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 #

 
 
  • 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)

  • 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)

  • 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)

  • 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)

  • Airlock

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

  • Ambient Temperature

    The air temperature of an environment. (TR58)

  • 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)

  • Analysis of Variance (ANOVA)

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

  • Analyte

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

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

  • Analytical Control

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

  • Analytical Instrument Qualification (AIQ)

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

  • Analytical Method Comparability (AMC)

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

  • Analytical Method Design

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

  • Analytical Method Development (AMD)

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

  • Analytical Method Qualification (AMQ)

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

  • Analytical Method Transfer (AMT)

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

  • Analytical Platform Technology (APT)

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

  • Analytical Procedure

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

  • 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)


  • Annealed

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

  • 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)

  • As Low as Reasonably Practicable (ALARP)

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

  • Aseptic Processing Simulation (APS)

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

  • 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)

  • 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)

  • Audit Trail Review Assessment (ATRA)

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

  • 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 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 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)

  • 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)

  • Blocking

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

  • Boundary Layer

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

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

  • British Thermal Unit (BTU)

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

  • 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)

  • 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)

  • CGMP Record (FDA)

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

  • Chamber Leak Test

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

  • Change Control

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

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • Condenser

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

  • Confidence Interval

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

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

  • 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)

  • 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)

  • Contextual Inquiry

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

  • 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 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)

  • 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)

  • 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)

  • Correlation Coefficient ( r )

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

  • 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)

  • 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)

  • Co-Validation

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

  • 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 Aspect Design Elements (CADE)

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

  • Critical 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)

  • 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)

  • Cryopreservation

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

  • 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)

  • Cytopathic Effect (CPe)

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

  • Cytopathic Virus

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

  • 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)

  • 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)

  • 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)

  • 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)

  • Dirty Hold Time

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

  • 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 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)

  • 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 Record Format (FDA)

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

  • 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)

  • Enabler

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

  • End-Of-Production Cells (EOPC)

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

  • Endogenous Virus

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

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

  • Endogenous Virus-Like Particles – (e.g., Type C endogenous retroviruses)

    Virus-like entity whose genetic material is stably integrated into the germ line of an organism or cell line. Cell lines (notably CHO) may constitutively produce virus-like particles, which are typically noninfectious but still of safety concern. Model retroviruses are generally used as surrogates to measure virus-like particle clearance. (TR41)

  • 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 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • Fermentation Broth

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

  • 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)

  • 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)

  • 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)

  • 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)

  • Free Drained Equipment

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

  • Freeze-Thaw

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

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • Harvest Testing

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

  • 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-Treated Wood Pallets

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

  • 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • Independent Replicates

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

  • 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)

  • Integrity Test

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

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

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

  • Integrity Testing

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

  • 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)

  • 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)

  • 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)

  • Investigator

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

  • 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)

  • 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)

  • Justification

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

  • Knowledge Management

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

  • Largest Daily Dose

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

  • 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)

  • 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)

  • 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)

  • Mandrel

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

  • 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)

  • 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)

  • Maximum Tolerated Dose (MTD)

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

  • 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 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)

  • 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 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)

  • 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)

  • Naturally Occurring Endotoxin (NOE)

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

  • 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)

  • Normal Dose

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

  • Nosocomial Infection (hospital-related infection)

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

  • Nucleic Acid Amplification Technique (NAT)

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

  • Nucleic Acid Sequence Based Amplification (NASBA)

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

  • Nucleic Acid Standard

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

  • 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)

  • Odor Perception

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

  • Odor Threshold

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

  • 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)

  • 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)

  • 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)

  • 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)
  • Passive System

    Systems without active temperature control. Refrigerants may be, for example, gel packs, dry ice, water, and/or ice. Examples include insulated containers, packouts and cool boxes/containers. (TR58)

    Systems without active temperature control (e.g., insulated containers with or without refrigerants). (TR39)

  • Passive Temperature-Controlled Transportation Systems

    Transportation systems without active temperature control (e.g., insulated containers with or without refrigerants). (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 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)

  • 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)

  • 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 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)

  • 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)

  • 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)

  • 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)

