Skip To The Main Content
background

PDA Glossary

PDA Glossary of Pharmaceutical and Biotechnology Terminology

PDA Technical Reports are highly valued membership benefits because they offer expert guidance and opinions on important scientific and regulatory topics and are used as essential references by industry and regulatory authorities around the world. These reports include terms which explain the material and enhance the reader’s understanding.

The database presented here includes the glossary terms from all current technical reports. The database is searchable by keyword, topic, or by technical report. Each definition provided includes a link to the source technical report within the PDA Technical Report Portal.

Browse Terms by Title

 

Browse Terms by TR #

 
 
  • “As Marketed”

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

  • Acceptable Quality Limit (AQL)

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

  • Acceptable Range

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

    Source
  • Acceptance Limit

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

  • Accuracy

    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)

  • Action Plan

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

  • Active Pharmaceutical Ingredient (API)

    Synonym: Drug Substance. (TR14) (TR42)

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

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

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

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

  • Active Pharmaceutical Ingredient (API) Equivalent to Drug Substance for large molecules

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

  • Active Pharmaceutical Ingredient (API) or (Drug substance)

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

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

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

  • Active Pharmaceutical Ingredient (API) Starting Material

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

  • Active Systems

    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)

  • 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)

  • Active Unit Load Device (Active ULD)

    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)

  • Active Unit Load Device (ULD)

    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)

  • Activity

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

  • Adsorption

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

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

  • Adverse Drug Reaction (ADR)

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

  • Adverse Event (AE) Report

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

  • Adverse Trend

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

  • Aggregation

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

  • Air Detector

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

  • Air Overpressure Sterilization Process

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

  • Air Removal Test

    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)

  • Airborne Particulate Count (Total Particulate Count)

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

  • Airborne Viable Particulate Count (Total Airborne Aerobic Microbial Count)

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

  • Airlock

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

  • Amplicon

    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)

  • Anaerobe

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

  • Anaerobic Microorganism

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

  • Ancillary Packaging Components/Systems

    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)

  • Animal-Derived Raw Materials (Primary)

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


  • Animal-Derived Raw Materials (Tertiary)

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

  • Anisotropic (Asymmetric) Membrane

    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)

  • Annealed

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

  • Annealing Temperature

    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)

  • Annual Product Review

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

  • Antimicrobial Chemical Agent

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

  • Archival (MHRA )

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

  • Archival (WHO)

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

  • Area Disinfection

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

  • Aseptic Filling

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

  • Aseptic Process

    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)

  • Aseptic Processing

    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)

  • Aseptic Processing Area (APA)

    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)

  • Aseptic Processing Simulation (APS)

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

  • Assay

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

  • Assess the Effects of the Change

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

  • Attachment (Adhesion)

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

  • Attribute

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

  • Attribute Sampling

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

  • Attributes (Process Performance Attribute)

    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)

  • Attributes (Quality Attribute)

    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)

  • Atypical Particles (AP)

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

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

  • Audit Trail (MHRA)

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

  • Audit Trail (WHO)

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

  • Autoclave

    A chamber for steam sterilization. (TR45)

  • Back Pressure

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

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

  • Backup (FDA)

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

  • Backup (MHRA)

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

  • Backup (WHO)

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

  • Batch

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

  • Bias

    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)

  • Bioanalytical Test Method

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

  • Bioassay

    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)

  • Bioburden

    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)

  • Biocide

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

  • Biofilm

    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)

  • Biofouling (or Biological Fouling)

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

  • Biological Active Substance

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

  • Biological Activity

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

  • Biological Indicator (BI)

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

  • Biological Indicator (BI) Challenge System

    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)

  • Biological Medicinal Product

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

  • Biological Qualification

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

  • Biological Safety Cabinet (BSC)

    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

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

  • Biologics License Application (BLA)

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

  • Biomethylation

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

  • Block Pallet

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

  • Break-loose Force

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

  • Breakthrough Limited

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

  • Brevundimonas Diminuta (B. diminuta)

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

  • British Thermal Unit (BTU)

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

  • Bubble Point

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

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

  • Bulk Packaged Product

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

  • Cake

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

  • Calibration

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

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

  • Calibration Curve

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

  • Calibration Tolerance

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

  • Campaign

    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)

  • Campaigning

    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)

  • Capsule

    A self-contained filter device. (TR45)

  • Capsule Filter

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

  • Captive Pallets

    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)

  • Carrier

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

  • Cartridge

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

  • Cartridge Filter

    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)

  • Cassette

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

  • CE Marking

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

  • Cell Line

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

  • Certificate of Analysis (CoA)

    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)

  • Change Management

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

  • Changeover

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

  • Characterization Method

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

  • Characterization Study

    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)

  • Chemical Compatibility

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

  • Chemical Indicator

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

  • Chemical Integrator

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

  • Chemistry Manufacturing and Controls (CMC)

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

  • Chromatogram

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

  • Chromatography

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

  • Chromatography Resin

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

  • Clarification

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

  • Class I Recall

    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)

  • Class II Recall

    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)

  • Class III Recall

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

  • Clean

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

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

  • Clean Hold Time

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

  • Clean in Place (CIP)

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

  • Clean Water Flux

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

  • Clean(liness)

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

  • Cleaning

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

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

  • Cleaning Agent

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

  • Cleaning Procedure

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

  • Cleaning Process

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

  • Cleaning Validation

    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)

