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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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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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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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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Validation, partial
A documented prospective study intended to demonstrate suitability for the intended use of previously validated methods, specifically for new products and/or processes. (TR57)
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Standard Deviation
<p>The statistical measure of the dispersion of the data. (TR57) </p>
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Specification
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. (TR14)
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR38) (TR57)
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use. Drug product and drug substance specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities (TR69)
A list of tests, references to analytical procedures, and appropriate acceptance criteria, which are numerical limits, ranges, or other criteria for the tests described. It establishes the set of criteria to which a drug substance, drug product, or materials at other stages of its manufacture should conform to be considered acceptable for its intended use. “Conformance to specification” means that the drug substance and drug product, when tested according to the listed analytical procedures, will meet the acceptance criteria. Specifications are critical quality standards that are proposed and justified by the manufacturer and approved by regulatory authorities as conditions of approval. (TR56) (TR74)
A list of tests, references to analytical procedures, and appropriate acceptance criteria that are numerical limits, ranges, or other criteria for the test described. It establishes the set of criteria to which a material should conform to be considered acceptable for its intended use (17). (TR60-3)(TR88)
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State of Control
A condition in which the set of controls consistently provides assurance of continued process performance and product quality. (TR57)
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Spiking
The addition of a small known amount of a known compound to a standard, sample, or placebo, typically for the purpose of confirming the performance of an analytical procedure or the calibration of an instrument. (TR57)
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Specificity
The ability of an analytical procedure to accurately measure or detect a target analyte in the presence of other components in the sample matrix. (TR50) The ability to assess unequivocally the analyte in the presence of components that may be expected to be present. Typically these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). (TR57) The ability to detect a range of microorganisms, which demonstrate that the method is fit for its intended use. (TR33)
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Stability-Indicating Analytical Method
A test procedure that is able to discern changes in an analyte due to degradation processes. It is capable of accurately measuring changes in the product that can occur under conditions of physical or chemical stress. (TR57)
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Superiority
A comparison with the primary objective of showing that the result from one method is superior to the method being compared. This is usually demonstrated by showing that the true difference is likely to lie between zero and the upper equivalence margin. (TR57)
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Suitability, system
Acceptance criteria for a valid reported result(s). [Synonym: Assay quality control] (TR57)
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Reproducibility
The precision among multiple laboratories (collaborative studies, usually applied to standardization of methodology). (TR57) The precision between laboratories, for example, through collaborative studies. (TR33)
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Replicates
Independent preparations of a sample or standard that are subject to the same treatment conditions. (TR57)
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Regression
A mathematical model in which the response of a dependent variable is a function of change in an independent variable, such as is seen in a concentration-response curve. Regression may be linear (e.g., a straight line) or non-linear (e.g., four parameter logistic). (TR57)
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Reportable result
The final analytical result. This result is defined in the written approved test method and derived from one full execution of that method, starting from the original sample. (TR57)
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Recovery
The mass of desired solute in the final product solution (either permeate or retentate, depending on the process), divided by the mass of the desired solute in the initial feed solution, expressed as a percentage. [Synonym: yield] (TR15) (TR45) A measure of the amount of analyte carried through the entire sample preparation and assay procedure and expressed as a percentage of the nominal concentration. (TR57)
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Repeatability
The precision under the same operating conditions over a short interval of time. (TR57)
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Robustness
The measure of capacity to remain unaffected by small, but deliberate, variations in method parameters and provides an indication of its reliability during normal usage. (TR57) (TR33)
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Process Validation
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or API (drug substance) meeting its predetermined specifications and quality attributes. (TR14) (TR42)
Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. (TR44)
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. (TR54) (TR57) (TR74)
The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product.
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, as described in EMA, EU GMP, Part 1, Annex 15, drug/medicinal product. (TR56)
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.
