Continuous Improvement
Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness. (TR88)
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Batch Record Review
Review by the quality control unit of the batch manufacturing record for accuracy and completeness and for absence of derivation from the approved manufacturing and testing processes. The batch record is inclusive of all in-process testing and release records for a batch. (TR88)
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Contaminants (Contamination)
Any adventitiously introduced materials (e.g., chemical, biochemical, or microbial species) not intended to be part of the manufacturing process of the drug substance or drug product (16). The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a raw material, intermediate, or API [drug substance] during production [manufacture], sampling, packaging or repackaging, storage or transport (17).
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Continuous Manufacturing
At least two process unit operations conducted under predetermined control conditions without process interruptions, where real-time process controls (PATs) may be used to meet the process requirements.
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Process Performance Qualification Protocol
A written plan preapproved by the quality unit that specifies critical steps, controls, and measurements. The process performance qualification protocol states how process performance qualification or other validation studies will be conducted, identifying sampling, assays, specific acceptance criteria, production equipment, and operating ranges. Results obtained for each study described in the protocol should be evaluated in an associated process validation report. (TR60)
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Ongoing Process Verification (OPV)
A formal plan to assure the process remains in its validated state during routine (post-PPQ) production and the process remains in a state of control (2, 3). (TR60-3)
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Shape factor (SF)/Circularity
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)
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Rect A
The longest side length when a rectangle is constructed around the particle. (TR85)
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Feret Min and Max
Feret Min is the minimum distance between parallel tangents at opposing particle borders. Feret Max is the maximum distance between parallel tangents at opposing particle borders.
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Length
The measure of the distance along its longest axis. Light obscuration (LO). Analytical technique measuring the size and quantity of subvisible particles. (TR85)
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Destructive
A method in which a sample cannot be subsequently utilized in any other analytical method or processed to a final product. (TR86)
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Nondestructive
A method in which a passing sample can subsequently be utilized in additional analytical methods or processed to a final product. (TR86)
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Maximum Allowable Leak Limit (MALL)
The greatest gap or leak rate that does not put product quality at risk (2). (TR86)
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Data Lake
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)
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Data Vulnerability
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)
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Data Process Flow Map
A flow map that uses a baseline process flow map and overlays the data flow. (TR84)
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Quality Unit
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)
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Historian
A type of database designed to archive automation and process data. (TR84)
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Peer Review
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)
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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.
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Biological Active Substance
Manufactured biological active substances and medicinal products involving biological processes and materials, such as cultivation of cells or extraction from living organisms. (TR56)
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Subject Matter Experts (SMEs)
Individuals with specific technical expertise such as engineers, quality experts, automation specialists, scientists, etc. (TR54-5)
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Qualification (Equipment and Systems)
Action of proving and documenting that equipment or ancillary systems are properly installed, work correctly, and will actually lead to the expected results. (TR54-5)
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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)
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Periodic Review
A documented review of pertinent data as appropriate (for example, manufacturing performance trend data, change history, deviation history) to confirm that a process/method/system continues to consistently produce a result meeting predetermined acceptance criteria. (TR54-5)
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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)
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Critical Aspects (CAs) of Manufacturing Systems
Critical aspects are constituent parts of a system or piece of equipment that provide the ability to control one or more critical process parameter of the associated process (e.g., temperature controller of a bioreactor). (TR54-5)
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Annual Product Review
GMP-mandated evaluation of the standards for each active pharmaceutical ingredient (API), drug product or biologics to determine the need for changes in drug product specifications and/ or manufacturing, control procedures or manufacturing processes. (TR54-5)
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Animal-Derived Raw Materials (Tertiary)
Sourced from synthetic components but includes animal-derived components used during the manufacture of the raw material that do not come in direct contact with the raw material, for example, polymers or elastomers used in process equipment or plumbing that may contain or may have been exposed to animal-sourced materials such as stearates or slip agents. (TR83)
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Animal-Derived Raw Materials (Secondary)
Non-animal in origin but may be derived from processes that include materials from animal components that come in direct contact with the raw material, for example, a recombinant protein produced in an E. coli fermentation that uses fermentation medium containing tryptone, or a recombinant protein expressed in plants that are exposed to bovine manure fertilizer. (TR83)
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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)
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Manual Inspection
Consists of manual handling and presentation of filled containers under controlled conditions of lighting and background to allow for human visual inspection. (TR79)
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Tyndall Lighting
Collimated lighting at right angle to the viewing direction, typically against a black or dark background, which is useful during manual visual inspection to detect fine dispersions of small particulate that scatter the light making them more detectable. (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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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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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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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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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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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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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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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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In-Process Observations
Observations or findings that are found during the processing of a product or products.(TR76)
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