  • Cleaning Verification

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

  • Cleanroom

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

  • Clinical Protocol

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

  • Clinical Trial Material (CTM)

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

  • Clinician

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

  • Cloning

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

  • Closed System

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

  • Coefficient of Determination (r²)

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

  • Cold Chain

    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)

  • Cold Chain Tolerance Groups

    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)

  • Cold Spot

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

  • Colloid

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

  • Colonization (Microbial)

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

  • Colony Forming Unit (CFU)

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

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

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

  • Color Changing Unit (CCU)

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

  • Column Load

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

  • Column Packing

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

  • Commissioning

    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)

  • Common Carrier

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

  • Comparability

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

  • Comparability Protocol

    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)

  • Comparability Study

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

  • Comparative Transfer

    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)

  • Compatibility

    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)

  • Compatibility (Filter)

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

  • Compendial Procedure

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

  • Complaint Files

    (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)

  • Complete Data (FDA)

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

  • Component, Primary

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

  • Component, Secondary

    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)

  • Composite Membrane

    A membrane consisting of multiple layers. (TR15)

  • Compounding

    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)

  • Compressor

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

  • Computerized System

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

  • Concentrate

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

  • Concentration Factor

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

  • Concentration Polarization

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

  • Condenser

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

  • Conformance Batches

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

  • Conformance Batches/Lots

    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)

  • Consumables

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

  • Contact Time

    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)

  • Container Closure Integrity (CCI)

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

  • Container Cold Spot

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

  • Contaminant

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

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

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

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

  • Contamination Rate

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

  • Continual Improvement

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

  • Continued Process Verification (CPV)

    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)

  • Continuous Convection Tunnel

    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)

  • Continuous Monitoring

    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)

  • Continuous Process Verification

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

  • Continuum of Criticality (As Used for Attributes)

    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)

  • Continuum of Criticality (As Used for Parameters)

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

  • Control Standard Endotoxin (CSE)

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

  • Control Strategy

    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)

  • Control Valve

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

  • Controlled Area

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

  • Controlled Environmental Space (CES)

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

  • Controlled Room Temperature (CRT)

    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)

  • Convection

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

  • Cool-Down Phase

    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)

  • Corked or Cork Taint

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

  • Corrective Action

    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)

  • Corrective Action and Preventative Action (CAPA)

    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)

  • Corrugate (also known as cardboard or fiberboard)

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

  • Corruption (Data) (FFIEC)

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

  • Cosmetics

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

  • Coupon

    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)

  • Coverage

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

  • Critical

    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)

  • Critical Area/Critical Zone

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

  • Critical Control Point

    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)

  • Critical Process (CP)

    A process that impacts a critical quality attribute of the intermediate, drug substance or drug product being manufactured and therefore should have established critical process parameters that can be monitored or controlled to ensure that the process produces the desired quality.

  • Critical Process Parameter (CPP) or Critical Operational Parameter

    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)

  • Critical Quality Attribute (CQA)

    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)

  • Critical Reagent

    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)

  • Critical Surface

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

  • Criticality

    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)

  • Cross-Flow Filtration

    See Tangential Flow Filtration. (TR15)

  • Cross-Flow Rate

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

  • Current Good Manufacturing Practices (CGMPs)

    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)

  • Cycle Development

    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)

  • Cycle Phases

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

  • Darcy Permeability

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

  • Darcy’s Law

    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)

  • Data (MHRA)

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

  • Data (WHO)

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

  • Data Integrity (FDA)

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

  • Data Integrity (MHRA)

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

  • Data Integrity (WHO)

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

  • Data Lifecycle (MHRA)

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

  • Data Lifecycle (WHO)

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

  • Date of Manufacture

    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)

  • Dead Leg

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

  • Deadlegs

    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)

  • Decision Maker(s)

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

  • Decommissioning

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

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

  • Decontamination

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

  • Dedicated Equipment

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

  • Defect

    (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)

  • Defect (ISO def.)

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

  • Degradation

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

  • Degradation Product

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

  • Deionized Water

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

  • Deployment

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

  • Depth Filter

    A matrix of randomly distributed fibers creating a tortuous path with pores of undefined size and shape. A filter that removes particles by a combination of adsorption and size exclusion within its porous matrix rather than on its frontal surface. (TR45)

  • Depyrogenation

    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)

  • Design of Experiments (DOE)

    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)

  • Design Qualification (DQ)

    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)

  • Design Space

    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)

  • Design, Experimental

    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)

  • Detectability

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

  • Detectability (D)

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

  • Detection

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

  • Detergent

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

  • Development Reports

    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)

  • Deviation

    Departure or digression from set parameters. (TR58)

  • Dew Point

    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)

  • Dextrans

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

  • Diafiltration

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

  • Diavolume (DV)

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

  • Differential Pressure

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

  • Difficult-to-inspect Parenterals (DIP)

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

  • Diffusion Flow Test

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

  • Diffusion Test (or Forward Flow Test)

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

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

  • Diffusive Flow

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

  • Diffusive/Forward Flow Test

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

  • Dimensional Product Quality

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

  • Direct Flow Filtration (DFF) or Normal Flow Filtration (NFF)

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

  • Direct Interception

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

  • Dirty Hold Time

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

  • Discrete Control Valve

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

  • Disinfectant

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

  • Disinfection

    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)

