non-sterile unit in a million units is expected, i.e., PNSU ≤ 10–6. [Synonym: Steriliy Assurance Level (SAL)] (TR01)

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

A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. (TR60) (TR60-2)

Studies performed during process development to establish acceptable ranges for key input vari­ables and critical operational parameters that de­fine the process design space. (TR56)

A study that evaluates the process to increase process knowledge and examines proposed ranges and their individual and/or combined impact on target protein quality. Process characterization studies include deliberate variation of parameters to determine their effect on product quality attributes, often conducted as small-scale studies. (Also known as process evaluation studies, process justification studies, engineering studies, development studies, robustness studies, or process design studies. (TR60)

Viral clearance studies in which nonspecific model viruses are used to assess the general virus clearance capacity of the manufacturing process to remove and/or inactivate viruses. (TR41)

A report that includes results from a study characterizing the performance of a unit operation and/or operations conducted in a process characterization study. The report describes process characteristics, the operational parameters (e.g., critical, key, and non-key) and their acceptable ranges (limits), and acceptance criteria for Validation

protocols. (TR14) (TR42)

A report that includes results from a process characterization study with information on the performance of one or several unit operation(s). The report describes process characteristics, the parameters (e.g., critical or noncritical) and their studied ranges (limits) and may outline acceptance criteria for process performance qualification protocols.(TR60)

Viral clearance studies in which relevant and/or specific “model” viruses are used to determine the ability of the manufacturing process to remove and/or inactivate these viruses. (TR41)

A document, typically prepared by R&D, that describes the intended manufacturing process. The PFD includes all relevant information for the operation of the manufacturing process, organized by unit operation. The PFD serves as the source document for the initial development of the master production records and is locked down once development has determined that the process can be controlled. (TR65)

A process variable, process value or process parameter is the current status of a process under control. An example of this would be the temperature of a furnace. (TR54-4)

An input variable or condition of the manufacturing process that can be directly controlled in the process. Typically, these parameters are physical or chemical (e.g., temperature, process time, column flow rate, column wash volume, reagent concentration, or buffer pH). (TR60-3)

Documented verification that a system is capable of consistently performing or controlling the activities of the processes it is required to perform or control, according to written and preapproved specifications, while operating in its specified operating environment. (TR01)

The second element of the Process Qualification. It includes a combination of the actual facility, utilities, equipment, and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches. A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected. Batches prepared are also called Conformance batches or PPQ batches. (TR60) (TR54-5)

Confirming that the manufacturing process, as designed, is capable of reproducible commercial manufacturing. (TR60-2)

The second stage of process qualification. It includes a combination of the actual facility, utilities, equipment, and trained personnel and the commercial manufacturing process, control procedures, and components to produce commercial batches. A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected. Batches prepared are also called conformance batches or PPQ batches. (TR60-3)

A written plan preapproved by the quality unit that specifies critical steps, controls, and measurements. The process performance qualification protocol states how process performance qualification or other validation studies will be conducted, identifying sampling, assays, specific acceptance criteria, production equipment, and operating ranges. Results obtained for each study described in the protocol should be evaluated in an associated process validation report. (TR60)

A report approved by the quality unit that summarizes specific tests performed, compares the test results with the protocol acceptance criteria, and addresses deviations encountered during the study. (TR60)

Documented verification that a system is capable of consistently performing or controlling the activities of the processes it is required to perform or control, according to written and preapproved specifications, while operating in its specified operating environment. (TR3)

Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. (TR54) (TR60) (TR54-5)

Ability of a process to tolerate variability of materials and changes of the process and equipment without negative impact on quality. (TR60)

Method of evaluating an aseptic process using a microbial growth medium employing methods which closely approximate those used for sterile materials. (TR28)

Method of evaluating an aseptic process employing methods which closely approximate those used for sterile materials using an appropriate material. (TR28)

An event that is a necessary part of the manufacturing procedure or unit operation. (TR44)

A discrete step or manipulation in a manufacturing process where process and operating parameters are defined to achieve a specific process objective.(TR60-3)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API (drug substance) meeting its predetermined specifications and quality attributes. (TR14) (TR42)

Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. (TR44)

The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. (TR54) (TR57) (TR74) 

