Manual Baseline
Data generated from visual inspection of a blinded set of seeded test containers that demonstrates the detection capability of human inspection. The test set is sometimes referred to as a “particle size threshold set,” where various foreign particulate types in a gradation of sizes are examined to yield a statistically significant probability of detection percentage for each unit. This allows the determination of what types and sizes of particulates can be reproducibly detected in a specific product/container system. (TR79)
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Lyophilized (Product Cake)
Freeze-dried product typically in the form of a solid plug or cake in the container. (TR79)
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Implants
Implants are long-acting dosage forms that provide continuous release of an API for periods of months to years. They are administered by the parenteral route. For systemic delivery, they may be placed subcutaneously or, for local delivery, they can be placed in a specific region in the body. (TR79)
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Gels
Gels (sometimes called jellies) are semisolid systems consisting either of suspensions of small inorganic particles or of organic molecules interpenetrated by a liquid. Gels can be classed either as single-phase or two-phase systems. (TR79)
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Emulsions
A dispersed colloidal system consisting of two immiscible liquid phases generally stabilized with one or more suitable agents. Injectable emulsions are sterile liquid dosage forms of drug substances dissolved or dispersed in a suitable emulsion medium. Injectable emulsions are for parenteral administration of poorly water-soluble drugs. (TR79)
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Difficult-to-inspect Parenterals (DIP)
When the nature of the product or package limits the ability to perform a thorough inspection for particles. (TR79)
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Automated Inspection
Consists of mechanical handling and presentation of product containers combined with automated inspection of the filled containers using image analysis and/or light obscuration. (TR79)
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“As Marketed”
Term used to describe the state or appearance of the product during 100% or AQL visual inspection (prior to labeling). As marketed refers to the product in-situ or the form in which it is distributed, for example clear liquid, lyophilized, powder, opalescent liquid, etc. (TR79)
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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)
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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)
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)
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Extrinsic Particles
Those particles that are not part of the formulation, package, or assembly process but rather are foreign and unexpected. Materials such as rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a product-contact material. (TR78)
Foreign material that comes from outside the primary process. Often these are from the manufacturing environment or incomplete cleaning of components. They are uncontrolled. (TR85)
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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)
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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)
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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)
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Parison
The “tube” of polymer extruded by the BFS machine from which the containers are formed. (TR77)
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Mandrel
Specialized filling needles on certain BFS machines which also act to form the container. (TR77)
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Dynamic (in operation)
BFS machine line fully operational and filling, with the number of allowed operating personnel present as during normal running conditions. (TR77)
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Critical Processing Zone
The location within the aseptic processing area in which product and product contact surfaces are exposed to the environment. The Critical Processing Zone is dependent upon machine design and includes, but is not necessarily limited to, the parison extrusion and cutting area, mold transfer area, air shower, and point-of-fill. (TR77)
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Air Shower
A device fitted to a BFS machine which provides, at a minimum, a continuous flow of Grade A quality air supply over the filling needles and the point-of-fill. The air shower is also known as a nozzle shroud in shuttle type machines. (TR77)
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Advanced Aseptic Process
A process in which direct intervention with open product containers or exposed product contact surfaces by operators wearing conventional cleanroom garments is not required and never permitted. (TR77)
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Tailgate Sample
Representative and random samples of the lot taken by the manufacturer during the packing process for the use of incoming inspection purposes. (TR76)
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Supplier
The entity with whom the agreement of the quality level is made and the transaction of purchase is made; the last link in the chain of manufacturers and distributors. The supplier may be the manufacturer.(TR76)
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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)
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Particulate Load
The total quantity of particles in solution as tested per qualified method. (TR76)
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Particles/Particulate (Intrinsic Particles)
Particles that arise from sources related to the materials of construction of the component. Examples of intrinsic particle materials include elastomeric particles of the same formulation or ingredients from elastomer for elastomeric components. (TR76)
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Particles/Particulate (Inherent Particles)
Particles that are expected from the drug formulation, and therefore not included as a category in this Lexicon.(TR76)
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Particles/Particulate (Extrinsic Particles)
Particles that are not part of the formulation but are foreign and unexpected. Examples of extrinsic particles include fibers (e.g., cellulous), clothing fragments, hair, foreign rubber (including degraded/reverted rubber of the same formulation), metal, plastic, and paint. Materials such as foreign rubber, metal, and plastic are defined as extrinsic in cases where the specific material identified is not a material of construction and therefore not considered part of the rubber formulation.(TR76)
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Nonconformity (ISO def.)
A condition of any product or component in which one or more characteristics do not conform to requirements. Includes failures, deficiencies, defects, and malfunctions. [Synonym: Defect](TR43)(TR76)
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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)
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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)
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In-Process Observations
Observations or findings that are found during the processing of a product or products.(TR76)
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Defect (ISO def.)
The nonfulfillment of intended usage requirements. The departure or absence of one or more quality characteristics from intended usage requirements. (TR76)
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Defect (ANSI def.)
A departure of a quality characteristic from its intended level or state that occurs with a severity sufficient to cause an associated product or service not to satisfy its intended normal or foreseeable usage requirements. (TR76)
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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)
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Nominal Value
The assumed activity of an endotoxin preparation, dilution, or "spike"; based on label-claim information.(TR82)
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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)
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Measured Values
Those values where activity is confirmed by interpolation from a reference standard curve.(TR82)
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Masking
A type of interference that may result in low endotoxin recovery.(TR82)
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Low Endotoxin Recovery (LER)
The inability to recover ≥50% activity over time when known amount of endotoxin is added to an undiluted product. LER cannot be overcome by dilution.(TR82)
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Reference Standard Endotoxin (RSE)
The primary standard from USP, EDQM, JP and WHO for use in the harmonized compendial bacterial endotoxins test (BET). The current 3rd International Standard (WHO), USP, and EDQM RS are lyophilized formulation that contains highly purified LPS that is chemically extracted and purified from E. coli strain O113:H10:K(-) and further formulated with stabilizers and excipients.(TR82)
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Control Standard Endotoxin (CSE)
Endotoxin preparations other than the international or national reference standards that are traceable in their calibration to the international endotoxin reference standard. A CSE is a secondary or tertiary standard, commonly purified from Escherichia coli, and is usually manufactured and certified by an LAL reagent manufacturer for use with a specific lot of reagent under defined assay conditions.(TR82)
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Activity
Ability of endotoxin (LPS) to initiate the LAL cascade in the compendial bacterial endotoxins test (BET) assay, or the ability to elicit a pyrogenic response in a compendial pyrogen test (2,10). Activity can be measured by other assays such as the monocyte activation test (MAT) or recombinant Factor C tests (rFc), if such tests have been validated, to demonstrate that decisions made from the results are comparable to or superior to the compendial assay. Activity is measured in endotoxin units (EU). In terms of activity, one EU = one IU, regardless of the source. Activity is generally expressed as a concentration, usually EU/mL.(TR82)
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Original Record (MHRA)
The first or source capture of data or information, e.g., original paper record of manual observation or electronic raw data file from a computerised system, and all subsequent data required to fully reconstruct the conduct of the GXP activity. Original records can be static or dynamic.(TR80)
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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)
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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)
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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)
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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)
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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)(TR84)
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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)(TR84)
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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)(TR84)
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