  • 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 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)

  • 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)

  • 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)

  • 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 Site

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

  • 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)

  • 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 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 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 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, 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)

  • 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)

  • 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)

  • 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)

  • 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)

  • 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 Strain

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

  • Registration Stability Lots

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

  • Rejection

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

  • Reporter Gene

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

  • Requalification

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

  • Requirements Traceability Matrix (RTM)

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

  • Reserve/Reference Samples

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

  • Residual Fit

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

  • Residual Risk

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

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

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

  • Residue

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

  • Resistance Temperature Detector(s) (RTDs)

    Resistance temperature detectors are temperature sensors in which the electrical resistance in the element increases with increases in temperature. This electrical resistance is then translated into a temperature value (expressed as a resistance versus temperature curve). (TR48)

  • Resistance Temperature Drive

    Sensors that exploit the predictable change in electrical resistance of some materials with changing temperature. (TR3)

  • Resistometer

    Test device designed to create defined combinations of the physical and/or chemical variables of a sterilization process. Resistometers were formally called biological indicator evaluator resistometer (BIER) vessels. The resistometer is used primarily in the laboratory to determine D and z-values. [Synonym: BIER Vessel] (TR30) (TR51)

  • Restricted Access Barrier System (RABS)

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

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

  • Retain (Retention) Samples

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

  • Retrospective Process Validation

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

  • Revalidation

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

  • Reverse Logistics

    The process of planning, implementing and controlling the efficient, cost-effective flow of raw materials, in-process inventory, finished goods and related information from the point of consumption to the point of origin for the purpose of recapturing value or proper disposal. (TR46)

  • Risk

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

  • Risk Acceptance

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

  • Risk Analysis

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

  • Risk Assessment

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

  • Risk Communication

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

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

  • Risk Control

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

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

  • Risk Decision

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

  • Risk Evaluation

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

  • Risk Identification

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

  • Risk Management

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

  • Risk Management Report

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

  • Risk Mitigation

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

  • Risk Prioritization Number (RPN)

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

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

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

  • Risk Prioritization Ranking (RPR)

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

  • Risk Priority Level

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

  • Risk Priority Number (RPN)

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

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

  • Risk Ranking and Filtering (RRF)

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

  • Risk Reduction

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

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

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

  • Risk Review

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

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

  • Risk-based Triage for Drug Shortages

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

  • Root Cause Analysis (RCA)

    An evaluation conducted for the purpose of identifying the cause of the deviation or non-conformance. (TR52)

  • Route of Administration

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

  • Routine Operational Cycle

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

  • Routine Operational Process

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

  • Ruggedness

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

  • Same

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

  • Sampling Plan

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

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

  • Sampling Plan True AQL

    The quality of product for which the percent of lots expected to be accepted (Pa) is 95.0. These values are found in Tables X-A-1 to X-R-1 in ANSI/ASQ Z1.4.(TR76)

  • Sanitization

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

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

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

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

  • Sanitize

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

  • Sanitizer

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

  • Scalability Studies

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

  • Scale-Down

    The process of decreasing the column volume. (TR38)

  • Scale-Down Model

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

  • Scale-up

    The process of increasing the column volume (TR38)

  • Screening Studies

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

  • Secondary (Working, In-house) Reference Standard

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

  • Semiautomated Inspection

    Consists of machine-assisted handling and pre­sentation of filled containers to allow for human visual inspection. (TR79)

  • Sending Unit (SU)

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

  • Senior Management

    Person(s) who direct and control a company or site at the highest levels with the authority and responsibility to mobilize resources within the company or site (TR54) (TR54-2)

  • Sensory Characteristic

    Olfactory sensation, odor threshold and taste threshold or organohalogen. (TR55)

  • Sensory Tests

    Affective and analytical are two major classifications of sensory tests. Affective tests determine consumer response to products, while analytical tests measure the perceived sensory attributes of products. Affective tests are usually commissioned by market researchers and include preference and hedonic (liking) tests to compare products. These tests support product launch decisions, and product positioning, including advertising. Analytical tests are used in the evaluation of product differences and similarities under controlled laboratory conditions to identify and quantify perceived sensory characteristics. Analytical tests include discrimination tests, grading tests, ratings by expert tasters, and descriptive methods such as the flavor profile. The descriptive methods have the greatest applicability to the development of palatable pharmaceuticals. The ASTM International Committee E-18 on Sensory Analysis of Products and Materials publishes a set of standard practices, guidelines and methods. (TR55)