The collection and evaluation of data, from the pro­cess design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.
The documented evidence that the process, op­erated within established parameters, can per­form effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes, as described in EMA, EU GMP, Part 1, Annex 15, drug/me­dicinal product. (TR56)

EMA: The documented evidence that the process, op­erated within established parameters, can per­form effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.
US FDA: The collection and evaluation of data, from the process design stage through commercial pro­duction, which establishes scientific evidence that a process is capable of consistently deliver­ing quality products. (TR60-2)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or drug substance meeting its predetermined specifications and quality attributes (1, 17). (TR60-3)

The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. (TR60) (TR54-5)

The collection and evaluation of data from the process design stage to commercial production,, which establishes scientific evidence that a process is capable of consistently delivering quality products. (TR60) (TR54-5)

A document that defines the process validation scope and rationale and that contains the list of process validation studies to be performed (Synonym: Validation Master Plan). (TR42) (TR60)

The plan that documents rationale for the approach to validation and lists all systems and their validation status. (Note: The VMP can be used to document the rationale for number of monitors and revalidation frequency, as well as other system justifications). (TR52)

A written plan pre-approved by the quality unit that specifies critical steps, controls, and measurements. The process validation protocol states how validation will be conducted, identifying sampling, assays, specific acceptance criteria, production equipment, and operating ranges. Results obtained for each study described in the protocol should be evaluated in an associated process Validation report. (TR14) (TR42)

A report approved by the quality unit that summarizes specific tests performed, compares the test results with the protocol acceptance criteria, and addresses deviations encountered during the study. (TR14) (TR42)

The duration of time for a phase of a manufacturing unit operation or the entire operation. (TR41)

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

All phases in the life of a product from the initial development through marketing until the product’s discontinuation (ICH Q8[R2]. (TR54) (TR54-5)

The process flow in which a product is manufactured.(TR43)

The process flow in which a product is manufactured that is often described in a process map.(TR 76)

A sterilization design approach that is based on the characteristics of the bioburden (on or in the load) and the heat sensitivity of the product that delivers the lethality needed to achieve a PNSU of 10^-6 on or in the items to be sterilized. (TR01) (TR3) (TR30)

A digital electronic apparatus with a programmable memory for storing instructions to implement specific functions, such as logic, sequencing, timing, counting and arithmetic, to control machines and processes. (TR48)

Control action in which the output is proportional to a linear combination of the input, the time integral of input, and the time rate-of-change of input. (TR48)

Validation conducted prior to the distribution of either a new product or a product made under a revised manufacturing process where the revisions may affect the product’s characteristics. (TR42) (TR74)

A predefined, written procedural method for the design and implementation of experiments to define and document the methodology and criteria required to assess the capability of a temperature-controlled system to achieve the desired result. (TR64)

A deviation that occurs when a result is unexpected (i.e., fails to meet the predetermined acceptance criteria) or a procedure in the protocol cannot be executed as written (e.g., when a challenge is conducted using a methodology other than that described in the protocol or a process/ piece of test equipment fails). (TR64)

A report generated at the completion of the activities identified in an individual validation protocol that summarizes deviations and conclusions. (TR64)

A characterized range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria. (TR60)  (TR60-2)

A characterized range of a process parameter for which operation within this range, while keeping other parameters constant, will result in producing a material meeting relevant quality criteria (8). (TR60-3)

Documented testing that demonstrates with a high degree of assurance that a specific process will meet its pre-determined acceptance criteria. (TR39) (TR58) (TR64)

Documentation to prove that an installation/ equipment/process is designed and/or tested according to predefined specifications. Documentation may include Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ). (TR58)

An assay that is not fully validated but is documented to be suitable for its intended use, including sample collection and handling procedures. Such an assay should be demonstrated to be accurate, precise, linear within the range of use, and show no interference from process stream components (i.e., spike recovery). (TR42) (TR60-3)

 

An individual as defined in the European Union pharmaceutical regulation as described in Direc­tive 2001/83/EC that has the legal responsibil­ity for batch release of medicinal products.
Note: See also EU GMP Annex 16, Certification by a Qualified Person and Batch Release. (TR56)

The degree to which a set of inherent properties of a product, system or process fulfills requirements. The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identity, strength and purity. (TR44) (TR57)

The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identity, strength and purity. (TR60) (TR60-2)