US FDA: The collection and evaluation of data, from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products. (TR60-2)
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce an intermediate or drug substance meeting its predetermined specifications and quality attributes (1, 17). (TR60-3)
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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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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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Method, Quantitative
An analytical procedure that yields numerical results compared to quantitative specification(s). (TR57)
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Method, Qualitative
An analytical procedure, based on the characteristics of a material that yields results that are not amenable to reliable enumeration. (TR57)
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Noninferiority
A comparison with the primary objective of showing that the result from one method is not inferior to the method being compared. This is usually demonstrated by showing that the true difference is likely to lie above the lower equivalence margin. (TR57)
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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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Limit, Quantitation (QL)
The lowest amount of analyte is a sample that can be quantitatively determined with suitable precision and accuracy by an individual analytical procedure. [Synonym: Limit of quantitation (LOQ)] (TR57)
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Limit, Detection (DL)
The lowest amount of analyte in a sample that can be detected but not necessarily quantitated as an exact value by an individual analytical procedure. [Synonym: Limit of detection (LOD)] (TR57)
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Matrix
The combination of materials (e.g., excipients, stabilizer components, etc.) which are components together with the measured analyte. (TR57)
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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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Method Development
A process that involves the selection, optimization, and qualification of a physical/chemical, biological, molecular, or microbiological test procedure. (TR57)
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Method Qualification
Formal or informal study performed to assess initial method performance prior to full ICH Q2 (R1) validation; assessment activity that culminates in a scientifically sound method that has an acceptable level of performance and is documented to be suitable for its intended use. (TR56)
Experimental studies performed to confirm the inherent performance capabilities of a test method for the material being analyzed and the intended use of the method. Method qualification can be performed during early development phases, prior to method validation. Specific method qualification characteristics (e.g., accuracy, specificity) should be confirmed based on the intended use of the analytical method and the relevant risk(s). (TR57)
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Linearity
The ability to elicit results that are proportional to the concentration of microorganisms present in the sample within a given range, where accuracy and precision are demonstrated. (TR33) The linearity of an analytical procedure is its ability (within a given range) to obtain test results that are directly proportional to the concentration (amount) of analyte in the sample. (TR57)
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Method Comparability
The demonstration of analytical method comparability (AMC) for method replacements. A study to demonstrate that a modification to an existing method either improves or does not significantly change the analytical procedure’s characteristics relative to the methods’ validation and intended use. (TR57)
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Identification
Use of an analytical procedure to determine the chemical and biochemical identity of a material. (TR57)
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Independent Replicates
Two or more measurements or observations that are generated from independently prepared samples and do not affect each other. (TR57)
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Impurity
Any component present in the drug substance or drug product that is not the desired product, a product-related substance, or excipient including buffer components. It may be either processor product-related. (TR14) (TR57) (TR74)
Any component present in the drug substance or drug product which is not the desired product, a product-related substance, or excipient. It may be either process- or product-related (17). (TR60)
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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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Excipient
A component of a drug formulation that has no active pharmacologic function. Excipients are commonly used in drug formulations as modulators of pH or osmolality for parenteral administration and as stabilizers for APIs. (TR54-4)
An ingredient added intentionally to the drug substance that should not have pharmacological properties in the quantity used. (TR57)
Inactive pharmaceutical ingredients in a product formulation that are responsible for the product’s manufacturability and physicochemical attributes. (TR67) (TR88)
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Equivalence Margin
The largest difference between the results from two methods that is considered as being scientifically and statistically acceptable. (TR57)
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Error
Deviation from expected value. Error may be random or systematic. (TR57)
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Drug Product (DP)
A pharmaceutical product type that contains a drug substance, generally, in association with excipients. [Synonym: Dosage Form; Finished Product] (TR57)(TR14)(TR42)
A finished dosage form (e.g., tablet, capsule, or solution) that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.(TR38) (TR67) (TR88)
The dosage form in the final immediate packaging intended for marketing.(TR60)(TR82)
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Drug Substance (DS)
The active ingredient that is subsequently formulated with excipients to produce the drug product. It can be composed of the desired product, product-related substances, and product- and process-related impurities. It may also contain excipients, including buffers and other components. [Synonyms: bulk drug substance, bulk material, active pharmaceutical ingredient (API)] (TR14) (TR57) (TR74) (TR60)
Active pharmaceutical ingredient in a drug product that is responsible for that product’s therapeutic activity.(TR67) (TR82) (TR88)
See Active Pharmaceutical Ingredient (API). (TR56)
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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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Degradation Product
Molecular variants resulting from changes in the desired product or product-related substance brought about over time and/or by the action of light, temperature, pH, water, etc., or by reaction with an excipient and/or the immediate container/ closure system. Such changes may occur because of manufacture and/or storage (e.g., deamidation, oxidation, aggregation, proteolysis). Degradation products may be either product-related substance or product-related impurities. (TR57)
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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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Correlation Coefficient ( r )
A measure of covariation, the square root of the coefficient of determination. (TR57)
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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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