  • Separative Enclosure

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

  • Severity (S)

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

  • Shelf Life (also referred to as expiration dating period)

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

  • Significant Body of Information

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

  • Similar

    Having a general likeness. (TR38)

  • Site Acceptance Testing

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

  • Specific Model Virus

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

  • Specified Microorganisms

    Microorganisms with limit tests for absence in 1 or 10 g of a drug product, as described in USP <62> Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms and USP <1111> Microbiological Quality of Nonsterile Pharmaceutical Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use. (TR67)

  • Spiking

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

  • Spore Log Reduction (SLR)

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

  • Sporicidal Process

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

  • Sporicidal Vapor Phase Decontamination

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

  • Sporicide

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

  • Sporulation

    The formation of a spore. (TR51)

  • Stability

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

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

  • Stability Budget

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

  • Stability Profile

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

  • Stability-Indicating Analytical Method

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

  • Stakeholder(s)

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

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

  • Standard Deviation

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

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

  • Static (at rest)

    BFS machine line with conveyor belts at rest but with air shower and room ventilation in operation, extruder (heated, not running) and mold carriage in standby. No operating personnel present. (TR77)
  • Static Record Format (FDA)

    A fixed-data document such as a paper record or an electronic image.(TR80)

  • Static Record Format (MHRA)

    A "fixed" record such as paper or pdf. (TR80)

  • Static Record Format (WHO)

    A static record format, such as a paper or pdf record, is one that is fixed and allows little or no interaction between the user and the record content (TR80)

  • Statistically Determined Limits

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

  • Sterile

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

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

  • Sterility Assurance

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

  • Sterility Assurance Level (SAL)

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

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

  • Sterility Test

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

  • Sterilization

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

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

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

  • Sterilization Cycle

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

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

  • Sterilization Process

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

  • Sterilization Run

    Execution of a sterilization cycle. (TR01)

  • Sterilizer Specification

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

  • Sterilizer Specification (Design Specification (DS))

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

  • Sterilizer Specification (Functional Specification (FRS))

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

  • Sterilizer Specification (User Requirement Specification (URS))

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

  • Sterilizer System Suitability Evaluations

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

  • Sterilizing Grade Filter

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

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

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

  • Stirred-Cell Filtration

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

  • Storage Solution

    A solution typically selected to control bioburden during column storage. (TR14)

  • Subject Matter Experts (SMEs)

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

  • SUS Interchangeability

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

  • System Integrity Test

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

  • System Integrity Test (Mass Flow Integrity Test)

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

  • System Integrity Test (System Pressure Hold Test)

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

  • System Integrity Test (System Vacuum Hold Test)

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

  • System Suitability Evaluations

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

  • System, Closed

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

  • System, Open

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

  • Systems (in computer or related systems) (FDA, attributed to ANSI)

    People, machines, and methods organized to accomplish a set of specific functions. Computer or related systems can refer to computer hardware, software, peripheral devices, networks, cloud infrastructure, operators, and associated documents(e.g., user manuals and standard operating procedures).(TR80)

  • Systems (in computer or related systems) (WHO)

    A computerized system collectively controls the performance of one or more automated processes and/or functions. It includes computer hardware, software, peripheral devices, networks and documentation, e.g., manuals and standard operating procedures, as well as the personnel interfacing with the hardware and software, e.g., users and information technology support personnel.(TR80)

  • Taints

    Taints are unpleasant odors and tastes due to low levels of organic compounds of natural or human-derived origin in food, beverages and drug products. Taints arise from an external source as opposed to off-odors or off-flavors from internal changes to a product (i.e., microbial spoilage). (TR55)