The sum total of the organized arrangements made with the object of ensuring that all materi­als are of the quality required for their intended use and that quality system is maintained. (TR56)

A molecular or product characteristic that is selected for its ability to help indicate the quality of the product, such as identity, purity, potency stability and safety. (TR57) (TR57-2)

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. (TR60-2)

QbD is utilization of a more systematic and scientific approach to development for enhanced process understanding, so that better controls may be implemented. (TR54-4)

A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. (TR60)(TR80) 

Framework enabling the attainment of the desired state; systematic approach to development that begins with predefined objectives and that emphasizes product and process understanding and process control based on sound science and quality risk management. (TR57-2)

System for Transport Service Providers:A QM system that may cover topics such as, but not limited to:(TR39) GMP/GDP relevant processes identified and described in standard procedures, a procedure to identify the main functions of individuals, roles and responsibilities, and contact information of relevant individuals in the case of a deviation, an adequate change control system and an adequate deviation management system, including procedures for corrective actions

A systematic process for the assessment, control, communication, and review of risk to the quality of the drug product across the product lifecycle.(TR43)(TR54-2)(TR54-3)(TR57)(TR67)(TR68)

Documentation to prove that an installation/ equipment/process is designed and/or tested according to predefined specifications. Documentation may include Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ).(TR58)

A systematic process for the assessment, control, communication, and review of risks to the quality of the drug (medicinal) product across the product lifecycle.(TR 54-5)(TR 76)(TR88)

A system that outlines the nonconformities, classifications and AQL’s. (TR43) (TR 76)

Formalized business practices that define management responsibilities for organizational structure, processes, procedures, and resources needed to fulfill product/service requirements, customer satisfaction, and continual improvement. (TR30) (TR44) 

The sum of all aspects of a system that imple­ments quality policy and ensures that quality ob­jectives are met. (TR54-5)

A prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product. (TR60) (TR54-4)(TR 81)(T60-3)

A target product profile is a prospective and dynamic summary of the quality characteristics of a drug product that ideally will be achieved to ensure that the desired quality, and hence the safety and efficacy, of a drug product is realized. The target product profile forms the basis of design for the development of the product (ICH Q8 [R2]). (TR54)

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

The interval between the upper and lower levels of microorganisms that have been demonstrated to be determined with accuracy, precision and linearity. (TR33)

The range of an analytical procedure is the interval between the lower and upper quantitation limits. Within this range, a suitable performance level for precision, accuracy, and linearity can be demonstrated. (TR57)

Prepared for loading with the pharmaceutical product. (TR73)

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

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

For analytical procedures, any substance used in a reaction for the purpose of detecting, measuring, examining, or analyzing other substances. (TR57)

Actions taken by a firm to remove a product from the marketplace; may be conducted on a firm’s own initiative or in response to an FDA request or order under the agency’s statutory authority. (TR67)(TR88)

Term for the internal or external recipient or site where the technology is being transferred to. (TR65)

The mass of desired solute in the final product solution (either permeate or retentate, depending on the process), divided by the mass of the desired solute in the initial feed solution, expressed as a percentage. [Synonym: yield] (TR15) (TR45) A measure of the amount of analyte carried through the entire sample preparation and assay procedure and expressed as a percentage of the nominal concentration. (TR57)

A microbial growth medium that has been validated for the germination of spores and the growth of vegetative cells. Such a medium should be optimized for the growth and germination of injured cells or spores. (TR51)

A laboratory study combining the sampling method and analytical method to determine the quantitative recovery of a specific residue for a defined surface. (TR29) A laboratory study combining the sampling method and analytical method to determine the quantitative recovery of a specific residue for a defined surface. (TR49)

The longest side length when a rectangle is constructed around the particle. (TR85)

The act of making changes to reduce risk. (synonym: mitigation) (TR44)

The viral clearance capacity of a particular unit operation. It is typically calculated as the log10 (virus input ÷ virus output). (See also log titer reduction or log reduction value.) (TR41)

A characterized biological material developed to monitor the performance of an assay. For example, the standards for NAT assays may be nucleic acid templates such as plasmids, genomic DNA, cellular or in vitro synthesized RNA. (TR50) The defining characteristics of a reference standard are:
1) it is stable;
2) it performs similarly (e.g., on dilution) to test materials in the assay; and
3) it is homogeneous. (TR57)

