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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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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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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Validation
A documented program that provides a high level of scientific assurance that a manufacturing process will reliably produce acceptable product. The proof of validation is obtained through rational experimental design and the evaluation of data, preferably beginning from the process development phase and continuing through the commercial production phase. (TR01)
A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (TR26) (TR57) (TR70) (TR74)
Documented testing, performed under highly controlled conditions, which demonstrates that a process consistently produces a result that meets predetermined acceptance a result that meets predetermined acceptance criteria. Used to test processes, methods, and systems for which conditions can be controlled in the real world (i.e., after completion of testing, when the process is in use). Transportation processes can be qualified but not validated; in the real world, it is not possible to exert control over all parameters that could affect the transportation process (e.g., weather, customs, traffic delays, mechanical failures, etc.). (TR58)
A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria. (Note: Validation is a lifecycle program which may include development and qualification activities for one or more elements/systems that form a process.) (TR54-5)
A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria (17). (TR60-3)
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Stakeholder(s)
Any individual, group or organization that can affect, be affected by or perceive itself to be affected by a risk. Decision makers might also be stakeholders. For the purposes of this guideline, the primary stakeholders are the patient, health-care professional, regulatory authority, and industry (ICH Q9). (TR54) (TR54-2)
Any individual, group, or organization that can affect, be affected by, or perceive itself to be affected by a risk. Decision makers might also be stakeholders. (TR54-5)
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Process 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. (TR3)
Confirming that the manufacturing process as designed is capable of reproducible commercial manufacturing. (TR54) (TR60) (TR54-5)
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Risk Management Report
Report that summarizes the outcomes of the QRM process. (TR54) (TR54-2) (TR54-5)
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Risk Evaluation
The comparison of the estimated risk to given risk criteria using a quantitative or qualitative scale to determine the significance of the risk (TR30) (TR54-2) (TR44) (TR58) (TR54-5)
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Risk Identification
The systematic use of information to identify potential sources of harm (hazards) referring to the risk question or problem description.(TR44) (TR54-2) (TR58) (TR54-5)
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Risk Analysis
The estimation of the risk associated with the identified hazards. (TR13) (TR30) (TR44) (TR54) (TR54-2) (TR58) (TR54-5)
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Risk Control
Items in place and/or actions to implement risk management decisions. (TR44)
Actions implementing risk management decisions. (TR54-2) (TR54-5) (TR84)
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Risk Review
An ongoing monitoring of events, output and results of the risk management process that takes into account new knowledge and experience. [A] step in the risk management process for taking in account of new knowledge and experiences. (TR44) (TR58)
Review or monitoring of output/results of the risk management process considering (if appropriate) new knowledge and experience about the risk. (TR54-2) (TR54-5)
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Risk Reduction
The process of decreasing the level of risk. (TR44)
Process for mitigation or avoidance of quality risk when it exceeds a specified (acceptable) level (e.g., reduce severity, probability of harm, and improves detectability of hazards and quality risks). (TR58)
Actions taken to lessen the probability of occurrence of harm and the severity of that harm. (TR54-2) (TR54-5)
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Risk Prioritization Number (RPN)
A quantitative method for determining the level of risk by multiplying the severity, occurrence and detectability rankings of the failure or event. (TR44)
The Risk Priority Number, or RPN, is a numeric assessment of risk assigned to a process, or steps in a process, as part of Failure Modes and Effects Analysis (FMEA), in which a team assigns each failure mode a numeric values that quantifies likelihood of occurrence, likelihood of detection, and severity of impact. (TR54-4)
A quantitative measure used when assessing the level of risk. (TR54-5)
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Quality System
Formalized business practices that define management responsibilities for organizational structure, processes, procedures, and resources needed to fulfill product/service requirements, customer satisfaction, and continual improvement. (TR30) (TR44)
The sum of all aspects of a system that implements quality policy and ensures that quality objectives are met. (TR54-5)
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Process Validation (EMA)
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes. (TR60) (TR54-5)
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Product Lifecycle
All phases in the life of a product from the initial development through marketing until the product’s discontinuation (ICH Q8[R2]. (TR54) (TR54-5)
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Quality Risk Management (QRM)
A systematic process for the assessment, control, communication, and review of risk to the quality of the drug product across the product lifecycle.(TR43)(TR54-2)(TR54-3)(TR57)(TR67)(TR68)
Documentation to prove that an installation/ equipment/process is designed and/or tested according to predefined specifications. Documentation may include Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ).(TR58)