  • Distribution

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

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

  • Distribution Temperature

    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)

  • Distribution Testing

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

  • Distribution Thermocouple

    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)

  • Documentation

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

  • Downstream

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

  • Downstream Side (of Filter)

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

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

  • Drug Development

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

  • Drug Product (DP)

    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)

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

  • Drug Shortage Prevention & Response Plan

    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)

  • Drug Shortage Risk Register

    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)

  • Drug Substance (DS)

    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) 

    See Active Pharmaceutical Ingredient (API). (TR56)

  • Dry Equipment

    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)

  • Dryness Fraction

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

  • Dryness Value

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

  • DT Value

    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)

  • D-Value

    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)

  • D-value (D10 -Value)

    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)

  • Dwell Time

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

  • Dynamic Light Scattering (DLS)

    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)

  • Dynamic Monitoring

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

  • Dynamic Record Format (FDA)

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

  • Dynamic Record Format (MHRA)

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

  • Dynamic Record Format (WHO)

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

  • Early Phase (Generally used to indicate the following clinical study activities)

    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)

  • Early Phase (Generally used to indicate the following clinical study activities) --Microdosing Studies

    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)

  • Early Phase (Generally used to indicate the following clinical study activities)--Phase 1 Trials

    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)

  • Early Phase (Generally used to indicate the following clinical study activities)--Phase 2 Trials

    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)

  • Early Phase (Generally used to indicate the following clinical study activities)--Phase 3 Trials

    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)

  • Economically Motivated Adulteration

    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)

  • Eductor

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

  • Effective Filtration Area

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

  • Effluent

    The liquid flowing out of a column. (TR14)

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

  • Elastomer

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

  • Electronic Nose

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

  • Electronic Record

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

  • Eluate

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

  • Elution

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

  • Emissivity (ƹ)

    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)

  • Emulsions

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

  • Enabler

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

  • Endospore

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

  • Endotoxin

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

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

  • Endotoxin Indicator (EI) for Depyrogenation

    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)

  • Endpoint PCR

    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)

  • Environmental Control Parameters

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

  • Environmental Flora (isolates)

    Microorganisms associated with a processing environment. (TR22)

  • Environmental Monitoring (EM)

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

  • Environmental Monitoring Program

    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)

  • Enzyme-Linked Immunosorbent Assay, or ELISA

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

  • Equilibration

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

  • Equilibration Time

    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)

  • Equilibria Moisture Content of Wood

    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)

  • Equipment

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

  • Equipment Train

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

  • Equivalence

    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)

  • Equivalence Margin

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

  • Equivalence Test

    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)

  • Equivalence/Comparative Testing

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

  • Error

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

  • Evaporator

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

  • Event Tree Analysis (ETA)

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

  • Excipient

    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)

  • Exclusivity

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

  • Excursion

    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)

  • Exotoxin

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

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

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

  • Exposure Phase

    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)

  • Extemporaneous Preparation (EP)

    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)

  • Extended Producer Responsibility (EPR)

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

  • Extracellular Polymeric Substance (EPS)

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

  • Extractable

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

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

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

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

  • Extrinsic Particles

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

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

  • F0

    <p>A term used when the specific reference conditions of T<sub>ref</sub>- = 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 F<sub>0</sub>, 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 F<sub>0</sub> of 8 minutes.   Note: The reference temperature used in calculating F<sub>0</sub> is 121.1&deg;C, which is the approximate mathematical equivalent of 250°F. (TR01) (TR30) (TR48) (TR61)</p>
  • Facilitator

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

  • Facility

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

  • Factor

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

  • Factory Acceptance Test (FAT)

    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)

  • Failure

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

  • Failure Effect

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

  • Failure Mode and Effects Analysis (FMEA)

    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)

  • False Negative

    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)

  • False Positive

    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)

  • FAO (Food and Agriculture Organization)

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

  • Fastidious strain (isolate)

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

  • Fault Tree Analysis (FTA)

    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)

  • FDA Form 483

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

  • Fed-Batch Filtration Process

    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)

  • Feed

    The starting solution prior to filtration. (TR15)

  • Feed (or Load or Feedstock or Feedstream)

    The fluid introduced into a process. (TR41)

  • Feed Pressure

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

  • Filter

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

  • Filter (verb)

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

  • Filter Area

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

  • Filter Efficiency

    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)

  • Filter Element

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

  • Filter Rating

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

  • Filterability Test

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

  • Filtrate

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

  • Filtrate Pressure

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

  • Filtration

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

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

  • Finished Materials

    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)

  • First Air

    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)

  • First Air (First Work Location)

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

  • First Expiration, First Out (FeFo)

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

  • Flexible 2D or 3D Bag

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

  • Flow Decay

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

  • Flow Decay Test

    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)

  • Flow Rate

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

  • Flow-through

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

  • Flux

    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)

  • Flux Decay

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

  • Focus Forming Unit (FFU)

    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)

  • Formal Experimental Design (Synonym – Design of Experiments)

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

  • Formative Usability Evaluation

    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)

  • Formulation

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

  • Foulant

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

  • Fouling (or Clogging)

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

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

  • Fraction-Negative Methods

    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)

  • Frank (Canonical) Pathogens

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

  • Free Drained Equipment

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

  • Frequent Monitoring

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

  • Frit

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

  • Full Loop Calibration

    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)