A reference standard, or reference material, is a substance prepared for use as the standard in an assay, identification, or purity test. It should have a quality appropriate to its use. It is often characterized and evaluated for its intended purpose by additional procedures other than those used in routine testing. For new drug substance reference standards intended for use in assays, the impurities should be adequately identified and/or controlled, and purity should be measured by a quantitative procedure. (TR63)

A well characterized, widely accepted preparation of viable organisms that is used to validate a microbiological assay. (TR50)

Operation performed to remove residual proteins, impurities, or contaminants from the resin. [Synonym: strip] (TR14)

The lots of drug substance manufactured to es­tablish the stability profile in support of the regu­latory filing. (TR56)

A mathematical model in which the response of a dependent variable is a function of change in an independent variable, such as is seen in a concentration-response curve. Regression may be linear (e.g., a straight line) or non-linear (e.g., four parameter logistic). (TR57)

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

Attribute determined after demonstration of precision, linearity, and specificity under deliberately varied conditions, such as across a range of sample dilutions in the presence of matrix interference. (TR57-2)

A virus used in process evaluation studies that either is the identified virus, or of the same species as the virus known to or likely to contaminate the cell substrate or any other reagents or materials used in the production process. (TR41)

The precision under the same operating conditions over a short interval of time. (TR57)

Independent preparations of a sample or standard that are subject to the same treatment conditions. (TR57)

The final analytical result. This result is defined in the written approved test method and derived from one full execution of that method, starting from the original sample. (TR57)

A coding sequence linked to a gene or promoter of interest. It is generally used to determine activation of the promoter or expression of the gene of interest in a cell or organism. (TR50)

Introducing an intermediate or API, including one that does not conform to standards or specifications, back into the process and repeating a crystallization step or other appropriate chemical or physical manipulation steps (e.g., distillation, filtration, chromatography, milling) that are part of the established manufacturing process. (TR74)

The precision among multiple laboratories (collaborative studies, usually applied to standardization of methodology). (TR57) The precision between laboratories, for example, through collaborative studies. (TR33)

Periodic confirmation to demonstrate that equipment performance has not changed from its qualified state. (TR3)

The RTM traces requirements to IQ/OQ and/or PQ (also known as User Acceptance Test), con­figuration, design, procedures, policies, and/or user manuals. (TR54-5)

An appropriately identified reserve sample that is representative of each lot of intermediate product and in each shipment of each active ingredient shall be retained (at least twice the quantity nec­essary for all tests required to determine whether the active ingredient meets its established specifi­cations; this is a regulatory Requirement). (TR56)

Signed difference between an observed value and the fitted value used to detect nonlinearity, unequal variances, and outliers. (TR57-2)

Risk remaining after risk control measures have been taken. (TR44) (TR58)

Risk remaining after risk control measures have been implemented (derived from ISO 14971:2007). (TR54) (TR54-2)

Risk remaining after risk control measures has been implemented. (TR54-5)

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

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

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

Intermediate and final and finished product samples that are stored for the intent of repeating any in-process or release analysis. Typically this is twice the amount of material that is required to perform these. (TR56)

Validation of an existing manufacturing process that occurs by reviewing data from relevant historical and test production records. (TR14) (TR42)

Repeating partial or full validation of a process after a process change is implemented. Re-validation is change-based, not time-based. (TR14) (TR3) (TR42)

Subjecting an intermediate or API that does not conform to standards or specifications to one or more processing steps that are different from the established manufacturing process to obtain acceptable quality intermediate or API (e.g., recrystallizing with a different solvent). (TR74)

The percentage of the time that a manufacturing process step, batch record, or in-process or laboratory test is successfully completed on the first attempt. (TR88)

The combination of the probability of occurrence of harm and the severity of that harm.(TR30) (TR44) (TR54) (TR54-2) (TR54-4) (TR58) (TR67) (TR68) (TR88)

The decision to accept risk (ISO Guide 73). (TR54) (TR54-2) (TR58)

The estimation of the risk associated with the identified hazards. (TR13) (TR30) (TR44) (TR54) (TR54-2) (TR58) (TR54-5)

A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of identification of hazards and the analysis and evaluation of risk associated with exposure to those hazards. (TR30) (TR44) (TR54) (TR58) (TR55) (TR67) (TR57-2) (TR54-5) (TR88)

