Validation Terminology PDF
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Uploaded by DarlingIris3230
State University of New York at Binghamton
Mokaram Hossain
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Summary
This document provides terminology related to validation, including definitions of key concepts such as validation (process related), validation (analytical method related), validation protocol, re-validation, and several other concepts. The concepts are explained in detail and provide a general overview of validation processes.
Full Transcript
TERMINOLOGY USED IN VALIDATION MOKARAM HOSSAIN 23-Nov-24 1 Validation (Process Related) Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre- determined specifications and quality att...
TERMINOLOGY USED IN VALIDATION MOKARAM HOSSAIN 23-Nov-24 1 Validation (Process Related) Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre- determined specifications and quality attributes. MOKARAM HOSSAIN 23-Nov-24 2 Validation (Analytical Method Related) Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use. The method validation process for analytical procedures begins with the planned and systematic collection by the applicant of the validation data to support analytical procedures. MOKARAM HOSSAIN 23-Nov-24 3 Validation is the assessment of the performance of a defined test method. The result of any successful validation exercise is a comprehensive set of data that will support the suitability of the test method for its intended use. MOKARAM HOSSAIN 23-Nov-24 4 A written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results. MOKARAM HOSSAIN 23-Nov-24 5 A repeat of the process validation to provide an assurance that changes in the process/equipment introduced in accordance with change control procedures do not adversely affect process characteristics and product quality. Repeated validation of an approved process (or a part thereof)to ensure continuous compliance with established requirements. MOKARAM HOSSAIN 23-Nov-24 6 A document describing the activities to be performed in a validation, including the acceptance criteria for the approval of a manufacturing process or a system-or a part thereof-for routine use. MOKARAM HOSSAIN 23-Nov-24 7 A document in which the records, results and evaluation of a completed validation programme are assembled and summarized. It may also contain proposals for the improvement of process and /or equipment. MOKARAM HOSSAIN 23-Nov-24 8 The VMP is a high-level document that establishes an umbrella validation plan for the entire project and summarizes the manufacturer’s overall philosophy and approach, to be used for establishing performance. It provides information on the manufacturer’s validation work programme and defines details of and timescales for the validation work to be performed, including a statement of the responsibilities of those implementing the plan. MOKARAM HOSSAIN 23-Nov-24 9 The application of methods, procedures, tests and other evaluations, in addition to monitoring, to determine compliance with the GMP principles. MOKARAM HOSSAIN 23-Nov-24 10 Numerical limits, range, or other suitable measures for acceptance of the results of analytical procedures/Process parameters. MOKARAM HOSSAIN 23-Nov-24 11 A dosage form that is identical to the drug product except that the drug substance is absent or replaced by an inert ingredient or a mixture of the drug product excipients quantitatively equivalent to th.ose found in the drug product dosage form MOKARAM HOSSAIN 23-Nov-24 12 The quality standard ( i.e. tests, analytical procedures, and acceptance criteria) provided in an approved application to confirm the quality of the drug substances, drug products, intermediates, raw material, reagents and other components including container closure systems, and in-process materials. MOKARAM HOSSAIN 23-Nov-24 13 The ratio of the output signal divided by the input signal. MOKARAM HOSSAIN 23-Nov-24 14 The value of the output signal when the input signal is zero. MOKARAM HOSSAIN 23-Nov-24 15 The gradual random change of the output signal with time when the input remains constant. MOKARAM HOSSAIN 23-Nov-24 16 The rapid random change of the output signal with time when the input remains constant. MOKARAM HOSSAIN 23-Nov-24 17 Category I: Validation of analytical methods for assay. Category II: Validation of analytical methods for impurities and degradants. Category III: I:Validation of analytical methods for dissolution. Category IV: I:Validation of analytical methods for identification. MOKARAM HOSSAIN 23-Nov-24 18 Accuracy Precision *Repeatability *Intermediate Precision *Reproducibility Specificity Detection Limit MOKARAM HOSSAIN 