  • Fumigation of Wood Pallets

    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)

  • F-Value (Lethality Factor)

    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 (Tref), delivered by a sterilization cycle. (TR1) (TR3) (TR30) (TR48) (TR61)

  • F-Value (Lethality Factor) -- FBiological

    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 NF) of the BI population achieved during the cycle. (TR1)

  • F-Value (Lethality Factor) -- FO

    A term used when the specific reference conditions of Tref = 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)

  • F-Value (Lethality Factor) -- Fphysical

    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 (Tref-) and z-value using the equation: L = 10(T-Tref- )/z. (TR1)

  • F-Value (Lethality Factor) -- F-Value for Depyrogenation

    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)

  • F-Value (Lethality Factor)-- FH

    A term used when the specific reference conditions of Tref = 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 FH, 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 FH of 8 minutes. (TR3)

  • Gamma Irradiation

    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)

  • Gauge Pressure

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

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

  • Gels

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

  • Generator Set (Genset)

    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)

  • Genetic Marker

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

  • Genome Copy (GC)

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

  • Genotypic

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

  • Germicide

    A compound that destroys all vegetative microorganisms. (TR70)

  • Glide Force

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

  • GMPs

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

  • Good Distribution Practices (GDPs)

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

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

  • Good Engineering Practice (GEP)

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

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

  • Gram Positive

    An organism that retains the Gram stain. (TR51)

  • Gravity Displacement

    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)

  • Grid Profiling

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

  • Grouping Strategy

    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)

  • Growth Promotion Test

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

  • GXP (WHO)

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

  • Half-Cycle Qualification

    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)

  • Harm

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

  • Hazard

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

  • Hazard Analysis and Critical Control Points (HACCP)

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

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

  • Hazard and Operability Analysis (HAZOP)

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

  • Hazardous Situation(s) [Cause(s

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

  • Health Hazard Evaluation (HHE)

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

  • Heat Penetration

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

  • Heat Transfer

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

  • Heating, Ventilating, and Air-Conditioning (HVAC)

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

  • Heat-Treated Wood Pallets

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

  • Heat-up Phase

    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 Constant

    Henry’s law can be put into mathematical terms (at constant temperature) as p=kH 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 kH 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)

  • HETP (Height Equivalent to the Theoretical Plate)

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

  • High Density-Polyethylene (HDPE)

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

  • High-Efficiency Particulate Air (HEPA) Filter

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

  • Highly Hazardous Drug Active

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

  • Historical Data

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

  • Hold-Up Volume (Residual Volume, Nonexpellable Volume, Dead Volume)

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

  • Host Cells/Parental Cells

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

  • Human Factors

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

  • Hybrid Approach (WHO)

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

  • Hydraulic Pressure

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

  • Hydraulic Shock

    See definition for Pressure Shock. (TR45)

  • Hydrophilic

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

  • Hydrophobic

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

  • IAEA (International Atomic Energy Agency)

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

  • Identification

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

  • Identity Test

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

  • Implants

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

  • Impurity

    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)

  • Impurity Profile

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

  • Incident

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

  • Incident Management System

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

  • Inclusivity

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

  • Incoming Inspection

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

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

  • Incoterms

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

  • Independent Replicates

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

  • Influent

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

  • Information-only Tests

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

  • Inlet Pressure

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

  • In-Process Control

    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)

  • In-Process Leachables

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

  • In-Process Material

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

  • In-Process Method (In-Process Control)

    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)

  • In-Process Observations

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

  • Inspection by Attributes

    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)

  • Installation Qualification (IQ)

    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)

  • Intended Use/Intended Purpose

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

  • Intermediate

    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)

  • Intermediate (or In-Process Material)

    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)

  • Intermediate Material

    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)

  • Intermodal Container

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

  • International Standards Organization (ISO) Container

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

  • Intervention

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

  • Intervention, Corrective

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

  • Intervention, Inherent

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

  • Intrinsic Particles

    Those particles that arise from sources related to the formulation, packaging, or assembly proces­ses. In each of these cases, the particle material (e.g., glass, stainless steel, rubber, or gasket ma­terial) could be identified as a known product-contact material. (TR78)

  • In-Use Testing (also called In-Situ Testing)

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

  • Investigational Medicinal Product

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

  • Irradiation

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

  • ISO 5

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

  • ISO 7

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

  • ISO 8

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

  • ISO/IEC

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

  • Isolated Intermediate

    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)

  • Isolates

    Microorganisms that are recovered from a facility. (TR70)

  • Isolator

    An industry-specific separative enclosure. (TR51)

  • Isolator, Closed

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

  • Isolator, Open

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

  • ISTA: International Safe Transit Association

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

  • Justification

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

  • Key Attributes

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

  • Kiln Drying (Wood Pallets)

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

  • Kilopascal (kPa)

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

  • Knowledge Management

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

  • Laminar Flow

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

  • Largest Daily Dose

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

  • Latent Virus

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

  • LD50/LC50

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

  • Leachable

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

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

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

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

  • Leak Rate

    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)

  • Leak Test

    See System Integrity Test. (TR61)

  • Lenticular Filters

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

  • Life Supporting or Life Sustaining Drug

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

  • Lifecycle

    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)

  • Ligand

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

  • Limit

    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)

  • Limit of Detection (LOD)

    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)

  • Limit of Quantification

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

  • Limit Sample

    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)

  • Limit Test

    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).

