PDA Glossary

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

Free from disease-producing microorganisms. (TR28)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A chamber for steam sterilization. (TR45)

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

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

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

A 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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A 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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The 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)

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)

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)

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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)

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

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

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

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

A particle that comes from within the primary process.  These are qualified product contact materials and are often associated with the primary packaging components.  They are unplanned but not unexpected.(TR85)

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

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

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

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)

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

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

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

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

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

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

The 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)

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

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

The 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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

Transportation systems without active temperature control (e.g., insulated containers with or without refrigerants). (TR64)

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

A review of data by a colleague who has a similar level of responsibilities as the person performing the activity or capturing the data. (TR84)

Peltier devices are small, solid-state ceramic and doped-semiconductor sandwiches designed to function in small cooling and heating applications. The devices can be “stacked” for greater cooling/heating but do draw considerable power. The advantage of these devices is that there are no moving parts, no maintenance, no refrigerant gasses, no noise, and no vibration. Disadvantages may include: high cost, fragility, and scalability, in addition to the aforementioned high power draw. (TR46)

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

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

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

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

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)

A method that is the converse of a deterministic leak test method, being stochastic in nature. Probabilistic tests rely on a series of sequential and/or simultaneous events, each associated with random outcomes described by probability distributions. (TR86)

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

An independent quality unit/structure with authority to fulfill certain pharmaceutical quality system responsibilities (7). (TR84)

An organizational element within a pharmaceutical company with the authority and responsibility for quality as defined by 21 CFR 211.22 (11). The quality control unit typically comprises the quality control and quality assurance functions. (TR88)

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)

Prepared for loading with the pharmaceutical product. (TR73)

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

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

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

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

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)

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

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)

The three letter code refers to the type of ULD. Position 1 letter identifies ULD category (certification, ULD type, thermal units). Position 2 letter identifies standard base dimensions. Position 3 letter identifies contour, forklift holes, and other miscellaneous information. Here R is standing for Thermal Certified Aircraft Container. K refers to the dimensions of the container (1,534 x 1,562 mm (60.4 x 61.5 in)). The third letter describes the container’s contour and fork lift capability. Refer to the IATA “ULD Technical Manual” for complete information. (TR58)

Plastic packaging with a horizontal design used to accommodate syringes during the manufacturing process. (TR73)

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)

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)

Optical inhomogeneities in transparent material not necessarily visible to the human eye. In the context of this technical report, Schlieren (from German Schliere, meaning “streak”) are due to localized variations in silicone oil thicknesses. (TR73)

A component that is not nor will not be in direct contact with the drug product (e.g., vial seals, overwraps, container labels). The purpose of secondary packaging is to identify, protect, market, and communicate information about the product. Examples of secondary packaging include labels, cartons/folding boxes, and leaflets. (TR39)

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

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

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

Provides information on the roundness of a particle. The SF value is between 0 and 1, where 1, represents a circle. A is the area of the particle and p is the perimeter. (TR85)

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)

An individual or company who tenders products for transportation. (TR39)

The person or organization responsible for arranging transportation of goods with carriers and/or freight forwarders. (TR58)

The transit of any material by land, sea, or air from one site to another. This may include intraplant movements. (TR39)

A standardized reusable metal box used for safe, efficient and secure storage and movement of materials and products within a global containerized intermodal freight transport system. Intermodal implies that the container can be moved from one mode of transport to another without unloading and reloading. They are the main type of equipment used in intermodal transport, particularly when one of the modes of transportation is by ship. They can also be referred to as ISO containers because the dimensions have been defined by ISO. Other types of transportation containers can include truck trailers. (TR55)

Documents that have been written for a particular shipment; for example, CMR (Convention Relative au Contract de Transport International de Marchandises par la Route), BOL (Bill of Lading) and/or AWB (airway bill). (TR58)

An established route of transportation between a specific point of origin to a specific destination. More defined routes will consistently use the same combination and types of transportation vehicles and transfer procedures, but this may not be observed through all shipping lanes throughout the last mile. (TR46)

Lane described by origin, transportation node(s) and destination in combination with the used transport mode(s) (truck, aircraft, etc.). (TR58)

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

Plastic sheets often made of polyethylene and sometimes used in distribution/transportation warehouse and shipping systems to separate pallet loads of product. Slip sheets may be important due to the ability of polyethylene to concentrate TBA in proximity to product. (TR55)

Sealing bag made at least partly of steam-permeable material to wrap and seal containers for sterilization (e.g., tub-nest configurations). (TR73)

The purported location on a container closure system beyond which no microorganism can pass under conditions qualified for the barrier. (TR86)

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

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

A continuous, longitudinal, solid or notched beam-component of a pallet used to support deck components, often identified by location as the outside or center stringer. (TR55)

A pallet that uses a frame of three or four parallel pieces of lumber (called stringers). The top decks are affixed to the stringers to create the pallet structure. (TR55)

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)

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)

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

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)

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

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)

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)

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

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

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)

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)

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)

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)

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)

A group of defect standards combined with good or blank units used to evaluate the probability of detection in visual inspection or testing system performance. Test sets can be used for inspec­tor training, validation of automated systems, or other special studies as needed. (TR79)

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)

The mass of material present multiplied by that material’s specific heat capacity. (TR64)

Disk at end of plunger rod. (TR73)

Plastic box that contains a vertically oriented syringe nest and is sealed with a lid. (TR73)

The verified clean testing materials undergo a cleaning or washing process to remove particu­lates with an evaluation for acceptance (e.g., blank) to assure the system’s suitability for use in testing or inspection. (TR79)

Particulate matter sized above the visible particle 70% probability of detection threshold are con­sidered in the visible range, typically >100-150 μm. (TR79)

Water Activity, A_w 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 A_w 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 A_w for an organism, microbial growth will not occur. (TR55) (TR67)