The sharing of information about risk and risk management between the decision maker and other stakeholders. (TR44)

The sharing of information about risk and risk management between the decision maker and other stakeholders. (TR54-2) (TR54-5)

Items in place and/or actions to implement risk management decisions. (TR44)

Actions implementing risk management decisions. (TR54-2) (TR54-5) (TR84)

A determination of acceptance or rejection of risk. (TR54) (TR54-2) (TR54-5)

The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk (TR30) (TR54-2) (TR44) (TR58) (TR54-5)

The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.(TR44) (TR54-2) (TR58) (TR54-5)

The systematic application of quality management policies, procedures and practices to the tasks of assessing, controlling, communicating and reviewing risk. (TR44) (TR54) (TR54-2) (TR55) (TR67) (TR54-5)

Report that summarizes the outcomes of the QRM process. (TR54) (TR54-2) (TR54-5)

Active systematic steps taken to reduce or limit risk. (TR55) (TR67)

A quantitative method for determining the level of risk by multiplying the severity, occurrence and detectability rankings of the failure or event. (TR44)

The Risk Priority Number, or RPN, is a numeric assessment of risk assigned to a process, or steps in a process, as part of Failure Modes and Effects Analysis (FMEA), in which a team assigns each failure mode a numeric values that quantifies likelihood of occurrence, likelihood of detection, and severity of impact. (TR54-4)

A quantitative measure used when assessing the level of risk. (TR54-5)

A qualitative method for determining the level of risk by combining severity, occurrence and detectability rankings of the failure or event. (TR44)

A relative priority ranking assigned to a risk based on a combination of a) therapeutic use of a product and patient impact due to product unavailability, b) availability of alternatives, and c) likelihood of a shortage. (TR68)

A quantitative measure used when assessing the level of risk. (TR54-2)

The product of severity (S), occurrence (O) and detection (D) used to determine the significance of the risk. (TR54-3)

Risk ranking and filtering is a tool for comparing and ranking risks. (TR54-4)

The process of decreasing the level of risk. (TR44)

Process for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level (e.g., reduce severity, probability of harm, and improves detectability of hazards and quality risks). (TR58)

Actions taken to lessen the probability of occurrence of harm and the severity of that harm. (TR54-2) (TR54-5)

An ongoing monitoring of events, output and results of the risk management process that takes into account new knowledge and experience. [A] step in the risk management process for taking in account of new knowledge and experiences. (TR44) (TR58)

Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. (TR54-2) (TR54-5)

A process of assessing and assigning priorities for managing drug shortage risks based on criticality and impact to patients (TR68)

The measure of capacity to remain unaffected by small, but deliberate, variations in method parameters and provides an indication of its reliability during normal usage. (TR57) (TR33)

The way in which a drug product or medical device is delivered based on the dosage form and therapeutic use. (TR67)

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

Parameters that are specified for ongoing operations. The operational process is typically controlled to produce additional lethality over the qualified minimum parameters (i.e., time and temperature) in order to provide increased sterility assurance. (TR3)

The degree of intermediate precision or reproducibility of test results obtained by assessing the same samples under a variety of normal test conditions. (TR33)

Agreeing in kind, amount; unchanged in character or condition. (TR38)

This indicates the number of units of product from each lot or batch which are to be inspected (sample size or series of sample sizes) and the criteria for determining the acceptability of the lot or batch (acceptance and rejection numbers). (TR43)

The number of units of product from each lot or batch that need to be inspected (sample size or series of sample sizes) and the criteria for determining the acceptability of the lot or batch (acceptance and rejection numbers). (TR 76)

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

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

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

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

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

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

Studies used to assess sizing for the appropriate performance of filter media at increased process volumes. (TR45)

The process of decreasing the column volume. (TR38)

A small-scale process step that has been demonstrated to be representative of a production-scale operation. (TR14)

The process of increasing the column volume (TR38)

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

Substance of established quality and purity that is qualified against, and used instead of, the primary reference standard; typically used as a reference standard for routine laboratory analysis. (TR57-2)

Term for the internal or external source or originator site of the technology to be transferred. (TR65)

Ability of a method to detect small changes in the quality attribute (e.g., changes in concentration or purity) being measured. (TR57-2)