  • Limit, Detection (DL)

    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)

  • Limit, Quantitation (QL)

    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)

  • Limulus Amebocyte Lysate (LAL) Test

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

  • Limulus Amoebocyte Lysate (LAL) Test

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

  • Linearity

    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)

  • Lipopolysaccharide

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

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

  • Liquid Load

    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)

  • Load Density

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

  • Load Monitor

    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)

  • Load Zone

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

  • Log Partition or Partition Coefficient

    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)

  • Lost Work Day (LWD)

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

  • Lot or Batch

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

  • Lyophilized (Product Cake)

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

  • Magnetic Capture Hybridization (MCH)

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

  • Mandrel

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

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

  • Manual Cleaning

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

  • Manual Integration

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

  • Manufacturing

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

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

  • Manufacturing System

    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)

  • Manufacturing System Lifecycle

    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)

  • Marker

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

  • Market Action

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

  • Market Package

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

  • Marketing Authorization Application (MAA)

    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)

  • Masking

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

  • Mass Spectroscopy

    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)

  • Master Cell Bank (MCB)

    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)

  • Master Cell Bank (mCb)/Master Virus Bank (mVb)

    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)

  • Master Seed Stock

    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)

  • Material Safety Data Sheet (MSDS)

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

  • Materials of Construction

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

  • Matrix Spike Control

    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)

  • Maximum Load

    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)

  • Maximum Tolerated Dose (MTD)

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

  • Mean Kinetic Temperature (MKT)

    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)

  • Meaningful Disruption

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

  • Measured Values

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

  • Media

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

  • Media Fill

    See Aseptic Processing Simulation. (TR22)

  • Medically Necessary Drug

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

  • Medium

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

  • Melting Temperature (Tm)

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

  • Membrane

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

  • Membrane (Synthetic)

    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)

  • Membrane Area

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

  • Metabolite

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

  • Metadata (FDA)

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

  • Metadata (MHRA)

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

  • Metadata (WHO)

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

  • Method Capability

    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)

  • Method Comparability

    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)

  • Method Development

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

  • Method Lifecycle

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

  • Method Operating Space

    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)

  • Method Parameter

    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).

    Source
  • Method Qualification

    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)

  • Method Validation

    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)

  • Method, Qualitative

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

  • Method, Quantitative

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

  • Microbial By-Products

    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)

  • Microbial Count Determination

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

  • Microbial Enumeration

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

  • Microbiological Examination Tests

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

  • Microbiological Identification

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

  • Micro-condensation

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

  • Microfiltration (MF)

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

  • Microorganism

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

  • Microorganism of Concern

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

  • Minimum Acceptable Cycle (MAC)

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

  • Minimum Load

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

  • Mixed Load

    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)

  • Mock Soil

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

  • Mock Soiling

    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)

  • Module

    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)

  • Moist Heat

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

  • Moist Heat Sterilizer

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

  • Moisture Content of Wood

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

  • Mollicutes

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

  • Monodispersed particles

    Particles of uniform size in a dispersed phase. In the case of viruses, this term refers to free virus particles not agglomerated to other viruses or proteins in solution. (TR41)

  • Most Probable Number (MPN) Method

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

  • Multiplicity of Infection (MOI)

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

  • Multi-Use System (MUS)

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

  • Mycoplasma

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

  • Needle (Cannula)

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

  • Needle Shield (Needle Cover)

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

  • Needle-Safety Device

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

  • Negative Control

    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)

  • Nest (Tub Nest)

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

  • Nominal Molecular-Weight Cutoff (NMWCO)

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

  • Nominal Pore Size Rating

    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)

  • Nonclinical Laboratory Study

    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)

  • Non-Condensable Gases

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

  • Nonconformity (ANSI def.)

    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)

  • Nonconformity (ISO def.)

    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)

  • Nonconformity Classifications

    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)

  • Non-fiber Releasing

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

  • Nonfiber Releasing Filter

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

  • Noninferiority

    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)

  • Normal Dose

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

  • Normal Operating Range (NOR)

    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)

  • Objectionable Microorganism

    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)

  • Occult Contamination

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

  • Occurrence

    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)

  • Occurrence (O)

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

  • Online Observations

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

  • Open System

    (See system, open) (TR28)

  • Operating Characteristic Curves

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

  • Operating Parameters

    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)

  • Operating Parameters (Critical Parameters)

    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)

  • Operating Parameters (Key Parameters)

    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)

  • Operating Principle

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

  • Operational Qualification (OQ)

    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)

  • Opportunistic Pathogens

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

  • Opportunity Costs

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

  • Optical Density (OD)

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

  • Organohalogens

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

  • Outlet Pressure

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

  • Overkill Design Approach

    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 FBIO and FPHYS are greater than 12 minutes. The required lethality may vary regionally. (Note: For typical SIP systems, the FPHYS will need to be greater than the FBIO.) (TR01) (TR3) (TR30) (TR61)

  • Over-the-Counter (OTC) Drug Products

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

  • Packaged Raw Material for Single-Use

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

  • Packout

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

  • Pallets

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

  • Parameters

    (TR14)

  • Parameters (Critical Operational Parameter)

    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)

  • Parameters (Critical Process Parameter (CPP; Synonym – Critical Operational Parameter))

    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)

  • Parameters (Key Operational Parameter)

    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)

