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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Audit Trail Review Assessment (ATRA)
A tool that can be used to help determine what elements within the audit trail should be reviewed, and the frequency at which the review should take place for each part of the audit trail where a review is required.
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Process Performance Attribute (or Process Performance Parameter)
An output variable or outcome that cannot be directly controlled but is an indicator that the process performed as expected. (TR60-2)
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Product Characterization
The characterization of quality attributes, such as peptide map, glycosylation, chromatography profile, molecular weight, gel chromatogram, polymorphs, etc. (TR56)
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Pharmacodynamics
How the drug works in the body, the biochemical and physiological effects of drug and its mechanisms of their actions. (TR56)
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Pedigree
A statement of origin for a drug, active ingredient, or other critical starting material that identifies the original source of the material and each sale, purchase, or trade prior to receipt by the user, including the dates, names, and addresses of all parties involved in such transactions. Note: Also called a “batch tree.” (TR56)
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Pharmacokinetics
How the body processes the drug; the study of the movement of drugs in the body, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. (TR56)
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Phase 3 Clinical Trials
Final clinical stage Phase 3 trials are designed to demonstrate the potential advantages of the new therapy; safety and efficacy of the new therapy are studied over a longer period of time, and more patients (1,000-3,000) are enrolled in the study with less restrictive eligibility criteria. Phase 3 studies are intended to help scientists identify rarer side effects of treatment and prepare for a broader application of the product. Phase 3 trials enroll patients to verify efficacy and monitor adverse reactions during long term use. (TR56)
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Phase 2 Clinical Trials
Once the initial safety of the study drug has been confirmed in Phase 1 trials, Phase 2 trials are performed on larger groups (20-300) and are designed to assess efficacy, as well as to continue safety assessments in a larger group of volunteers and patients. Phase 2a is specifically designed to assess dosing requirements (how much drug should be given). Phase 2b trials are specifically designed to study efficacy (how well the drug works at the prescribed dose(s). (TR56)
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Phase 1 Clinical Trials
Phase 1 trials are the first stage of testing in human subjects. Often, a small (20-100) group of healthy volunteers will be selected. For life-threatening indications such as oncology, these can be patients that have the target disease but may not yet be the ideal target population. This Phase includes trials designed to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. These trials are often conducted in an inpatient clinic, where the subject can be observed by full-time staff. (TR56)
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New Drug Application (NDA)
An application filed with the FDA used for the regulation and control of new drugs in the United States; the goal is to provide enough information to permit the FDA reviewer to reach the following key decisions: whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks; whether the drugs proposed labeling (package insert) is appropriate, and what it should contain; whether the methods used in manufacturing the drug, and the controls used to maintain the drug’s quality are adequate to preserve the drug’s identity, strength, quality, and purity. (TR56)
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Microdosing Studies
Studies designed to speed up the development of promising drugs by establishing early on whether the drug or agent behaves in human subjects as was expected from preclinical studies. May include the administration of single subtherapeutic doses of the study drug to a small number of subjects (10 to 15) to gather preliminary data on the agent’s pharmacokinetics and pharmacodynamics. A Microdosing study gives no data on safety or efficacy, being by definition a dose too low to cause any therapeutic effect. (TR56)
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Early Phase
Generally used to indicate Phase 1 and A clinical studies.(TR 56)
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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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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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User Requirements
Requirements defined by the end user that provide the basis for the development of the equipment specification. They combine the product, process, regulatory, and business needs of a manufacturing system. (TR54-5)
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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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Requirements Traceability Matrix (RTM)
The RTM traces requirements to IQ/OQ and/or PQ (also known as User Acceptance Test), configuration, design, procedures, policies, and/or user manuals. (TR54-5)
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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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Manufacturing System Lifecycle
All phases in the life of a manufacturing system from the initial development until the manufacturing system retirement, including specification design, fabrication, installation, commissioning, qualification, operation, maintenance, change, decommissioning and retirement. (TR54-5)
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Manufacturing System
The term system or systems represents equipment, facility, critical utilities, instruments, and other entities which perform the process or provide the conditions under which the process is performed. (TR54-5)
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Design Specification
Controlled documentation that clearly and explicitly defines the manufacturing system details, codes, and standards to be followed during fabrication and construction to meet associated requirements. (TR54-5)
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Design Reviews
Planned and systematic reviews of specifications, design, and design development and continuous improvement changes performed as appropriate throughout the lifecycle of the manufacturing system. Design reviews evaluate deliverables against standards and requirements, identify problems, and propose required corrective actions. (TR54-5)
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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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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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Working Cell Bank (WCB)
The WCB is derived from one or more vials of cells from the MCB, which are expanded by serial subculture. The pooled cells are dispensed into individual vials and cryopreserved to form the WCB. (TR54-4)
The WCB is derived from one or more vials of cells from the MCB, which are expanded by serial subculture. The pooled cells are dispensed into individual vials and cryopreserved and stored in the vapor phase of liquid nitrogen. (TR83)
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Host Cells/Parental Cells
A non-transfected cell substrate that is generally well-characterized and banked. It can be manipulated to generate a cell substrate for production of a biological medicinal product. (TR83)
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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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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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Visible Particle Range
Particulate matter sized above the visible particle 70% probability of detection threshold are considered in the visible range, typically >100-150 μm. (TR79)
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Verified Clean
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)
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Test Sets
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)
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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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Suspensions
A suspension is a biphasic preparation consisting of solid particles dispersed throughout a liquid phase. Some suspensions are prepared and ready for use, and others are prepared as solid mixtures intended for reconstitution with an appropriate vehicle just before use. (TR79)
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Supplemental Testing or Inspection
Destructive reconstitution, dilution, transfer, clearing, solubilizing, filtration, screening, or sieving that allows a product to be visually examined or evaluated microscopically to determine the presence, type, and size of foreign particulate contamination present within the product, container, or device. (TR79)
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Sub-Visible Particle Range
Particulate matter sized below the visible particle 70% probability of detection threshold are considered in the sub-visible range, typically <100- 150 μm. (TR79)
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Semiautomated Inspection
Consists of machine-assisted handling and presentation of filled containers to allow for human visual inspection. (TR79)
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Qualification or Validation Set
A set is used for the qualification of manual, semiautomated, and validation of automated inspection to determine the acceptability of performance. (TR79)
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Probability of Detection
The likelihood of detecting a defective unit during an inspection process expressed as a probability, quantitatively as a number (0–1) or as a percentage (0–100%). (TR79)
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Powders
Powders are defined as a solid or a mixture of solids in a finely divided state intended for internal or external use. Powders used as pharmaceutical dosage forms may contain one or more APIs and can be mixed with water for oral administration or injection. (TR79)
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Particulate Matter
Particulate matter consists of mobile, randomly-sourced, extraneous substances, other than gas bubbles, that cannot be quantitated by chemical analysis due to the small amount of material that it represents and its heterogeneous composition. (TR79)
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