The target for an operational parameter. The range around the set point is commonly stated in the manufacturing procedures or batch records. (TR42)(TR60-3)

The specific temperature programmed by the user into the TCU that establishes the target temperature in the CES (cold room, truck/trailer, intermodal container, or ULD). (TR64)

The value to which an operational parameter is set. The process should operate in a range around a given a set-point that is stated in the manufacturing procedures or batch records. (TR14)

A measure of the possible consequences of a hazard. (TR44) (TR54) (TR54-2) (TR54-3)(TR54-4) (TR54-5)

The time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label. (TR63)

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

A means to quantify the ability to discern between signal and noise. According to the theory, there are a number of determiners of how a detecting system will detect a signal, and where its threshold levels will be. The theory can explain how changing the threshold will affect the ability to discern, often exposing how adapted the system is to the task, purpose or goal at which it is aimed. (TR55)

A significant body of information on the stability of the drug product is likely to exist after 5 years of commercial experience for new molecular entities, or 3 years of commercial experience for new dosage forms (TR38)

Having a general likeness. (TR38)

The quality of product for which the percent of lots expected to be accepted (Pa) is 95.0. These values are found in Tables X-A-1 to X-R-1 in ANSI/ASQ Z1.4-2003. (TR43)

The SAT is a series of tests that are performed as part of commissioning after the unit has been installed in the final location. (TR48)

Virus that is closely related to the known or suspected virus (same genus or family), having similar physical and chemical properties as those of the observed or suspected virus. (TR41)

A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. (TR14)

A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR38) (TR57)

A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR69)

A list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a drug substance, drug product, or materials at other stages of its manufacture should conform to be considered acceptable for its intended use. “Conformance to specification” means that the drug substance and drug product, when tested according to the listed analytical procedures, will meet the acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval. (TR56) (TR74)

A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use (17). (TR60-3)(TR88)

The ability of an analytical procedure to accurately measure or detect a target analyte in the presence of other components in the sample matrix. (TR50)

The ability to assess unequivocally the analyte in the presence of components that may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). (TR57)

The ability to detect a range of microorganisms, which demonstrate that the method is fit for its intended use. (TR33)

The addition of a small known amount of a known compound to a standard, sample, or placebo, typically for the purpose of confirming the performance of an analytical procedure or the calibration of an instrument. (TR57)

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

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

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

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

The formation of a spore. (TR51)

The capacity of a drug substance or a drug product to remain within specifications established to ensure its identity, strength, quality, and purity throughout the retest period or expiration dating period, as appropriate. (TR39)

The chemical/biological fidelity of an analyte in a given solvent/matrix under specific conditions. (TR57)

A stability budget considers the results of long-term, accelerated, freeze-thaw, and temperature cycling studies to determine the amount of time out of storage that a drug substance may experience without any significant risk to its quality. Firms have used the idea of a stability budget to assign permissible time out of storage for packaging and labeling operations for refrigerated drug products for some time. This concept has been expanded in the present document to include storage and distribution as well. (TR53)

The physical, chemical, biological, and microbiological behavior of a drug substance or drug product as a function of time when stored under the defined environmental conditions of an approved protocol. (TR39)

A test procedure that is able to discern changes in an analyte due to degradation processes. It is capable of accurately measuring changes in the product that can occur under conditions of physical or chemical stress. (TR57)

Any individual, group or organization that can affect, be affected by or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, health-care professional, regulatory authority, and industry (ICH Q9). (TR54) (TR54-2)

Any individual, group, or organization that can affect, be affected by, or perceive itself to be af­fected by a risk. Decision makers might also be stakeholders. (TR54-5)

<p>The statistical measure of the dispersion of the data. (TR57) </p>

A pressure of 1 atmosphere (14.70 psi or 760 mm of mercury) to which measurements of quantities dependent on pressure are often referred. (TR45)

A condition in which the set of controls consistently provides assurance of continued process performance and product quality. (TR57)

Limits calculated from historical data that takes into account the distribution of the data (i.e., normal, log-normal, exponential, etc), the variability of the data, and the sample size of the data set. These can be two-sided or one-sided. The mean (average) plus and/or minus 3 standard deviations or a confidence interval for the mean are not statistically correct methods for setting these limits. The correct method is to calculate a statistical tolerance interval as described in Hahn and Meeker, 1991. (TR38)