  • Parameters (Key Process Parameter (KPP; Synonym – Key Operational Parameter)

    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)

  • Parameters (Non-Critical Operational Parameter)

    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)

  • Parameters (Non-Key Operational Parameter)

    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)

  • Parameters (Non-Key Process Parameter (Non- KPP; Synonym – Non-key Operational Parameter) )

    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)

  • Parameters (Operational Parameter)

    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)

  • Parameters (Performance Parameter)

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

  • Parameters (Process Parameter (Synonym – Operational Parameter)

    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)

  • Parametric Release

    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)

  • Parison

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

    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)

  • Part per Trillion (ppt)

    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)

  • Partial-Cycle Qualification

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

  • Particle

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

  • Particles/Particulate (Extrinsic Particles)

    Particles that are not part of the formulation but are foreign and unexpected. Examples of extrinsic particles include fibers (e.g., cellulous), clothing fragments, hair, foreign rubber (including degraded/reverted rubber of the same formulation), metal, plastic, and paint. Materials such as foreign rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a material of construction and therefore not considered part of the rubber formulation.(TR76)

  • Particles/Particulate (Inherent Particles)

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

  • Particles/Particulate (Intrinsic Particles)

    Particles that arise from sources related to the materials of construction of the component. Examples of intrinsic particle materials include elastomeric particles of the same formulation or ingredients from elastomer for elastomeric components. (TR76)

  • Particulate

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

  • Particulate Load

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

  • Particulate Matter

    Particulate matter consists of mobile, randomly-sourced, extraneous substances, other than gas bubbles, that cannot be quantitated by chemical analysis due to the small amount of material that it represents and its heterogeneous composition. (TR79)

  • Passaging

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

  • Passive Holdover

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

  • Pathogen

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

  • Peak Asymmetry

    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)

  • Peak Intergration

    Process used to by a chromatographic system to determine the peak area (based on height and width) and obtain the quantitation of the peak of interest. The measurement is based on the integral technique of splitting the peak into a large number of rectangles, which are then summed to provide an estimate of the total area under the peak. (TR80)

  • Pedigree, e-pedigree

    A pedigree is a record, containing information regarding each transaction, resulting in a change of ownership of a prescription drug, from sale by a manufacturer, through acquisition and sale by a wholesaler, until final sale to a pharmacy or person furnishing, administering or dispensing the prescription drug. (TR46)

  • Penetration Probe

    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)

  • Penetration Thermocouple

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

  • Penicylinder

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

  • Performance Attribute

    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)

  • Performance Qualification (PQ)

    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)

  • Periodic Requalification

    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)

  • Permeability

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

  • Permeate

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

  • Pesticide

    Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest. Any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant and any nitrogen stabilizer. (TR70)

  • Pharmaceutical Dosage Form

    General classification of drug products based largely on their route of administration and presentation (e.g., compressed tablets, powder-filled capsules, topical creams and nasal sprays). (TR67)

  • Pharmaceutical Ingredients

    Includes drug substances, excipients, processing aids and ingredient water. (TR67)

  • Pharmaceutical Quality System (PQS)

    Management system to direct and control a pharmaceutical company with regard to quality. (TR54) (TR54-5)

  • Pharmacist in Charge

    A licensed pharmacist who is assigned the responsibility and authority for establishing and implementing policies and procedures for all operations of the pharmacy and to ensure the pharmacy operations and practices comply with all requirements of national and local pharmacy and drug laws, rules, and regulations. (TR63)

  • Pharmacy Manual

    A manual typically created and provided by the study sponsor that contains specific information and documentation to allow the clinical sites to properly receive, store, prepare, label, dispense and return clinical trial material and document the related activities at the clinical site. Note: For this report, the pharmacy manual will also contain specific instructions for the extemporaneous preparation, labeling and dispensing of clinical trial materials. (TR63)

  • Phase Change Material (PCM)

    A physical material that stores and releases thermal energy when freezing or melting. A PCM releases energy when freezing [latent heat energy] and absorbs energy when melting. (TR46)

  • Physical Qualification

    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)

  • Pilot Scale

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

  • Piping and Instrumentation Diagram (P&ID)

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

  • Planktonic (Free Floating)

    Suspended in the bulk phase of a fluid as opposed to being attached to surfaces. (TR69)

  • Planning Bill of Materials (BOM)

    A complete list of the raw material (chemicals, media, powders, resin, etc.) and consumables/components (filters, bags, tubing, containers, etc.) that are required to manufacture the product. (TR65)

  • Plant Utilities

    Utilities include pharmaceutical-grade water systems, compressed gases, pharmaceutical-grade air systems, heating, ventilation and air conditioning systems, and space pressurization. (TR67)

  • Plaque Forming Unit (PFU)

    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)

  • Plaque Purification

    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)

  • Plasmid

    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)

  • Plate-and-Frame

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

  • Platform Manufacturing

    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)

  • Platform-Based Method

    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)

  • Plunger

    The combined components of the plunger rod and plunger stopper. (TR73)

  • Plunger Rod

    Portion of the plunger assembly which provides a thumb pad for depressing the plunger and is attached to the plunger stopper inside the syringe barrel. (TR73)

  • Plunger Stopper (Piston, Stopper, Plunger, Gasket, Plug, Bung, Closure)

    Elastomeric component, which acts as a seal to prevent product leakage and also as the portion of the syringe which forces the expulsion of the contents of the syringe when depressed. (TR73)