  • Targeted Species

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

  • TCld50 Assay

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

  • Technical Diligence

    The means by which the technical capabilities of the SUS, its supplier and its fit with the end user are verified. It is complimentary to a quality audit program and becomes a recurring theme over the implementation process and subsequent routine procurement. (TR66)

  • Technically Unavoidable Particles (TUPs)

    Particles that are visibly different from the bulk of the material when viewed with the naked eye within the container or against a suitable back­ground (e.g., size, shape, color, number, texture) and are inherent to the manufacturer’s process, product, or raw materials. The unintended pres­ence of a small quantity of particles, stemming from impurities of natural or synthetic ingre­dients, the manufacturing process, storage, or migration from packaging that is technically un­avoidable in good manufacturing practice, and do not pose a risk to patient safety. (TR78)

  • Temperature Control Unit (TCU)

    A unit that controls the refrigeration and heating systems. It typically contains a microprocessor and thermostat to maintain the set temperature. (TR64)

  • Temperature Controlled

    The sequence of transportation events, from the manufacturer of the API up to the receipt of the final packaged product by the end user, which maintains temperature sensitive products within approved temperature specifications. Maintaining temperature control during these transportation events assures that product quality is maintained. (TR39)

  • Temperature Excursion

    Any event in which product is exposed to temperatures outside of the recommended storage and/or transport temperature range. (TR39)(TR58)

  • Temperature Monitor

    A unit that measures the prevailing temperature. Several types exist, including:
    • Stationary monitors installed in (cold) storage warehouses or storage facilities;
    • Mobile monitors that include:
    • Chemical indicators that change color when exposed to temperature over time
    • Electronic indicators that indicate temperature excursions, but provide little or no summary data
    • Electronic or mechanical data loggers that record and store temperature data for retrieval after arrival
    • Transmitting monitors that transmit near real-time data and excursion events using wireless/satellite interfaces and software for “logical analysis” of data. (TR58)

  • Temperature Probe

    A sensor (e.g., thermocouple or resistance temperature detector (RTD)) that has been specifically designed to measure temperature. Temperature probes may be control, resident, surface mounted, validation, mapping, or permanent. (TR61)

  • Temperature Profile

    Anticipated ambient temperature variation and duration to which product may be exposed during transportation. (TR39)

  • Temperature Sensitive Products

    Products whose quality may be adversely affected by temperature extremes (e.g., frozen, refrigerated, and certain controlled room temperature products). (TR39)

  • Temperature-Controlled Distribution

    Material handling and movement of goods from an origin site to a receiving site, where the goods are kept within a specified temperature range using active and/or passive systems. (TR58)

  • Temperature-Controlled Ocean Container

    An actively cooled metal box, most commonly 20 or 40 foot long which can be easily transferred between different modes of transportation, such as ships, trains and trucks. Sometimes it is called a reefer container or intermodal container. (TR58)

  • Temperature-Controlled Ocean Container (Reefer, Intermodal Container)

    An actively cooled metal box (commonly 20 or 40 ft long) that can be easily transferred between different modes of transportation, such as between ships, trains, and trucks. (TR64)

  • Temperature-Controlled Truck or Trailer

    A cargo box attached to a truck chasse or as a trailer pulled by a truck that is equipped with a temperature control unit (TCU) to provide active cooling or heating control inside the box. Refrigerated trucks or trailers are sometimes referred to as “reefers”. The temperature control units are typically powered by an integrated engine or gen-set and not the engine that is used to propel the truck. (TR58)

    A cargo box attached to a truck chassis or consisting of a trailer pulled by a truck that is equipped with a TCU to provide active cooling or heating control inside the box (refrigerated trucks or trailers are sometimes referred to as “reefers”). (TR64)

  • Tertiary Packaging Component

    A component that is used to assemble secondary or primary packages in the form of the basic transportation unit and to provide protection against mechanical impact. Examples are corrugated cardboard boxes, but corresponding plastic boxes/containers are also used. (TR39)

  • Test Article

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

  • The Last Mile

    This is a multidimensional cross-industry term that defines a point in the supply chain where the product or service directly faces the customer, end user or patient. (TR46)