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

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

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

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

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

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

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

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

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

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

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

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

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

Execution of a sterilization cycle. (TR01)

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

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

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

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

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

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

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

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

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

The temperature range listed on the medicinal product label specified for long term storage. (TR39)

A store is a temperature-controlled and / or temperature- monitored warehouse, chamber, or cabinet where pharmaceutical products are stored. (TR58)

Studies undertaken to elucidate the intrinsic stability of the drug substance and/or drug product; part of the development strategy and normally carried out under more severe conditions (e.g., high or low pH or oxidation levels, or shaking) than those used for accelerated testing. (TR57-2)

Individuals with specific technical expertise such as engineers, quality experts, automation special­ists, scientists, etc. (TR54-5)

Acceptance criteria for a valid reported result(s). [Synonym: Assay quality control] (TR57)

Evaluative testing providing evidence to show that representative users in the expected use conditions can perform all essential and critical tasks required for safe and effective use of the device. (TR73)

A comparison with the primary objective of showing that the result from one method is superior to the method being compared. This is usually demonstrated by showing that the true difference is likely to lie between zero and the upper equivalence margin. (TR57)

A model process fluid used in a small-scale validation study. The fluid is intended to either match or resemble an actual process fluid as closely as is feasible. (TR41)

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

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

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

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

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

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

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

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

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

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

Numerical limits, ranges, or other suitable measures of target performance levels of an analytical method that indicate suitable performance for intended use. For a method entering qualification, this is a target performance criterion that, when assessed, indicates that the method is qualified for its intended purpose. (TR57-2)

A format for a summary of a drug development program described in terms of labeling concepts to facilitate communication regarding a particular drug development program. (TR60) (TR60-2)

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

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

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

A generic term used to describe any type of temperature measuring device that works through contact with the material or atmosphere to be measured. [Synonyms: Load Probe, Heat Penetration Probe, Temperature Distribution Probe, Drain Probe] (TR48)

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

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

Any food additive, color additive, drug, biologi­cally derived product, etc., for human use or any other article subject to regulation. “Test Article,” in this report’s context, referring to the samples used for toxicity and stability studies. (TR56)

A device for measuring temperature in which a pair of wires of different metals are joined and the free ends of the wires are connected to an instrument (such as a voltmeter) that measures the electrical potential difference created at the junction of the two metals. (TR3)

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

The amount of solution that passes through a filter, described as volume per membrane area. [Synonym: capacity.] (TR15)

The amount of solution that passes through a filter. It is described as volume through the membrane area. [Synonym: capacity] (TR26)

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

The sum of all impurities observed. (TR38)

An indirect measure of organic molecules present in pharmaceutical waters measured as carbon. (TR45)

Measurement term for the total organic carbon in a sample. (TR70)

In vivo or in vitro experiments in which test ar­ticles are studied prospectively in test systems un­der laboratory conditions with the primary goals of identifying the following: 1) an initial safe dose and subsequent dose es­calation schemes in humans; 2) potential target organs for toxicity and for the study of whether such toxicity is reversible; and, 3) safety param­eters for clinical monitoring after the appropriate dosing and administering schedule is followed (relevant to the drug being studied). In toxicity studies, the test animals are examined by histo­logical or serological methods in order to iden­tify toxic, mutagenic, or teratogenic effects of the drug. It is sometimes possible to collect physi­ological data from the animals prior to sacrifice. Some toxicity studies may be performed using cell culture methods. Toxicity studies are also de­scribed by the U.S. FDA as “nonclinical labora­tory studies” and by ICH as “preclinical safety evaluations”. 