  • Plunger Stopper-Barrel Interface

    Circumferential contact points between the ribs of the plunger stopper and the inner diameter of the syringe barrel. (TR73)

  • Polymerase Chain Reaction (PCR)

    A technique widely used in molecular biology in which a DNA polymerase is used to amplify a piece of DNA by in vitro enzymatic replication. As PCR progresses, the DNA thus generated is itself used as a template for replication. This sets in motion a chain reaction in which the DNA template is exponentially amplified. This technique may be used to quantify virus. (TR41) (TR47)

  • Pore

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

  • Pore Size

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

  • Pore-Size Distribution

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

  • Porosimetry (Gas-Liquid and Liquid-Liquid)

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

  • Porosity

    The ratio of void volume to bulk volume of the filter media. (TR26)

  • Porosity (Synonym:Void volume)

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

  • Porous/Hard Goods Load (P/HG)

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

  • Positive Control

    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)

  • Positive Control Filter Membrane (Penetration Control)

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

  • Positive Unit

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

  • Post-fill Inspection

    Inspection of glass containers after product filling. (TR43)

  • Potency

    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)

  • Potential Drug Shortage

    A potential drug shortage is described as the occurrence of internal or external situations (single or in a combination of both), which could result in an interruption of supplies of a medicinal product, if not properly addressed and controlled. (TR68)

  • Powders

    Powders are defined as a solid or a mixture of sol­ids in a finely divided state intended for internal or external use. Powders used as pharmaceutical dosage forms may contain one or more APIs and can be mixed with water for oral administration or injection. (TR79)

  • Practice of Pharmacy

    The interpretation, evaluation and implementation of medical orders which may include the administering, preparing, compounding, preserving, and/or the dispensing of drugs, medicines and therapeutic devices on the basis of prescriptions, clinical protocol or other legal authority. Note: Many localities have broader definitions describing very specific activities and responsibilities that further defines the practice of pharmacy. (TR63)

  • Precision

    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)

  • Precision, Intermediate

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

  • Precision, Repeatability

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

  • Precision, Reproducibility

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

  • Prefillable

    Syringes and associated components considered as starting material for the filling and assembling process of a prefilled syringe. (TR73

  • Prefilled

    Syringe assembly after being filled with pharmaceutical product and being closed. (TR73)

  • Prefilled Syringe

    A syringe that has been prefilled to contain a specific dose of medication. (TR73)

  • Pre-Filter

    Any filter placed upstream of the final filter. (TR26)

  • Preliminary Hazard Analysis (PHA)

    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 (ICH Q9). (TR54) (TR54-2) (TR54-3) (TR54-4)

  • Preliminary/Process Hazard Analysis (PHA)

    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)
  • Preparation Record

    An approved document that gives the detailed instructions for preparation of the Clinical Trial Materials (CTM). (TR63)

  • Preparation Site

    The location where extemporaneous preparations of Clinical Trial Materials (CTM) are made. (TR63)

  • Pressure

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

  • Pressure Decay Test

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

  • Pressure Hold Test (or Leak Test)

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

  • Pressure Shock

    An unanticipated rapid increase in fluid flow. [Synonym: Hydraulic Shock] (TR45)

  • Pressure Shock (Backward Pressure Shock)

    Rapid backward fluid flow that may result in filter rupture. (TR45)

  • Pressure Shock (Forward Pressure Shock)

    Rapid increase in forward fluid flow that may dislodge particulates. (TR45)

  • Presterilization Bioburden

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

  • Pre-Vacuum Process

    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)

  • Preventative Action

    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)

  • Primary (Gold-Standard) Reference Standard

    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)

  • Primary Contact Surfaces

    All process surfaces that have a direct influence on the quality of the drug substance being manufactured, including surfaces processing equipment, storage containers, and of processing aids during manufacturing operations. (TR54-4)

  • Primary Pack

    Packaging that protects the inoculated carrier from damage and contamination without preventing penetration of the sterilizing agent(s). (TR51)

  • Primary Packaging Component

    A component that is (or may be) in direct contact with the dosage form. Some examples of primary components are glass vials, syringe barrels, bottles, rubber closures, and container or closure liners. (TR39)

  • Probability of a Non-Sterile Unit (PNSU)

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

  • Process

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

  • Process Analytical Technology (PAT)

    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)

  • Process Characterization

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

  • Process Characterization of Viral Clearance

    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)

  • Process Characterization Report

    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)

  • Process Control Parameters

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

  • Process Evaluation Studies of Viral Clearance

    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)

  • Process Flow Diagram (PFD)

    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)

  • Process Parameter (PP)

    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)

  • Process Performance Attribute (or Process Performance Parameter)

    An output variable or outcome that cannot be directly controlled but is an indicator that the process performed as expected. (TR60-2)

  • Process Performance Qualification

    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)

  • Process Performance Qualification (PPQ)

    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)

  • Process Qualification

    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)

  • Process Robustness

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

  • Process Simulation (with microbiological growth media)

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

  • Process Simulation (without microbiological growth media)

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

  • Process Step

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

  • Process Validation

    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)

  • Process Validation (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. (TR60) (TR54-5)

  • Process Validation (US FDA)

    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)

  • Process Validation Master Plan (PVMP)

    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)

  • Process Validation Protocol

    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)

  • Process Validation Report

    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)