A systematic process for the assessment, control, communication, and review of risks to the quality of the drug (medicinal) product across the product lifecycle.(TR 54-5)(TR 76)(TR88)
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Operational Qualification (OQ)
Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR14) (TR61) (TR64) (TR72)
The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges. (TR54-5)
Documented verification that the equipment or systems, as installed or modified, perform as intended throughout the anticipated operating ranges (17). (TR60-3)
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Performance Qualification (PQ)
Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications. (TR3) (TR14) (TR45) (TR42) (TR48) (TR61) (TR64)
Transport tests of product or representative product that is conducted during actual transportation or distribution. (TR39)
Documented evidence that provides a high degree of assurance that the equipment and/or system functions accurately and consistently according to predetermined specifications in its operating environment. (TR54-5)
Documented verification that the equipment and ancillary systems, as connected together, can perform effectively and reproducibly based on the approved process method and specifications (17). (TR60-3)
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Knowledge Management
Systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components (ICH Q10). (TR54) (TR68) (TR54-5)
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Installation Qualification (IQ)
Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements. (TR14) (TR42) (TR48) (TR61) (TR64)
The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations. (TR54-5)
Documented verification that the equipment or systems, as installed or modified, comply with the approved design, the manufacturer’s recommendations, and/or user requirements (17). (TR60)
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Good Engineering Practice (GEP)
Documented proven and accepted engineering methods and practices that applied throughout the project life-cycle to deliver solutions that are cost effective, are compliant with regulations and meet the requirements of the user. (TR48)
Those established engineering methods and standards that are applied throughout the lifecycle to deliver appropriate and cost-effective solutions. (TR60) (TR54-5)
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Fault Tree Analysis (FTA)
A deductive technique used to analyze the causes of faults (defects). The technique visually models how logical relationships between failures, human errors, and external events can combine to cause specific faults. (TR54) (TR54-2) (TR54-3) (TR54-5)
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Facilitator
Independent QRM expert who facilitates risk assessment; guides documentation, risk control, and risk review; and helps present risk assessment results and risk control proposals. (TR54-2) (TR54-5)
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Decommissioning
A planned and orderly removal of a facility, operation or system from use. (TR48)
The process of retiring equipment/systems/facilities from production use. (TR54-5)
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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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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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Control Strategy
A planned set of controls, derived from current product and process understanding, which ensures process performance and product quality. The controls can include parameters and attributes related to drug substance and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. (TR 54) (TR 60) (TR 54-5) (TR56)
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Commissioning
A well planned, documented and managed engineering approach to the start-up and transfer of facilities, systems and equipment to the end-user that results in a safe and functional environment that meets established design and user requirement specifications. Commissioning precedes Qualification and includes three phases:
1. Inspection, testing, and regulation
2. Adjustment and setting of work
3. Functional testing (TR 3)
A prescribed number of activities designed to take equipment and systems from a static, substantially complete state to an operable state. (TR 48)
A well planned, documented, managed engineering approach to the start-up and turnover of facilities, systems, and equipment to the end-user, that results in a safe and functional environment that meets established design requirements and stakeholder expectations.(TR 54) (TR 54-5)
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Change Management
A systematic approach to proposing, evaluating, approving, implementing, and reviewing changes. (TR 51) (TR 54-5)
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Acceptance Criteria
Numerical limits, ranges, or other suitable measures for acceptance of test results. (TR 14) (TR 29) (TR 38) (TR 64)
Numerical limits, ranges, or other suitable measures for acceptance of test results. Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation. Exceeding the operating range should be documented and explained in the validation report and evaluated for validation study impact. (TR 42)
The pre-defined specifications, standards or ranges that must be met under stated test conditions. (TR 48)
Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical method validation that is satisfied to determine suitability of test method performance.(TR 57) (TR 69) (TR 72) (TR 74)
The criteria that a system or component must satisfy in order to be accepted by a user or other authorized entity. (TR 54-5)
Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures which the drug substance or drug product or materials at other stages of their manufacture should meet (16). Exceeding the acceptable range for a critical parameter during subsequent validation studies may result in questionable product quality that would require initiation of an investigation and possible batch rejection. (TR60)
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