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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Target Criteria
Numerical limits, ranges, or other suitable measures of target performance levels of an analytical method that indicate suitable performance for intended use. For a method entering qualification, this is a target performance criterion that, when assessed, indicates that the method is qualified for its intended purpose. (TR57-2)
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Stress Studies (Degradation Pathway Studies)
Studies undertaken to elucidate the intrinsic stability of the drug substance and/or drug product; part of the development strategy and normally carried out under more severe conditions (e.g., high or low pH or oxidation levels, or shaking) than those used for accelerated testing. (TR57-2)
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Relative Accuracy
Attribute determined after demonstration of precision, linearity, and specificity under deliberately varied conditions, such as across a range of sample dilutions in the presence of matrix interference. (TR57-2)
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Risk Assessment
A systematic process of organizing information to support a risk decision to be made within a risk management process. It consists of identification of hazards and the analysis and evaluation of risk associated with exposure to those hazards. (TR30) (TR44) (TR54) (TR58) (TR55) (TR67) (TR57-2) (TR54-5) (TR88)
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Secondary (Working, In-house) Reference Standard
Substance of established quality and purity that is qualified against, and used instead of, the primary reference standard; typically used as a reference standard for routine laboratory analysis. (TR57-2)
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Sensitivity
Ability of a method to detect small changes in the quality attribute (e.g., changes in concentration or purity) being measured. (TR57-2)
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Quality Attribute
A molecular or product characteristic that is selected for its ability to help indicate the quality of the product, such as identity, purity, potency stability and safety. (TR57) (TR57-2)
A molecular or product characteristic that is selected for its ability to indicate the quality of the product. Collectively, the quality attributes define identity, purity, potency, and stability of the product, and safety with respect to adventitious agents. Specifications measure a selected subset of the quality attributes. (TR60-2)
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Platform-Based Method
Existing method based on the same basic principles and steps as a new method that is required and defined in the design/strategy phase; applies to multiple sample types and requires minimal changes or refinements based on specific product requirements. (TR57-2)
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Method Validation
A formal, archived demonstration of the analytical capacity of an assay that provides justification for use of the assay for an intended purpose. (TR56)
A formal, archived demonstration of the analytical capacity of an assay that provides justification for use of the assay for an intended purpose. Validations are conducted prospectively according to a written, approved plan that states acceptance criteria. (TR57) (TR57-2)
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Method Lifecycle
All stages in the life of a method, from the initial development through marketing, until the method’s discontinuation. (TR57-2)
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Matrix Effect
The direct or indirect alteration or interference in response due to the presence of additional sample components due to sample preparation (for analysis) or other interfering substances in the sample (product related excipients or residuals). (TR57) (TR57-2)
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In-Process Method (In-Process Control)
Checks performed during production to monitor and, if appropriate, adjust the process to ensure that the intermediate or active pharmaceutical ingredient conforms to its specifications. (TR57-2)
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Factor
Independent variables that may influence assay outcome. (May be modified with confounded, crossed, fixed, interaction, level, modifying, nested, random). (TR57) (TR57-2)
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Design of Experiments (DOE)
A method for carrying out carefully planned experiments on a process. Usually, DoE involves a series of experiments that initially involves evaluating many variables and then focuses on a few critical ones. (TR54-4)
A structured, organized method for determining the relationship between factors affecting an assay and output of that assay. (TR57) (TR57-2) (TR74)
A structured, organized method for determining the relationship between factors affecting a process and the output of that process (8). (TR60)
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Design Space
The multidimensional combination and interaction of input variables (e.g., material attributes) and operational parameters that have been demonstrated demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (TR30) (TR60) (TR 57-2)
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Critical Reagent
A component of the test method that may have a substantial impact on the consistency and reliability of method performance. Features of critical reagents include: 1. A reagent that requires qualification of each new batch prior to routine use in an analytical procedure, or 2. A material whose method performance characteristics may change over time, during handling, or from lot to lot. 3. An analytical reagent that may be purchased only from a single vendor. Reagent Examples: antibodies or enzymes that require titration prior to use, tissue culture treated plates when only one vendor’s plates give acceptable results for a bioassay, growth factors for bioassay cells, conjugated proteins that require custom preparations, or reference or system suitability standards. (TR57) Function related: assay reagents that have been shown through development and/or robustness studies to have the potential to generate measurable differences that can significantly affect assay performance, such as sensitivity, specificity, and precision. (TR57-2)
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Comparative Transfer
Transfer of a method that involves the analysis of a predetermined number of samples of the same lot by both the sending and the receiving unit. (TR 57-2)
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Characterization Method
Scientifically sound method of a generally complex nature that is used for nonroutine assessment of specific biochemical, chemical, physicochemical, immunochemical, microbiological, and biological characteristics or inherent properties of a compound. (TR 57-2)
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Bias
A systematic difference in a method that manifests itself as a deviation of the method mean from an expected value. (TR57) Total systematic error, in contrast to random error. Measurement centered on the true result is said to be unbiased or have no systematic error. The distance between the center of a large (infinite) number of measurements and the correct value is the bias. (TR 57-2)
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Analytical Control
Material used to monitor the performance of a method to assess the integrity and validity of the results. (TR57-2)
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Analytical Method Transfer (AMT)
Documented process that qualifies a laboratory (receiving unit) to use an analytical test procedure that originates in another laboratory (the transferring unit, also known as the sending unit), thus ensuring that the receiving unit has the knowledge and ability to perform the transferred analytical procedure as intended. (TR57-2)
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Analytical Method Design
Collection of activities performed to define the intended purpose of the method, select the appropriate technology to implement the method, and identify the critical method variables that need to be controlled to ensure that the method is robust and rugged. (TR57-2)
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Analytical Method Development (AMD)
Collection of activities performed to select an appropriate technique and method conditions to meet the Analytical Target Profile (ATP) requirements. (TR57-2)
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Accelerated Stability Testing
Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies. (TR57-2)
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