  • Thermometric Study

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

  • Tissue Culture Infectious Dose – TCID50

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

  • Total Impurities

    The sum of all impurities observed. (TR38)

  • Total Organic Carbon (TOC)

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

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

  • Toxicity

    The capacity of a substance to confer morbidity or mortality. In the context of virus assays, the ability of a buffer or other process components to kill or otherwise harm the functionality of indicator cell lines. This is independent of the infection by the virus. (TR41)

  • Toxicity Studies (also referred to as “Tox” studies)

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

    The definition does not include studies using human subjects or clinical studies, field trials in animals, or any basic exploratory studies car­ried out to determine whether a test article has any potential utility or to determine physical or chemical characteristics as described in ICH S6 and 21 CFR Part 58 (GLP). (TR56)

     

  • Transcription-Mediated Amplification (TMA)

    An isothermal NAT method that can amplify RNA or DNA targets a billion-fold in less than one hour. TMA technology uses two primers and two enzymes: RNA polymerase and reverse transcriptase. (TR50)

  • Transfer Disinfection

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

  • Transportation Study

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

  • Trend

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

  • Trend Analysis

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

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

  • True Copy (FDA)

    21 CFR 211.180(d) requires records to be retained "either as original records or true copies such as photocopies, microfilm, microfiche, or other accurate reproductions of the original records". Electronic copies can be used as true copies of paper or electronic records, provided the copies preserve the content and meaning of the original or raw data, which includes associated metadata and the static or dynamic nature of the original records.(TR80)

  • True Copy (MHRA)

    A copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure as the original.(TR80)

  • True Copy (WHO)

    A true copy is a copy of an original recording of data that has been verified and certified to confirm it is an exact and complete copy that preserves the entire content and meaning of the original record including, in the case of electronic data, all essential metadata and the original record format as appropriate.(TR80)

  • Turbulent Flow

    Movement of a fluid in which its velocity at any point varies in a random or erratic (nonlaminar) manner. (TR69)

  • Unwanted Event or Condition

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

  • User Requirements

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

  • Use-related Risk Analysis

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

  • Value Stream Map

    A tool used to document, analyze, understand and improve the flow of information or materials required to produce a product or service for a customer as it makes its way through the value stream. (TR68)

  • Value-added Activities

    Includes the management of materials, operations, qualification, verification, vender audits, materials testing, and shop-floor oversight that allows an SUS to be used in operations. (TR66)

  • Virus (Specific Model Virus)

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

  • Visually Clean

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

  • Warning Letters

    Type of correspondence that notifies a regulated industry about violations that FDA has documented during its inspections or investigations. (TR67)

  • Water Activity (Aw)

    Water Activity, Aw is the ratio of the vapor pressure of water in a product (P) to the vapor pressure of water in a product (P) to the vapor pressure of pure water (Po) at the same temperature. It is numerically equal to 1/100 of the RH generated by the product in a closed system. It is a measure of the free or available moisture in the material. Note: Water activity ≠ water content. RH can be calculated from direct measurements partial vapor pressure or dew point, or from indirect measurements by sensors whose physical or electric characteristics are altered by the RH to which they are exposed. Microorganisms need available water within a pharmaceutical product, as well as nutrients and minerals, to proliferate. Water activity, and not water content, is a better measure of the free water, in contrast to bound water that microbial cells require for metabolic activity and osmotic regulation. Effects of reduced Aw on microbial growth include a longer lag phase, slower growth rate, lower numbers of organisms in the stationary phase, and reduced microbial toxin production; below a specified Aw for an organism, microbial growth will not occur. (TR55) (TR67)

  • Water for Bacterial Endotoxin Test (BET)

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

  • Water for Injection (WFI)

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

  • Work Breakdown Structure (WBS)

    A hierarchical and incremental decomposition of a project into phases, deliverables, and work packages; commonly a tree structure that shows a subdivision of effort required to achieve an objective. (TR65)

  • Working Cell Bank (WCB)/Working Virus Bank (WVB)

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

  • Working Seed Lot

    A seed lot generated from the master seed stock by a single passage. (TR51)

  • Worst Case

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

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

  • Zone of Protection/Machine Shroud

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