23-Nov-24 19 Quantitation limit Linearity Range Robustness System suitability Determination Forced degradation studies MOKARAM HOSSAIN 23-Nov-24 20 Solution stability studies Filter retention studies Extraction efficiency studies Additional methods validation information Representative instrument output Representative calculations Listing and characterization of known impurities Degradation pathways(if known) MOKARAM HOSSAIN 23-Nov-24 21 The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found. This is sometimes termed trueness. MOKARAM HOSSAIN 23-Nov-24 22 The precision of an analytical procedure expresses 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. MOKARAM HOSSAIN 23-Nov-24 23 Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision. MOKARAM HOSSAIN 23-Nov-24 24 Intermediate precision (ruggedness) expresses within- laboratories variations: different days, different analysts, different equipment, etc. MOKARAM HOSSAIN 23-Nov-24 25 Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology). MOKARAM HOSSAIN 23-Nov-24 26 Specificity (selectivity)is the ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically these might include impurities, degradants, matrix, etc. MOKARAM HOSSAIN 23-Nov-24 27 The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value. MOKARAM HOSSAIN 23-Nov-24 28 The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products. MOKARAM HOSSAIN 23-Nov-24 29 The linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. MOKARAM HOSSAIN 23-Nov-24 30 The range of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. MOKARAM HOSSAIN 23-Nov-24 31 The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage. MOKARAM HOSSAIN 23-Nov-24 32 a purified and characterized sample of a related substance. Authentic samples are used in method development to identify related substances in the analysis. they are used extensively to prepare the spiked samples in method validation. MOKARAM HOSSAIN 23-Nov-24 33 sample added with a known amount of related substances, prepared from authentic samples during method development or validation. MOKARAM HOSSAIN 23-Nov-24 34 a representative batch of drug substance (or drug product). MOKARAM HOSSAIN 23-Nov-24 35 the response of drug substance or related substances per unit weight. Typically, the response factor of drug substance (or related substance) can be calculated by the following equation: MOKARAM HOSSAIN 23-Nov-24 36 MOKARAM HOSSAIN 23-Nov-24 37 the ratio of the response factor of individual related substance to that of a drug substance to correct for differences in the response of related substances and that of the drug substance. It can be determined using the following equation: MOKARAM HOSSAIN 23-Nov-24 38 MOKARAM HOSSAIN 23-Nov-24 39 Relative response factor. MOKARAM HOSSAIN 23-Nov-24 40 % related substance = Area( related substance) x 100% / Total area where the area (related substance) is the peak area of the individual related substance and the total area is the peak area (i.e., response) of the drug substance plus the peak areas of all related substances. MOKARAM HOSSAIN 23-Nov-24 41 Area Percent is the preferred approach as long as the method performance meets the criteria described below. Linearity over a Wide Range of Concentration. Sample Concentration (Method Sensitivity). Response Factor MOKARAM HOSSAIN 23-Nov-24 42 chromatogram from high concentration MOKARAM HOSSAIN 23-Nov-24 43 High-Low chromatogram from low concentration MOKARAM HOSSAIN 23-Nov-24 44 Single-point calibration MOKARAM HOSSAIN 23-Nov-24 45 Multi-point calibration MOKARAM HOSSAIN 23-Nov-24 46 Quantitation limit MOKARAM HOSSAIN 23-Nov-24 47 MOKARAM HOSSAIN 23-Nov-24 48 Impact of relative response factor MOKARAM HOSSAIN 23-Nov-24 49 Intrinsic accuracy indicates the bias caused by sample matrix and sample preparation. MOKARAM HOSSAIN 23-Nov-24 50 Intrinsic accuracy MOKARAM HOSSAIN 23-Nov-24 51 Matrix effect Sample preparation Calculation error MOKARAM HOSSAIN 23-Nov-24 52 MOKARAM HOSSAIN 23-Nov-24 53 A validated quantitative analytical procedure that can detect the changes with time in the pertinent properties(e.g. active ingredient, preservatives level)of the drug substance and drug product. A stability-indicating assay accurately measures the active ingredients without interfering from degradation products, process impurities, excipients, or other potential impurities. MOKARAM HOSSAIN 23-Nov-24 54 A group of equipment with a common purpose. MOKARAM HOSSAIN 23-Nov-24 55 The set of operation that establish, under specified conditions, the relationship between values indicates by an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the values represented by a material measure , and