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). (TR56)

 

A disinfection process conducted on materials and equipment that coats the surface for a validated wetted time to remove bioburden prior to introducing such items into classified areas. (TR70)

Mathematical evaluation of the chromatogram tracing as the mobile phase changes from one solution to another. An alternative to HETP and peak asymmetry for evaluating column packing and performance. (TR14)

Study performed to generate data to evaluate the effect of temperature variation on the product during transportation on product quality. Other test, such as vibration, pressure, and drop tests, may be considered. (TR39)

A statistical term referring to the direction or rate of change of a variable(s) (ICH Q9). (TR54) (TR54-2)

Analysis of environmental data over time indicating a shift; adverse trends require investigation. (TR70)

A review performed in response to an alert or action condition. This review provides an analysis of specific environmental monitoring data to identify adverse trends.(TR13)

A method for declaring the comparability of equivalence that is built around comparing two or more group means and their respective mean difference confidence intervals against predetermined equivalence limits. (TR57-2)

Requirements defined by the end user that provide the basis for the development of the equipment speci­fication. They combine the product, process, regula­tory, and business needs of a manufacturing system. (TR54-5)

A systematic assessment of all of the user steps involved in using the device with particular consideration of the potential use errors, their associated clinical consequences along with the risk-mitigation strategies, and the method of validating the risk-mitigation strategies. (TR73)

A documented program that provides a high level of scientific assurance that a manufacturing process will reliably produce acceptable product. The proof of validation is obtained through rational experimental design and the evaluation of data, preferably beginning from the process development phase and continuing through the commercial production phase. (TR01)

A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (TR26) (TR57) (TR70) (TR74)

Documented testing, performed under highly controlled conditions, which demonstrates that a process consistently produces a result that meets predetermined acceptance a result that meets predetermined acceptance criteria. Used to test processes, methods, and systems for which conditions can be controlled in the real world (i.e., after completion of testing, when the process is in use). Transportation processes can be qualified but not validated; in the real world, it is not possible to exert control over all parameters that could affect the transportation process (e.g., weather, customs, traffic delays, mechanical failures, etc.). (TR58)

A documented program that provides a high de­gree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (Note: Vali­dation is a lifecycle program which may include development and qualification activities for one or more elements/systems that form a process.) (TR54-5)

A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria (17). (TR60-3)

Reference standard preparations used for method validations. (TR50)

A documented prospective study intended to demonstrate suitability for the intended use of previously validated methods, specifically for new products and/or processes. (TR57)

A systematic approach to verify that manufacturing systems, acting singly or in combination, are fit for intended use, have been properly installed, and are operating correctly. This is an umbrella term that encompasses all types of approaches to assuring equipment is fit for use. Approaches include qualification, commissioning and qualification, verification, system validation, or other. (TR3) (TR60)

A systematic approach to verify that manufactur­ing systems, acting alone or in combination, are fit for intended use, have been properly installed, and are operating correctly. This is an umbrella term that encompasses types of approaches such as qualification, commissioning and qualifica­tion, verification, and system validation. (TR60-2)

An accreditation governed by the U.S. National Association of Boards of Pharmacy for pharmaceutical wholesale distribution facilities indicating that they are in compliance with state and federal laws. (TR52)

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

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

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

Absence of materials that would adulterate a product when inspected with the eyes. (TR70)

See Porosity. (TR45)

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

Sterile Water for Injection or other water that shows no reaction with the specific bacterial endotoxin test reagent with which it is to be used, at the limit of sensitivity of such reagent. (TR3)

Water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms and contains no added substances. (TR45)

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

A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure. (TR60)

A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, that pose the greatest chance of process or product failure (when compared to ideal conditions). Such conditions do not necessarily induce product or process failure. (TR62) (TR60-2)

The load configuration that is determined to be most difficult to sterilize. This is a function of the cycle control strategy and load item characteristics (e.g., mass, configuration, or air removal challenges). For porous/hard goods loads, this may not necessarily be the minimum or maximum load. (TR01)

The load configuration that is determined to be most difficult to sterilize or depyrogenate. This is a function of the process control strategy and load item characteristics (e.g., mass, configuration). (TR3)

A soil that is the most difficult to clean from production equipment based on knowledge generated from laboratory studies, scientific properties, and/or production experience. (TR29)

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

A condition or set of conditions encompassing upper and/or lower processing limits and circumstances, within standard operating procedures, which pose the greatest chance of product or process failure when compared to ideal conditions (such conditions do not necessarily induce product or process failure). (TR29)

The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale or manufacturing data. (TR45)

The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production. (TR45)

The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat as the temperature changes during the heating and cooling phases of a sterilization cycle. (TR01) (TR3)

The number of degrees of temperature change necessary to change the D-value by a factor of 10. The z-value allows integration of the lethal effects of heat over time (i.e., calculation of F₀) as the temperature changes in a cycle. (TR61)