Continuous Improvement
Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness. (TR88)
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Correction
Repair, rework, or adjustment relating to the disposition of an existing deviation. (TR88)
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Cross-Functional Team
An investigatory team, comprising representatives including QCU microbiologists, manufacturing, engineering, and maintenance personnel, and other appropriate SMEs, with the purpose of conducting a manufacturing investigation. (TR88)
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Container Closure System (CCS)
The sum of packaging components (primary and secondary) and materials that together contain and protect a product.(TR86)
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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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Concurrent Process Validation
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 testing of the drug substance batches (1, 17). (TR60-3)
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Container Closure Integrity Test (CCIT)
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)
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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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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)
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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)
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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)
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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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Cell Line
Type of cell population with defined characteristics that originates by serial subculture of a primary cell population that can be banked. (TR83)
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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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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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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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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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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)
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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)
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Concentrate
The concentrated feed solution after the removal of filtered liquid through the membrane and into the filtrate. [Synonym: retentate, retentate solution] (TR15)
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Cytopathic Virus
Viruses where infection of cells results in microscopically visible degeneration of the cells or other morphological changes. (TR47)
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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)
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Concurrent Validation
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)
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Concentration Factor
The ratio of the initial feed volume to the retentate volume. (TR15)
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Concentration Polarization
A phenomenon in which the concentration of retained solutes increases in the region adjacent to the membrane surface due to limitations in particle transport back into the bulk solution. (TR15)
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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)
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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)
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Culture Medium
The nutritional medium which supports the growth of the given microorganism. (TR75)
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Consumables
This refers to items (e.g., SUS, storage bags, tubing, filters, diaphragms, flasks, etc.) that form or are a part of process equipment and are used on a per batch basis. (TR66)
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Container Cold Spot
The location within a sealed liquid container that achieves the lowest process lethality (F0) during a sterilization process. (TR01)
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Convection
The transfer of heat by the circulation or movement of the heated liquid or gas. (TR3)
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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)
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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)
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Cosmetics
Personal care product formulations used to enhance an individual’s visual appearance or eliminate odor. This broad definition also applies to any material intended for use as a component of a cosmetic product. Note: The FDA specifically excludes soap from this category. (TR67)
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Controlled Area
An area constructed and operated in such a manner that some attempt is made to control the introduction of potential contamination (an air supply approximating to Grade D may be appropriate), and the consequences of accidental release of living organisms. The level of control exercised should reflect the nature of the organism employed in the process. At a minimum, the area should be maintained at a pressure positive to the immediate external environment and allow for the efficient removal of small quantities of airborne contaminants. (TR13)
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Cycling
A study designed to stress test the product and provide specific information on its ability to withstand transient high and low temperature excursions during distribution and storage. Typically the study conditions are outside of ICH accelerated conditions.(TR53)
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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)
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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)
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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)
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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)
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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)
An input process parameter that should be controlled within a meaningful operating range to ensure that drug substance critical quality attributes meet their specifications. Although parameters with wide operating ranges may also impact product quality, they are generally easily controlled and not as likely to result in excursions that impact quality and are therefore low risk of occurrence. (TR60-3)
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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)
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Customer
In distribution, the trading partner or reseller, and In direct-to-consumer, the end customer or user (TR46)
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Crj:CD
The International Genetic Standardization System designator for Sprague Dawley (SD) rats. The SD (Crj:CD) is a general multipurpose rat model, used for safety and efficacy testing, aging, nutrition, diet-induced obesity, oncology. (TR55)
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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)
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. (TR84)
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Corrugate (also known as cardboard or fiberboard)
A thin, stiff material made of pressed paper pulp or pasted sheets of paper and used, for example, for making cartons or fiberpak drums. (TR55)
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Cross-Flow Filtration
See Tangential Flow Filtration. (TR15)
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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)
A subsystem used to collect and analyze information, identify and investigate product and quality problems, and take appropriate and effective measures to prevent recurrence of the identified problem (8). (TR88)
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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)
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