the corresponding known values of a reference standard. MOKARAM HOSSAIN 23-Nov-24 56 The setting up, adjustment and testing of equipment or a system to ensure that it meets all the requirements as specified in the user requirement specification (URS), and capacities as specified by the designer or developer. Commissioning is carried out before qualification and validation. MOKARAM HOSSAIN 23-Nov-24 57 Established engineering methods and standards that are applied throughout the project life-cycle to deliver appropriate , cost-effective solutions. MOKARAM HOSSAIN 23-Nov-24 58 Action of providing and documenting that any premises, system and equipment are properly installed, and/or work correctly and lead to the expected results. Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone do not constitute process validation. MOKARAM HOSSAIN 23-Nov-24 59 Design qualification (DQ) Installation qualification (IQ) Operational qualification (OQ) Performance qualification (PQ) MOKARAM HOSSAIN 23-Nov-24 60 Design qualification (DQ) is the documented collection of activities that define the functional and operational specifications of the instrument and criteria for selection of the vendor, based on the intended purpose of the instrument. MOKARAM HOSSAIN 23-Nov-24 61 Installation qualification (IQ) is the documented collection of activities necessary to establish that an instrument is delivered as designed and specified, and is properly installed in the selected environment, and that this environment is suitable for the instrument. MOKARAM HOSSAIN 23-Nov-24 62 Operational qualification (OQ) is the documented collection of activities necessary to demonstrate that an instrument will function according to its operational specification in the selected environment. MOKARAM HOSSAIN 23-Nov-24 63 Performance qualification (PQ) is the documented collection of activities necessary to demonstrate that an instrument consistently performs according to the specifications defined by the user, and is appropriate for the intended use. MOKARAM HOSSAIN 23-Nov-24 64 Process Validation (PV) verifies the performance of the overall product manufacturing process. PV is performed on the entire product manufacturing process, which includes all support, processes, preparation of media, components, buffers, formulation, filtration, filling, and packaging. MOKARAM HOSSAIN 23-Nov-24 65 Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics. MOKARAM HOSSAIN 23-Nov-24 66 Process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality product MOKARAM HOSSAIN 23-Nov-24 67 Establishing confidence through appropriate testing that the finished product produced by a specified process meets all release requirements for functionality and safety. MOKARAM HOSSAIN 23-Nov-24 68 Validation conducted prior to the distribution of either a new product, or product made under a revised manufacturing process, where the revisions may affect the product's characteristics. MOKARAM HOSSAIN 23-Nov-24 69 Validation of a process for a product already in distribution based upon accumulated production, testing and control data. MOKARAM HOSSAIN 23-Nov-24 70 In-process monitoring of critical processing steps and end- product testing of current production can provide documented evidence to show that the manufacturing process is in a state of control. MOKARAM HOSSAIN 23-Nov-24 71 Represents the methods used to determine the critical unit operations or processing steps and their process variables, that usually affect the quality and consistency of the product outcomes or product attributes. MOKARAM HOSSAIN 23-Nov-24 72 A set of conditions encompassing upper and lower processing limits and circumstances, including those within standard operating procedures, which pose the greatest chance of process or product failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure. They are sometimes called "most appropriate challenge" conditions. MOKARAM HOSSAIN 23-Nov-24 73 Regulatory aspect: Process validation is a requirement of the Current Good Manufacturing Practices Regulations for Finished Pharmaceuticals, 21 CFR Parts 210 and 211, and of the Good Manufacturing Practice Regulations for Medical Devices, 21 CFR Part 820, and therefore, is applicable to the manufacture of pharmaceuticals and medical devices. MOKARAM HOSSAIN 23-Nov-24 74 Quality aspect: Due to the complexity of today's medical products, routine end-product testing alone often is not sufficient to assure product quality for several reasons. Some end-product tests have limited sensitivity. Process validation is a key element in assuring that quality assurance goals are met. MOKARAM HOSSAIN 23-Nov-24 75 THANK YOU MOKARAM HOSSAIN 23-Nov-24 76