  • Processing Time

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

  • Product Changeover

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

  • Product Characterization

    The characterization of quality attributes, such as peptide map, glycosylation, chromatography pro­file, molecular weight, gel chromatogram, poly­morphs, etc. (TR56)


  • Product Complaint

    A complaint by a customer is any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a product on the market. Complaint Systems are used to collect and categorize information on the condition of regulated products on the market with which consumers are dissatisfied. (TR55) (TR67)

  • Product Lifecycle

    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)

  • Product Recalls

    Product recalls are actions taken by a firm to remove or correct one or more batches of product from the market that are considered to be in violation of one or more laws or rules in that country. Recalls may be conducted on a firm’s own initiative, by Regulatory Agency request, or by order under statuatory authority. These drug recall classifications are specified by the FDA. (TR55)

  • Product Related

    A microorganism that can adversely affect the appearance, physicochemical attributes or therapeutic effect of a nonsterile product. (TR67)

  • Product Stream

    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)

  • Product-specific Design Approach

    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)

  • Programmable Logic Controller (PLC)

    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)

  • Proportional Control Valve

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

  • Proportional, Integral, Derivative (PID)

    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)

  • Prospective Process Validation

    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)

  • Protocol

    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)

  • Protocol Deviation

    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)

  • Protocol Summary Report

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

  • Proven Acceptable Range (PAR)

    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)

  • Psid

    Pound-force per square-inch differential is the difference in pressure; for example, the pressure differential between the upstream (influent) and downstream (effluent) sides of a filter. (TR75)

  • Psoralen

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

  • Pyrogen

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

    Fever-producing substance (TR69)

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

  • Q-PCR Probe

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

  • Qualification

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

  • Qualification Documentation

    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)

  • Qualification or Validation Set

    A set is used for the qualification of manual, semiautomated, and validation of automated inspection to determine the acceptability of per­formance. (TR79)

  • Qualified Assay

    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)

  • Qualified Person (QP)

    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)

  • Qualified Shipping Packaging

    Packaging that has been subjected to document testing that demonstrates with a high degree of assurance that a specific process will meet its predetermined acceptance criteria. Due to the “real world” nature of transportation, a qualified process may change over time, requiring appropriate monitoring. (TR46)

  • Quality

    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)

  • Quality Assurance (QA)

    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)

  • Quality Attribute

    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)

  • Quality by Design (QbD)

    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)

  • Quality Management (QM)

    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

  • Quality Risk Management (QRM)

    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)

  • Quality Specification System

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

  • Quality System

    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)

  • Quality Target Product Profile (QTPP)

    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)

  • Quality Target Profile (QTP)

    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)

  • Quantitative PCR (Q-PCR or qPCR) or Real-time PCR

    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)

  • Radio Frequency Identification (RFID)

    Is an automatic technique for identifying objects using radio frequency transmissions. An RFID system generally consists of a tag, reader, antenna, and software. An RFID tag is simply another type of data carrier. Essentially, tags compromise a semiconductor chip with memory, processing capability and a transmitter connected to an antenna (aerial). (TR46)

    RFID is a method commonly used in retail of single directional data transfer from an identification tag (e.g., a data logger) to a stationary gateway or scanner; it is not to be confused with real-time monitoring. (TR58)

  • Range

    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)

  • Rapid Microbiological Methods (RMMs; Alternative Microbiological Methods)

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

  • Raw Data (FDA)

    Any laboratory worksheets, records, memoranda, notes, or exact copies thereof that are the result of original observations and activities of a nonclinical laboratory study and are necessary for the reconstruction and evaluation of the report of that study. Raw data may include photographs, microfilm or microfiche copies, computer printouts, magnetic media, including dictated observations, and recorded data from automated instruments.(TR80)

  • Raw Data (MHRA)

    The original record (data) which can be described as the first-capture of information, whether recorded on paper or electronically. Information that is originally captured in a dynamic state should remain available in that state.(TR80)

  • Raw Materials

    Starting materials, reagents, and solvents used in the production of intermediates or APIs/drug substance. (TR54-4) (TR83)

  • Ready for Filling

    Prepared for loading with the pharmaceutical product. (TR73)

  • Ready-To-Use

    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)

  • Reagent

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

  • Recalls

    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)

  • Receiving Unit (RU)

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

  • Recipient Related

    A microorganism that, due to its numbers and pathogenicity, can cause infection, allergic response or toxemia in patients receiving the product. (TR67)

  • Recovery

    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)

  • Recovery Medium

    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)

  • Recovery Study

    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)

  • Reduction

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

  • Reduction Factor

    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)

  • Redundant Filtration

    A type of serial filtration in which a second sterilizing-grade filter is used as a backup in the event of an integrity failure of the primary sterilizing filter. (TR26)

  • Reefer Container

    Refrigerated shipping container for transporting perishables, having its own stand-alone (selfpowered) cooling system. (TR54-2)

  • Reference Standard

    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)

  • Reference Standard Endotoxin (RSE)

    The primary standard from USP, EDQM, JP and WHO for use in the harmonized compendial bacterial endotoxins test (BET). The current 3rd International Standard (WHO), USP, and EDQM RS are lyophilized formulation that contains highly purified LPS that is chemically extracted and purified from E. coli strain O113:H10:K(-) and further formulated with stabilizers and excipients.(TR82)

  • Reference Strain

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