Right First Time
The percentage of the time that a manufacturing process step, batch record, or in-process or laboratory test is successfully completed on the first attempt. (TR88)
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Out-of-Specification Result
Any unexplained deviation or the failure of a pharmaceutical ingredient, drug substance, or drug product batch to meet any of its regulatory-release and shelf-life specifications. (TR88)
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Correction
Repair, rework, or adjustment relating to the disposition of an existing deviation. (TR88)
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Error, Laboratory
A self-evident documented mistake that will bring the validity of a laboratory test into question. (TR88)
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Error, Manufacturing
A self-evident documented mistake that will bring the manufacturing process into question. (TR88)
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Invalid Test
Laboratory test that, as a result of the laboratory (Phase I) investigation, did not meet the test method requirements and whose results would not be deemed valid. This may also apply to a test which was aborted (e.g. breakdown of isolator during sterility testing). (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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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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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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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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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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Subject Matter Experts (SMEs)
Individuals with specific technical expertise such as engineers, quality experts, automation specialists, scientists, etc. (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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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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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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In-Process Observations
Observations or findings that are found during the processing of a product or products.(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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Pressure
Force applied per unit area, usually expressed as psi, mbar, kPa or kg/cm2. (TR45) (TR26)
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Precision, Intermediate
The closeness of agreement between a series of measurements obtained within laboratory variations (e.g., different days, different analysts, different equipment). (TR57)
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Primary (Gold-Standard) Reference Standard
Substance shown by extensive analytical testing to be authentic, representative material; can be 1) obtained from an officially recognized source,2) prepared by independent synthesis, 3) obtained from existing production material, or 4) prepared by further purification of existing product material; is representative of the production process, so distinct reference materials for product-related substances, product-related impurities, and process-related impurities may need to be established. (TR57-2)
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Positive Unit
Unit filled in an aseptic processing simulation that exhibits detectable microbial growth after incubation. (TR22) (TR62)
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Process Characterization
Studies performed during process development to establish acceptable ranges for key input variables and critical operational parameters that define the process design space. (TR56)
A study that evaluates the process to increase process knowledge and examines proposed ranges and their individual and/or combined impact on target protein quality. Process characterization studies include deliberate variation of parameters to determine their effect on product quality attributes, often conducted as small-scale studies. (Also known as process evaluation studies, process justification studies, engineering studies, development studies, robustness studies, or process design studies. (TR60)
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Process Analytical Technology (PAT)
A system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality. (TR60) (TR60-2)
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Precision
The degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of the same suspension of microorganisms and using different suspensions across the range of the test. Also known as repeatability. (TR33)
The closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision, and reproducibility. It is usually expressed as the variance, standard deviation, or coefficient of variation of a series of measurements. (TR57)
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Process Characterization of Viral Clearance
Viral clearance studies in which nonspecific model viruses are used to assess the general virus clearance capacity of the manufacturing process to remove and/or inactivate viruses. (TR41)
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Pressure Decay Test
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)
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Process Evaluation Studies of Viral Clearance
Viral clearance studies in which relevant and/or specific “model” viruses are used to determine the ability of the manufacturing process to remove and/or inactivate these viruses. (TR41)
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Process Performance Qualification
Documented verification that a system is capable of consistently performing or controlling the activities of the processes it is required to perform or control, according to written and preapproved specifications, while operating in its specified operating environment. (TR01)
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Process Flow Diagram (PFD)
A document, typically prepared by R&D, that describes the intended manufacturing process. The PFD includes all relevant information for the operation of the manufacturing process, organized by unit operation. The PFD serves as the source document for the initial development of the master production records and is locked down once development has determined that the process can be controlled. (TR65)
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Post-fill Inspection
Inspection of glass containers after product filling. (TR43)
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Probability of a Non-Sterile Unit (PNSU)
The number that expresses the probability of occurrence of a non-sterile unit after exposure to a sterilization process. Within the pharmaceutical industry, a design end point better than or equal to the probability of one non-sterile unit in a million units is expected, i.e., PNSU ≤ 10–6. [Synonym: Steriliy Assurance Level (SAL)] (TR01)
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Process
A series of operations and/or actions used to produce a desired result. (TR38)
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Preventative Action
Action to eliminate the cause of a potential non-conformity or other undesirable potential situation. NOTE: Preventative action is taken to prevent occurrence whereas corrective action is taken to prevent recurrence. (TR54)
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Precision, Reproducibility
The closeness of agreement between a series of measurements for the same sample obtained among different laboratories. (TR57)
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Potency
The measure of the biological activity using a suitably quantitative biological assay, based on the attribute of the product that is linked to the relevant biological properties. (TR57)
An expression of the activity of a secondary calibration standard to relate units of weight (ng/ vial or ng/mL) to units of activity (EU/ng) in a preparation.(TR82)
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Pressure Hold Test (or Leak Test)
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)
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Volumetric Throughput (Vmax)
The maximum volume that can be processed through a filter area. It is the volumetric capacity of the filter for a given process fluid and generally expressed in L/m2. (TR41) (TR47)
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Void Volume
See Porosity. (TR45)
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Water for Injection (WFI)
Water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms and contains no added substances. (TR45)
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